Clinical trial NCT03989440
Conditions: Chronic Spinal Cord Injury
Keywords: myelin-associated inhibitor Nogo-A MAG OMgp Nogo Receptor
Sponsor: ReNetX Bio, Inc.
Start date: 2019-07-16; Completion date: 2022-06-21
Enrollment: 52 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This two-part trial will assess the safety, tolerability, pharmacokinetics, and efficacy of AXER-204 administered by lumbar puncture and slow bolus infusion. Part 1 will evaluate the safety, tolerability, and pharmacokinetics of single ascending doses of AXER-204. Part 2 will evaluate the safety, tolerability, pharmacokinetics, and efficacy of repeated doses AXER-204 in comparison to placebo.

Detailed description:
AXER-204 is a human fusion protein that acts as a soluble decoy/trap for the myelin-associated inhibitors of axonal growth known as Nogo-A, MAG, and OMgp. AXER-204 and a surrogate protein used in early preclinical studies have been found to promote axon growth and recovery of function in animal models of spinal cord injury.

Part 1 of the trial is a multicenter, open-label, single ascending dose study in participants with chronic cervical spinal cord injury. Four cohorts of 6 participants each are planned, with participants within each cohort expected to receive the same dose of AXER-204.

Part 2 is a multicenter, randomized, double-blind, placebo-controlled, repeat dose study in chronic cervical spinal cord injury participants. Approximately 32 participants will be randomized (ratio 1:1) to receive repeated doses of AXER-204 or placebo (a phosphate buffered saline formulation). The dose level and dose frequency will be dependent upon outcomes from Part 1.

Arms: arm 1: Part 1 - Single ascending doses; Part 2 - Repeated dose arm 2: Part 2 only - Repeated dose
Interventions: intervention 1: AXER-204 intervention 2: Placebo
Intervention descriptions: intervention 1: human NoGo Trap fusion protein intervention 2: Phosphate buffered saline formulation

Protocol documents:
ICF_002.pdf: 
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INFORMED CONSENT  
 
 
TITLE: A Multicenter, Two Part (Open-Label Single-Ascending Dose Followed by  
            Double-Blind, Placebo-Controlled Repeat Dose) Study to Evaluate the  
            Safety, Tolerability, Pharmacokinetics, and Efficacy of AXER-204 in  
            Subjects with Chronic Spinal Cord Injury (the RESET* Study) 
 
SHORT TITLE:  *RESET- Chronic SCI Study.  ReNetX Safety Efficacy and 
     Tolerability of AXER-204 for Chronic SCI 
 
 
PROTOCOL NO.: RNX-AX204-101 
 
 
 
Part 2  
 
CLINICALTRIALS.GOV IDENTIFIER:  NCT03989440 
 
SPONSOR:   
                    ReNetX Bio, Inc. 
       157 Church St. 19th Floor 
New Haven, CT 06510 
 
 
 
 
INVESTIGATOR: 
 
«PI_FIRST_NAME» «PI_LAST_NAME» 
 
TELEPHONE: 
 
«PHONE_NUMBER» 
 
INTRODUCTION 
Before agreeing to participate in this research study, it is important that you read and 
understand the following explanation of the proposed research study.  This consent 
document describes the purpose, procedures, benefits, risks, discomforts and 
precautions of the study.  It also describes the alternative procedures that are available 
to you and your right to withdraw from the study at any time.  No guarantees or 
assurances can be made as to the results of the study. 
 
If you are not completely truthful with your study doctor regarding your health history, 
you may harm yourself by participating in this study. 
 
The study is being conducted for ReNetX Bio, Inc.  Your study doctor is being paid by 
ReNetX Bio, Inc. (ReNetX) to conduct this study.  
 
  
BACKGROUND AND PURPOSE  
 
You are being asked to participate in this research study because you have been 
diagnosed with chronic spinal cord injury (CSCI). CSCI occurs when an injury takes 
place that causes nerve damage and interrupts the fibers between nerve cells.   


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This is a 2-part study consisting of Part 1 and Part 2. The length of time that you would 
be asked to participate and some of the requirements and procedures in each part is 
also different. You are being asked to participate in Part 2 of the study.  
 
The purpose of Part 2 of this research study is to determine if repeated doses of the 
study drug, AXER-204 can be safely administered and tolerated. AXER-204 is 
investigational and is not approved by the United States Food and Drug Administration 
(FDA). “Investigational” means that the study drug is currently being tested.   
 
This study will also evaluate the pharmacokinetics (or “PK”) (measurement of how the 
drug moves within the body) of repeat doses of AXER-204 at several time points before, 
during and after the administration of study drug. Your blood samples will also be tested 
to determine if your body has formed antibodies to AXER-204. Antibodies are protein 
substances that your body produces in your blood that help the body to reject foreign 
substances. They help to fight diseases but also can cause allergic reactions. The study 
will also explore biomarkers, substances that your body makes that can indicate how 
your spinal cord is responding to AXER-204. 
 
This is a double-blind study, which means you, the study doctor and the study staff will 
not know if you are receiving AXER-204 (200 mg) or placebo. A ‘placebo’ looks like the 
study drug but does not have any active substance in it. The term “study drug” refers to 
either AXER-204 or placebo. You will be randomly assigned like the flip of a coin to 
receive  either AXER-204 or placebo. You will have a 50% chance of receiving either 
AXER-204 or placebo which will be administered once every 3 weeks for 15 weeks. The 
dose and dose interval may be changed during the study based on study data as 
determined by the Sponsor. 
NUMBER OF SUBJECTS 
About 32 subjects from the ages of 18 to 65 years will participate in Part 2 at 
approximately 5 centers in the United States.   
 
LENGTH OF PARTICIPATION  
 
Your participation in this study will last approximately 12 months and include up to 11 
visits to the study center. If at any time you decide you don’t want to be in the study, you 
can choose not to participate.    
  
 
EXPECTATIONS  
 
If you participate in this study, you will be expected to:  
• Attend each study visit as requested 


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• Follow instructions of the study doctor regarding washout of any prohibited 
medication that you are taking and informing the study staff if you take any new 
medications or undergo any medical procedures during the entire study period 
• Notify the study staff if you have a bad reaction after receiving the study drug 
• Follow instructions provided to you for care after completion of each lumbar 
puncture 
 
PROCEDURES  
 
If you agree to participate in the study, you will first sign (written or electronically) this 
consent form. You will then have a screening visit to determine if you are eligible to 
participate. The following tests and procedures will be performed during the screening 
visit to determine if you qualify to take part in this study:   
 
Screening Period  
WASHOUT 
 
If you are taking certain medications that are prohibited by the study, you may need to 
stop taking them prior to enrolling in the study. This is called a washout period during 
which time the effects of these medications leave your body. The study doctor will 
decide if it is safe for you to stop taking these medications and will let you know when 
you must stop taking these medications. It is important to let your study doctor know all 
the medications you are taking as some may affect how the study drug works. 
OTHER MEDICATIONS – Stable Dose 
If you are taking certain anti-depressants, anti-spasmodic or anti-spasticity drugs and 
have been on a stable dose for at least 12 weeks before you sign this informed consent 
form and you agree to stay on the same dose throughout the study, you may be able to 
be enrolled in this study.   
SCREENING 
Visit 1, (Study Days -84 through -1) 
 
The Screening period is the first visit in the study and can take place over up to an 84-
day period (Days -84 to -1). During this visit, the study doctor will discuss the study with 
you and the procedures you will undergo to understand whether you can participate. 
The study doctor will also review with you the medications you are taking.  
 
• 
If you are female, you cannot participate in the study if you are pregnant, 
lactating, or nursing. If you suspect that you might be pregnant, please inform 
your study doctor. Blood will be collected for a pregnancy test.    
• 
You will be assigned a 6-digit subject identification number which will be used to 
identify you throughout the study and entered on all of your study-related 
documentation. 


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• 
Your study doctor will record your age, gender and race, medical and surgical 
history, and medications that you have taken in the past or are currently taking.   
• 
You will undergo a complete physical examination and your height and weight 
will be measured. Your vital signs (blood pressure, pulse rate, respiratory rate or 
the oxygen levels in your blood, and oral body temperature) will be taken after 
you have been in a sitting position for 5 minutes. 
• Blood samples (about 2 to 3 tablespoons) will be obtained for clinical laboratory 
tests.  The blood samples will be taken within 28 days of study drug 
administration (i.e. within 28 days of Visit 2). Your blood may also be analyzed 
for biological markers. 
• Your blood will also be tested to see if you test positive for viruses including the 
human immunodeficiency virus (HIV), hepatitis B surface antigen, and hepatitis C 
antibody. If the results of these viral tests are positive, you will not be able to 
participate in this study.   
• 
You will be asked to provide a urine sample for routine clinical laboratory testing.  
Your urine will also be tested for drugs of abuse. If positive, you may be 
precluded from participation in the study.  
• 
Three, 12-lead electrocardiograms (ECGs), a measurement and recording of the 
electrical activity of the heart, will be taken 5 minutes apart and after you have 
been in a supine (resting) position for at least 5 minutes. 
• A study staff member will administer several assessments using questionnaires 
and evaluations. You will be asked to respond to these questionnaires.  If you are 
not able to complete a response yourself on the questionnaire, you will be asked 
to verbally provide your responses to the questions to a member of the study 
staff who will collect the results. These results will be entered into an electronic 
data capture (EDC) system. You will also undergo physical assessment for 
motor, sensory and autonomic function (i.e. blood pressure regulation) and 
detailed assessment of ability to use arms and hands. This assessment will be 
video recorded. 
• A Magnetic Resonance Imaging (MRI) scan will be scheduled and you must 
complete this before you complete the Screening visit and before you can 
continue in the study. An MRI is a test that uses powerful magnets, radio waves, 
and a computer to make detailed pictures of the inside of your body. Your study 
doctor will use this test to view your spinal column. In addition to MRI, your study 
doctor may elect to evaluate your spine and brain using either X-ray imaging or 
CT scans (an X-ray image made using a form of tomography in which a 
computer controls the motion of the X-ray source and detectors, processes the 
data, and produces the image). 


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• If all results of your required study entry screening procedures are found to be 
acceptable, you will be given an appointment for the next study visit.   
• If any results of your required study entry screening procedures are found to be 
unacceptable for you to continue in the study, your participation in this study will 
end at this visit. 
• If you will be continuing on to the next Study visit, you will be given an 
appointment reminder card that contains the date and time for your next visit. 
You will receive an appointment reminder card for each scheduled visit during 
the study. 
Treatment Period 
Visit 2 (Study Day 1) 
The following procedures will occur at this visit: 
 
• Your medical and surgical history, as well as your prior and current medications 
will be reviewed for a second time to determine if you still remain eligible for the 
study. If you do not remain eligible for the study, your participation in this study 
will end at this visit. 
• You will be randomly assigned to receive either AXER-204 or placebo. 
• You will undergo a shortened physical examination.  
• Your vital signs (blood pressure, pulse rate, respiratory rate or the oxygen levels 
in your blood, and oral body temperature) will be taken pre-dose, post-dose and 
then every 2 hours until you leave the clinic. Each time your vitals are taken, it 
will be after you have been in a sitting position for 5 minutes. 
• Three, 12-lead electrocardiograms (ECGs) will be taken 5 minutes apart after 
you have been in a supine (resting) position for at least 5 minutes. 
• A study staff member will administer several assessments using questionnaires 
and evaluations. You will also undergo physical assessment for motor, sensory 
and autonomic function and detailed assessment of ability to use arms and 
hands. This assessment will be video recorded. 
• If you are a female of childbearing potential, you will be given a urine pregnancy 
test. You must have a negative urine pregnancy test to continue in the study. 
• Blood will be collected for clinical laboratory tests, pharmacokinetic (PK) analysis, 
and anti-drug antibody (ADA) testing. PK collections will occur pre-dose and 4 
hours post-dose. Your blood may also be analyzed for biological markers of drug 
activity. 


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• You will be asked to provide a urine sample for routine clinical laboratory testing. 
• You will have a lumbar puncture and approximately 9-20 mL of cerebrospinal 
fluid (CSF) collected prior to receiving study drug: 
o The study requires that you have lumbar punctures (also known as spinal 
taps) performed. A trained and qualified medical designee will perform the 
lumbar puncture and study drug administration. Prior to the lumbar 
puncture procedure, you may be given a local anesthetic (numbing/pain-
relieving medication). 
o If the study doctor is not able to collect the appropriate amount of CSF for 
you to receive study drug, you may be asked to return the following day 
for another attempt.  
o To administer the study drug, the physician will place a needle between 2 
lumbar bones (vertebrae) in your lower back, into your spinal canal. This is 
known as an intrathecal injection. During this procedure, a small amount 
of CSF (equivalent to one-half to one-and-a half tablespoons) will be 
collected into a test tube. The CSF is the fluid that surrounds your brain 
and spinal cord to protect them from injury. The CSF will undergo tests to 
see how much drug stays in your spinal fluid analysis and may also be 
analyzed for markers of drug activity. Following the withdrawal of the CSF, 
the study drug in a quantity approximately equal to the amount of CSF that 
was withdrawn, will be injected into your spinal canal.  
o You will be asked to remain in the hospital for at least 4 hours after dosing 
for observation. In addition, your study doctor may have you stay 
overnight in the hospital or at a nearby accommodation for safety 
monitoring. 
On Study Day 8, a member of the study team will call you to see how you are doing. 
You may be asked to come into the clinic for an evaluation. 
Visits 3, 5, and 7 (Study Days 21, 63, and 104) 
The following procedures will occur at these visits: 
 
• Your medications will be reviewed, your general health will be monitored, and 
you will be asked how you are feeling. You must let the study doctor know of any 
symptoms you are experiencing. 
• You will undergo a shortened physical examination. 
• Your vital signs (blood pressure, pulse rate, respiratory rate or the oxygen levels 
in your blood, and oral body temperature) will be taken pre-dose, post-dose and 
then every 2 hours until you leave the clinic. Each time your vitals are taken, it 
will be after you have been in a sitting position for 5 minutes. 


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• Three, 12-lead electrocardiograms (ECGs) will be taken 5 minutes apart after 
you  have been in a supine (resting) position for at least 5 minutes. This will be 
done pre-dose.  
• A study staff member will administer various assessments using questionnaires 
and evaluations. At Visits 5 and 7, you will also undergo physical assessment for 
motor, sensory and autonomic function and detailed assessment of ability to use 
arms and hands. This assessment will be video recorded. 
• Blood will be collected for clinical laboratory tests, pharmacokinetic (PK) analysis, 
and anti-drug antibody (ADA) testing. PK collections will occur pre-dose and 4 
hours post-dose. Your blood may also be analyzed for biological markers of drug 
activity. 
• You will have a lumbar puncture and cerebrospinal fluid (CSF) collected. 
Following the withdrawal of the CSF, the study drug will be injected into your 
spinal canal. The CSF will undergo tests to see how much drug stays in your 
spinal fluid analysis and may also be analyzed for markers of drug activity 
• If you are female of childbearing capacity, you will have a urine pregnancy test. 
• You will be asked to provide a urine sample for routine clinical laboratory testing. 
Visits 4 and 6 (Study Days 42 and 84) 
The following procedures will occur at these visits: 
 
• Your medications will be reviewed, your general health will be monitored and you 
will be asked how you are feeling. You must let the study doctor know of any 
symptoms you are experiencing. 
• 
You will undergo a shortened physical examination.  
 
• Your vital signs (blood pressure, pulse rate, respiratory rate or the oxygen levels 
in your blood, and oral body temperature) will be taken pre-dose, post-dose, and 
then every two hours until you leave the clinic. Each time your vitals are taken, it 
will be after you have been in a sitting position for 5 minutes. 
• Three, 12-lead electrocardiograms (ECGs) will be taken 5 minutes apart after 
you have been in a supine (resting) position for at least 5 minutes. This will be 
done pre-dose. 
• Blood will be collected for pharmacokinetic (PK) analysis and anti-drug antibody 
(ADA) testing. ADA will be collected pre-dose. PK collections will occur pre-dose 
and 4 hours post-dose. Your blood may also be analyzed for biological markers 
of drug activity. 


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• You will have a lumbar puncture and cerebrospinal fluid (CSF) collected. 
Following the withdrawal of the CSF, the study drug will be injected into your 
spinal canal. The CSF will undergo tests to see how much drug stays in your 
spinal fluid analysis and may also be analyzed for markers of drug activity. 
• If you are female of childbearing capacity, you will have a urine pregnancy test. 
• You will be asked to provide a urine sample for routine clinical laboratory testing. 
Phone Call (Month 5) 
On Study Day 137 (Month 5), a member of the study team will call you to see how you 
are doing. You may be asked to come into the clinic for an evaluation. 
 
Follow-Up Period 
Visit 8 (Study Day 169/Month 6) 
The following procedures will occur at this visit: 
 
• Your medications will be reviewed, your general health will be monitored, and 
you will be asked how you are feeling. You must let the study doctor know of any 
symptoms you are experiencing. 
• 
You will undergo a shortened physical examination and your vital signs (blood 
pressure, pulse rate, respiratory rate or the oxygen levels in your blood, and oral 
body temperature) will be taken after you have been in a sitting position for 5 
minutes. 
 
• Three, 12-lead electrocardiograms (ECGs) will be taken 5 minutes apart after 
you have been in a supine (resting) position for at least 5 minutes. 
• A study staff member will administer several assessments using questionnaires 
and evaluations. You will also undergo physical assessment for motor, sensory 
and autonomic function and detailed assessment of ability to use arms and 
hands. This assessment will be video recorded. 
• Blood will be collected for clinical laboratory tests, pharmacokinetic (PK) analysis, 
and anti-drug antibody (ADA) testing. Your blood may also be analyzed for 
biological markers of drug activity. Your blood will also be retested HIV, hepatitis 
B surface antigen, and hepatitis C antibody.   
• If you are female of childbearing capacity, you will have a urine pregnancy test. 
• You will be asked to provide a urine sample for routine clinical laboratory testing. 
Visit 9 (Study Day 253/Month 9) or Early Termination 
The following procedures will occur at this visit or at your final visit if you leave the study 
early: 


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• Your medications will be reviewed, your general health will be monitored, and 
you will be asked how you are feeling. You must let the study doctor know of any 
symptoms you are experiencing. 
• You will undergo a complete physical examination and your height and weight 
will be measured. Your vital signs (blood pressure, pulse rate, respiratory rate or 
the oxygen levels in your blood, and oral body temperature) will be taken after 
you have been in a sitting position for 5 minutes. 
• Three, 12-lead electrocardiograms (ECGs) will be taken 5 minutes apart after 
you have been in a supine (resting) position for at least 5 minutes. 
• A study staff member will administer several assessments using questionnaires 
and evaluations.  You will also undergo physical assessment for motor, sensory 
and autonomic function and detailed assessment of ability to use arms and 
hands. This assessment will be video recorded. 
• You will have a lumbar puncture and cerebrospinal fluid (CSF) collected. The 
CSF may undergo tests to see how much drug stays in your spinal fluid analysis 
and may also be analyzed for markers of drug activity.  
• Blood will be collected for clinical laboratory tests, pharmacokinetic (PK) analysis, 
and anti-drug antibody (ADA) testing. Your blood may also be analyzed for 
biological markers of drug activity. Your blood will also be retested HIV, hepatitis 
B surface antigen, and hepatitis C antibody.  
• If you are female of childbearing capacity, you will have a urine pregnancy test. 
• You will be asked to provide a urine sample for routine clinical laboratory testing. 
 
RISKS, SIDE EFFECTS AND/OR DISCOMFORTS  
 
AXER-204 is a new investigational drug and has not previously been given to humans.   
Immune response (reaction within the body that is caused by foreign substances) to 
AXER-204 in pre-clinical (animal) testing has been limited to the development of serum 
anti-drug antibodies. 
 
In 14-day studies of rats and monkeys given daily intrathecal doses (injection into the 
spinal canal) of AXER-204, the drug was found to not be harmful to these animals. In 
other studies, rats were given injections of AXER-204 into the spinal canal every other 
day for 2 months and monkeys were given AXER-204 also into the spinal canal for up to 
110 days.  Again, AXER-204 was found to not be poisonous or harmful to these 
animals.    
No human experience is available regarding the risk of immune response to AXER-204.  
In the administration of any biologic protein (drugs made from a living organism or its 


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products) such as AXER-204, there is a chance of adverse reactions arising from immune 
reactions. These reactions include but are not limited to:  anaphylaxis (acute allergic 
reaction [for example like that of a bee sting] to which the body has become 
hypersensitive, and delayed hypersensitivity reactions. Symptoms associated with these 
reactions may include: fever, rash, arthralgia (joint pain), myalgia (muscle pain), 
hematuria (presence of blood in the urine), proteinuria (abnormal quantities of protein in 
the urine), serositis (inflammation of certain types of tissues such as those that line the 
lungs, heart, and abdomen), central nervous system (CNS) complications, and hemolytic 
anemia.  Injection site reactions may also occur. In rare instances, antibodies may form 
against proteins in your own body requiring long-term treatment.   
 
If you are assigned to receive placebo, you will not be receiving treatment and your 
condition may become worse or stay the same.  
 
There may be possible risks associated with certain study procedures and medications 
administered before the LP. These are included in the table below.  
 
Table 3   POSSIBLE RISKS FROM STUDY PROCEDURES 
Procedure 
Possible Risks  
Lumbar puncture 
Bleeding at the injection site; Infection; Post-lumbar puncture 
headaches (small risk); needle injury; injury to the spinal 
cord or nerve pain 
Allergic reaction 
Allergic reactions, while rare, can occur, and include fever, 
rash, myalgia (muscle pain), hematuria (blood in your urine), 
proteinuria (presence of abnormal amount of protein in your 
urine), serositis (inflammation of a serous membrane for 
example the  membrane that is found around the lung), 
central nervous system complications and hemolytic anemia 
(condition where red blood cells are destroyed and removed 
from the blood before their normal lifespan is over), skin 
irritations, breathing difficulties (similar to asthma), feeling 
flush, itching and shock.   
If you are allergic or have sensitivity to the pain-relieving 
medication, iodine or latex that may be used during the 
lumbar puncture, please talk to your study doctor ahead of 
the lumbar puncture.  
ECG 
Skin redness, itching, and irritation could occur from the skin 
sensors that are placed on your skin.  
Blood Draws 
Possible side effects from blood drawing may include 
faintness, inflammation of the vein, pain, bruising, or 
bleeding at the site of needle puncture.  There is also a slight 
possibility of infection.  


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MRI 
You must notify the study doctor if you have any type of 
metal implants (staples, screws, clips, pins, plates, stents, 
artificial heart valves) in your body as well as any metal in 
your body related to your SCI since the MRI scan involves a 
machine that has powerful magnets. If you are 
claustrophobic, you may feel uncomfortable while in the MRI 
machine. 
X-ray Imaging/CT Scans 
Procedures such as X-ray imaging, CT-scans, and 
fluoroscopy may be used during this research study to 
assess your spine and head. The cumulative radiation 
exposure from these tests is considered small and is not 
likely to adversely affect you. However, the effects of 
radiation add up over a lifetime.  It is possible that having 
several of these tests may add to your risk of injury or 
disease. When deciding to enter this study, think about your 
past and future contact with radiation. Examples of contact 
with radiation include x-rays taken for any reason or 
radiation therapy for cancer treatment. 
 
 
Fluoroscopy: 
If the physician is having difficulty placing the needle for a lumbar puncture, or he/she 
does not obtain enough CSF after two attempts, you may have to have fluoroscopy to 
assist with the placement. Fluoroscopy is a real-time X-ray of the part of your body where 
the LP needle will be placed.   
 
Please tell the study doctor or study staff right away if you have any of the above or other 
side effects. Please tell them if you have any other problems with your health or the way 
you feel during the study. 
Intrathecal Administration of study drug: 
The study drug is given to you by intrathecal administration (injection into the spinal 
canal).  In general, adverse events associated with the use of intrathecal therapy are 
rare.  Your study doctor will provide you with additional instructions after the procedure.  
However, you should immediately notify the study doctor if you experience any side 
effects following administration of the study drug. 
 
UNFORESEEN RISKS  
Since the study drug is in a new investigational preparation and not previously tested in 
humans, there may be other risks that are unknown. All drugs have a potential risk of an 
allergic reaction, which if not treated promptly, could become life-threatening. 
 


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PREGNANCY / BIRTH CONTROL  
Taking the study drug may involve unknown risks to a pregnant woman, an embryo, 
fetus (unborn baby) or nursing infant. Therefore, if you are pregnant, planning to 
become pregnant or are breastfeeding a child, you cannot participate in this study. 
 
If, during this study, you become pregnant, you should notify the study doctor as soon 
as possible.  If your pregnancy occurs during the Screening phase, your participation in 
the study will end and you will not receive study drug.   Information about your 
pregnancy and its outcome will be collected and used to learn more about the effects of 
the study drug on pregnancy. 
A serum pregnancy test will be done at Screening, and a urine pregnancy test will be 
done each time before you receive study drug. However, at any time during the study, if 
you feel that you may be pregnant, talk to your study doctor. 
If you are a male subject and you impregnate your partner during the study period after 
you have received your dose of study drug, please notify the study doctor.  The study 
doctor will ask permission from your partner in order to conduct any follow-up or collect 
any information. 
Payment for all aspects of obstetrical care, child-or related care will be your 
responsibility. 
In order to reduce the risk of pregnancy, you must use an effective method of birth 
control while you are participating in this study (and for at least 7 days after you 
complete the study treatment). Acceptable methods of birth control for use in this study 
include:  double barrier contraception (e.g., condom plus spermicide in combination with 
a female condom, diaphragm, cervical cap, contraceptive sponge, implants, injectables, 
combined oral contraceptives, sexual abstinence (total abstinence from sexual 
intercourse as the preferred lifestyle of the patient; periodic abstinence is not 
acceptable), or sexual intercourse with only a vasectomized partner. If you or your 
partner is surgically sterile or if the study doctor confirms that you are postmenopausal, 
then you are exempt from this requirement. 
If you are already using a method of birth control, the study doctor or study staff will 
discuss with you whether your current method of birth control is acceptable for use 
during this study.  
 
HUMAN BIOLOGICAL SAMPLES 
While you are in this study, you will have sample(s) taken from you. These samples will be 
used for commercial medical research to support this study protocol which will be 
performed by the laboratory described below.  
WHAT SAMPLES WILL BE USED FOR:  
a. Your CSF and blood samples will be used for the research purposes explained in 
the procedures section of this form. 


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b. Your samples will not be sold or used directly for the production of commercial 
products.  
c. In case of any commercial gain based on research results from your samples, 
ReNetX Bio, Inc. will have the ownership of the research results and may file 
patents. The research done with your samples may help to develop new products, 
new medical tests or treatments in the future that have commercial value. There will 
be no financial benefit to you for any commercial findings or products as a result of 
your sample use. By agreeing to take part in this clinical research study, you agree 
to give up your rights for any commercial value resulting from your samples and 
data. 
d. Your samples may be provided to a third party for testing and research use and 
storage purposes done for and on behalf of the sponsor of this study and its third 
party collaborators.  
e. Your samples will be coded to protect your identity. 
f. Reports about research done with your samples will not be put in your 
health/medical record and will be kept confidential to the best of our ability within the 
law. 
 
ALTERNATIVE TREATMENT 
 
You do not have to be in this study to receive treatment for your chronic spinal cord injury.  
Your options include: prevention of complications, bladder and bowel management, 
intensive rehabilitation, physical therapy, and analgesia. Your doctor will discuss the risks 
and benefits of your options.  
 
NEW FINDINGS  
 
Any new important information that is discovered during the study and which may 
influence your willingness to continue participation in the study will be made available to 
you. 
 
BENEFITS 
 
Your condition may or may not get better from participating in this study. There is no 
guarantee that you will benefit from your participation in this study. You may receive 
placebo and therefore will not receive any treatment for your condition. Results from this 
study may help us to treat people with your condition in the future.  
 
COMPENSATION FOR PARTICIPATION  
 
You will be paid $XX at the completion of each study visit for transportation to and from 
the study site.   
 
CONFIDENTIALITY    


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Records of your participation in this study will be held confidential except when sharing 
the information is required by law or as described in this informed consent. The study 
doctor, the sponsor or persons working on behalf of the sponsor, and under certain 
circumstances, the United States Food and Drug Administration (FDA) and the 
Institutional Review Board (IRB) will be able to inspect your original medical records and 
copy confidential study-related records which identify you by name for verification of 
study data and procedures. This means that absolute confidentiality cannot be 
guaranteed. If the results of this study are published or presented at meetings, you will 
not be personally identified. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law. This Web site will not include information that can identify you.  At 
most, the Web site will include a summary of the results.  You can search the Web site 
at any time. 
 
REIMBURSEMENT FOR MEDICAL EXPENSES RELATED TO INJURY 
 
If you are injured as a result of being in this study, you should seek medical help 
immediately and arrange to notify the study doctor as soon as possible.   
 
If you suffer a physical injury that is directly related to the proper administration of the 
study drug(s) or the proper performance of a procedure done for the purpose of this 
study, the sponsor will reimburse those reasonable and necessary medical expenses 
you incur to treat such injury as long as such injury is not a result of (a) a healthcare 
provider’s failure to follow the study protocol, requirements of the Institutional Review 
Board (IRB) that oversees the study at the institution conducting the study, written 
instructions from the sponsor, or applicable laws or regulations, (b) your failure to follow 
your study doctor’s or the study staff’s instructions for the study or (c) a pre-existing 
condition or underlying illness, whether previously diagnosed or not.  The sponsor will 
determine if the injury is caused by the study drug and the reasonableness of the 
expenses taking into consideration the study doctor’s evaluation, other physicians’ 
evaluations of the patient, sponsor’s experience with the study drug and other relevant 
factors.   You must also have called and told your study doctor as soon as possible of 
your injury.   The sponsor has no plans to reimburse for any such expenses that are 
covered by your medical insurance or any other third-party coverage.  No other form of 
compensation is available, except remedies available under the law.  You will not lose 
any of your legal rights or release the Sponsor, the study doctor, the study staff, or 
study site from liability for mistakes or intentional misconduct by signing this consent 
document. 
 
If you are injured during this study, your study doctor will discuss with you the available 
medical treatment options. 
 
COSTS 


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There will be no charge to you for your participation in this study. The study drug, 
placebo for reconstitution, the study related procedures, study related medical visits, 
and laboratory tests related to this study will be paid for by the study site through the 
study Sponsor (ReNetX Bio, Inc.). You will not need to pay for any tests or procedures 
that are done for the sole purposes of this study. You or your insurance company will be 
charged for any other portion of your care that is considered standard of care.  You will 
be responsible for any co-payments and deductibles for your insurance plan’s coverage 
of care that is considered standard of care. Please ask your study doctor if you have 
questions about what you may have to pay for during your participation in this study.   
 
EMERGENCY CONTACT / IRB CONTACT  
 
During the study, if you experience any medical problems, suffer a research-related 
injury, or have questions, concerns or complaints about the study, please contact the 
study doctor at the telephone number listed on page one of this consent document.  If 
you seek emergency care, or hospitalization is required, alert the treating physician that 
you are participating in a research study being conducted by the study doctor listed on 
page one of this document.   
 
If you have any questions about your rights as a research subject, and/or concerns or 
complaints regarding this research study, you should write to «Insert IRB address and 
contact» 
 
VOLUNTARY PARTICIPATION / WITHDRAWAL  
 
Your decision to participate in this study is voluntary.  You may choose to not participate 
or you may withdraw from the study for any reason without penalty or loss of benefits to 
which you are otherwise entitled and without any effect on your future medical care.  
There are no consequences or safety considerations if you decide to withdraw from 
study participation. 
 
The study doctor or the sponsor can stop your participation at any time without your 
consent for the following reasons: 
 
• If it appears to be medically harmful to you; 
• If you fail to follow directions for participating in the study; 
• If it is discovered that you do not meet the study requirements; 
• If the study is canceled; or  
• For administrative reasons, including competitive enrollment - the target number of 
subjects has entered the study. 
 
If you leave the study for any reason, the study doctor may ask you to have some end-
of-study tests for your safety.   
 
PRIMARY CARE PHYSICIAN / SPECIALIST NOTIFICATION OPTION 
 


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Please indicate below whether you want us to notify your primary care physician or your 
specialist of your participation in this study. 
 
________ 
Yes, I want the study doctor to inform my primary care physician/specialist 
of my participation in this study. 
 
________ 
No, I do not want the study doctor to inform my primary care 
physician/specialist of my participation in this study. 
 
________ 
I do not have a primary care physician/specialist. 
 
________ 
The study doctor is my primary care physician/specialist. 
 
 


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CONSENT   
 
I have read and understand the information in this informed consent document.  I have 
had an opportunity to ask questions and all of my questions have been answered to my 
satisfaction. I voluntarily agree to participate in this study until I decide otherwise.  I do 
not give up any of my legal rights by signing this consent document.  I will receive a 
copy of this signed consent document. 
 
 
____________________________________  
 
 
Subject’s Printed Name  
 
 
____________________________________  
 
_________  
Subject’s Signature  
 
 
 
 
 
Date 
 
 
____________________________________  
 
 
Printed Name of the Person Conducting the  
 
 
 
Consent Discussion  
 
 
 
_____________________________________  
 
___________ 
Signature of the Person Conducting the   
 
 
Date  
Consent Discussion  
 
 
 
 
 
 
 
 
 
 


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AUTHORIZATION TO USE AND DISCLOSE 
PROTECTED HEALTH INFORMATION 
 
During your participation in this research study, the study doctor and study staff will 
collect or create personal health information about you (for example, medical histories 
and results of any tests, examinations or procedures you undergo while in the study) 
and record it on study documents.  The study doctor will keep this personal health 
information in your study-related records (that we will refer to as "your study records").  
In addition, the study doctor may obtain, and include in your records, information 
regarding your past, present and/or future physical or mental health and/or condition.  
Your study doctor may ask you to sign a separate authorization to obtain some or all of 
your medical records from your doctor.  Your study records may include other personal 
information (such as social security number, medical record numbers, date of birth, 
etc.), which could be used to identify you.  Health information that could identify you is 
called "Protected Health Information" (or "PHI").   
 
Under federal law (the "Privacy Rule"), your PHI that is created or obtained during this 
research study cannot be "used" to conduct the research or "disclosed" (given to 
anyone) for research purposes without your permission.  This permission is called an 
"Authorization".  Therefore, you may not participate in this study unless you give your 
permission to use and disclose your PHI by signing this Authorization.  By signing, you 
are agreeing to allow the study doctor and staff to use your PHI to conduct this study.   
 
By signing this Authorization, you also are agreeing to allow the study doctor to disclose 
PHI as described below: 
 
• The sponsor of this study and anyone working on behalf of the sponsor to conduct 
this study (referred to as "the sponsor").  The sponsor will analyze and evaluate the 
PHI and may use it to develop new tests, procedures and commercial products.  The 
study staff will assign a code number and/or letters to your records, which means 
that you will not ordinarily be identified in the records sent to the sponsor.  The 
sponsor may, however, look at your complete study records that identify you.  In 
addition, the sponsor may visit the study site to oversee the way the study is being 
conducted and may review your PHI during these visits to make sure the information 
is correct.   
• The Institutional Review Board ("IRB") may have access to your PHI in relation to its 
responsibilities as an Institutional Review Board. 
• Your PHI may be seen by A Data Safety Monitoring Board that will be convened to 
review data for this study 
 
The study doctor or sponsor may disclose your PHI to the United States Food and Drug 
Administration ("FDA") or similar regulatory agencies in the United States and/or foreign 
countries. 
 
These disclosures also help ensure that the information related to the research is 
available to all parties who may need it for research purposes. 


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Except for the disclosures described above, your PHI will not be shared with others 
unless required by law.  If your PHI is given to the parties listed above and/or to others 
who are not required to comply with the federal law, your PHI will no longer be protected 
by this law and could possibly be used or disclosed in ways other than those listed here.  
 
You have a right to see and make copies of your PHI.  You are agreeing, however, by 
signing this document, not to see or copy some or all of your PHI until the sponsor has 
completed all work related to this study.  At that time, you may ask to see your records. 
 
This Authorization will expire 50 years from the date you sign it unless you revoke 
(cancel or withdraw) it sooner.   
 
You have a right to revoke your Authorization at any time.  If you revoke it, your PHI will 
no longer be used for this study, except to the extent the parties to the research have 
already taken action based upon your Authorization or need the information to complete 
analysis and reports for this research.  To revoke your Authorization, you must write to 
the study doctor, stating that you are revoking your Authorization to Use and Disclose 
Protected Health Information.  If you revoke this Authorization, you will not be allowed to 
continue to be in this study. 
 
You will receive a copy of this Authorization after you have signed it. 
 
 
____________________________________ 
Printed Name of Subject 
 
____________________________________  
__________ 
Signature of Subject 
 
 
 
 
 
Date 
 
____________________________________ 
Printed Name of the Person Obtaining the  
Authorization 
 
____________________________________  
__________ 
Signature of the Person Obtaining the 
 
 
Date 
Authorization  
 
   


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INFORMED CONSENT  
 
 
TITLE: A Multicenter, Two Part (Open-Label Single-Ascending Dose Followed by  
            Double-Blind, Placebo-Controlled Repeat Dose) Study to Evaluate the  
            Safety, Tolerability, Pharmacokinetics, and Efficacy of AXER-204 in  
            Subjects with Chronic Spinal Cord Injury (the RESET* Study) 
 
SHORT TITLE:  *RESET- Chronic SCI Study.  ReNetX Safety Efficacy and 
     Tolerability of AXER-204 for Chronic SCI 
 
 
PROTOCOL NO.: RNX-AX204-101 
 
 
 
Part 1  
 
CLINICALTRIALS.GOV IDENTIFIER:  NCT03989440 
 
SPONSOR:   
                    ReNetX Bio, Inc. 
       157 Church St. 19th Floor 
New Haven, CT 06510 
 
 
 
 
INVESTIGATOR: 
 
«PI_FIRST_NAME» «PI_LAST_NAME» 
 
TELEPHONE: 
 
«PHONE_NUMBER» 
 
INTRODUCTION 
Before agreeing to participate in this research study, it is important that you read and 
understand the following explanation of the proposed research study.  This consent 
document describes the purpose, procedures, benefits, risks, discomforts and 
precautions of the study.  It also describes the alternative procedures that are available 
to you and your right to withdraw from the study at any time.  No guarantees or 
assurances can be made as to the results of the study. 
 
If you are not completely truthful with your study doctor regarding your health history, 
you may harm yourself by participating in this study. 
 
The study is being conducted for ReNetX Bio, Inc.  Your study doctor is being paid by 
ReNetX Bio, Inc. (ReNetX) to conduct this study.  
 
 «Insert IRB name» has approved the information in this consent document and has 
given approval for the study doctor to do the study.  An institutional review board (IRB) 
is an independent committee established to help protect the rights of research 
subjects.  This does not mean the IRB has approved your participation in the 
study.  You must think about the information in this consent document for yourself.  You 
must then decide if you want to be in the study. 


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BACKGROUND AND PURPOSE  
 
You are being asked to participate in this research study because you have been 
diagnosed with chronic spinal cord injury (CSCI). CSCI occurs when an injury takes 
place that causes nerve damage and interrupts the fibers between nerve cells.   
 
This is a 2-part study consisting of Part 1 and Part 2.  The length of time that you would 
be asked to participate and some of the requirements and procedures in each part is 
also different.  You cannot participate in both parts of the study.  Based on the 
information presented to you, you have indicated to the study doctor and staff that you 
are willing to participate in Part 1 of the study and therefore, you are being provided this 
informed consent form.   
 
The purpose of this research study is to determine if a single dose of the study drug, 
AXER-204 can be safely administered and tolerated.  AXER-204 is investigational and 
is not approved by the United States Food and Drug Administration (FDA).  
“Investigational” means that the study drug is currently being tested.   
 
This study will also evaluate the pharmacokinetics (or “PK”) (measurement of how the 
drug moves within the body) of a single dose of AXER-204 at several time points 
before, during and after the administration of study drug.  Your blood samples will also 
be tested to determine if your body has formed antibodies to AXER-204.  Antibodies are 
protein substances that your body produces in your blood that help the body to reject 
foreign substances. They help to fight diseases but also can cause allergic reactions. 
 
This is an open-label study, which means you, the study doctor and the study staff will 
know that you are receiving the study drug, AXER-204.  You will be assigned to one of 
4 dose groups also known as a cohort. Each dose group will receive a different dose of 
the study drug as described in the table below. You will be informed by the study doctor 
which dose group you have been assigned to. 
NUMBER OF SUBJECTS 
About 24  subjects between the ages of 18 and 65 years will participate in Part 1.   Each 
group will initially consist of 6  subjects as shown in the table below.   
Table 1   Treatment by Group- Part 1  
Group 
Treatment 
Number Subjects 
1 
3 mg AXER-204 
6  
2 
30 mg AXER-204 
6  
3 
90 mg AXER-204 
6  
4 
200 mg AXER204 
6  
 


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Because you will receive only 1 dose of study drug, the Sponsor plans to offer subjects 
who receive study drug in Part 1 of the study the opportunity to be screened for a 
subsequent open label repeat dose study.  If you are enrolled in that open label study, 
you would receive repeat dose treatment with AXER-204 matching treatment in Part 2 
of the trial. Initiation of the open label study is not guaranteed and will be based on 
satisfactory results from both parts of the current clinical study, continued development, 
funding, as well as regulatory and Institutional Review Board (IRB) approvals. 
 
LENGTH OF PARTICIPATION  
 
Your participation in this study will last approximately 16 weeks and include up to 5 visits 
to the study center with one of the visits having a 3-day in-patient stay. If at any time you 
decide you don’t want to be in the study, you can choose not to participate.   After 
administration of the study drug, you will be required to remain in the in-patient clinical 
unit for 3 days so that you can be monitored for safety. 
  
 
EXPECTATIONS  
 
If you participate in this study, you will be expected to:  
• Attend each study visit as requested 
• Follow instructions of the study doctor regarding washout of any prohibited 
medication that you are taking and informing the study staff if you take any new 
medications or undergo any medical procedures during the entire study period 
• Notify the study staff if you have a bad reaction after receiving the study drug 
• Follow instructions provided to you for care after completion of each lumbar 
puncture 
 
SPECIAL PROCEDURES (Lumbar Puncture and CSF Collection)  
 
Before any study-related tests and procedures are performed, you will be asked to read 
and sign this informed consent document.  The study requires that you have lumbar 
punctures (also known as spinal taps) performed. A trained and qualified medical 
designee will perform the lumbar puncture and study drug administration.  Prior to the 
lumbar puncture procedure, you may be given a local anesthetic (numbing/pain-
relieving medication).     
To administer the study drug, the physician will place a needle between 2 lumbar bones 
(vertebrae) in your lower back, into your spinal canal.  This is known as an intrathecal 
injection.  During this procedure, a small amount of cerebrospinal fluid or CSF (9-20 
milliliters) which is equivalent to one-half to one-and-a half tablespoons will be collected 
into a test tube.  The CSF is the fluid that surrounds your brain and spinal cord to 
protect them from injury.  The CSF will undergo PK analysis and may also be analyzed 
for markers of drug activity.  Following the withdrawal of the CSF, the study drug in a 
quantity approximately equal to the amount of CSF that was withdrawn will be injected 
into your spinal canal 


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Table 2 below lists the schedule (Study Days) when you will have lumbar punctures 
performed and CSF collected for analyses.  During the study you will have 5 lumbar 
punctures performed; the first one will be done before you receive your dose of study 
drug on Study Day 1.  Only a single dose of study drug will be given in Part 1 and you 
will not receive study drug after Day 1.   You will also have lumbar punctures on Study 
Days 2, 4, 8 and 29 to collect CSF.  Approximately 5 mL of CSF will be collected on 
Days 2, 4, 8, and 29 for PK analysis. 
 
Table 2:   Schedule of Lumbar Punctures & CSF Collection 
 
Study Day 1 
(Dosing day) In 
Clinical Unit 
Study Day 
2 (24 
hours 
after dose 
±10 min) 
(In Clinic) 
Study Day 4, (72 
hours after dose ± 
10 min) In 
Clinic/Day of 
Discharge 
Study Day 
8 (± 1 day) 
Study Day 29 (± 2 
days) or Early 
Termination from 
Study 
Lumbar 
Puncture 
Before Dose 
X 
X 
X 
X 
CSF 
Collection 
Before Dose  
X 
X 
X 
X 
 
 
PROCEDURES 
 
The following tests and procedures will be performed to determine if you qualify to take 
part in this study:   
 
Screening Period (including Washout) 
WASHOUT 
 
If you are taking certain medications such as opiates (used for pain reduction, and can 
cause drowsiness), sedatives (eg, Valium®  or Librium®, used to reduce tension, 
anxiety, and can cause drowsiness),, or tranquilizers (medications that help to reduce 
tension or anxiety), and the study doctor agrees that it is safe for you to stop taking 
these medications for at least 2 weeks prior to Visit 2, Study Day 1, and remain off 
these medications until the final study visit is completed, you may be able to be enrolled 
in this study.   This is called a washout period during which time the effects of these 
medications leave your body.  The study doctor will let you know when you must stop 
taking these medications. 
OTHER MEDICATIONS – Stable Dose 
If you are taking any pain or anti-inflammatory medication such as acetaminophen, 
medication used to treat swelling, joint, or muscle stiffness, or certain anti-depressants 
or St. John’s Wort and have been on a stable dose for at least 12 weeks before you 
sign this informed consent form and you agree to stay on the same dose throughout the 
study, you may be able to be enrolled in this study.   


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If you are using anti-inflammatory medication on an as needed basis (ie. not a stable 
dose) then you need to stop use of medication two weeks before the dose and stay off 
of the medication until two days after the dose of study drug. 
SCREENING 
Visit 1, Study Days -84 through -1 
 
The Screening period is the first visit in the study and can take place over up to an 84-
day period (Days -84 to -1).  During this visit, the study doctor will discuss the study with 
you and the procedures you will undergo to understand whether you can participate. 
The study doctor will also review with you the medications you are taking.  
 
• 
If you are female, you cannot participate in the study if you are pregnant, 
lactating, or nursing.  If you suspect that you might be pregnant, please inform 
your study doctor    
• 
You will be assigned a 6-digit subject identification number which will be used to 
identify you throughout the study and entered on all of your study-related 
documentation 
• 
Your study doctor will record your age, gender and race, medical and surgical 
history, and medications that you have taken in the past or are currently taking   
• 
You will undergo a complete physical examination and your height and weight 
will be measured. Your vital signs (blood pressure, pulse rate, respiratory rate or 
the oxygen levels in your blood, and oral body temperature) will be taken after 
you have been in a sitting position for 5 minutes 
• Blood samples (about 2 to 3 tablespoons) will be obtained for clinical laboratory 
tests. If you are female, your blood will be tested to make certain that you are not 
pregnant.  The blood samples will be taken within 28 days of study drug 
administration (i.e. within 28 days of Visit 2). 
• Your blood will also be tested to see if you test positive for viruses including the 
human immunodeficiency virus (HIV), hepatitis B surface antigen, and hepatitis C 
antibody.  If the results of these viral tests are positive, you will not be able to 
participate in this study.   
• 
You will be asked to provide a urine sample for routine clinical laboratory testing.  
Your urine will also be tested for drugs of abuse including marijuana.  If positive- 
you may be precluded from participation in the study. If you live in a state where 
marijuana use is legal, you should abstain from using marijuana at least 3 days 
before the Screening Visit (Visit 1).  
• 
Three, 12-lead electrocardiograms (ECGs), a measurement and recording of the 
electrical activity of the heart, will be taken 5 minutes apart and after you have 
been in a supine (resting) position for at least 5 minutes. 


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• A study staff member will administer several assessments using questionnaires 
and evaluations.  You will be asked to respond to these questionnaires.  If you 
are not able to complete a response yourself on the questionnaire, you will be 
asked to verbally provide your responses to the questions to a member of the 
study staff who will collect the results.  These results will be entered into an 
electronic data capture (EDC) system.  You will also undergo physical 
assessment for motor, sensory and autonomic function (i.e. blood pressure 
regulation) and detailed assessment of ability to use arms and hands. A 
Magnetic Resonance Imaging (MRI) scan will be scheduled and you must 
complete this before you complete the Screening visit and before you can 
continue in the study.  A MRI is a test that uses powerful magnets, radio waves, 
and a computer to make detailed pictures of the inside of your body.  Your study 
doctor will use this test to view your spinal column. In addition to MRI, your study 
doctor may elect to evaluate your spine and brain using either X-ray imaging or 
CT scans (an X-ray image made using a form of tomography in which a 
computer controls the motion of the X-ray source and detectors, processes the 
data, and produces the image) 
• If all results of your required study entry screening procedures are found to be 
acceptable, you will be given an appointment for the next study visit    
• If any results of your required study entry screening procedures are found to be 
unacceptable for you to continue in the study, your participation in this study will 
end at this visit 
• If you will be continuing on to the next Study visit, you will be given an 
appointment reminder card that contains the date and time for your next visit 
In- Clinic Treatment (Pre-Dose & Post-Dose) Visit 2 
The second visit of the study is the In-Clinic Treatment Visit to be conducted at Visit 2, 
Study Days 1 through 4 
 
Study Day 1, PRE-DOSE 
 
• Your medical and surgical history, as well as your prior and current medications 
will be reviewed for a second time to determine if you still remain eligible for the 
study.  If you do not remain eligible for the study, your participation in this study 
will end at this visit 
• If you remain eligible to continue in the study, you will be admitted to the in-
patient clinical unit where you will remain in the unit for the next 3 days 
• You will undergo a shortened physical examination and your vital signs (blood 
pressure, pulse rate, respiratory rate or the oxygen levels in your blood, and oral 
body temperature) will be taken after you have been in a sitting position for 5 
minutes 


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• Three, 12-lead electrocardiograms (ECGs) will be taken 5 minutes apart before 
you receive your dose of study medication, and after you have been in a supine 
(resting) position for at least 5 minutes 
• If you are a female, you will be given a urine pregnancy test. You must have a 
negative urine pregnancy test to continue in the study 
• A blood sample  will be drawn to check for bleeding problems.  Some of this 
blood sample will also be used for clinical laboratory testing, pharmacokinetic 
(PK) analysis, and anti-drug antibody (ADA) testing. 
Study Day 1, POST-DOSE 
• Your medications will be reviewed, your general health will be monitored, and 
you will be asked how you are feeling.  You must let the study doctor know of any 
symptoms you are experiencing 
• Three, 12-lead electrocardiograms (ECGs) will be taken 5 minutes apart after 
you receive your dose of study medication, and after you have been in a supine 
(resting) position for at least 5 minutes 
• Your vital signs (blood pressure, pulse rate, respiratory rate or the oxygen levels 
in your blood, and oral body temperature) will be taken after you have been in a 
sitting position for 5 minutes 
• At 1 hour, 6 hours and 12 hours after you receive your dose of study drug, blood 
will be drawn and serum, a part of your blood, obtained for PK analysis  
Study Day 2, POST-DOSE 
• Your medications will be reviewed, your general health will be monitored and you 
will be asked how you are feeling.  You must let the study doctor know of any 
symptoms you are experiencing 
• Your vital signs (blood pressure, pulse rate, respiratory rate or the oxygen levels 
in your blood, and oral body temperature) will be taken after you have been in a 
sitting position for 5 minutes 
• You will have blood drawn for clinical laboratory testing  and for PK analysis. 
• You will remain in the unit for the next 2 days 
Study Day 3, POST-DOSE 
• Your medications will be reviewed, your general health will be monitored and you 
will be asked how you are feeling.  You must let the study doctor know of any 
symptoms you are experiencing 


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• Your vital signs (blood pressure, pulse rate, respiratory rate or the oxygen levels 
in your blood, and oral body temperature) will be taken after you have been in a 
sitting position for 5 minutes 
• You will have blood drawn for clinical laboratory testing  
Study Day 4, POST-DOSE 
• Any medications you are taking will be reviewed, your general health will be 
monitored, and you will be asked how you are feeling 
• Three, 12-lead electrocardiograms (ECGs) will be taken 5 minutes apart after 
you have been in a supine (resting) position for at least 5 minutes 
• You will undergo a shortened physical examination.  Your vital signs (blood 
pressure, pulse rate, respiratory rate or the oxygen levels in your blood, and oral 
body temperature) will be taken after you have been in a sitting position for 5 
minutes 
• You will have blood drawn for clinical laboratory testing and PK analysis. 
• You will be discharged from the clinical unit to home.  You should make 
arrangements for transportation or the site will make arrangements for you since 
you should not drive immediately after the lumbar puncture 
• You will be reminded that you will receive telephone calls from the clinical site on 
Study Days, 5, 6, and 7 to inquire about your general health and to see how you 
are doing 
• You will be given an appointment reminder for your next visit to the clinical site  
Post-Treatment Follow-up Study Days 5, 6, 7, 8 (±1 day), 15 (±1 day) & 29 (± 2 days)  
Study Days 5, 6 and 7 
 
You will not need to come to the clinical site on these days.  Instead a member of the 
study staff will contact you by phone to inquire about any changes to the medications 
you were previously taking or any new medications you have taken since your last visit.  
They will also inquire about your general health and to see how you are doing. 
 
Visit 3, Study Day 8 (at Clinical Site) 
 
• 
Any medications you are currently taking will be reviewed, the study staff will 
inquire about your general health and you will be monitored before and after the 
lumbar puncture 


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• Your vital signs (blood pressure, pulse rate, respiratory rate or the oxygen levels 
in your blood, and oral body temperature) will be taken after you have been in a 
sitting position for 5 minutes 
 
• You will have blood drawn for PK analysis and ADA testing 
 
 
• You will be given an appointment reminder for your next visit to the clinical site  
Visit 4, Study Day 15 (at Clinical Site) 
• Any medications you are currently taking will be reviewed, and the study staff will 
inquire about your general health  
• Your vital signs (blood pressure, pulse rate, respiratory rate or the oxygen levels 
in your blood, and oral body temperature) will be taken after you have been in a 
sitting position for 5 minutes 
 
• Blood samples (about 2 to 3 tablespoons) will be obtained for clinical laboratory 
tests and PK analysis. You will be given an appointment reminder for your next 
and last visit to the clinical site  
Visit 5, Study Day 29 (at Clinical Site) 
This will be the final visit for the study. This visit will last longer than the other visits you 
have had since you received your dose of study drug.  The research staff will let you 
know how long you will be at the clinical site.  For scheduling purposes, this visit may be 
scheduled either 2 days before or delayed for up to 2 days after your scheduled visit 
day.  If prior to this visit, you were to be removed from the study by the Study Doctor, 
you will be asked to have these same procedures performed.   
  During this visit: 
• You will undergo a complete physical examination, your height and weight will be 
measured, and your vital signs (blood pressure, pulse rate, respiratory rate or the 
oxygen levels in your blood  and oral body temperature) will be taken after you 
have been in a sitting position for 5 minutes 
• A study staff member will administer several assessments using questionnaires 
and evaluations.  You will be asked to respond to these questionnaires.  If you 
are not able to complete a response yourself on the questionnaire, you will be 
asked to verbally provide your responses to the questions to a member of the 
study staff who will collect the results.  These results will be entered into an 
electronic data capture (EDC) system.  You will also undergo physical 
assessment for motor, sensory and autonomic function (i.e. blood pressure 
regulation) and detailed assessment of ability to use arms and hands. Blood 
samples (about 2 to 3 tablespoons) will be obtained for clinical laboratory tests, 


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PK analysis, and ADA testing.  You will also be asked to provide a urine sample 
for clinical laboratory analysis 
• If you are female, you will be given a urine pregnancy test to make certain that 
you are not pregnant  
• Your blood will also be tested to see if you test positive for viruses including the 
human deficiency virus (HIV), hepatitis B surface antigen, and hepatitis C 
antibody.  If the results of these viral tests are positive, you will be counseled by 
the study doctor or your personal physician about treatment options   
• Three, 12-lead electrocardiograms (ECGs), a measurement and recording of the 
electrical activity of the heart, will be taken 5 minutes apart and after you have 
been in a supine (resting) position for at least 5 minutes 
 
RISKS, SIDE EFFECTS AND/OR DISCOMFORTS  
 
AXER-204 is a new investigational drug and has not previously been given to humans.   
Immune response (reaction within the body that is caused by foreign substances) to 
AXER-204 in pre-clinical (animal) testing has been limited to the development of serum 
anti-drug antibodies. 
 
In 14-day studies of rats and monkeys given daily intrathecal doses (injection into the 
spinal canal) of AXER-204, the drug was found to not be poisonous or harmful to these 
animals.  In other studies, rats were given injections of AXER-204 into the spinal canal 
every other day for 2 months and monkeys were given AXER-204 also into the spinal 
canal for up to 110 days.  Again, AXER-204 was found to not be poisonous or harmful 
to these animals.    
 
No human experience is available regarding the risk of immune response to AXER-204.  
In the administration of any biologic protein (drugs made from a living organism or its 
products) such as AXER-204, there is a chance of adverse reactions arising from immune 
reactions.  These reactions include but are not limited to:  anaphylaxis (acute allergic 
reaction [for example like that of a bee sting] to which the body has become 
hypersensitive, and delayed hypersensitivity reactions.  Symptoms associated with these 
reactions may include:  fever, rash, arthralgia (joint pain), myalgia (muscle pain), 
hematuria (presence of blood in the urine), proteinuria (abnormal quantities of protein in 
the urine), serositis (inflammation of certain types of tissues such as those that line the 
lungs, heart, and abdomen), central nervous system (CNS) complications, and hemolytic 
anemia.  Injection site reactions may also occur.  In rare instances, antibodies may form 
against proteins in your own body requiring long-term treatment.   
 
During the washout phase, you will not be receiving certain medications that you must 
washout of and your condition may become worse, stay the same or improve.  
 


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There may be possible risks associated with certain study procedures and medications 
administered before the LP.  These are included in the table below.  
 
Table 3   POSSIBLE RISKS FROM STUDY PROCEDURES 
Procedure 
Possible Risks  
Lumbar puncture 
Bleeding at the injection site; Infection; Post-lumbar puncture 
headaches (small risk); needle injury; injury to the spinal 
cord or nerve pain 
Allergic reaction 
Allergic reactions, while rare, can occur, and include fever, 
rash, myalgia (muscle pain), hematuria (blood in your urine), 
proteinuria (presence of abnormal amount of protein in your 
urine), serositis (inflammation of a serous membrane for 
example the  membrane that is found around the lung), 
central nervous system complications and hemolytic anemia 
(condition where red blood cells are destroyed and removed 
from the blood before their normal lifespan is over), skin 
irritations, breathing difficulties (similar to asthma), feeling 
flush, itching and shock.   
If you are allergic or have sensitivity to the pain-relieving 
medication, iodine or latex that may be used during the 
lumbar puncture, please talk to your study doctor ahead of 
the lumbar puncture.  
ECG 
Skin redness, itching, and irritation could occur from the skin 
sensors that are placed on your skin  
Blood Draws 
Possible side effects from blood drawing may include 
faintness, inflammation of the vein, pain, bruising, or 
bleeding at the site of needle puncture.  There is also a slight 
possibility of infection.  
MRI 
You must notify the study doctor if you have any type of 
metal implants (staples, screws, clips, pins, plates, stents, 
artificial heart valves) in your body as well as any metal in 
your body related to your SCI since the MRI scan involves a 
machine that has powerful magnets. If you are 
claustrophobic, you may feel uncomfortable while in the MRI 
machine. 
X-ray Imaging/CT Scans 
Procedures such as X-ray imaging, CT-scans, and 
fluoroscopy may be used during this research study to 
assess your spine and head. The cumulative radiation 
exposure from these tests is considered small and is not 
likely to adversely affect you. However, the effects of 
radiation add up over a lifetime.  It is possible that having 
several of these tests may add to your risk of injury or 
disease. When deciding to enter this study, think about your 


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past and future contact with radiation. Examples of contact 
with radiation include x-rays taken for any reason or 
radiation therapy for cancer treatment. 
 
 
Fluoroscopy: 
If the physician is having difficulty placing the needle for a lumbar puncture you may have 
to have fluoroscopy to assist with the placement.  Fluoroscopy using radiation to get a 
real-time X-ray of the part of your body where the LP needle will be placed.  Usually you 
will only be exposed to this radiation for a short time.  A 5-minute exposure to Fluoroscopy 
is equivalent to about 5 years of background radiation from living on earth.  Please talk to 
your study doctor if you have any concerns about radiation exposure from the 
fluoroscopy.  
 
Please tell the study doctor or study staff right away if you have any of the above or other 
side effects.  Please tell them if you have any other problems with your health or the way 
you feel during the study. 
 
Intrathecal Administration of study drug: 
The study drug is given to you by intrathecal administration (injection into the spinal 
canal).  In general, adverse events associated with the use of intrathecal therapy are 
rare.  Your study doctor will provide you with additional instructions after the procedure.  
However, you should immediately notify the study doctor if you experience any side 
effects following administration of the study drug. 
UNFORESEEN RISKS  
 
Since the study drug is in a new investigational preparation and not previously tested in 
humans, there may be other risks that are unknown. All drugs have a potential risk of an 
allergic reaction, which if not treated promptly, could become life-threatening. 
 
PREGNANCY / BIRTH CONTROL  
Taking the study drug may involve unknown risks to a pregnant woman, an embryo, 
fetus (unborn baby) or nursing infant.  Therefore, if you are pregnant, planning to 
become pregnant or are breastfeeding a child, you cannot participate in this study. 
 
If, during this study, you become pregnant, you should notify the study doctor as soon 
as possible.  If your pregnancy occurs during the Screening phase, your participation in 
the study will end and you will not receive study drug.   Information about your 
pregnancy and its outcome will be collected and used to learn more about the effects of 
the study drug on pregnancy. 


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 A serum pregnancy test will be done at Screening, and a urine pregnancy test will be 
done before you receive study drug at Study Day 1 pre-dose.  A urine pregnancy test 
also will be done at Visit 5, Study Day 29 (or at early termination from the study.)  
However, at any time during the study, if you feel that you may be pregnant, talk to your 
study doctor 
If you are a male subject and you impregnate your partner during the study period after 
you have received your dose of study drug, please notify the study doctor.  The study 
doctor will ask permission from your partner in order to conduct any follow-up or collect 
any information. 
Payment for all aspects of obstetrical care, child-or related care will be your 
responsibility. 
In order to reduce the risk of pregnancy, you must use an effective method of birth 
control while you are participating in this study (and for at least 7 days after you 
complete the study treatment).  Acceptable methods of birth control for use in this study 
include:  double barrier contraception (e.g., condom plus spermicide in combination with 
a female condom, diaphragm, cervical cap, contraceptive sponge, implants, injectables, 
combined oral contraceptives, sexual abstinence (total abstinence from sexual 
intercourse as the preferred lifestyle of the patient; periodic abstinence is not 
acceptable), or sexual intercourse with only a vasectomized partner. If you or your 
partner is surgically sterile or if the study doctor confirms that you are postmenopausal, 
then you are exempt from this requirement. 
If you are already using a method of birth control, the study doctor or study staff will 
discuss with you whether your current method of birth control is acceptable for use 
during this study.   
 
ALTERNATIVE TREATMENT 
 
You do not have to be in this study to receive treatment for your chronic spinal cord injury.  
Your options include: prevention of complications, bladder and bowel management, 
intensive rehabilitation, physical therapy, and analgesia.   
 
NEW FINDINGS  
 
Any new important information that is discovered during the study and which may 
influence your willingness to continue participation in the study will be made available to 
you. 
 
BENEFITS 
 
This is a single dose, safety, tolerability and pharmacokinetics study. There is no 
guarantee that you will benefit from your participation in this study.  Results from this 
study may help us to find the best dose to continue into clinical trials including Part 2 of 
this study and results may benefit others with CSCI in the future.  
 


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COMPENSATION FOR PARTICIPATION  
 
You will be paid $XX at the completion of each study visit for transportation to and from 
the study site.  You will receive $XX for Visit 2 when you will stay in the clinical unit for 3 
days.   You will receive an additional payment of $XX each for each visit in Study Day 8, 
15 and 29. This amount will be paid to you when you complete your participation in the 
study. 
 
CONFIDENTIALITY    
 
Records of your participation in this study will be held confidential except when sharing 
the information is required by law or as described in this informed consent.  The study 
doctor, the sponsor or persons working on behalf of the sponsor, and under certain 
circumstances, the United States Food and Drug Administration (FDA) and the 
Institutional Review Board (IRB) will be able to inspect and copy confidential study-
related records which identify you by name.  This means that absolute confidentiality 
cannot be guaranteed.  If the results of this study are published or presented at 
meetings, you will not be personally identified. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law.  This Web site will not include information that can identify you.  
At most, the Web site will include a description of the study, who was involved in 
sponsoring and conducting the study, and a summary of the results when the study is 
completed.  You can search the Web site at any time to view the study posting. 
 
REIMBURSEMENT FOR MEDICAL EXPENSES RELATED TO INJURY 
 
If you are injured as a result of being in this study, you should seek medical help 
immediately and arrange to notify the study doctor as soon as possible.   
 
If you suffer a physical injury that is directly related to the proper administration of the 
study drug(s) or the proper performance of a procedure done for the purpose of this 
study, the sponsor will reimburse those reasonable and necessary medical expenses 
you incur to treat such injury as long as such injury is not a result of (a) a healthcare 
provider’s failure to follow the study protocol, requirements of the Institutional Review 
Board (IRB) that oversees the study at the institution conducting the study, written 
instructions from the sponsor, or applicable laws or regulations, (b) your failure to follow 
your study doctor’s or the study staff’s instructions for the study or (c) a pre-existing 
condition or underlying illness, whether previously diagnosed or not.  The sponsor will 
determine if the injury is caused by the study drug and the reasonableness of the 
expenses taking into consideration the study doctor’s evaluation, other physicians’ 
evaluations of the patient, sponsor’s experience with the study drug and other relevant 
factors.   You must also have called and told your study doctor as soon as possible of 
your injury.   The sponsor has no plans to reimburse for any such expenses that are 
covered by your medical insurance or any other third-party coverage.  No other form of 
compensation is available, except remedies available under the law.  You will not lose 
any of your legal rights or release the Sponsor, the study doctor, the study staff, or 


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study site from liability for mistakes or intentional misconduct by signing this consent 
document. 
 
If you are injured during this study, your study doctor will discuss with you the available 
medical treatment options. 
 
COSTS 
There will be no charge to you for your participation in this study.  The study drug, 
placebo for reconstitution, the study related procedures, study related medical visits, 
and laboratory tests related to this study will be paid for by the study site through the 
study Sponsor (ReNetX Bio, Inc.).  You will not need to pay for any tests or procedures 
that are done for the sole purposes of this study.  You or your insurance company will 
be charged for any other portion of your care that is considered standard of care.  You 
will be responsible for any co-payments and deductibles for your insurance plan’s 
coverage of care that is considered standard of care.  Please ask your study doctor if 
you have questions about what you may have to pay for during your participation in this 
study.   
 
EMERGENCY CONTACT / IRB CONTACT  
 
During the study, if you experience any medical problems, suffer a research-related 
injury, or have questions, concerns or complaints about the study, please contact the 
study doctor at the telephone number listed on page one of this consent document.  If 
you seek emergency care, or hospitalization is required, alert the treating physician that 
you are participating in a research study being conducted by the study doctor listed on 
page one of this document.   
 
If you have any questions about your rights as a research subject, and/or concerns or 
complaints regarding this research study, you should write to «Insert IRB address and 
contact» 
 
VOLUNTARY PARTICIPATION / WITHDRAWAL  
 
Your decision to participate in this study is voluntary.  You may choose to not participate 
or you may withdraw from the study for any reason without penalty or loss of benefits to 
which you are otherwise entitled and without any effect on your future medical care.  
There are no consequences or safety considerations if you decide to withdraw from 
study participation. 
 
The study doctor or the sponsor can stop your participation at any time without your 
consent for the following reasons: 
 
• If it appears to be medically harmful to you; 
• If you fail to follow directions for participating in the study; 
• If it is discovered that you do not meet the study requirements; 
• If the study is canceled; or  


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• For administrative reasons, including competitive enrollment - the target number of 
subjects has entered the study. 
 
If you leave the study for any reason, the study doctor may ask you to have some end-
of-study tests for your safety.   
 
PRIMARY CARE PHYSICIAN / SPECIALIST NOTIFICATION OPTION 
 
Please indicate below whether you want us to notify your primary care physician or your 
specialist of your participation in this study. 
 
________ 
Yes, I want the study doctor to inform my primary care physician/specialist 
of my participation in this study. 
 
________ 
No, I do not want the study doctor to inform my primary care 
physician/specialist of my participation in this study. 
 
________ 
I do not have a primary care physician/specialist. 
 
________ 
The study doctor is my primary care physician/specialist. 
 
 


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CONSENT   
 
I have read and understand the information in this informed consent document.  I have 
had an opportunity to ask questions and all of my questions have been answered to my 
satisfaction. I voluntarily agree to participate in this study until I decide otherwise.  I do 
not give up any of my legal rights by signing this consent document.  I will receive a 
copy of this signed consent document. 
 
 
____________________________________  
 
 
Subject’s Printed Name  
 
 
____________________________________  
 
_________  
Subject’s Signature  
 
 
 
 
 
Date 
 
 
____________________________________  
 
 
Printed Name of the Person Conducting the  
 
 
 
Consent Discussion  
 
 
 
_____________________________________  
 
___________ 
Signature of the Person Conducting the   
 
 
Date  
Consent Discussion  
 
 
 
 
 
 
 
 
 
 


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AUTHORIZATION TO USE AND DISCLOSE 
PROTECTED HEALTH INFORMATION 
 
During your participation in this research study, the study doctor and study staff will 
collect or create personal health information about you (for example, medical histories 
and results of any tests, examinations or procedures you undergo while in the study) 
and record it on study documents.  The study doctor will keep this personal health 
information in your study-related records (that we will refer to as "your study records").  
In addition, the study doctor may obtain, and include in your records, information 
regarding your past, present and/or future physical or mental health and/or condition.  
Your study doctor may ask you to sign a separate authorization to obtain some or all of 
your medical records from your doctor.  Your study records may include other personal 
information (such as social security number, medical record numbers, date of birth, 
etc.), which could be used to identify you.  Health information that could identify you is 
called "Protected Health Information" (or "PHI").   
 
Under federal law (the "Privacy Rule"), your PHI that is created or obtained during this 
research study cannot be "used" to conduct the research or "disclosed" (given to 
anyone) for research purposes without your permission.  This permission is called an 
"Authorization".  Therefore, you may not participate in this study unless you give your 
permission to use and disclose your PHI by signing this Authorization.  By signing, you 
are agreeing to allow the study doctor and staff to use your PHI to conduct this study.   
 
By signing this Authorization, you also are agreeing to allow the study doctor to disclose 
PHI as described below: 
 
• The sponsor of this study and anyone working on behalf of the sponsor to conduct 
this study (referred to as "the sponsor").  The sponsor will analyze and evaluate the 
PHI and may use it to develop new tests, procedures and commercial products.  The 
study staff will assign a code number and/or letters to your records, which means 
that you will not ordinarily be identified in the records sent to the sponsor.  The 
sponsor may, however, look at your complete study records that identify you.  In 
addition, the sponsor may visit the study site to oversee the way the study is being 
conducted and may review your PHI during these visits to make sure the information 
is correct.   
• The Institutional Review Board ("IRB") may have access to your PHI in relation to its 
responsibilities as an Institutional Review Board. 
• Your PHI may be seen by A Data Safety Monitoring Board that will be convened to 
review data for this study 
 
The study doctor or sponsor may disclose your PHI to the United States Food and Drug 
Administration ("FDA") or similar regulatory agencies in the United States and/or foreign 
countries. 
 
These disclosures also help ensure that the information related to the research is 
available to all parties who may need it for research purposes. 


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Except for the disclosures described above, your PHI will not be shared with others 
unless required by law.  If your PHI is given to the parties listed above and/or to others 
who are not required to comply with the federal law, your PHI will no longer be protected 
by this law and could possibly be used or disclosed in ways other than those listed here.  
 
You have a right to see and make copies of your PHI.  You are agreeing, however, by 
signing this document, not to see or copy some or all of your PHI until the sponsor has 
completed all work related to this study.  At that time, you may ask to see your records. 
 
This Authorization will expire 50 years from the date you sign it unless you revoke 
(cancel or withdraw) it sooner.   
 
You have a right to revoke your Authorization at any time.  If you revoke it, your PHI will 
no longer be used for this study, except to the extent the parties to the research have 
already taken action based upon your Authorization or need the information to complete 
analysis and reports for this research.  To revoke your Authorization, you must write to 
the study doctor, stating that you are revoking your Authorization to Use and Disclose 
Protected Health Information.  If you revoke this Authorization, you will not be allowed to 
continue to be in this study. 
 
You will receive a copy of this Authorization after you have signed it. 
 
 
____________________________________ 
Printed Name of Subject 
 
____________________________________  
__________ 
Signature of Subject 
 
 
 
 
 
Date 
 
____________________________________ 
Printed Name of the Person Obtaining the  
Authorization 
 
____________________________________  
__________ 
Signature of the Person Obtaining the 
 
 
Date 
Authorization  
 
   


IRB Approved Template 
MUST BE APPROVED 
FOR SITES BEFORE USE 
Mar 07, 2019 
 
 
Page 1 of 4 
Version 1.0 
SUPPLEMENTARY INFORMED CONSENT ADDENDUM - BIOBANKING OF 
SAMPLES 
 
TTLE:   
A Multicenter, Two Part (Open-Label Single-Ascending Dose 
Followed by Double-Blind, Placebo-Controlled Repeat Dose) 
Study to Evaluate the Safety, Tolerability, Pharmacokinetics, 
and Efficacy of AXER-204 in Subjects with Chronic Spinal 
Cord Injury (the RESET* Study) 
 
PROTOCOL NO.:   
RNX-AX204-101 
 
CLINICALTRIALS.GOV IDENTIFIER:  NCT03989440 
 
SPONSOR:            
ReNetX Bio, Inc. 
                                
157 Church St 19th Fl 
                                
New Haven, CT 06510 
 
<<CF-Main Header Block - Investigator>> 
 
STUDY RELATED 
PHONE NUMBER(S): 
<<CF-Main User Defined #1>> 
 


IRB Approved Template 
MUST BE APPROVED 
FOR SITES BEFORE USE 
Mar 07, 2019 
 
 
Page 2 of 4 
Version 1.0 
INTRODUCTION 
You have previously signed the main informed consent for the above-named research 
study and in so doing have agreed to participate in that study including undergoing all 
study-related procedures, and collection and analyses of your blood, serum, and 
cerebrospinal fluid (CSF).  Other details related to the study can be found in the main 
Informed Consent Form including details on confidentiality and data protection. All 
information in the main informed consent form and HIPAA Authorization still applies. 
You have also agreed to have Magnetic Resonance Imaging (MRI) scans obtained of 
your spinal cord and spinal canal.    
 
You are being presented with this supplementary (additional) informed consent that 
informs you that some of your blood, CSF, and MRI scans and clinical data collected in 
the study will be stored for future research, with your permission. This process is called 
Biobanking.  Biobanking allows samples and clinical information to be used for research 
studies that we have not yet thought about. The benefit of biobanking is that any sample 
which is left over sample from the initial study that you participated in can be stored and 
used in another research project. It also means that over time researchers can build a 
biobank or library of valuable samples for more research. The goal is that more 
research will lead to improved understanding of health and disease. In addition to the 
samples that are collected from you, personal information will be collected about you 
and stored in a secure biobank database. This database can only be accessed by 
members of the biobank team, but the data allows us to know which samples are from 
you. Each sample and record in the database are assigned a code number so that 
when the samples are given out for research they are labelled with the code number 
and nobody will know they are from you. It is important that you read and understand 
the information below before you agree to participate in this part of the study.   
 
By providing your signature at the end of this form, you indicate that you understand 
and agree to the following: 
 
I give my consent to the storage and analysis of my blood, CSF, MRI scans and clinical 
data from previous studies I have participated in for future research into spinal cord 
injury (SCI) and other related diseases. I understand that all samples, imaging, and 
clinical data will be coded and used anonymously.  None of my identifying information 
will be known to persons conducting the research. 
 
I give my consent to the storage and analysis of my blood, CSF, MRI scans, and clinical 
data for research into SCI and other diseases. I understand that my blood sample and 
related information will be coded and used anonymously, and that no additional 
information will be provided to me. 
 
I understand that my anonymized blood, CSF samples, MRI scans, and clinical data 
may be shared with other biomedical researchers conducting ethically approved 
studies, including those from countries outside the US involved in medical research. I 


IRB Approved Template 
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FOR SITES BEFORE USE 
Mar 07, 2019 
 
 
Page 3 of 4 
Version 1.0 
understand that this information will be anonymous and that I will not be recognized or 
identified. 
 
I understand that my anonymized blood, CSF samples, MRI scans, and clinical data 
may be shared with companies developing medicines and tests for SCI or related 
diseases. I understand that such information will only be used for research purposes to 
improve health care. I agree that the researchers of this study may approach other 
health professionals (study doctor or personal health physician) involved in my care to 
obtain information. 
 
Where required, I agree to my personal physician or other health care professionals 
being informed of my participation in the biobank. 
 
I agree to allow research staff involved in the study to contact me for follow up for 
research purposes, and understand that such follow-up may be undertaken over 
periods up to several years after the injury.  I understand that I can choose to withdraw 
from such follow-up at any stage without having to provide reasons. 
 
I agree to take part in the above biobanking process. 
 
I confirm that I have read and understand this supplementary Informed Consent form for 
the above study.  I have had the opportunity to consider the information and ask 
questions and have had these answered to my satisfaction. 
 
I understand that my participation in this biobanking part of the study is voluntary and 
that I am free to withdraw my consent at any time and for any reason and that this will 
not affect my clinical management or my legal rights. 
 
I understand that key sections of my medical records and data collected during the main 
research study may be looked at by responsible individuals from the Sponsor and their 
representatives, study doctor, study staff, and regulatory authorities when this is 
relevant to my taking part in this research.  I give permission for these individuals to 
access my records. 
 
I agree that my coded data and coded and anonymized samples can be stored. 
 


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Mar 07, 2019 
 
 
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Version 1.0 
SUPLEMENTARY INFORMED CONSENT SIGNATURE PAGE FOR BIOBANKING 
I have read and understand the information in this informed consent document.  I have 
had an opportunity to ask questions and all of my questions have been answered to my 
satisfaction. I voluntarily agree to participate in this study until I decide otherwise.  I do 
not give up any of my legal rights by signing this consent document.  I will receive a 
copy of this signed consent document. 
 
 
____________________________________  
 
 
Subject’s Printed Name  
 
 
____________________________________  
 
_________  
Subject’s Signature  
 
 
 
 
 
Date 
 
 
____________________________________  
 
 
Printed Name of the Person Conducting the  
 
 
 
Consent Discussion  
 
 
 
_____________________________________  
 
___________ 
Signature of the Person Conducting the   
 
 
Date  
Consent Discussion  
 
 
 
 
 
 
 
 

Prot_000.pdf: 
Protocol RNX-AX204-101 
FINAL V 4.0 October 1, 2020 
1 
ReNetX Bio, Inc. 
Confidential 
A Multicenter, Two Part (Open-Label Single-Ascending 
Dose Followed by Double-Blind, Placebo-Controlled Repeat 
Dose) Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics, and Efficacy of AXER-204 in Subjects 
with Chronic Spinal Cord Injury (the RESET* Study) 
*RESET- Chronic SCI Study.  ReNetX Safety Efficacy and Tolerability
of AXER-204 for Chronic SCI 
PROTOCOL RNX-AX204-101 
PHASE 1B/2A 
AXER-204 
IND #: 135648 
Sponsor: 
ReNetX Bio, Inc. 
157 Church St 19th Fl 
New Haven, CT 06510 
www.renetx.com  
Date of Issue:  FINAL V 4.0 October 1, 2020 
This document is confidential and is the sole property of ReNetX Bio, Inc. It is to be distributed 
for review only to investigators, potential investigators, consultants, trial staff, and applicable 
independent ethics committees or institutional review boards. The contents of this document 
shall not be disclosed to others without written authorization from ReNetX Bio, Inc., unless it is 
necessary to obtain informed consent from potential trial subjects. 
NCT03989440


Protocol RNX-AX204-101 
 
FINAL V 4.0 October 1, 2020  
 
2 
 
ReNetX Bio, Inc. 
  
Confidential 
PROCEDURES IN CASE OF EMERGENCY 
Table 1: 
Emergency Contact Information 
Role in Study 
Name 
Email Address and Telephone 
Number 
Study Medical Monitor 
 
 
Study Director 
George Maynard, PhD 
President and CSO 
 
 
24-Hour emergency 
contact 
Primary:   
 
 
Back-up: 
 
 
 
 
 
 
 
 


Digitally signed by George D. 
Maynard 
Date: 2020.10.01 11:02:25 
-04'00'
 
 
 
Protocol RNX-AX204-101 
FINAL V 4.0 October 1, 2020 
PROTOCOL SPONSOR SIGNATURE PAGE 
Title of Study 
A Multicenter, Two Part (Open-Label Single-Ascending Dose followed by 
Double-Blind, Placebo-Controlled Repeat Dose) Study to Evaluate the Safety, 
Tolerability, Pharmacokinetics, and Efficacy of AXER-204 in Subjects with 
Chronic Spinal Cord Injury 
George Maynard, PhD 
President and Chief Scientific 
Officer, ReNetX Bio, Inc. 
Gilbert Block, MD, PhD 
Sponsor 
ReNetX Bio, Inc. 
157 Church St 19th Fl 
New Haven, CT 06510 
www.renetx.com 
 
Signature 
Clinical Consultant to ReNetX. Bio, 
Inc. 
-
 
Study Medical Monitor
 
ReNetX Bio, Inc. 
Signature 
Signature 
3 
Date 
.l Odctv ;;,oar) 
Date 
Date 
Confidential 


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1. 
SYNOPSIS 
Name of Sponsor/Company: 
ReNetX Bio, Inc. 
Name of Investigational Product: 
AXER-204 
Name of Active Ingredient: 
hNgR(310)-Fc 
Title of Study:  
A Multicenter, Two Part (Open-Label Single-Ascending Dose followed by Double-Blind, Placebo-
Controlled Repeat Dose) Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy 
of AXER-204 in Subjects with Chronic Spinal Cord Injury   
Study center(s): Approximately 5 study centers in the United States (US) 
Studied period (years):  
Estimated date first subject enrolled: July 2019 (Part 1) 
Estimated date last subject completed: November 2020 (Part 1) 
Estimated date first subject enrolled:  February 2021 (Part 2) 
Estimated date last subject completed: June 2022 (Part 2) 
Phase of development: 1b and 2a 
 
Objectives:  
Study RNX-AX204-101 is a two-part (Part- 1 and 2) study that will be run sequentially.  Part 1 is 
considered a Phase 1b study, while Part 2 is considered a Phase 2a study.  Each part has unique 
objectives.  
Part 1 Single Ascending Dose 
Primary Objectives 
To evaluate the safety, tolerability, and pharmacokinetics (PK) of ascending, single intrathecal lumbar 
slow bolus infusions of AXER-204 in subjects with chronic spinal cord injury (CSCI). 
Part 2 Repeat Dose 
Primary Objectives 
1. To evaluate the safety and tolerability of repeat intrathecal lumbar slow bolus infusions of 
AXER-204 compared to placebo in subjects with CSCI.  
2. To evaluate the pharmacokinetics of repeat doses of AXER-204 in subjects with CSCI 
Secondary Objectives (Part 2 only) 
To assess the efficacy of repeat dose therapy of AXER-204 compared to placebo on function and 
activities of daily living (ADL) measures as assessed by: 
• 
International Standards for Neurological Classification of SCI (ISNCSCI) Upper 
Extremity Motor Score (UEMS). 
• 
Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) 
prehension performance 
• 
Version III of the Spinal Cord Independence Measure (SCIM III) self-care  
Exploratory Objectives (Part 2 only) 


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To evaluate the efficacy of repeat dose therapy of AXER-204 compared to placebo as assessed by the 
following:   
• 
ISNCSCI lower extremity motor and sensory scores  
• 
GRASSP strength, sensation and prehension ability scores 
• 
SCIM III mobility scores 
• 
International Standards to document remaining Autonomic Function after Spinal Cord 
Injury (ISAFSCI) 
• 
Patient Reported Outcomes 
− 
CUE-Questionnaire (CUE-Q).  Assesses subject-reported upper limb function. 
− 
SF-36 v2.  Provides a patient-reported Quality of Life (QoL) assessment.  SF-36 will 
provide data on the subjects' perceived health and well-being over the course of the 
study.   
− 
Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL) 
− 
Patient’s Global Impression of Change (PGIC) – Chronic SCI 
Exploratory biomarkers of target engagement and axonal growth may be assessed   
Methodology:  
Study RNX-AX204-101 is a two-part study that will be run sequentially, with Part 2 planned to start 
after Part 1 has been completed.  Each Part will be conducted at approximately 5 centers in the United 
States.   
Eligible subjects will be ages 18 to 65 years inclusive, male or female, with a traumatic spinal cord 
injury that occurred at least 1 year prior to the screening date.  Subjects must have significant 
neurological impairment of the hands and arms.  Subjects who participated in Part 1 may be evaluated 
for enrollment in Part 2 provided at least 6 months will have elapsed between the dose received in 
Part 1 and the initiation of dosing in Part 2.   
Part 1 
Part 1 is a multicenter, open-label, single ascending dose study in subjects with chronic spinal cord 
injury.  Four cohorts of 6 subjects each are planned, with subjects within each cohort expected to 
receive the same dose of study drug.  Thus, up to 24 subjects will be enrolled in Part 1, and all will 
receive AXER-204.   
Study drug will be administered sequentially, with at least 3 days between subjects being dosed 
within each cohort (following 72-hour safety assessment review by sponsor in conjunction with the 
investigators and medical monitor for each prior subject). 
The study stages for Part 1 are: 
• 
Screening (within 84 days prior to Day 1).  Patients have 84 days from the time of 
signing informed consent to complete their screening assessments and, if needed, their 
washout period for prohibited concomitant medications. The screening laboratory tests 
must be completed within 28 days prior to Day 1. 
• 
Treatment period:  Check-in Day 1, administration of study drug, 3-night in-clinic stay, 
and discharge on Day 4 following the completion of all scheduled procedures.  


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• 
Follow-up: Subjects will have follow-up visits for up to 29 days post-dose as follows: 
subjects will receive a phone call on Study Days 5, 6, and 7 to inquire about their general 
health and will return to the clinic for visits on Study Day 8 (± 1 day), Study Day 15 (±3 
days), and Study Day 29 or Early Termination (± 4 days).  For each cohort in Part 1, the 
same general procedures will be applied, as follows.   
Screening 
All subjects must sign/e-sign an Informed Consent Form (ICF) prior to undergoing any screening 
procedures.  Screening procedures will take place up to 84 days.  Subjects will undergo an MRI to 
determine spinal cord structure and intrathecal space (Appendix 12); MRIs will be run locally and 
evaluated by a sponsor-arranged expert.  Additional radiological assessments may be performed at the 
discretion of the Principal Investigator, including CT or MRI of the head and X-ray of the lumbar 
spine as additional evaluations to rule out potential contraindications for lumbar puncture.  The 
subject’s demographics, medical and surgical history, and prior and concomitant medications will be 
recorded.  Screening/baseline assessments will be performed, and subjects will undergo blood draws 
where blood, serum collection, viral serology will be obtained, and urine samples will be collected. 
The screening laboratory tests must be completed within 28 days prior to Day 1. 
Subjects will also be presented with a separate biobank ICF for review.  If a subject agrees, samples 
of his/her CSF, blood, MRI scans and data collected in the study, will be stored for future research.  A 
subject does not have to agree or sign the biobank ICF in order to be eligible to participate in this 
main study.   
Prospective subjects must follow dosing restrictions as specified in the protocol for each medication 
listed in Exclusion Criteria. 
Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, 
marijuana, opiates, phencyclidine, barbiturates, benzodiazepines, methadone, and propoxyphene). 
Subjects using marijuana /THC-CBD preparations, opiates, sedative hypnotics, or tranquilizers may 
be permitted to participate in the trial provided the dosage and frequency of use are not considered 
likely to interfere with evaluation of safety and efficacy endpoints in the trial.  Determination of 
exclusion due to use of a specific medication from these classes of medications will be made by the 
Principal Investigator in conjunction with the Medical Monitor and sponsor physician based on 
medical assessment of factors including the dosage, frequency of use, and medical condition being 
treated.    
In the event that a subject is rescreened, the original screening MRI and expert review of the images 
may be used for the rescreening provided the MRI was completed within 6 months of rescreening.  
Similarly, neurological examinations and questionnaires do not need to be repeated provided the 
rescreening occurs within 84 days of the time of data collection. 
In-Clinic Treatment Period: 
Eligible subjects will be admitted to the clinic on the evening prior to or on the day of dosing (Study 
Day 1) dependent on clinical site requirements.  Following final pre-treatment assessments, subjects 
will undergo a lumbar puncture (LP) and receive their single dose of study drug administered via 
intrathecal lumbar slow bolus infusion by the Principal Investigator or a trained and licensed 
designee.  Dosing will be according to Table 2.   
Subjects will remain in-clinic until discharge on Study Day 4 and will undergo daily safety 
assessments and observation.  
Blood and CSF samples will be obtained.  The timing for serum and CSF sample collection may be 
adjusted for subsequent cohorts based on PK data from the preceding cohorts. In addition to 
undergoing PK analysis, serum samples obtained from blood collected at pre-dose and on Study Days 
8 and 29 will be analyzed for the presence of anti-drug antibodies (ADA). 


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Table 2: 
Treatment by Cohort - Part 1 (Study RNX-AX204-101) 
Cohort 
Treatment 
Number Subjects 
1 
3 mg AXER-204 
6 
2 
30 mg AXER-204 
6 
3 
90 mg AXER-204 
6 
4 
200 mg AXER-204 
6 
Follow-up:  
Sites will contact the subjects via telephone on Study Days 5, 6, and 7 to inquire as to their general 
health status.   
Subjects will return to the Clinic on Study Days 8 (±1d), 15 (±3d), and 29 (±4d).  On Study Days 8 
(±1d) and 29 (±4d), CSF and serum PK samples will be collected.  Blood will be collected for clinical 
laboratory testing and serum for PK on Day 15 (±3d).  Vital signs, AEs, and general health status will 
be assessed at each follow-up visit and end of study assessments will be performed on Study Day 29 
(±4d). 
Dose Escalation in Part 1 
Dose escalation decisions will be made jointly by the investigators, sponsor, and medical monitor.  
The investigators, sponsor, and medical monitor may also make adjustments to the dosing plan, as 
appropriate for reasons of safety and tolerability.   
Data and Safety Monitoring Board (DSMB) 
In order to ensure the utmost safety of subjects, the sponsor will also use an independent Data and 
Safety Monitoring Board (DSMB).  Each time the DSMB is engaged, a recommendation to proceed 
from the DSMB will be required in order for the study to continue (i.e. to resume if stopped or 
ongoing study will be stopped if DSMB does not recommend proceeding).  During Part 1, the DSMB 
will be consulted prior to resuming the study if any of the stopping criteria are met.  The DSMB will 
also be asked to review the safety and tolerability data from Part 1 before starting Part 2.  The DSMB 
will meet during Part 2 after the first subject has completed 3 months of dosing and approximately 
every 3 months thereafter while dosing continues in the study (allowing for potential scheduling 
logistics). In addition to the pre-determined DSMB data review meeting, the DSMB may be engaged 
at any time at the request of an investigator, the sponsor, or medical monitor. A charter will be written 
to describe the DSMB’s objectives, schedule for data reviews, and general responsibilities in respect 
to the study.  All DSMB decisions will be documented in writing, and where required, submitted to 
the institutional review board (IRB) for their review or information.    
Dose Escalation Rules for Part 1 
Dose escalation (for each sequential cohort) will not occur until 6 subjects in the prior cohort have 
completed the initial 3 day in-clinic period AND at least two subjects have completed their Day 29 
post-dose follow-up visit.  Determination of whether to escalate dose in the subsequent cohort will be 
made by the sponsor in conjunction with the investigators and medical monitor after review of all 
clinical and any available PK data.  Review will include adverse events (AEs) and serious AEs 
(SAEs), and specifically the following potential stopping criteria will be evaluated prior to each dose 
escalation.  If the dose is well tolerated in the completed dose group, the sponsor, in conjunction with 
the investigators and medical monitor, will recommend escalation to the next dose level.   
Stopping Rules/Study Interruption/Discontinuation Notice 
The investigators and medical monitor in conjunction with the sponsor may elect to stop dosing or 
stop the study based on any treatment emergent concerns.  Dosing will be stopped due to the 


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occurrence of any individual adverse events which, in the judgment of the investigators and medical 
monitor in conjunction with the sponsor, need further characterization with respect to progression and 
reversibility before further dosing is conducted.  Such adverse events may include non-serious 
unusual events.  If dosing is stopped, review of the data by the investigators and medical monitor in 
conjunction with the sponsor and the DSMB must occur before dosing can be resumed.  Dosing will 
only be resumed with DSMB approval.   
Pharmacokinetic and anti-drug antibody test results will not be required for dose escalation unless it is 
determined to be advisable by the sponsor in conjunction with the investigators and medical monitor 
based on emergent data from the study.  CSF and serum samples will be analyzed for each cohort 
immediately after all subjects have been dosed.  The sponsor may direct earlier analysis of a partially 
completed cohort if completion of the cohort is delayed or partial cohort data is desired to aid in 
interpretation of any emergent clinical data.   
Part 2 
Part 2 is a multicenter, randomized, double-blind, placebo-controlled, repeat dose study in CSCI 
subjects.  Approximately 32 subjects will be randomized (ratio 1:1) to receive AXER-204 or placebo 
(an isotonic phosphate buffered saline formulation).  Subject to review of the safety, tolerability, and 
pharmacokinetic data from Part 1 and DSMB approval, the dose will be 200 mg given once every 3 
weeks for 15 weeks as outlined in the schedule of events.  Subject to DSMB approval, the dose may 
be reduced to 90 mg and the dose interval may be modified based on data from Part 1 but is not 
expected to be less than once every 14 days or more than 28 days.  Subject to DSMB approval, the 
dose and dose frequency may also be adjusted during Part 2 based on emergent safety and tolerability 
data. 
The study stages for Part 2 are: 
• 
Screening (within 84 days prior to Day 1).  Patients have 84 days from the time of 
signing informed consent to complete their screening assessments and, if needed, their 
washout period for prohibited concomitant medications.  The screening laboratory tests 
must be completed within 28 days prior to Day 1. 
• 
Treatment Period (15 weeks).  Investigational product given approximately every 21 days 
for up to 104 days per subject.  A telephone call to assess status regarding any adverse 
events will be conducted on Study Day 8 (±3 days). 
• 
Follow-up (21 weeks).  Following the last Treatment Period dose of investigational 
product or Early Termination of dosing, a telephone call to assess status regarding any 
adverse events will be conducted on Study Day 137 (± 7 days) and two follow-up visits 
will occur at Study Days 169 (± 7 days) and 253 (± 7 days). 
Screening 
All subjects must sign/e-sign an Informed Consent Form (ICF) prior to undergoing any screening 
procedures.  Screening procedures will take place up to 84 days.  Subjects will undergo an MRI to 
determine spinal cord structure and intrathecal space; MRIs will be run locally and evaluated by a 
sponsor-arranged expert. Additional radiological assessments may be performed at the discretion of 
the Principal Investigator, including CT or MRI of the head and X-ray of the lumbar spine as 
additional evaluations to rule out potential contraindications for lumbar puncture. The subject’s 
demographics, medical and surgical history, and prior and concomitant medications will be recorded.  
Screening assessments will be performed, and subjects will undergo blood draws where blood, serum 
collection, viral serology will be obtained, and urine samples will be collected. The screening 
laboratory tests must be completed within 28 days prior to Day 1. 


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Subjects will also be presented with a separate biobank ICF for review. If a subject agrees samples of 
his/her CSF, blood, MRI scans and data collected in the study, will be stored for future research.  A 
subject does not have to agree or sign the biobank ICF in order to be eligible to participate in the main 
study.   
Prospective subjects must follow dosing restrictions as specified in the protocol for each medication 
listed in Exclusion Criteria. 
Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, 
marijuana, opiates, phencyclidine, barbiturates, benzodiazepines, methadone, and propoxyphene).  
Subjects using marijuana /THC-CBD preparations, opiates, sedative hypnotics, or tranquilizers may 
be permitted to participate in the trial provided the dosage and frequency of use are not considered 
likely to interfere with evaluation of safety and efficacy endpoints in the trial.  Determination of 
exclusion due to use of a specific medication from these classes of medications will be made by the 
Principal Investigator in conjunction with the Medical Monitor and sponsor physician based on 
medical assessment of factors including the dosage, frequency of use, and medical condition being 
treated.   
In the event that a subject is rescreened, the original screening MRI and expert review of the images 
may be used for the rescreening provided the MRI was completed within 6 months of rescreening.  
Similarly, neurological examinations and questionnaires do not need to be repeated provided the 
rescreening occurs with 84 days of the time of data collection. 
Treatment Period 
Eligible subjects will be randomized to either AXER-204 or to placebo.  The randomization will be 
stratified based on pre-treatment American Spinal Injury Association Impairment Scale (AIS) grade 
(AIS A,B vs. AIS C,D) and prior receipt of study drug in Part 1 (Received AXER-204 in Part 1 vs. 
Did not receive AXER-204 in Part 1).  
Subjects will receive their baseline assessments and assigned (double-blind) treatment on Study Day 
1.  A telephone call to assess status regarding any adverse events will be conducted on Study Day 8 (± 
3 days).  Subjects will then return to the Clinic on Day 21 (± 5 days) for safety, efficacy, and PK 
assessments and their second dose of investigational product.  Thereafter, subjects will return 
approximately every 21 days, at Study Days 42 (± 5 days) (third dose), 63 (± 5 days) (fourth dose), 84 
(± 5 days) (fifth dose), 104 (± 5 days) (sixth dose), for safety, efficacy, and PK assessments (pre-
dose) and investigational product administration.     
Cerebrospinal fluid samples will be collected pre-dose at each treatment (dosing) visit, including 
Study Day 1, during a single LP procedure for collecting and dosing.  Serum for PK and 
immunogenicity (ADA) testing will be collected pre-dose at the timepoints specified in the schedule 
of events within 4 hours prior to investigational product administration.  Serum will also be collected 
for PK at 4 h post-dose at specified visits. 
For dosing visits that include neurological exams and questionnaires (e.g. ISNCSCI, GRASSP, SCIM 
III self-care and mobility), these assessments should be performed prior to dosing. Depending on 
scheduling considerations, subjects may be asked to return the following day for dose administration.  
Under this circumstance, nearby overnight accommodations will be arranged for the subject upon 
request. 
Following dosing, patients will remain under the observation of study personnel in the hospital setting 
(eg, may include infusion center, PACU, recovery suite, observation unit, short stay center) for 4 
hours for safety monitoring. Thereafter, if deemed clinically stable by the Investigator, patients may 
leave the hospital setting.  If further safety observation is directed by the investigator, the subject may 
be directed to remain at a nearby overnight accommodation or home (if within a reasonable distance) 
and report the next morning for examination or to remain in the hospital overnight.  Note that, under 
these circumstances, there is no requirement for an overnight hospital stay; if a decision is made to 


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keep the patient overnight for convenience (e.g. travel issues), this hospitalization should not initiate a 
serious adverse event report (e.g. local alternate accommodations not readily available). 
Follow-Up 
Study personnel will conduct telephone call with subjects on Study Day 137 (± 7 days) to assess 
status regarding any adverse events.  Depending on the results, the subject may be asked to come to 
the clinic for evaluation.  Subjects will return at Study Days 169 (± 7 days) and 253 (± 7 days) for 
safety and efficacy assessments.   
Stopping Rules/Study Interruption/Discontinuation Notice 
The investigators and medical monitor in conjunction with the sponsor may elect to stop dosing or 
stop the study based on any treatment emergent concerns.  Dosing will be stopped due to the 
occurrence of any individual adverse events which, in the judgment of the investigators and medical 
monitor in conjunction with the sponsor, need further characterization with respect to progression and 
reversibility before further dosing is conducted.  Such adverse events may include non-serious 
unusual events.  If dosing is stopped, review of the data by the sponsor in conjunction with the 
investigators and medical monitor in conjunction with the sponsor and the Data and Safety 
Monitoring Board (see below regarding DSMB composition and charter) must occur before dosing 
can be resumed.  Dosing will only be resumed with DSMB approval. 
Data and Safety Monitoring Board (DSMB)   
In order to ensure the utmost safety of subjects, the Sponsor will also use a Data and Safety 
Monitoring Board (DSMB).  Each time the DSMB is engaged, a recommendation to proceed from the 
DSMB will be required in order for the study to continue (i.e. to resume if stopped or ongoing study 
will be stopped if DSMB does not recommend proceeding).  The DSMB will review the safety and 
tolerability data from Part 1 before recommending starting Part 2.  In addition to the pre-determined 
DSMB data review meetings, the DSMB may be engaged at any time at the request of an investigator, 
the sponsor, or medical monitor. A charter will be written to describe the DSMB’s objectives, its 
membership, schedule for data reviews, and general responsibilities with respect to the study.  All 
DSMB decisions will be documented in writing, and where required, submitted to the institutional 
review board (IRB) for their review or information.   
Number of Subjects (planned):  
Part 1 will enroll up to 24 subjects in cohorts of 6 subjects each. Part 2 will enroll approximately 32 
subjects, randomized in a 1:1 ratio (and thus approximately 16 subjects per arm) to repeated doses of 
AXER-204 or of matching placebo. 
Diagnosis and main criteria for eligibility:  
Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 
1. Men or women between the ages of 18 and 65 years, inclusive 
2. Traumatic spinal cord injury that occurred ≥ 1 year ago  
3. Cervical spinal cord injury with serious neurological deficit as evidenced by 1) bilateral ISNCSCI 
UEMS between 4 and 36 points inclusive, and 2) bilateral GRASSP prehension ability score 
between 4 and 17 points inclusive 
4. Confirmation by MRI of the following: 
a. Chronic SCI (persistent spinal cord lesion) 
b. For AIS grade of A without sensory or motor zone of partial preservation extending at 
least two levels caudal to the level of injury, no apparent transection of the cord  


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c. CSF space spanning the lesion 
5. Read, understood, and provided written informed consent after the nature of the study has been 
fully explained and must be willing to comply with all study requirements and procedures. 
Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from the study: 
1. Penetrating injury to the cord or spinal cord trauma caused by ballistic injury including gunshot 
that did not penetrate the spinal cord 
2. Women who are pregnant or lactating, and women of childbearing potential except those using 
adequate birth control measures. All female subjects must have a negative serum pregnancy test 
at Screening and women of childbearing potential must have a negative urine pregnancy run 
locally at the Randomization/Pre-Dose Visit on Study Day 1.  All subjects (male and female) as 
well as non-study female partners of male subjects, must use adequate birth control measures 
during the course of the study and for at least 10 weeks after the subjects’ last dose of 
investigational product  
• 
Adequate or effective contraception is defined as double barrier contraception (eg, 
condom plus spermicide in combination with a female condom, diaphragm, cervical cap, 
contraceptive sponge, implants, injectables, combined oral contraceptives, sexual 
abstinence (total abstinence from sexual intercourse as the preferred lifestyle of the 
subject; periodic abstinence is not acceptable), or sexual intercourse with only a 
vasectomized partner.  Subjects and/or partners who are surgically sterile or women with 
confirmed postmenopausal status are exempt from this requirement.   
3. History of stroke, cerebrovascular injury, or elevated intracranial pressure 
4. Contraindications for lumbar puncture 
5. Requiring mechanical ventilatory assistance of any type 
6. Body mass index (BMI) ≥ 35 kg/m2 or body weight <50 kg 
7. Botulinum toxin injection, with the exception of bladder treatments, within 4 months prior to 
study 
8. History of life threatening allergic or immune-mediated reaction to vaccines, or biologic drugs, at 
any time or any life threatening allergic or immune-mediated reaction within the past 12 months. 
9. Systemic use of immunosuppressants within the past 2 months with the exception of 
mineralocorticoids 
10. Significant deformities, contractures (with less than 50% of normal range of motion at affected 
joints), or any issues that limit completion of UEMS with the ISNCSCI exam 
11. Recent changes in anti-spasmodic or anti-spasticity medications.  Anti-spasmodic or anti-
spasticity medication is permitted providing that the subject has been on a stable dose for at least 
12 weeks before the Screening Visit (Visit 1) and agrees to remain on a stable dose throughout 
the course of the study 
12. Any orthopedic injury, recent surgeries, or current diagnosis of any primary diseases affecting 
upper limb function outside of SCI (eg, infection, tumor, congenital malformations, Huntington’s 
disease, Parkinson’s disease) 
13. Subjects fitted with an implanted pump or port for delivery of therapeutics to the CSF 


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14. Uncontrolled medical condition including but not limited to cardiovascular disease, sleep apnea, 
obstructive lung disease, severe neuropathic or severe chronic pain, severe autonomic dysreflexia 
15. Participation in any other investigational drug or device trial within 30 days or within 5 half-lives 
of the investigational drug or any past participation in a SCI cellular therapy trial. 
16. Regular use of the following concomitant medications that might confound efficacy and/or safety 
assessments is prohibited, including, but not limited to, the following:  
a. Antipsychotic drugs with the exception of use of these mood stabilizers for the 
adjunctive treatment of depression provided the subject is on a stable dose for at least 12 
weeks prior to Screening and the dose is not anticipated to change during participation in 
the trial. 
b. Anticoagulants, however, daily low dose aspirin (81mg) therapy is permitted. 
c. Opiates, sedative hypnotics, or tranquilizers unless used to treat anxiety, pain, or sleep 
disorder and the dosage and frequency of use are not considered likely to interfere with 
evaluation of safety and efficacy endpoints in the trial. Determination of exclusion due to 
use of a specific medication from these classes of medications will be made by the 
Principal Investigator in conjunction with the Medical Monitor and sponsor physician 
based on medical assessment of factors including the dosage, frequency of use, and 
medical condition being treated.   
d. Use of tumor necrosis factor [TNF] inhibitors 
e. Use of Class 1 antiarrhythmic.  
17. Use of antidepressants (SSRI, SNRI, TCA, buspirone) is PERMITTED but limited to subject 
being on a stable dose for at least 12 weeks 
18. History of severe acute or chronic medical or psychiatric condition or laboratory abnormality that 
could increase the risk associated with trial participation or investigational product administration 
or could interfere with the interpretation of trial results and including but not limited to the 
following:  
• 
human immunodeficiency virus (HIV) infection 
• 
active chronic hepatitis B or hepatitis C infection including hepatitis B surface antigen 
and hepatitis C antigen positive subjects with or without abnormal liver enzymes 
• 
immunosuppressive disease 
• 
chronic renal disease/failure as evidenced by estimated glomerular filtration rate (eGFR) 
of <60 
• 
concurrent neurodegenerative disease 
• 
cardiovascular: uncontrolled hypertension, unstable angina, myocardial infarction or 
symptomatic congestive heart failure within the past 12 months or serious uncontrolled 
and clinically significant cardiac arrhythmia as determined by the investigator 
• 
dementia or significantly altered mental status including brain injury with ongoing 
cognitive signs and symptoms that would prohibit the understanding or rendering of 
informed consent and compliance with the requirements of the protocol 
19. Evidence or self-report of alcohol or drug abuse within the previous 12 months 


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20. Any conditions that in the judgement of the investigator would make the subject inappropriate for 
entry into the trial 
Investigational product, dosage and mode of administration:  
AXER-204 is a human fusion protein to promote axon growth and recovery of neurological function.  
AXER-204 is administered by intrathecal lumbar slow bolus injection.   
Part 1:  
Dosage will be by cohort, with 4 sequentially-treated cohorts planned.  Intrathecal doses of AXER-
204 below 90 mg will be diluted and delivered as a solution in 10 mL of isotonic phosphate buffered 
saline.  Both the 90 mg dose and 200 mg dose will be dosed with the current study drug 
concentration.  All administration will be given following a removal of an equivalent volume of CSF.  
Intrathecal injections will be given at a rate of 100 mL/hr using a medically approved syringe pump 
(eg, 12 minutes to administer 20 mL) to avoid significant disruption of natural CSF flow and pressure 
and monitored by medical personnel.   
The starting dose of 3 mg is estimated to be below the pharmacologically active dose.  Dose 
escalation will proceed to 30 mg, 90 mg, 200 mg contingent on safety, tolerability, and available PK.  
Thus, dosing volumes will be given as follows: 
• 
Cohort 1:  3 mg, 10 mL 
• 
Cohort 2:  30 mg, 10 mL 
• 
Cohort 3:  90 mg, 9 mL 
• 
Cohort 4:  200 mg, 20 mL 
Part 2 
Subject to review of the safety, tolerability, and pharmacokinetic data from Part 1 and DSMB 
approval, the dose will be 200 mg given once every 3 weeks for 15 weeks as outlined in the schedule 
of events.  Subject to DSMB approval, the dose may be reduced to 90 mg and the dose interval may 
be modified based on data from Part 1 but is not expected to be less than once every 14 days or more 
than 28 days.  Subject to DSMB approval, the dose and dose frequency may also be adjusted during 
Part 2 based on emergent safety and tolerability data. 
The maximum volume of injection by intrathecal lumbar slow bolus injection is limited to 20 mL in 
this study based on published tolerance data from studies with other agents employing the same route 
of administration.  If an injection volume of 20 mL, corresponding to a 200 mg dose of AXER-204, is 
reached in Part 1 dose escalation portion of the study with acceptable safety and tolerance, the 200 mg 
dose will be designated as the dose for Part 2 at the discretion of the Sponsor in conjunction with the 
investigators, DSMB, and medical monitor.   
Duration of treatment:  
Part 1 is a single-dose treatment for each subject.  Subjects will have up to an 84-day screening 
period, a 3-day in-clinic treatment period, and a follow-up period through 29 days post-dose.  Thus, 
study participation for each subject in Part 1 is expected to be approximately up to 16 weeks in 
duration.  
Part 2 Placebo-controlled Repeat Dose Portion.  Subjects will have up to an 84-day screening period, 
a 104-day treatment period with injections given every 21 days through Day 104, and then post 
treatment follow-ups at Study Days 137, 169, and 253.  The follow-up on Study Day 137 will consist 
of a telephone call conducted by study personnel to assess status regarding any adverse events.  Thus, 
study participation for each subject in Part 2 is expected to be up to approximately 337 days in 
duration. 


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Reference therapy, dosage and mode of administration:  
Part 1 does not include placebo. 
Part 2 includes a matching placebo control, to be given at the same intervals and volume as the 
investigational product.  Placebo consists of a phosphate buffered saline formulation.  
At each study site, for each dose to be administered in Part 2, an unblinded pharmacist will prepare 
prefilled syringes for dose administration in order to maintain the blind for study personnel 
administering the investigational product and performing all other study procedures. 
Criteria for evaluation: 
Pharmacokinetics: 
Both serum and cerebrospinal fluid samples will be collected for analyses, as shown in Table 3 and 
Table 4. 
In Part 1, a window relative to the nominal timepoint is allowed for sample collection as follows: 
• 
Blood serum pharmacokinetic samples will be collected at 0 hour (immediately pre-
dose), and 1 h (±10 min), 6 h (±10 min), 12 h (±10 min), and 24 h (±10 min) post-dose, 
as well as at Study Day 4 (72h ± 10 min), 8 (±1d), 15 (±3d), and 29 (±4d).   
• 
Cerebrospinal fluid samples (CSF) will be collected via lumbar puncture at 0 hour 
(immediately pre-dose), 24 h (±2h) Study Day 4 (72 h ±4h), and Study Days 8 (±1d), and 
29 (±4d).  
The timing for serum and CSF sample collection may be adjusted for subsequent cohorts based on 
pharmacokinetic data from the preceding cohorts.  Serum PK samples collected at pre-dose and on 
Study Days 8 and 29 will be analyzed for the presence of anti-drug antibodies (ADA). 
In Part 2, Visits 3-7 (Study Days 21, 42, 63, 84, 104) will have a window of ±5 days and Visits 8 and 
9 (Study Days 169 and 253) will have a window of ±7 days.  CSF samples will be collected for PK 
analysis pre-dose on Study Days 1, 21, 42, 63, 84, and 104.  The CSF sample collected on Study Day 
253 will also be analyzed for PK.  Serum samples will be collected for PK analysis pre-dose and 4 h 
post-dose on Study Days 1, 21, 42, 63, 84, and 104.  Serum will also be collected for PK analysis on 
Study Days 169 and 253.  Pre-dose serum will be collected for ADA analysis on Study Days 1, 21, 
42, 63, 84, and 104.  Serum will also be collected for ADA analysis on Study Days 169 and 253.  A 
subset of the CSF samples may also be analyzed for ADAs depending on development and presence 
of ADAs in the serum.  Part 2 serum and CSF from subjects receiving placebo will be collected but 
will not be analyzed for PK and ADAs. 
In Part 2 on Study Days 1, 21, 42, 63, 84, and 104 a window relative to the nominal timepoint is 
allowed for sample collection as follows: 
• 
Blood serum pharmacokinetic samples will be collected at 0 hour (within 4 h pre-dose), 
and 4 h (±10 min) post-dose 
• 
Cerebrospinal fluid samples (CSF) will be collected via lumbar puncture at 0 hour 
(immediately pre-dose) 
Table 3: 
Part 1 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) 
 
Day 1 (Dosing day)  
Day 2 (24 hours 
post-dose) 
Day 4 (72 hours 
post-dose)  
Day 
8 
Day 
15 
Day 
29 
Cerebrospinal 
Fluid  
Pre-Dose 
X 
X 
X 
 
X 


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Serum 
Pre-Dose, and post-dose at 
Hours 1, 6, 12 
X 
X 
X 
X 
X 
Serum aliquot for 
ADA 
X (Pre-Dose) 
 
 
X 
 
X 
Table 4: 
Part 2 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) 
Study Phase 
Treatment Phase 
Window at Visits 3-7 ± 5 days 
Follow-Up 
± 7 days 
Study Day 
Month (M) 
1 
21 
 
42 
 
63 
84 
 
104 
 
169 
M6 
253/ET 
M9 
Visit Number 
2 
3 
4 
5 
6 
7 
8 
9 
Cerebrospinal Fluid  
X 
X 
X 
X 
X 
X 
X 
Serum 
X 
X 
X 
X 
X 
X 
X 
X 
Serum aliquot for 
ADA 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations:  M = month, ET = Early Termination 
 
Efficacy 
Part 1  
Part 1 is focused on safety, tolerability, and pharmacokinetics.  However, a subset of efficacy 
assessments are to be performed including:  
• 
ISNCSCI.  ISNCSCI is a comprehensive clinician-administered neurological exam for 
SCI. It is widely used for research and clinical (neurologic) description to fully assess 
sensory and motor functioning and level of injury in traumatic SCI.  The UEMS will be 
calculated from the ISNCSCI. 
• 
GRASSP.  GRASSP is a clinician administered test that assesses strength in 10 key 
muscles in the upper extremity as well as dexterity and fine motor skills. 
• 
SCIM III self-care and mobility scores.  SCIM III measures functional outcomes in three 
sections:  self-care, respiration and sphincter management, and mobility.  The current 
study will employ the self-care and mobility subscores. 
Part 2 
The primary objective of Part 2 is to evaluate the safety, tolerability, and pharmacokinetics of repeat 
dosing.  In addition, a number of efficacy assessments are included as secondary endpoints.  The key 
secondary efficacy endpoint for Part 2 will be within-subject change from pre-treatment baseline and 
slope for UEMS as compared to placebo.  The same trained raters should be used for a particular 
patient as much as possible.  The assessments will be performed in the order outlined in Section 11.2. 
Additional secondary efficacy endpoints will include within-subject changes from pre-treatment 
baseline and slope for: 
• 
GRASSP prehension performance scores.  GRASSP is a clinician-administered test with 
three subset scores that assesses strength in 10 key muscles in the upper extremity as well 
as dexterity and fine motor skills. 
• 
SCIM III self-care scores.  Although the SCIM III measures functional outcomes in three 
sections:  self-care, respiration and sphincter management, and mobility, the current study 
will employ the self-care and mobility subscores.  The evaluation will be administered by 
interview of the patient by a clinician. 
Exploratory endpoints will include within-subject changes over time from pre-treatment in: 


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• 
ISNCSCI lower extremity motor and sensory scores.  ISNCSCI is a comprehensive 
clinician-administered neurological exam for SCI. It is widely used for research and 
clinical (neurological) description to fully assess sensory and motor functioning and level 
of injury in traumatic SCI.   
• 
GRASSP strength, sensation and prehension ability scores   
• 
SCIM III mobility scores 
• 
ISAFSCI.  The ISAFSCI will be used to document autonomic control of the heart, blood 
pressure, sweating, and temperature regulation.  Lower urinary tract function, bowel 
function, and sexual function will be scored. 
• 
Patient Reported Outcomes 
− 
CUE-Questionnaire (CUE-Q).  Assesses subject-reported upper limb function. 
− 
SF-36 v2.  Provides a patient-reported Quality of Life (QoL) assessment.  SF-36 will 
provide data on the subjects' perceived health and well-being over the course of the 
study.   
− 
Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL) 
− 
PGIC – Chronic SCI 
Exploratory biomarkers of target engagement and axonal growth may be assessed.  
Safety: 
Safety will be evaluated similarly for both Parts, through the collection of data from: 
• 
Physical examinations 
• 
Vital signs 
• 
12-lead electrocardiograms 
• 
Laboratory parameters (hematology, blood chemistry, and urinalysis).  Analysis of CSF 
for protein, cell count, and glucose. 
• 
Treatment-emergent adverse events (TEAEs).   
− 
TEAEs will be defined as any AE occurring during or after the injection of study 
drug or placebo.   
− 
TEAEs will be limited to those events occurring within 28 days after the last visit. 
Condition-specific safety outcomes will include adverse changes in: 
• 
ISNCSCI, GRASSP and all of the neurological measures evaluated for efficacy 
• 
Spasticity (Modified Ashworth Scale).  A clinician administered examination for 
spasticity which measures muscle tone.  A score of 0-4 is assigned to each muscle group 
evaluated.  Note: Testing will exclude fingers and thumb. 
• 
Pain (BPI). A self-administered questionnaire used to assess the severity of a subject's 
pain and the impact of this pain on the subject's daily functioning.  
Statistical Methods 


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A general description is included here for the investigator.  A detailed Statistical Analysis Plan will be 
submitted to the IND prior to unblinding the database for Part 2. 
Sample Size  
The Part 1 sample size was derived empirically from experience with previous single ascending dose 
clinical studies in other disorders and is deemed appropriate to achieve the study objectives. 
The Part 2 sample size was selected to ensure adequate power for detecting treatment-related change 
in bilateral UEMS (Score from 0 to 50). 
A 5-point difference, between the treated and placebo groups, in the change from baseline to 6 
months in bilateral UEMS is considered clinically meaningful. Analysis of historical data for cervical 
SCI patients for the period between ~6-12 months following acute SCI indicates a standard deviation 
of bilateral UEMS change over 6 months to be around 3 to 4 points. 
With a sample size of 12 subjects per active and placebo group, Part 2 of the study has 80% power 
with Type I error of α=0.05 (two sided), assuming a 5-point difference as indicated above, and with a 
common standard deviation within each treatment group of approximately 4 in the change from 
baseline to 6 months in bilateral UEMS.  
Accounting for uncertainties in the assumptions based upon historical data used to extrapolate for 
estimating the sample size in this study and the need for estimation of missing data a sample size of 
approximately 16 subjects per treatment arm (32 total) will be randomized.    
Stages of Analysis 
The analysis for this study will be performed in three stages, with the first analysis performed upon 
completion of the clinical portion of Part 1, the second analysis (including the core efficacy 
assessment) performed upon completion Day 169 of Part 2 (ie, after all subjects have completed 
through Study Day 169), and the final analysis performed upon completion of the post-treatment 
follow-up phase of Part 2 (Day 253).  The methods applied to each analysis will be consistent with 
the objectives of the study.   
The blind will be maintained for all blinded study personnel (including investigators and subjects) 
through the completion of Day 169 of Part 2.  After completion of Day 169, designated sponsor staff 
and external consultants/contractors required to perform the analysis will be unblinded to the 
treatment allocations in order to complete data analysis though Day 169.  The blind will be 
maintained for site investigators and subjects through completion of Day 253 unless the blind must be 
broken sooner for safety or regulatory reasons.   
General Methods 
Data will be tabulated using both descriptive and inferential statistics where specified.   
• 
For Part 1, data will be tabulated by dose cohort as well as pooled (all subjects 
combined), and no inferential statistics are planned. 
• 
For Part 2, data will be tabulated for each treatment group separately (placebo and 
AXER-204) to allow for visual inspection of outcomes between the arms.  Inferential 
statistical comparison of the treatment groups is planned. 
For both Parts, all data collected will be included in by-domain data listings, sorted by subject number 
and time point, or as appropriate. 
No hypothesis testing will be performed for demographics, background, or safety data.  
Continuous data will be summarized by presenting the number of subjects (n), means, mean changes 
from baseline, mean % changes from baseline (where appropriate), standard deviations, minimum, 
First quartile (Q1), median, third quartile (Q3), and maximum values. The number of subjects with 
missing data will be indicated. 


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Categorical data will be summarized by presenting the number of subjects (n), the number of subjects 
with missing data as well as counts and percentages in each of the categories. Percentages will be 
based upon the number of subjects with available data. 
When inferential testing is applied to all efficacy assessments, dichotomous/binary categorical 
efficacy endpoints will be assessed via a 2-sided Fisher’s Exact test or Chi-square test as appropriate.  
Continuous efficacy endpoints will also present least-squares means and p-values from hypothesis 
testing of efficacy endpoints using mixed-effects model for repeated measures (MMRM). 
Additional details will be included in the statistical analysis plan (SAP) which will be finalized prior 
to unblinding Part 2 of the study and any amendments to it made prior to locking the database and 
unblinding the study.   
Handling of Missing Data 
Every attempt will be made to collect all protocol required data at each time point.     
Imputations will only be performed for efficacy data and for missing or partial dates, missing severity 
or relationship to investigational product. Missing AE or CM dates and missing severity or 
relationship to study drug will always use a conservative approach. Details will be included in the 
SAP.  
For subjects who discontinue treatment (for any reason), subjects will continue to be followed and 
key efficacy endpoints and safety data collected where possible. 
Analysis Populations 
Safety Population:  Safety outcomes will be assessed for all subjects who are given at least one dose 
of investigational product.  
Full Analysis Set (FAS) Population:  Efficacy outcomes will be evaluated using the FAS, defined as 
all subjects randomized, treated with at least 1 dose of investigational product, and with at least one 
post-baseline assessment of efficacy. 
Per Protocol Population: The per protocol population will be a subset of FAS and include subjects 
who received at least 80% of study drug and have no major protocol deviations that would impact 
efficacy assessment.  
Alpha Level Considerations 
All inferential testing will be performed using two-sided 5% Type I error (α), and therefore 2-sided p-
values ≤ 0.05 will be considered statistically significant in this study. 
The first hypothesis test will be the key secondary efficacy endpoint of change in bilateral UEMS 
from baseline to Study Day 169 using the MMRM model as detailed below. Additional secondary 
efficacy endpoints tested will be the change in GRASSP prehension performance from baseline and 
slope to Study Day 169 and of change in SCIM self-care from baseline to Study Day 169.  
Efficacy Endpoints 
Changes from pre-treatment to each on-treatment time point will be calculated, with the primary time 
point at Day 169.  Shifts over time in ordinal endpoints will be presented, with comparisons between 
treatment groups assessed using a CMH row mean scores statistic at each time point.  Slope of change 
will also be evaluated. 
Safety Endpoints 
Changes from pre-treatment will be calculated in a similar fashion as for the efficacy endpoints, but 
no inferential statistics will be provided for safety endpoints.  Shifts from baseline in 
electrocardiogram (ECG) will be tabulated for heart rate and QTcF.  Other endpoints will be assessed 
according to the scale of the variable. 
Pharmacokinetic Endpoints 


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Concentration data in both blood serum and in CSF will be assessed descriptively over time.  
Correlation with efficacy and safety outcomes may be performed, as the data warrant. 
Potential Open-Label Extension Study 
The sponsor may, pending data outcomes from this current study, initiate an open-label extension 
study at a later date.  This study would provide subjects who participated in Study RNX-AX204-101, 
during either Part 1 only and those receiving placebo in Part 2, the potential opportunity to participate 
in a repeat-dose study with AXER-204.   
Initiation of the open-label extension study will be contingent on satisfactory results from the current 
clinical study (Part 1 and Part 2) supportive of continued development, funding, and the requisite 
regulatory and IRB approvals. 
 


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Table 5: 
Part 1 Schedule of Events (Study RNX-AX204-101)1 
Study Phase 
Screening 
In-Clinic Treatment 
Post-Treatment Follow-Up 
 
Study Day 
-84 
through -1 
1 
2 
3 
4 
5, 6, 72 
8 
± 1 days 
15 
± 3 days 
29/ET3 
± 4 days 
Pre-Dose 
Post 
Visit Number 
1 
2 
 
 
 
 
Phone 
Call4 
3 
4 
5 
Informed consents (Main & Biobank) 
X 
 
 
Register Subject/Contact EDC/Assign Subject ID  
X 
 
 
 
 
 
 
 
 
 
Inclusion & Exclusion Criteria 
X 
X 
 
 
Instructions for potential washout period for concomitant medications 
and for alcohol use 
X 
 
 
 
 
 
 
 
 
 
Urine sample for drug screen5 
X 
 
 
 
 
 
 
 
 
 
Medical/Disease History 
X 
X 
 
 
Full Physical Examination & Ht/Wt 
X 
 
 
 
 
 
 
 
 
X 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Vital signs (BP, pulse, RR or pulse ox, oral temp)6 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
ECG7 
X 
X 
X 
 
 
X 
 
 
 
 
Serum pregnancy, chorionic gonadotropin  
X 
 
 
MRI8 
X 
 
 
ISNCSCI assessment, including AIS (Clinician Assessed) 
X 
 
 
 
 
 
 
 
 
X 
SCIM III self-care and mobility subscores (Clinician Assessed) 
X 
 
 
X 
GRASSP (Clinician Assessed) 
X 
 
 
X 
Admission/Discharge to/from Clinic 
 
Admit 
 
 
 
Discharge 
 
 
 
 
Physical Examination (abbreviated) 
 
X 
 
 
 
X 
 
 
 
 
CSF collection (for PK assessment)10 
 
X 
 
X 
 
X 
 
X 
 
X 
Dosing of Investigational Product 
 
Dosing 
 
 
 
 
 
 
 
 
Study Drug Accountability 
 
 
X 
 
 
 
 
 
 
 
Serum (for PK and ADA assessment)9 
 
X 
Hr 1, 6, 
12 
X 
 
X 
 
X 
X 
X 
Modified Ashworth Scale (Clinician Assessed) 
X 
 
 
X 
SF-36 v2 Health Survey (Subject Reported) 
X 
 
 
X 
Neuro-QOL v1.0 – Upper Extremity Function (Fine Motor, 
ADL) (Subject Reported) 
X 
 
 
 
 
 
 
 
 
X 
Brief Pain Inventory (Subject Reported) 
X 
 
 
X 
ISAFSCI (Clinician Assessed) 
X 
 
 
X 
Clinical laboratory sample collection10 
X 
X 
X 
X 
X 
 
X 
X 
Viral Serology11 
X 
 
 
X 
Urinalysis  
X 
 
 
X 


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Study Phase 
Screening 
In-Clinic Treatment 
Post-Treatment Follow-Up 
 
Study Day 
-84 
through -1 
1 
2 
3 
4 
5, 6, 72 
8 
± 1 days 
15 
± 3 days 
29/ET3 
± 4 days 
Pre-Dose 
Post 
Visit Number 
1 
2 
 
 
 
 
Phone 
Call4 
3 
4 
5 
Urine pregnancy test12 
 
X 
 
 
 
 
 
 
 
X 
Prior and Concomitant Medications 
Prior 
 
Concomitant (On-going) 
Adverse Events13 
 
 
Treatment-Emergent (On-going) 
Serious Adverse Events 
Pre-
Treatment 
 
Treatment-Emergent (On-going) 
 
1 Abbreviations:  AE = adverse events, ECG = electrocardiogram, EDC = electronic data capture. ET = early termination.  ID = identification, PK = 
pharmacokinetic, SAE = serious adverse event 
2 Note:  Day 7 phone call may be skipped if Day 8 visit actually occurs on Day 7. 
3 ET:  early termination.  Subjects who terminate the treatment prematurely (including those withdrawn from the study) should have all assessments performed 
according to the protocol.  However, subjects who discontinue from the study may only have assessments performed per the ET visit. 
4 Phone calls from the site to the subject will be made each day (Study Days 5, 6, and 7) after discharge from the clinic.  Subjects will be queried for general health. 
5 Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, marijuana, opiates, phencyclidine, barbiturates, 
benzodiazepines, methadone, and propoxyphene).  Patients must abstain from drinking alcohol and using recreational marijuana in US states where marijuana is 
legal, for at least 3 days prior to laboratory screening assessments on nominal Day-28. 
6 Vital signs (blood pressure, pulse rate, respiratory rate or pulse oximetry, and oral body temperature) will be measured after the patient has been in a sitting or 
recumbent position for 5 minutes. Frequency noted below: 
Screening visit - Once 
Day 1 - Pre-dose, post-dose, then every 3 hours for 1st 24 h following dosing 
Day 2-Day 4 (until discharge from the clinical unit) - Starting at 24 h post-dose, take vitals every 6 hours 
Day 8, 29 - Pre-LP, post-LP, then every 3 hours until subject leaves the unit 
Day 15 - Pre-blood draw 
7 ECGs will be taken in triplicate, 5 minutes apart, will be obtained after the patient has been in a supine (resting) position for at least 5 minutes. At Visit 2, 
triplicate ECGs will be taken twice, pre-and post-dose.  All ECGs will be read locally. 
8 MRIs will be read by a sponsor-arranged expert prior to subject enrollment into the study 
9 Serum samples collected and analyzed for ADA pre-dose and on Study Days 8 and 29 
10 Clinical Laboratory Sample Collection: Sample collected on Study Days 1-4 are to be processed locally.  INR/PTT is required prior to the Day 1 lumbar 
puncture procedure with repeat INR/PTT tests on subsequent Study Days at the direction of the Principal Investigator.   
11 Infectious disease testing at Screening and Visit 5 (Study Day 29/ET) will include:  HIV-1/HIV-2 antibody, hepatitis B surface antigen, hepatitis C antibody. 
12 Urine Pregnancy Test will be performed locally on site for women of childbearing potential. 
13 Adverse Events are only collected upon the start of study drug.  Events occurring prior to this are to be reported as part of the subject medical history.  
However, SAEs are to be collected from the time of informed consent. 


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Table 6: 
Part 2 Schedule of Events (Study RNX-AX204-101)1 
Study Phase 
Screening 
Treatment Phase 
Window at Visits 3-7 ± 5 days 
Follow-Up 
± 7 days 
Study Day 
-84 
through 
-1 
1 
8 
(±3 
days) 
21 
 
42 
 
63 
84 
 
104 
 
137 
Month 5 
169 
Month 6 
253/ET2 
Month 9 
Visit Number 
1 
2 
 
3 
4 
5 
6 
7 
 
8 
9 
Informed consents (Main & Biobank) 
X 
 
 
Register Subject/Contact EDC/Assign Subject ID  
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X 
 
 
Instructions for potential washout period for concomitant 
medications and for alcohol use 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical/Disease History 
X 
X 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
MRI2  
X 
 
 
 
 
 
 
 
 
 
 
Telephone call3 
 
 
X 
 
 
 
 
 
X 
 
 
Full Physical Examination & Ht/Wt 
X 
 
 
 
 
 
 
 
 
 
X 
Physical Examination (abbreviated) 
 
X 
 
X 
X 
X 
X 
X 
 
X 
 
Vital Signs (BP, pulse, RR or Pulse Ox, oral temp)4 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
ECG5 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
ISNCSCI assessment including AIS  
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
GRASSP6  
X 
X 
 
X 
X 
X 
X 
SCIM III self-care and mobility subscores 
 
X 
 
 
 
X 
 
X 
 
X 
X 
Modified Ashworth Scale 
 
X 
 
 
 
 
 
 
 
X 
X 
Brief Pain Inventory 
 
X 
 
 
 
 
 
 
 
X 
X 
Neuro-QOL v1.0 – Upper Extremity Function (Fine Motor, ADL)  
 
X 
 
 
 
 
 
 
 
X 
X 
SF-36 v2 Health Survey  
 
X 
 
 
 
 
 
 
 
X 
X 
CUE-Q 
 
X 
 
 
 
 
 
 
 
X 
X 
PGIC Chronic SCI 
 
X 
 
 
 
 
 
 
 
X 
X 
ISAFSCI 
X 
 
 
X 
X 
CSF collection (pre-dose if dosing visit)7 
 
X 
 
X 
X 
X 
X 
X 
 
 
X 
Clinical laboratory sample collection (CSF) 
 
X 
 
X 
X 
X 
X 
X 
 
 
X 
Dosing of Investigational Product 
 
X 
 
X 
X 
X 
X 
X 
 
 
 
Investigational Product Accountability 
 
X 
 
X 
X 
X 
X 
X 
 
 
 
Serum collection for PK (pre-dose & 4 h post-dose if dosing visit) 
 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
Serum collection for ADA (pre-dose if dosing visit) 
 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
Clinical laboratory sample collection8 
X 
X 
 
X 
X 
X 
X 
X 
Viral Serology9 
X 
 
 
X 
X 
Serum pregnancy, chorionic gonadotropin  
X 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy Test10 
 
X 
 
X 
X 
X 
X 
X 
 
X 
X 


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Study Phase 
Screening 
Treatment Phase 
Window at Visits 3-7 ± 5 days 
Follow-Up 
± 7 days 
Study Day 
-84 
through 
-1 
1 
8 
(±3 
days) 
21 
 
42 
 
63 
84 
 
104 
 
137 
Month 5 
169 
Month 6 
253/ET2 
Month 9 
Visit Number 
1 
2 
 
3 
4 
5 
6 
7 
 
8 
9 
Urine sample for drug screen11 
X 
 
 
 
 
 
 
 
 
 
 
Urinalysis  
X 
X 
 
X 
X 
X 
X 
X 
Prior and Concomitant Medications 
Prior 
Concomitant (On-going) 
Post-Trt 
Adverse Events12 
 
Treatment-Emergent (On-going) 
Post-Trt 
Serious Adverse Events 
Pre-Trt 
Treatment-Emergent (On-going) 
Post-Trt 
 
1 Abbreviations:  ADA = anti-drug antibody, AE = adverse events, ECG = electrocardiogram, EDC = electronic data capture. ET = early termination.  ID = 
identification, PK = pharmacokinetic, SAE = serious adverse event 
2 MRIs will be run locally and findings read by a sponsor-arranged expert prior to subject enrollment into the study. 
3 Telephone call to inquire about any AEs and determine if subject should come to clinic for evaluation. 
4 Vital signs (blood pressure, pulse rate, respiratory rate or pulse oximetry, and oral body temperature) will be measured after the patient has been in a sitting or 
recumbent position for 5 minutes.  Vitals will be taken pre-dose, post dose, then every 2 hours until subject leaves the unit 
5 ECGs will be taken in triplicate, 5 minutes apart, and will be obtained after the patient has been in a supine (resting) position for at least 5 minutes. ECGs are 
taken pre-dose at visits where study drug is administered.  ECGs will be read locally. 
6 GRASSP prehension ability and prehension performance testing will be video recorded. 
7 Remove aliquot for CSF labs before processing CSF for pharmacokinetics/biomarkers and biobank samples. 
8 Clinical Laboratory Sample Collection: INR/PTT is required prior to the Day 1 lumbar puncture procedure with repeat INR/PTT tests on subsequent Study 
Days only if directed by the Principal Investigator.  Screening labs must be completed within 28 days of enrollment. 
9 Infectious disease testing at Screening, Visit 8 (Month 6) and Visit 9 (Month 9) will include:  HIV-1/HIV-2 antibody, hepatitis B surface antigen, hepatitis C 
antibody. 
10 Urine Pregnancy Test will be performed locally on site for women of childbearing potential. 
11 Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, marijuana, opiates, phencyclidine, barbiturates, 
benzodiazepines, methadone, and propoxyphene).   
12 Adverse Events are only collected upon the start of study drug.  Events occurring prior to this are to be reported as part of the subject medical history.  
However, SAEs are to be collected from the time of informed consent. 


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2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
1. 
SYNOPSIS ...................................................................................................................4 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............24 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................31 
4. 
INVESTIGATORS AND STUDY PERSONNEL .....................................................33 
5. 
INTRODUCTION ......................................................................................................34 
5.1. 
AXER-204, a Human NoGo Trap Fusion Protein ......................................................34 
5.2. 
Nonclinical Summary .................................................................................................36 
5.3. 
Clinical Experience with AXER-204 and Lumbar Puncture ......................................36 
5.4. 
Rationale for Dose Selection ......................................................................................37 
6. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................39 
6.1. 
Part 1 Single Ascending Dose ....................................................................................39 
6.1.1. 
Primary Objective .......................................................................................................39 
6.2. 
Part 2 Placebo-Controlled Repeat Dose .....................................................................39 
6.2.1. 
Primary Objectives .....................................................................................................39 
6.2.2. 
Secondary Objectives .................................................................................................39 
6.2.3. 
Exploratory Objectives ...............................................................................................39 
7. 
INVESTIGATIONAL PLAN .....................................................................................41 
7.1. 
Overall Study Design ..................................................................................................41 
7.1.1. 
Part 1 ...........................................................................................................................41 
7.1.1.1. 
Screening ....................................................................................................................41 
7.1.1.2. 
In-Clinic Treatment Period .........................................................................................42 
7.1.1.3. 
Follow-Up ...................................................................................................................43 
7.1.2. 
Part 2 ...........................................................................................................................43 
7.1.2.1. 
Screening ....................................................................................................................43 
7.1.2.2. 
Treatment Phase ..........................................................................................................44 
7.1.2.3. 
Follow-Up ...................................................................................................................44 
7.2. 
Number of Subjects ....................................................................................................45 
7.3. 
Treatment Assignment ................................................................................................45 
7.3.1. 
Part 1 ...........................................................................................................................45 


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7.3.2. 
Part 2 ...........................................................................................................................45 
7.3.3. 
Dose Escalation Decisions and Data and Safety Monitoring Board (DSMB) 
Dose Escalation in Part 1 ............................................................................................46 
7.3.3.1. 
Stopping Rules/Study Interruption/Discontinuation Notice (Part 1) ..........................46 
7.3.3.2. 
Stopping Rules/Study Interruption/Discontinuation Notice (Part 2) ..........................46 
7.3.4. 
Data and Safety Monitoring Board .............................................................................47 
7.4. 
Criteria for Study Termination ...................................................................................47 
8. 
STUDY ENTRY CRITERIA .....................................................................................48 
8.1. 
Subject Inclusion Criteria ...........................................................................................48 
8.2. 
Subject Exclusion Criteria ..........................................................................................48 
9. 
WITHDRAWAL OF SUBJECTS ..............................................................................51 
9.1. 
Subject Withdrawal Criteria .......................................................................................51 
10. 
TREATMENT OF SUBJECTS ..................................................................................52 
10.1. 
Description of Study Drug & Placebo ........................................................................52 
10.2. 
Concomitant Medications ...........................................................................................52 
10.3. 
Treatment Compliance ................................................................................................53 
10.4. 
Randomization and Blinding ......................................................................................54 
10.4.1. 
Part 1 ...........................................................................................................................54 
10.4.2. 
Part 2 ...........................................................................................................................54 
11. 
STUDY PROCEDURES ............................................................................................56 
11.1. 
Part 1 ...........................................................................................................................56 
11.1.1. 
Screening Period, Visit 1 (Study Days -84 through -1) ..............................................56 
11.1.2. 
In-Clinic Treatment, Visit 2 (Study Days 1 to 4 [Pre-Dose and Post-Dose]).............58 
11.1.3. 
Post-Treatment Follow-up Phone Calls, Study Days 5, 6, and 7 ...............................59 
11.1.4. 
Post Treatment Follow-up Visits 3 & 4 (Study Days 8 and 15) .................................59 
11.1.5. 
Post Treatment Follow-up Visit 5 (Study Day 29/ET) ...............................................59 
11.2. 
Part 2 ...........................................................................................................................60 
11.2.1. 
Screening Period, Visit 1 (Study Days -84 through -1) ..............................................61 
11.2.2. 
Treatment Phase, Visits 2 through 7 (Study Days 1 through 104) .............................62 
11.2.3. 
Follow-up on Study Day 137 ......................................................................................65 
11.2.4. 
Follow-up Visits 8 and 9 (Study Days 169 and 253)..................................................65 
12. 
INVESTIGATIONAL PRODUCT MATERIALS AND MANAGEMENT .............66 
12.1. 
Study Drug ..................................................................................................................66 


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12.2. 
Investigational Product Packaging and Labeling .......................................................66 
12.3. 
Investigational Product Storage ..................................................................................66 
12.4. 
Investigational Product Preparation ............................................................................67 
12.5. 
Investigational Product Management .........................................................................67 
12.6. 
Investigational Product Accountability ......................................................................67 
12.7. 
Investigational Product Handling and Disposal .........................................................67 
13. 
ASSESSMENT OF EFFICACY AND PHARMACOKINETICS .............................69 
13.1. 
Efficacy .......................................................................................................................69 
13.1.1. 
Part 1 ...........................................................................................................................69 
13.1.2. 
Part 2 ...........................................................................................................................69 
13.2. 
Pharmacokinetics ........................................................................................................70 
13.2.1. 
Serum ..........................................................................................................................73 
13.2.2. 
Cerebrospinal Fluid ....................................................................................................73 
13.2.3. 
Shipment of Pharmacokinetic Samples ......................................................................73 
14. 
ASSESSMENT OF SAFETY .....................................................................................74 
14.1. 
Safety Parameters .......................................................................................................74 
14.1.1. 
Demographic/Medical History ...................................................................................74 
14.1.2. 
Vital Signs ..................................................................................................................74 
14.1.3. 
Physical Examination .................................................................................................75 
14.1.4. 
Electrocardiogram (ECG) ...........................................................................................75 
14.1.5. 
Laboratory Assessments .............................................................................................75 
14.1.5.1. 
Other Laboratory Tests ...............................................................................................77 
14.1.5.2. 
Virus Serology ............................................................................................................77 
14.1.5.3. 
Drug Screen ................................................................................................................77 
14.2. 
Adverse and Serious Adverse Events .........................................................................77 
14.2.1. 
Definition of Adverse Events .....................................................................................77 
14.2.2. 
Abnormal Test Findings .............................................................................................78 
14.2.3. 
Adverse Events of Special Interest (AESI) ................................................................78 
14.2.4. 
Serious Adverse Event (SAE) ....................................................................................79 
14.2.4.1. 
Hospitalization ............................................................................................................79 
14.2.5. 
Adverse Event Reporting ............................................................................................80 
14.2.5.1. 
Severity Assessment ...................................................................................................81 
14.2.5.2. 
Causality Assessment .................................................................................................81 


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14.2.5.3. 
Exposure in Utero .......................................................................................................82 
14.2.5.4. 
Reporting Requirements .............................................................................................83 
14.2.5.5. 
Non-Serious Adverse Event Reporting Requirements ...............................................83 
14.2.5.6. 
Sponsor Reporting Requirements to Regulatory Authorities .....................................84 
15. 
STATISTICS ..............................................................................................................85 
15.1. 
Sample Size ................................................................................................................85 
15.2. 
Stages of Analysis .......................................................................................................85 
15.3. 
General Methods .........................................................................................................85 
15.4. 
Handling of Missing Data ...........................................................................................86 
15.5. 
Subgroups ...................................................................................................................86 
15.6. 
Analysis Populations ..................................................................................................86 
15.7. 
Alpha Level Considerations .......................................................................................87 
15.8. 
Subject Disposition and Exposure ..............................................................................87 
15.9. 
Demographics and Baseline Characteristics Analyses ...............................................87 
15.10. 
Efficacy Endpoints ......................................................................................................87 
15.10.1. 
Part 2 Efficacy Endpoints ...........................................................................................87 
15.11. 
Safety Endpoints .........................................................................................................88 
15.12. 
Pharmacokinetic Endpoints ........................................................................................90 
16. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................91 
17. 
ETHICS ......................................................................................................................92 
17.1. 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ..................92 
17.2. 
Ethical Conduct of the Study ......................................................................................92 
17.3. 
Subject Information and Consent ...............................................................................92 
17.4. 
Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP .........93 
18. 
DATA HANDLING AND RECORDKEEPING .......................................................94 
18.1. 
Case Report Forms .....................................................................................................94 
18.2. 
Record Retention ........................................................................................................94 
19. 
PUBLICATION POLICY ..........................................................................................95 
19.1. 
Publications by Investigators ......................................................................................95 
20. 
LIST OF REFERENCES (ALPHABETICAL) ..........................................................96 
21. 
INVESTIGATORS AGREEMENT ...........................................................................99 
APPENDIX 1. INTERNATIONAL STANDARDS TO DOCUMENT REMAINING 
AUTONOMIC FUNCTION AFTER SPINAL CORD INJURY (ISAFSCI) ..........100 


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APPENDIX 2. CUE-Q SAMPLE SCALE ...............................................................................101 
APPENDIX 3. ISNCSCI SAMPLE FORM (INCLUDES KEY SECONDARY 
EFFICACY SCORE) ................................................................................................105 
APPENDIX 4. GRASSP SAMPLE FORM ..............................................................................107 
APPENDIX 5. MODIFIED ASHWORTH SCALE SAMPLE ................................................109 
APPENDIX 6. SF-36 V2 HEALTH SURVEY ........................................................................112 
APPENDIX 7. NEURO-QOL UPPER EXTREMITY FUNCTION SAMPLE .......................118 
APPENDIX 8. SPINAL CORD INDEPENDENCE MEASURE SAMPLE ............................120 
APPENDIX 9. BRIEF PAIN INVENTORY SAMPLE ...........................................................122 
APPENDIX 10. PATIENT’S GLOBAL IMPRESSION OF CHANGE ..................................124 
APPENDIX 11. AXER-204 AND PLACEBO DOSE ADMINISTRATION 
PROCEDURE...........................................................................................................125 
APPENDIX 12. MAGNETIC RESONANCE IMAGING (MRI) PROCEDURES .................129 
 


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LIST OF TABLES 
Table 1: 
Emergency Contact Information ...................................................................................2 
Table 2: 
Treatment by Cohort - Part 1 (Study RNX-AX204-101) .............................................7 
Table 3: 
Part 1 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) ....................14 
Table 4: 
Part 2 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) ....................15 
Table 5: 
Part 1 Schedule of Events (Study RNX-AX204-101) ................................................20 
Table 6: 
Part 2 Schedule of Events (Study RNX-AX204-101) ................................................22 
Table 7: 
Abbreviations and Specialist Terms (Study RNX-AX204-101) ................................31 
Table 8: 
Treatment by Cohort (Part 1, Study RNX-AX204-101) ............................................42 
Table 9: 
Study Drug and Placebo (Study RNX-AX204-101) ..................................................52 
Table 10: Part 1 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) ....................72 
Table 11: Part 2 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) ....................72 
Table 12: Laboratory Parameters to be Assessed (Study RNX-AX204-101) ............................76 
Table 13: Moderate and Marked Liver Function Abnormality Thresholds (Study RNX-
AX204-101) ................................................................................................................76 
Table 14: Relatedness Definitions (Study RNX-AX204-101) ...................................................81 
 


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LIST OF FIGURES 
Figure 1: 
Key Components Regulating Axonal Growth in the Adult Mammalian 
Central Nervous System .............................................................................................34 
Figure 2: 
Putative Mechanism of AXER-204 ............................................................................35 
 
  


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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 7: 
Abbreviations and Specialist Terms (Study RNX-AX204-101) 
Abbreviation or Specialist 
Term 
Explanation 
ADA 
Anti-drug antibodies 
ADL 
Activities of daily living 
AE 
Adverse event 
AESI 
Adverse events of special interest 
AIS 
American Spinal Injury Association Impairment Scale 
ANCOVA 
Analysis of Covariance 
BMI 
Body mass index 
BPI 
Brief Pain Inventory 
BUN 
Blood urea nitrogen 
CMH 
Cochran-Mantel-Haenszel 
CNS 
Central nervous system 
CRO 
Contract research organization 
CSCI 
Chronic Spinal Cord Injury 
CSF 
Cerebrospinal fluid 
CTCAE 
Common Terminology Criteria for Adverse Events 
CUE-Q 
Capabilities of Upper Extremity – Questionnaire  
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
eGFR 
Estimated Glomerular Filtration Rate 
ER 
Emergency room 
ET 
Early termination 
FAS 
Full analysis set population 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GRASSP 
Graded Redefined Assessment of Strength, Sensation and Prehension 
HED 
Human equivalent dose 
HIV 
Human immunodeficiency virus 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
DSMB 
Data and Safety Monitoring Board 


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Abbreviation or Specialist 
Term 
Explanation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
IRT 
Integrated response technology 
ISAFSCI 
International Standards to document remaining Autonomic Function after 
Spinal Cord Injury 
ISNCSCI 
International Standards for Neurological Classification of SCI 
LP 
Lumbar Puncture 
LSMean 
Least Square Means 
MEP 
Motor Invoked Potentials 
MRI 
Magnetic Resonance Imaging 
MTD 
Maximum Tolerated Dose 
NOAEL 
No Observed Adverse Effect Level 
NOEL 
No Observed Effect Level 
OAE 
Other significant adverse event 
PACU 
Post-Anesthesia Care Unit 
PGIC 
Patient’s Global Impression of Change 
PI 
Principal Investigator   
PK 
Pharmacokinetics 
PRN 
Pro re nata (as needed) 
QoL 
Quality of Life 
QTcF 
QT interval using Fridericia Correction Formula 
SAE 
Serious adverse event 
SCIM III 
Version III of the Spinal Cord Independence Measure 
SF-36 
 Short Form - 36 v2 Health Survey 
SNRI 
serotonin norepinephrine reuptake inhibitor 
SOC 
system organ class 
SSRI 
selective serotonin reuptake inhibitor 
TEAE 
treatment-emergent adverse event 
TNF 
tumor necrosis factor 
UEMS 
upper extremity motor score 
UMC 
Uppsala Monitoring Centre 
US 
United States 
WHO 
World Health Organization 


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4. 
INVESTIGATORS AND STUDY PERSONNEL 
This study will be conducted by qualified investigators under the Sponsorship of ReNetX Bio, 
Inc. (the sponsor) at approximately 5 investigational centers in the United States. 
The contact information for the Medical Monitor along with the telephone numbers of the other 
contact persons for the sponsor are listed in Table 1.  Contact information for 
, the 
designated Contract Research Organization, (CRO), and other vendors are listed in the 
Investigator Site File provided to each site. 


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5. 
INTRODUCTION 
5.1. 
AXER-204, a Human NoGo Trap Fusion Protein 
Mammalian brain and spinal cord networks stabilize during development, such that axonal 
growth in the adult CNS is either non-existent or extremely limited. After adult CNS injury, the 
extracellular factors that maintain axonal stability restrict axonal growth and permit only 
severely limited recovery of function. Adult extracellular axonal growth inhibitors include a 
group of proteins from the oligodendrocyte, Nogo-A, MAG, OMgp, and ephrin-B3, which 
interact with axonal receptors, including NgR1, NgR2, PirB, and EphA4 [Liu 2006, Schwab 
2014].  Extracellular proteoglycans, containing chondroitin sulfates, also inhibit axonal sprouting 
in the adult CNS, particularly near sites of astrogliosis and scar formation [Ohtake 2015, Sharma 
2012].  There is substantial molecular cross talk between ligands and receptors.  The key 
inhibitory ligands Nogo, MAG, and OMgp all bind and activate NgR1 on axons to inhibit axonal 
extension.  Likewise, PirB (LILRB2) has been found to bind Nogo, MAG, and OMgp and to 
mediate axonal growth inhibition.  Consistent with partially overlapping roles in axonal 
inhibition, simultaneous genetic deletion of Nogo, MAG, and OMgp has greater impact on 
axonal growth and functional recovery following CNS injury than deletion of a single inhibitor 
[Cafferty 2010].  A representation of the role of Nogo, MAG, and OMgp and other key 
regulators of axonal growth in the adult CNS is presented in Figure 1.  
Figure 1: 
Key Components Regulating Axonal Growth in the Adult Mammalian 
Central Nervous System 
 
Targeting one ligand or one receptor in the inhibitory adult CNS pathways has been shown to 
yield some benefit in certain specific pre-clinical spinal cord injury (SCI) models.  Based on 
these observations, anti-Nogo antibodies are entering clinical trials for new (subacute) SCI. In 
distinction, NoGo Trap (AXER-204, Nogo Receptor decoy, hNgR1(310)ecto-Fc Ala Ala) 


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represents a mechanistically superior approach to promoting axonal growth following injury as it 
binds three key inhibitors, Nogo, MAG, and OMgp, and blocks their interaction with 
endogenous NgR1 and other receptors (Figure 2).  Consistent with this mechanism, NoGo Trap 
has been shown in multiple laboratories to promote axonal growth and recovery of function in a 
variety of pre-clinical models of CNS injury including stroke [Lee 2004], dorsal root crush injury 
[Harvey 2009], acute transection SCI [Li 2004], and acute/sub-acute contusion SCI [Ji 2006, 
Wang 2006, Wang 2014].  Most critically, NoGo Trap supports axonal growth and functional 
recovery in chronic contusion SCI [Wang 2011], while no other blocker of extrinsic signals has 
reported efficacy in this setting.  Recent pre-clinical studies have shown that intrathecal lumbar 
administration results in broad CNS distribution in rat and non-human primate and that 
intermittent intrathecal bolus injection of the protein provides equivalent restoration of function 
in rat contusion SCI in comparison to previously obtained results employing continuous infusion 
[Wang 2014].  AXER-204 promotes corticospinal axon growth and the use of the impaired 
forelimb during spontaneous feeding and the impaired hindlimb during locomotion non-human 
primates with cervical hemisection SCI [Wang 2020]. 
Figure 2: 
Putative Mechanism of AXER-204 
 
 
The present clinical evaluation of AXER-204 is being conducted in subjects with chronic SCI.  
This plan is based on the enhanced feasibility for detecting treatment-related functional 
improvements in subjects with otherwise stable deficits [Fawcett 2007, NSCISC 2018].  The 


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substantially larger chronic SCI patient population compared to acute SCI cases should facilitate 
enrollment of this study and has the potential to translate into benefit for many more individuals. 
5.2. 
Nonclinical Summary 
Nonclinical data are summarized for AXER-204.  In addition, data from nonclinical studies with 
various surrogate proteins, primarily a rat form of the NoGo Trap protein, are included.  AXER-
204 binds to the myelin associated ligands Nogo (measured using Nogo-66 fragment), MAG, 
and OMgp in ELISA format in vitro.  Likewise, binding to MAG and OMgp has been measured 
using a Fluorescence Resonance Energy Transfer (FRET) assay.  Consistent with the binding 
profile, AXER-204 prevents Nogo-22 mediated inhibition of cultured axon growth.  AXER-204 
promotes functional recovery following contusion spinal cord injury in rat with either continuous 
infusion into the cerebrospinal fluid (CSF) via intracerebroventricular cannula or intermitted 
bolus intrathecal administration.  Moreover, the intermittent intrathecal treatment increased the 
growth of raphespinal axons after injury.  
A number of additional evaluations in spinal cord injury models were conducted using the rat 
form of the protein.  Overall, the pharmacological effects include functional recovery and 
enhanced axon growth.  Of particular importance, NoGo Trap was found to enhance functional 
recovery in chronic contusion injury in rat – supporting evaluation in chronic SCI.  In 
pharmacokinetics studies, AXER-204 distributed broadly in the CSF, spinal cord tissue, and 
brain tissue following intrathecal administration.  Tissue half-life was prolonged over the half-
life in CSF.  Daily intrathecal bolus infusions of AXER-204 in non-GLP 14-day range finder 
toxicology studies in rat and monkey did not identify adverse effects from test article (No 
observed adverse effect level [NOAEL] was maximum feasible dose volume for each study). 
CSF and serum exposure were confirmed in each study.  Similarly, no test article-related toxicity 
was observed in GLP toxicology studies with administration of AXER-204 by intrathecal bolus 
infusions every other day in rat for two months and in monkey for up to 108 days. Accordingly, 
the no observed effect level (NOEL) for rat and monkey was equivalent to the maximum feasible 
dose.  Toxicology studies employed frequent bolus infusions in order to maximize the 
cumulative dose evaluated.  
Off-target effects such as toxicity due to systemic exposure are not anticipated with AXER-204 
because the requisite ligands Nogo, MAG, and OMgp are mostly localized in the CNS and 
AXER-204 exposure is predominantly localized to the CNS following intrathecal administration 
in animal studies.  Nonetheless, a one-month GLP rat toxicology study employing intravenous 
dosing was completed and the maximum dose tested was found to be equivalent to the NOAEL. 
Please refer to the AXER-204 Investigator’s Brochure for a more detailed description of 
toxicology investigations. 
5.3. 
Clinical Experience with AXER-204 and Lumbar Puncture 
The present study represents the first evaluation of AXER-204 in humans.   
There is extensive published clinical experience with lumbar puncture (LP) procedures 
representative of those required for administration of AXER-204.  The most common adverse 
events (AEs) associated with LP consist of post-LP back pain and post-LP headache. This 
protocol includes procedures designed to minimize the incidence and severity of AEs associated 


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with LP including optimal choice of spinal needle, removal of an equivalent volume of CSF 
relative to the volume of investigational product injected, and a controlled rate of slow bolus 
injection of investigational product. 
5.4. 
Rationale for Dose Selection 
In Part 1, the initial dose escalation sequence for the study is 3, 30, 90, and 200 mg. The starting 
dose 3 mg was selected to be 30-fold below the estimated human pharmacologically active dose 
of 90 mg.  Adjusting for cross-species scaling by CSF volume, toxicology studies did not 
identify AXER-204 related toxicity when given at equivalent (monkey) or at three-fold higher 
(rat) doses vs. the maximum planned human dose when given every other day by slow bolus 
intrathecal administration for up to 57 days in rat and 108 days in monkey.  Similarly, adjusting 
for cross-species scaling by CSF volume and accounting for the more frequent dosing in the GLP 
toxicology studies, the cumulative doses given in rat and monkey toxicology exceeded the 
maximum feasible human dose by at least 21-fold and 8-fold respectively.  The maximum doses 
in toxicology were the maximum feasible doses based on the tolerable volumes for intrathecal 
administration.  The 3 and 30 mg doses will be diluted from the formulation to provide a 
constant injection volume of 10 mL.  The 90 mg and 200 mg doses will be given without dilution 
resulting in dosing volumes of 9 mL and 20 mL respectively.  The dose volumes were selected 
based on published studies and drug label information for other therapeutics describing safety 
and drug distribution following intrathecal administration. 
A conservative approach was applied in deriving the starting dose in Part 1 in order to enhance 
safety.  For drugs delivered intrathecally, published FDA guidance suggests scaling based on 
compartment volumes and concentrations of the therapeutic [Guidance for Industry, FDA].  
Using compartment volumes, the pharmacologic human equivalent dose (HED) is calculated by 
dividing the rat effective dose by rat CSF volume and multiplying by the CSF volume for 
human. This yields an estimated pharmacologic HED of 90 mg.  The starting dose of 3 mg is 
anticipated to be free of detectable pharmacological effects using the method outlined in the 
Draft Guidance for Industry and Reviewers of November 2005 entitled “Estimating the 
Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult healthy 
Volunteers” and incorporates a safety factor of 30 compared to the estimated human 
Pharmacologically Active Dose of 90 mg.  The maximum dose volume of 20 mL represents 
approximately 10-15% of total average CSF volume for adults and roughly 30% of spinal CSF 
volume [Kroin 1992, Thorne 2001, Sakka 2011].  The dose will be introduced immediately 
following collection of an equivalent volume of CSF and at a controlled constant rate of 100 
mL/h (12 min for 20 mL).  The bolus injection rate selected is five times the average time 
required to regenerate the CSF collected (20 mL/h) [Hladky 2014].  The time required to 
regenerate CSF collected by lumbar puncture has been found to approximately equal the time 
needed to normalize CSF pressure [Brinker 2014, Masserman 1934].  Thus, the sequence of CSF 
collection followed by controlled bolus infusion of an equivalent volume of investigational 
product is designed to reduce the impact on CSF pressure and flow.  The controlled bolus 
injection rate selected is slower than the rate of injection specified for several marketed products 
administered intrathecally including:  Omnipaque 10-17 mL injected over 1-2 min, a small 
amount of CSF may be removed prior to injection [OMNIPLAQUE Package Insert]; 
Methotrexate, usually 2-6 mL (up to 10 mL) injected over 1-3 min following removal of an 
equivalent volume of CSF; Spinraza 5 mL injected in children over 1-3 min after removal of 5 


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mL CSF [SPINRAZA Package Insert].  Published results indicate that volumes ranging from 10-
30 mL of CSF can be administered in humans without adverse effects beyond occasional mild 
headache provided an equivalent volume of CSF is first removed [Papisov 2013, Rieselbach 
1962a, Rieselbach 1962b, Rieselbach 1963].  The conservative controlled injection rate of 
AXER-204 following collection of an equivalent volume of CSF is designed to reduce the 
potential for adverse effects arising from disruption of CSF pressure and flow.   
Distribution following bolus intrathecal administration is reported to depend strongly on 
injection volume, with smaller volumes favoring less rapid distribution.  Rapid broad distribution 
to the cisterna magna is reported following bolus intrathecal lumbar administration provided a 
volume over 10% of total CSF is given [Papisov 2013, Rieselbach 1962a].  Estimates of total 
subarachnoid CSF volume in adults generally range between 90-170 mL and 150 mL is 
commonly taken as the volume for dose modeling [Brinker 2014, Kuttler 2010].  Thus, the range 
of AXER-204 dose volumes of 9-20 mL are selected to facilitate rapid and broad distribution 
over the length of the cord.  
To ensure subject safety, dose selection for Part 2 of the study will be based on safety, 
tolerability, and pharmacokinetics data generated in Part 1 and the DSMB will review and 
approve dosing frequency and level before recommending starting Part 2.  The maximum safe 
dose identified in Part 1 will be selected for repeated administration in Part 2.  The frequency of 
dosing in Part 2 will be determined based on analysis of pharmacokinetic data.  In addition, 
biomarkers of target engagement and mechanism engagement are under development with the 
objective of implementing these assays to aid in guiding dose frequency in Part 2.  The dosing 
will be no more frequent than once every two weeks or as long as once every 4 weeks for Part 2. 
As described for Part 1, repeat-dose toxicology studies with much more frequent administration 
in rat and cynomolgus monkey did not identify AXER-204 toxicity. 


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6. 
TRIAL OBJECTIVES AND PURPOSE 
Study RNX-AX204-101 is a two-part (Parts 1 and 2) study that will be run sequentially.  Part 1 
is considered a Phase 1b study, while Part 2 is considered a Phase 2a study.  Each part has 
unique objectives. 
6.1. 
Part 1 Single Ascending Dose 
6.1.1. 
Primary Objective 
To evaluate the safety, tolerability, and pharmacokinetics (PK) of ascending, single intrathecal 
lumbar slow bolus infusions of AXER-204 in subjects with chronic spinal cord injury (CSCI). 
6.2. 
Part 2 Placebo-Controlled Repeat Dose 
6.2.1. 
Primary Objectives 
1. To evaluate the safety and tolerability of repeat intrathecal lumbar slow bolus infusions 
of AXER-204 compared to placebo in subjects with CSCI.  
2. To evaluate the pharmacokinetics of repeat doses of AXER-204 in subjects with CSCI 
6.2.2. 
Secondary Objectives 
To assess the efficacy of repeat dose therapy of AXER-204 compared to placebo on functional 
and activities of daily living (ADL) measures as assessed by: 
• International Standards for Neurological Classification of SCI (ISNCSCI) Upper 
Extremity Motor Score (UEMS) 
• Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) 
prehension performance 
• Version III of the Spinal Cord Independence Measure (SCIM III) self-care  
6.2.3. 
Exploratory Objectives 
In Part 2, the efficacy of repeat dose therapy of AXER-204 compared to placebo as assessed by 
the following:  
• ISNCSCI lower extremity motor and sensory scores  
• GRASSP strength, sensation and prehension ability scores 
• SCIM III mobility scores 
• International Standards to document remaining Autonomic Function after Spinal 
Cord Injury (ISAFSCI) 
• Patient Reported Outcomes 
− CUE-Questionnaire (CUE-Q).  Assesses subject-reported upper limb function. 


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− SF-36 v2.  Provides a patient-reported Quality of Life (QoL) assessment.  SF-36 
will provide data on the subjects' perceived health and well-being over the course 
of the study.   
− Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL) 
− 
PGIC – Chronic SCI 
Exploratory biomarkers of target engagement and axonal growth may be assessed.  


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7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
Study RNX-AX204-101 is a two-part study that will be run sequentially, with Part 2 planned to 
start after Part 1 has completed. Each Part will be conducted at approximately 5 centers in the 
United States.   
For each Part, eligible subjects will be ages 18 to 65 years inclusive, male or female, with a 
traumatic spinal cord injury that occurred at least 1 year prior to the screening date.  Subjects 
must have significant neurological impairment of the hands and arms.  Subjects who participated 
in Part 1 may be evaluated for enrollment in Part 2 provided at least 6 months will have elapsed 
between the dose received in Part 1 and the initiation of dosing in Part 2.   
7.1.1. 
Part 1 
Part 1 is a multicenter, open-label, single ascending dose study in subjects with chronic spinal 
cord injury.  Four cohorts of 6 subjects each are planned, with subjects within each cohort 
expected to receive the same dose of study drug.  Thus, up to 24 subjects will be enrolled in Part 
1, and all will receive AXER-204.  
If the Maximum Tolerated Dose (MTD) is reached prior to the fourth cohort, the sponsor may 
enroll the remaining subjects (up to a total enrollment of 24 for the study) to obtain further data 
at the tolerated dose levels.  The sponsor in conjunction with the investigators and medical 
monitor will determine dose escalation according to the methods described in Section 7.3.3. 
Study drug will be administered sequentially, with at least 3 days between subjects being dosed 
within each cohort (following 72-hour safety assessment review by the sponsor in conjunction 
with the investigators and medical monitor for each prior subject). 
The study stages for Part 1 are: 
• Screening (within 84 days prior to Day 1).  Patients have 84 days from the time of 
signing informed consent to complete their screening assessments and, if needed, 
their washout period for prohibited concomitant medications. The screening 
laboratory tests must be completed within 28 days prior to Day 1. 
• Treatment period:  Check-in Day 1, administration of study drug, 3-night in-clinic 
stay, and discharge on Day 4 following the completion of all scheduled procedures.  
• Follow-up: Subjects will have follow-up visits for up to 29 days post-dose as follows: 
subjects will receive a phone call on Study Days 5, 6, and 7 to inquire about their 
general health and will return to the clinic for visits on Study Day 8 (± 1 day), Study 
Day 15 (±3 days) and Study Day 29 or Early Termination (± 4 days).  See Table 5 for 
the Schedule of Events for Part 1. 
7.1.1.1. 
Screening 
All subjects must sign/e-sign an Informed Consent Form (ICF) prior to undergoing any screening 
procedures.  Screening procedures will take place up to 84 days.  Subjects will undergo an MRI 
to determine spinal cord structure and intrathecal space (Appendix 12); MRIs will be run locally 
and evaluated by a sponsor-arranged expert.  Additional radiological assessments may be 


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performed at the discretion of the Principal Investigator, including CT or MRI of the head and X-
ray of the lumbar spine as additional evaluations to rule out potential contraindications for 
lumbar puncture. The subject’s demographics, medical and surgical history, and prior and 
concomitant medications will be recorded.  Screening/baseline assessments will be performed, 
and subjects will undergo blood draws where blood, serum collection, viral serology will be 
obtained, and urine samples will be collected.  
Subjects will also be presented with a separate biobank ICF for review. If a subject agrees, 
samples of his/her CSF, blood, MRI scans and data collected in the study, will be stored for 
future research.  A subject does not have to agree or sign the biobank ICF in order to be eligible 
to participate in this main study.   
Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, 
marijuana, opiates, phencyclidine, barbiturates, benzodiazepines, methadone, and 
propoxyphene).  Subjects using marijuana /THC-CBD preparations, opiates, sedative hypnotics, 
or tranquilizers may be permitted to participate in the trial provided the dosage and frequency of 
use are not considered likely to interfere with evaluation of safety and efficacy endpoints in the 
trial.  Determination of exclusion due to use of a specific medication from these classes of 
medications will be made by the Principal Investigator in conjunction with the Medical Monitor 
and sponsor physician based on medical assessment of factors including the dosage, frequency of 
use, and medical condition being treated.   
In the event that a subject is rescreened, the original screening MRI and expert review of the 
images may be used for the rescreening provided the MRI was completed within 6 months of 
rescreening.  Similarly, neurological examinations and questionnaires do not need to be repeated 
provided the rescreening occurs within 84 days of the time of data collection. 
7.1.1.2. 
In-Clinic Treatment Period 
Eligible subjects will be admitted to the clinic on the evening prior to or on the day of dosing 
(Study Day 1) dependent on clinical site requirements.  Following final pre-treatment 
assessments, subjects will undergo a lumbar puncture (LP) and receive their single dose of study 
drug administered via intrathecal lumbar slow bolus infusion by the Principal Investigator or a 
trained and licensed designee.  Dosing will be according to Table 8.  
Subjects will remain in-clinic until discharge on Study Day 4 and will undergo daily safety 
assessments and observation.  
Blood and CSF samples will be obtained.  The timing for serum and CSF sample collection may 
be adjusted for subsequent cohorts based on PK data from the preceding cohorts. In addition to 
undergoing PK analysis, serum samples obtained from blood collected at pre-dose and on Study 
Days 8 and 29 will be analyzed for the presence of anti-drug antibodies (ADA). 
 
Table 8: 
Treatment by Cohort (Part 1, Study RNX-AX204-101) 
Cohort 
Treatment 
Number of Subjects 
1 
3 mg AXER-204 
6 
2 
30 mg AXER-204 
6 


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3 
90 mg AXER-204 
6 
4 
200 mg AXER204 
6 
7.1.1.3. 
Follow-Up 
Sites will contact the subjects via telephone on Study Days 5, 6, and 7 to inquire as to their 
general health status.   
Subjects will return to the Clinic on Study Day 8 (±1d), for CSF and serum PK assessments, on 
Day 15 (±3d) for blood collection (serum PK analysis), and again on Study Day 29 (±4d) (for 
end of study assessments).  Vital signs, concomitant medications, AEs, and general health status 
will be assessed at each visit. 
7.1.2. 
Part 2 
Part 2 is a multicenter, randomized, double-blind, placebo-controlled, repeat dose study in CSCI 
subjects.  Approximately 32 subjects will be randomized (ratio 1:1) to receive AXER-204 or 
placebo (an isotonic phosphate buffered saline formulation).  Subject to review of the safety, 
tolerability, and pharmacokinetic data from Part 1 and DSMB approval, the dose will be 200 mg 
given once every 3 weeks for 15 weeks as outlined in the schedule of events.  Subject to DSMB 
approval, the dose may be reduced to 90 mg and the dose interval may be modified based on data 
from Part 1 but is not expected to be less than once every 14 days or more than 28 days.  Subject 
to DSMB approval, the dose and dose frequency may also be adjusted during Part 2 based on 
emergent safety and tolerability data. 
The study stages for Part 2 are: 
• Screening (within 84 days prior to Day 1).  Patients have 84 days from the time of 
signing informed consent to complete their screening assessment and, if needed, their 
washout period for prohibited concomitant medications.  The screening laboratory 
tests must be completed within 28 days prior to Day 1. 
• Treatment Period (15 weeks). Study treatment given every 2-4 weeks for 15 weeks in 
total per subject.   
• Follow-up (21 weeks).  Following the last Treatment Period dose of investigational 
product or Early Termination of dosing, a telephone call to assess status regarding 
any adverse events will be conducted on Study Day 137 (± 7 days) and follow-up 
visits will occur at Study Days 169 (± 7 days) and 253 (± 7 days). 
See Table 6 for the Schedule of Events for Part 2. 
7.1.2.1. 
Screening 
All subjects must sign/e-sign an Informed Consent Form (ICF) prior to undergoing any screening 
procedures.  Screening procedures will take place up to 84 days.  Subjects will undergo an MRI 
to determine spinal cord structure and intrathecal space; MRIs will be run locally and evaluated 
by a sponsor-arranged expert.  Additional radiological assessments may be performed at the 
discretion of the Principal Investigator, including CT or MRI of the head and X-ray of the 
lumbar spine as additional evaluations to rule out potential contraindications for lumbar 


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puncture. The subject’s demographics, medical and surgical history, and prior and concomitant 
medications will be recorded.  Screening assessments will be performed, and subjects will 
undergo blood draws where blood, serum collection, viral serology will be obtained, and urine 
samples will be collected.  
Subjects will also be presented with a separate biobank ICF for review. If a subject agrees, 
samples of his/her CSF, blood, MRI scans and data collected in the study, will be stored for 
future research.  A subject does not have to agree or sign the biobank ICF in order to be eligible 
to participate in this main study.   
Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, 
marijuana, opiates, phencyclidine, barbiturates, benzodiazepines, methadone, and 
propoxyphene).  Subjects using marijuana /THC-CBD preparations, opiates, sedative hypnotics, 
or tranquilizers may be permitted to participate in the trial provided the dosage and frequency of 
use are not considered likely to interfere with evaluation of safety and efficacy endpoints in the 
trial.  Determination of exclusion due to use of a specific medication from these classes of 
medications will be made by the Principal Investigator in conjunction with the Medical Monitor 
and sponsor physician based on medical assessment of factors including the dosage, frequency of 
use, and medical condition being treated.   
In the event that a subject is rescreened, the original screening MRI and expert review of the 
images may be used for the rescreening provided the MRI was completed within 6 months of 
rescreening.  Similarly, the ISNCSCI and GRASSP do not need to be repeated provided the 
rescreening occurs with 84 days of the time of data collection. 
7.1.2.2. 
Treatment Phase 
Eligible subjects will be randomized to either AXER-204 or to placebo.  The randomization will 
be stratified based on pre-treatment AIS grade (AIS A,B vs. AIS C,D) and prior receipt of study 
drug in Part 1 (Received AXER-204 in Part 1 vs. Did not receive AXER-204 in Part 1). 
Subjects will undergo baseline assessments and receive their assigned (double-blind) treatment 
on Study Day 1.  Study personnel will conduct telephone call with subjects on Study Day 8 (± 3 
days) to assess status regarding any adverse events.  Subjects will then return to the Clinic on 
Day 21 (± 5 days) for safety, efficacy, and PK assessments and their second dose of study 
investigational product.  Thereafter, subjects will return approximately every 21 days, at Study 
Days 42 (± 5 days) (third dose), 63 (± 5 days) (fourth dose), 84 (± 5 days) (fifth dose), 104 (± 5 
days) (sixth dose), for safety, efficacy, and PK assessments (pre-dose) and investigational 
product administration.   
Cerebrospinal fluid samples will be collected pre-dose at each treatment (dosing) visit, including 
Study Day 1, during a single LP procedure for collecting and dosing.  Serum for PK and 
immunogenicity (ADA) testing will be collected pre-dose at specified visits (See Table 11), 
within 4 hours prior to investigational product administration.  Serum will also be collected for 
PK at 4 h post-dose at specified visits. 
7.1.2.3. 
Follow-Up 
Study personnel will conduct telephone call with subjects on Study Day 137 (± 7 days) to assess 
status regarding any adverse events.  Depending on the results, the subject may be asked to come 


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to the clinic for evaluation. Subjects will return at Study Days 169 (± 7 days), and 253 (± 7 days) 
for safety and efficacy assessments.   
7.2. 
Number of Subjects 
Part 1 will enroll up to 24 subjects in cohorts of 6 subjects each.  
Part 2 will enroll approximately 32 subjects, randomized in a 1:1 ratio (and thus approximately 
16 subjects per arm) to repeated doses of AXER-204 or of matching placebo.   
If the dropout rate is such that the power of the study could be compromised, or that the study 
objectives cannot reliably be achieved, the Sponsor may elect to replace those subjects who 
discontinue prematurely, provided discontinuation is not due to adverse events related to 
investigational product administration. 
7.3. 
Treatment Assignment 
7.3.1. 
Part 1 
Dosage will be by cohort, with 4 sequentially-treated cohorts planned.  Intrathecal doses of 
AXER-204 below 90 mg will be diluted and delivered as a solution in 10 mL of isotonic 
phosphate buffered saline.  Both the 90 mg dose and 200 mg dose will be dosed with the current 
study drug concentration.  All administration will be given following a removal of an equivalent 
volume of CSF. Intrathecal injections will be given at a rate of 100 mL/hr using a medically 
approved syringe pump (eg, 12 minutes to administer 20 mL) to avoid significant disruption of 
natural CSF flow and pressure.   
The starting dose of 3 mg is estimated to be below the pharmacologically active dose.  Dose 
escalation will proceed to 30 mg, 90 mg, 200 mg contingent on safety, tolerability, and available 
PK.  Thus, dosing volumes will be given as follows: 
• Cohort 1:  3 mg, 10 mL 
• Cohort 2:  30 mg, 10 mL 
• Cohort 3:  90 mg, 9 mL 
• Cohort 4:  200 mg, 20 mL 
7.3.2. 
Part 2 
Subject to review of the safety, tolerability, and pharmacokinetic data from Part 1 and DSMB 
approval, the dose will be 200 mg given once every 3 weeks for 15 weeks as outlined in the 
schedule of events.  Subject to DSMB approval, the dose may be reduced to 90 mg and the dose 
interval may be modified based on data from Part 1 but is not expected to be less than once every 
14 days or more than 28 days.  Subject to DSMB approval, the dose and dose frequency may 
also be adjusted during Part 2 based on emergent safety and tolerability data. 
The maximum volume of injection by intrathecal lumbar slow bolus injection is limited in this 
study to approximately 20 mL based on published tolerance data from studies with other agents 
employing the same route of administration.  If an injection volume of 20 mL, corresponding to a 
200 mg dose of AXER-204, is reached in Part 1 dose escalation portion of the study with 


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acceptable safety and tolerance, the 200 mg dose will be designated as the dose for Part 2 at the 
discretion of the Sponsor in conjunction with the investigators, DSMB, and medical monitor.   
7.3.3. 
Dose Escalation Decisions and Data and Safety Monitoring Board (DSMB) Dose 
Escalation in Part 1 
Dose escalation decisions will be made jointly by the investigator, sponsor, and medical monitor.  
The investigator, sponsor, and medical monitor may also make adjustments to the dosing plan, as 
appropriate for reasons of safety and tolerability.  Dose escalation (for each sequential cohort) 
will not occur until 6 subjects in the prior cohort have completed the initial 3 day in-clinic period 
AND at least two subjects have completed their Day 29 post-dose follow-up visit.  
Determination of whether to escalate dose in the subsequent cohort will be made jointly by the 
investigators, sponsor, and medical monitor after review of all clinical and available PK data.  
Review will include AEs and serious AEs (SAEs), and specifically the following potential 
stopping criteria will be evaluated prior to each dose escalation. 
7.3.3.1. 
Stopping Rules/Study Interruption/Discontinuation Notice (Part 1) 
The investigators and medical monitor in conjunction with the sponsor may elect to stop dosing 
or stop the study based on any treatment emergent concerns.  Dosing will be stopped due to the 
occurrence of any individual adverse events which, in the judgment of the investigators and 
medical monitor in conjunction with the sponsor, need further characterization with respect to 
progression and reversibility before further dosing is conducted.  Such adverse events may 
include non-serious unusual events.  If dosing is stopped, review of the data by the investigators 
and medical monitor in conjunction with the sponsor and the DSMB must occur before dosing 
can be resumed.  Dosing will only be resumed with DSMB approval. 
Pharmacokinetic and anti-drug antibody test results will not be required for dose escalation 
unless it is determined advisable by the sponsor in conjunction with the investigators and 
medical monitor based on emergent data from the study.  CSF and serum samples will be 
analyzed for each cohort immediately after all subjects have been dosed.  The sponsor may direct 
earlier analysis of a partially completed cohort if completion of the cohort is delayed or partial 
cohort data is desired to aid in interpretation of any emergent clinical data.   
If the investigators and medical monitor in conjunction with the sponsor determine that the dose 
is well tolerated in the completed dose group, dosing will proceed to the next dose level.   
7.3.3.2. 
Stopping Rules/Study Interruption/Discontinuation Notice (Part 2) 
The investigators and medical monitor in conjunction with the sponsor may elect to stop dosing 
or stop the study based on any treatment emergent concerns.  Dosing will be stopped due to the 
occurrence of any individual adverse events which, in the judgment of the investigators and 
medical monitor in conjunction with the sponsor, need further characterization with respect to 
progression and reversibility before further dosing is conducted.  Such adverse events may 
include non-serious unusual events.  If dosing is stopped, review of the data by the sponsor in 
conjunction with the investigators and medical monitor in conjunction with the sponsor and the 
Data and Safety Monitoring Board (see below regarding DSMB composition and charter) must 
occur before dosing can be resumed.  Dosing will only be resumed with DSMB approval. 


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7.3.4. 
Data and Safety Monitoring Board 
In order to ensure the utmost safety of subjects, the sponsor will also use a Data and Safety 
Monitoring Board (DSMB).  Each time the DSMB is engaged, a recommendation to proceed 
from the DSMB will be required in order for the study to continue (i.e. to resume if stopped or 
ongoing study will be stopped if DSMB does not recommend proceeding).  The DSMB will 
review the safety and tolerability data from Part 1 before recommending starting Part 2 and 
during Part 2 after the first subject has completed 3 months of dosing and approximately every 3 
months thereafter while dosing continues in the study (allowing for potential scheduling 
logistics). In addition to the pre-determined DSMB data review meetings, the DSMB may be 
engaged at any time at the request of an investigator, the sponsor, or medical monitor, or if 
stopping rules are triggered. A charter will be written to describe the DSMB’s objectives, its 
membership, schedule for data reviews, and general responsibilities in respect to the study.  All 
DSMB decisions will be documented in writing, and where required, submitted to the 
institutional review board (IRB) for their review or information.   
7.4. 
Criteria for Study Termination 
If the dosing is stopped during the study due to safety and tolerability concerns, a 
recommendation from the DSMB that it is safe to resume dosing will be required in order to 
continue dosing. 
All decisions will be documented in writing, and where required, submitted to the institutional 
review board/independent ethics committee (IRB/IEC) for their review or information.   


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8. 
STUDY ENTRY CRITERIA 
8.1. 
Subject Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study: 
1. Men or women between the ages of 18 and 65 years, inclusive  
2. Traumatic spinal cord injury that occurred ≥ 1 year ago  
3. Cervical spinal cord injury with serious neurological deficit as evidenced by 1) bilateral 
ISNCSCI UEMS between 4 and 36 points inclusive, and 2) bilateral GRASSP prehension 
ability score between 4 and 17 points inclusive 
4. Confirmation by MRI of the following: 
a. Chronic SCI (persistent spinal cord lesion) 
b. For AIS grade of A without sensory or motor zone of partial preservation 
extending at least two levels caudal to the level of injury, no apparent transection 
of the cord  
c. CSF space spanning the lesion 
5. Read, understood, and provided written informed consent after the nature of the study has 
been fully explained and must be willing to comply with all study requirements and 
procedures. 
8.2. 
Subject Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from the study: 
1. Penetrating injury to the cord or spinal cord trauma caused by ballistic injury including 
gunshot that did not penetrate the spinal cord 
2. Women who are pregnant or lactating, and women of childbearing potential except those 
using adequate birth control measures. All female subjects must have a negative serum 
pregnancy test at Screening and women of childbearing potential must have a negative 
urine pregnancy at the Randomization/Pre-Dose Visit on Study Day 1. All subjects (male 
and female) as well as non-study female partners of male subjects, must use adequate 
birth control measures during the course of the study and for at least 10 weeks after the 
subjects’ last dose of investigational product  
• Adequate or effective contraception is defined as double barrier contraception (eg, 
condom plus spermicide in combination with a female condom, diaphragm, cervical 
cap, contraceptive sponge, implants, injectables, combined oral contraceptives, sexual 
abstinence (total abstinence from sexual intercourse as the preferred lifestyle of the 
subject; periodic abstinence is not acceptable), or sexual intercourse with only a 
vasectomized partner.  Subjects and/or partners who are surgically sterile or women 
with confirmed postmenopausal status are exempt from this requirement.   
3. Contraindications for lumbar puncture 
4. History of stroke, cerebrovascular injury, or elevated intracranial pressure 


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5. Requiring mechanical ventilatory assistance of any type 
6. Body mass index (BMI) ≥ 35 kg/m2 or body weight <50 kg 
7. Botulinum toxin injection, with the exception of bladder treatments, within 4 months 
prior to study 
8. History of life threatening allergic or immune-mediated reaction to vaccines, or biologic 
drugs, at any time or any life threatening allergic or immune-mediated reaction within the 
past 12 months. 
9. Systemic use of immunosuppressants within the past 2 months with the exception of 
mineralocorticoids 
10. Significant deformities, contractures (with less than 50% of normal range of motion at 
affected joints), or any issues that limit completion of UEMS with the ISNCSCI exam 
11. Recent changes in anti-spasmodic or anti-spasticity medications.  Anti-spasmodic or anti-
spasticity medication is permitted providing that the subject has been on a stable dose for 
at least 12 weeks before the Screening Visit (Visit 1) and agrees to remain on a stable 
dose throughout the course of the study 
12. Any orthopedic injury, recent surgeries, or current diagnosis of any primary diseases 
affecting upper limb function outside of SCI (eg, infection, tumor, congenital 
malformations, Huntington’s disease, Parkinson’s disease) 
13. Subjects fitted with an implanted pump or port for delivery of therapeutics to the CSF 
14. Presence of a self-reported uncontrolled medical condition including but not limited to 
cardiovascular disease, sleep apnea, obstructive lung disease, severe neuropathic or 
severe chronic pain, severe autonomic dysreflexia 
15. Participation in any other investigational drug or device trial within 30 days or within 5 
half-lives of the investigational drug or any past participation in a SCI cellular therapy 
trial 
16. Regular use of the following concomitant medications that might confound efficacy 
and/or safety assessments is prohibited, including, but not limited to, the following:  
a. Antipsychotic drugs with the exception of use of these mood stabilizers for the 
adjunctive treatment of depression at least 12 weeks prior to Screening and the dose is 
not anticipated to change during participation in the trial. 
b. Anticoagulants, however, daily low dose aspirin (81 mg) therapy is permitted. 
c. Opiates, sedative hypnotics, or tranquilizers unless used to treat anxiety, pain, or 
sleep disorder and the dosage and frequency of use are not considered likely to 
interfere with evaluation of safety and efficacy endpoints in the trial. Determination 
of exclusion due to use of a specific medication from these classes of medications 
will be made by the Principal Investigator in conjunction with the Medical Monitor 
and sponsor physician based on medical assessment of factors including the dosage, 
frequency of use, and medical condition being treated.   
d. Tumor necrosis factor (TNF) inhibitors 
e. Use of Class 1 antiarrhythmic. 


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17. Use of antidepressants (SSRI, SNRI, TCA, buspirone) is PERMITTED but limited to 
subject being on a stable dose for at least 12 weeks 
18. History of severe acute or chronic medical or psychiatric condition or laboratory 
abnormality that could increase the risk associated with trial participation or 
investigational product administration or could interfere with the interpretation of trial 
results and including but not limited to the following:  
• human immunodeficiency virus (HIV) infection 
• active chronic hepatitis B or hepatitis C infection including hepatitis B surface 
antigen and hepatitis C antigen positive subjects with or without abnormal liver 
enzymes 
• immunosuppressive disease 
• chronic renal disease/failure as evidenced by estimated glomerular filtration rate 
(eGFR) of <60 
• concurrent neurodegenerative disease 
• cardiovascular: uncontrolled hypertension, unstable angina, myocardial infarction or 
symptomatic congestive heart failure within the past 12 months or serious 
uncontrolled and clinically significant cardiac arrhythmia as determined by the 
investigator 
• dementia or significantly altered mental status including brain injury with ongoing 
cognitive signs and symptoms that would prohibit the understanding or rendering of 
informed consent and compliance with the requirements of the protocol 
19. Evidence or self-report of alcohol or drug abuse within the previous 12 months 
20. Any conditions that in the judgement of the investigator would make the subject 
inappropriate for entry into the trial 
Note:  GFR will be estimated using the Cockcroft-Gault equation [Cockcroft and Gault 1976]. 


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9. 
WITHDRAWAL OF SUBJECTS 
9.1. 
Subject Withdrawal Criteria 
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioral, or 
administrative reasons.  The reason for a subject discontinuing from the study will be recorded in 
the source documents and electronic case report form (eCRF).  A discontinuation occurs when an 
enrolled subject ceases participation in the study, regardless of the circumstances, prior to 
completion of the protocol.  If a subject does not return for a scheduled visit, every effort should 
be made to contact the subject.  A subject will be considered lost-to-follow-up after 3 failed 
attempts to contact subject are made.  Efforts should be documented on the subject’s record.  In 
any circumstance, every effort should be made to document subject outcome, if possible.  The 
Site Principal Investigator must determine the primary reason for discontinuation.  Withdrawal 
due to adverse event should be distinguished from withdrawal due to insufficient response 
according to the definition of adverse event noted earlier.  A discontinuation must be reported 
immediately to the sponsor if it is due to a serious adverse event.  The final evaluation required 
by the protocol will be performed (as per the early termination assessments).  The Site Principal 
Investigator will record the reason for study discontinuation, provide or arrange for appropriate 
follow-up (if required) for such subjects, and document the course of the subject’s condition. 
If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such withdrawal 
of consent. 
If the dropout rate is such that the power of the study could be compromised, or that the study 
objectives cannot reliably be achieved, the sponsor may elect to replace those subjects who 
discontinue prematurely. 


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10. 
TREATMENT OF SUBJECTS 
Part 1 is a single-dose treatment for each subject.  Subjects will have an approximate 84-day 
screening period, a 3-day in-clinic treatment period, and a follow-up through 28 days post-dose.  
Thus, study participation for each subject in Part 1 is expected to be approximately 16 weeks in 
duration. 
Part 2 includes a repeat dose injection regimen.  Subjects will have an approximate 84-day 
screening period, a 104-day treatment period (with injections given approximately every 21 days 
through Day 104) and then post treatment follow-ups at Study Days 137, 169, and 253.  Thus, 
study participation for each subject in Part 2 is expected to be up to approximately 337 days in 
duration. 
10.1. 
Description of Study Drug & Placebo 
Investigational product will be packaged in single use identical vials containing 5 mL.  Each vial 
contains placebo or 50 mg of AXER-204.  Vials will be packaged appropriately for shipment.   
Study drug and placebo will be distributed to the clinical site from a designated distribution 
center.  The sponsor will provide the investigator with adequate quantities of study drug, 
placebo, and supplies to dose each subject. Specific details regarding study drug, placebo, dose 
preparation, and accountability will be described in a pharmacy manual at the clinic. 
Table 9: 
Study Drug and Placebo (Study RNX-AX204-101) 
 
Study Drug & Placebo 
Product Name: 
Placebo (Part 2 and used in 
preparing low doses in Part 1) 
AXER-204 
Route of Administration 
Intrathecal injection 
Intrathecal injection 
Physical Description 
Colorless solution 
Colorless solution, may 
contain white or translucent 
particles * 
Manufacturer 
 
 
* AXER-204 drug product may contain inherent proteinaceous particles.  These are removed by 
filtration during dose preparation.  Studies have been completed confirming the potency, purity, 
and safety of AXER-204 after filtration. 
10.2. 
Concomitant Medications 
All concomitant medications, whether prescription, over-the-counter, herbal treatments, or other 
therapy, taken or used by the patient within 28 days of screening through end of study 
assessments will be recorded in the subject’s medical record and in the Concomitant Medications 
eCRF.  


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Regular use of medications which, in the assessment of the Principal Investigator, may confound 
efficacy and/or safety assessments is prohibited.  Such medications may include but are not 
limited to: 
• Anticoagulants 
• antipsychotic drugs 
• marijuana 
• opiates 
• sedative hypnotics 
• tranquilizers.  
Daily low dose aspirin (81 mg) therapy is permitted. 
Antipsychotic drugs used as mood stabilizers for the adjunctive treatment of depression as well 
as antidepressants (SSRI, SNRI, TCA, buspirone) are permitted provided the subject is on a 
stable dose for at least 12 weeks prior to Screening and the dose is not anticipated to change 
during participation in the trial. 
Marijuana /THC-CBD preparations, opiates, sedative hypnotics, or tranquilizers are permitted 
only if the dosage and frequency of use are not considered likely to interfere with evaluation of 
safety and efficacy endpoints in the trial.  As needed (PRN) use of nonsteroidal anti-
inflammatories and acetaminophen is permitted. 
Prospective subjects who at the time of screening are taking medications that the Principal 
Investigator judges may confound efficacy and/or safety assessments (listed in Exclusion 
Criteria, Section 8.2) must stop them, after signing Informed Consent and receiving instructions 
on the discontinuation of these medications, two weeks or five half-lives –whichever is longer- 
prior to investigational product administration. The prospective subject must be willing to 
discontinue treatment and the Investigator must deem this feasible. The prospective subject 
taking prohibited medication at the time of screening will be considered eligible at the time of 
investigational product administration (Visit 2, Study Day 1) provided no reintroduction of the 
prohibited medication is being considered, the appropriate time window since last administration 
has elapsed, and the subject continues to meet other eligibility criteria.  Subjects must remain off 
prohibited medications until all assessments are completed in the study. Determination of 
exclusion due to use of a specific medication from these classes of prohibited medications will 
be made by the Principal Investigator in conjunction with the Medical Monitor based on medical 
assessment of factors including the dosage, frequency of use, and medical condition being 
treated.   
Concomitant medications will be coded using the World Health Organization (WHO Drug) 
Dictionary.  
10.3. 
Treatment Compliance 
Treatment compliance with investigational product during the treatment periods is expected to be 
high, as subjects will be dosed directly in the clinic under well-controlled conditions.  The date, 
start and stop time of investigational product administration, dose and quantity of investigational 


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product administered will be recorded on the source documents and eCRF.  Non-compliance 
with other aspects of the study protocol (eg, use of prohibited medications, missed study visits) 
will be documented on the subject’s source document and on the eCRF.  
10.4. 
Randomization and Blinding 
10.4.1. 
Part 1 
Part 1 does not include placebo, is open-label, and there is no randomization.  Subjects will be 
enrolled and treated sequentially, with at least 3 days (72 hours) between dosing of consecutive 
patients.  This wait-period will allow for a review of safety data collected during the in-clinic 
treatment phase prior to each new subjects’ dosing.   
10.4.2. 
Part 2 
Central randomization will be implemented in the study.  At the pre-dose visit (Visit 2) Study 
Day 1, eligible subjects will be randomly assigned in a 1:1 ratio to one of two treatment groups 
based on a randomization schedule prepared prior to study start by a statistician.  To enroll the 
patient on Study Day 1, the investigator or designee will enter the subject identification number 
that was assigned at Screening Visit on the enrollment page in the electronic data capture (EDC) 
system. The EDC will assign a unique treatment code, which will be linked to the appropriate 
treatment group as assigned by the randomization schema.    
Eligible subjects will be randomized to either AXER-204 or to placebo.  The randomization will 
be stratified based on pre-treatment AIS grade (AIS A,B vs. AIS C,D) and prior receipt of study 
drug in Part 1 (Received AXER-204 in Part 1 vs. Did not receive AXER-204 in Part 1). 
The blind will be maintained for all blinded study personnel (including investigators and 
subjects) through the completion of Day 169 of Part 2, and thus only designated Sponsor staff, 
members of the DSMB, and other designated unblinded personnel will have access to unblinded 
information prior to database lock for the Day 169 analysis.  At each study site, an unblinded 
pharmacist will prepare prefilled syringes for dose administration in order to maintain the blind 
for study personnel administering the investigational product and performing all other study 
procedures.  After completion of Day 169, designated sponsor staff and external 
consultants/contractors required to perform the analysis will be unblinded to the treatment 
allocations in order to complete data analysis though Day 169.  The blind will be maintained for 
site investigators and subjects through completion of Day 253 unless the blind must be broken 
sooner for safety or regulatory reasons. 
At the initiation of the study, the study site will be instructed on the method for breaking the 
blind.  A formal unblinding process will be used to ensure security and maintenance of the blind.  
However, the investigator should contact the sponsor before breaking the blind.  When the blind 
has been broken for a subject, the reason must be fully documented and entered on the source 
document and eCRF for that subject. 
Data that may potentially unblind the treatment assignment (eg, PK samples) will be handled 
such that the integrity of the blind is maintained and the potential for bias minimized.  This may 
include making special provisions such as segregating the data in question from view by the 
investigator and site study staff, sponsor clinical team, and others as appropriate. 


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The bioanalytical laboratory personnel will be open to the randomization codes in order to 
facilitate PK analytical work and ADA testing.  Personnel are not to communicate or imply in 
any manner, information associated with this to others at the clinical site, the sponsor, its 
consultants, designated CRO, or other vendors. 
A formal analysis of the data will be performed once all subjects have completed their treatment 
period and follow-up assessments through Day 169.  This efficacy analysis will be performed as 
the primary assessment of efficacy in the study; the study will continue through the follow-up 
period to Study Day 253.  A second efficacy analysis will be conducted at Study Day 253. 


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11. 
STUDY PROCEDURES 
11.1. 
Part 1  
Each investigator will be assigned a unique site code. This site code will be concatenated with 
the screening number to assure that each subject will be uniquely identified in the clinical 
database. Site numbering will begin with 01 preceded by the number 1, and screening numbers 
will begin with 001. As subjects are screened, the next subject qualified chronologically at a site 
will be assigned the next number in ascending numerical order.  Thus, the subject identification 
number for the first subject enrolled in Cohort 1 at the first site activated will be 101-001.  The 
first subject enrolled in Cohort 1 at the second site activated will be 102-001 and so on. 
Subjects will participate in the study for a total duration of up to 16 weeks.  Visits will be 
scheduled at: 
• Screening Visit 1 (Study Days -84 to -1) 
• In-Clinic Treatment Visit 2 (Study Days 1 through 4) 
• Post Treatment Follow-up  
− Phone calls on Study Days 5, 6, and 7 
− Visits 3 and 5 (Study Days 8 and 29/early termination [ET]) 
− Visit 4 (Study Day 15) 
− Refer to the Schedule of Events (Table 5) for all the procedures and assessments 
to be performed during Part 1. The following sections provide important details of 
the procedures to be completed for each period. 
11.1.1. 
Screening Period, Visit 1 (Study Days -84 through -1) 
Subjects will sign an ICF before any screening-related procedures are performed. The Screening 
Visit (Visit 1) should occur between Study Days -84 to -1 and screening procedures completed 
during this time period.  
Subjects will also be presented with a separate biobank ICF for review. If a subject agrees, 
samples of his/her CSF, blood, MRI scans and data collected in the study, will be stored for 
future research.  A subject does not have to agree or sign the biobank ICF in order to be eligible 
participate in the main study.   
Once the subject has consented to participate in the study (including having blood samples drawn 
and CSF and serum collection for PK assessment), the subject should be registered in the EDC 
system and a 6-digit subject identification number assigned by the designated study site 
personnel.  This number will be used to identify each subject throughout the study and will be 
entered on all study-related documentation and subject medical chart.   
• Note: At either Screening (Visit 1) or Pre-Dose (Visit 2), if a subject is a screen 
failure, not eligible to receive study drug, or if the subject withdraws or is 
discontinued from the study, his/her subject identification number cannot be reissued 
or assigned to another subject. 


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The inclusion and exclusion criteria should be carefully assessed.  The subject’s demographics, 
medical and surgical history, and prior and concomitant medications will be recorded.  
Each subject will undergo a full physical examination including height and weight. The physical 
examination may be performed by the investigator, a sub-investigator who is a medical doctor, or 
a qualified nurse practitioner or physician’s assistant in accordance with the site’s current 
practice and in accordance with local requirements as applicable.  
Blood samples will be obtained for biochemistry, hematology laboratory tests, and viral 
serology.  A urine sample for urinalysis will be collected. 
A serum pregnancy test will be obtained on all female subjects.  
Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, 
marijuana, opiates, phencyclidine, barbiturates, benzodiazepines, methadone, and 
propoxyphene). Subjects using marijuana /THC-CBD preparations, opiates, sedative hypnotics, 
or tranquilizers may be permitted to participate in the trial provided the dosage and frequency of 
use are not considered likely to interfere with evaluation of safety and efficacy endpoints in the 
trial.  Determination of exclusion due to use of a specific medication from these classes of 
medications will be made by the Principal Investigator in conjunction with the Medical Monitor 
and sponsor physician based on medical assessment of factors including the dosage, frequency of 
use, and medical condition being treated.   
Vital signs (blood pressure, pulse rate, respiratory rate or pulse oximetry, and oral body 
temperature) will be obtained after the subject has been in a sitting (or recumbent) position for 5 
minutes.  A 12-lead ECG will be taken in triplicate, 5 minutes apart, after the patient has been in 
a supine (resting) position for at least 5 minutes. 
Subjects will have several scales administered by a clinician who is trained to administer these.  
Where possible, the order for evaluating these scales should be followed as defined in Section 
11.2.  These include the full ISNCSCI scale, SCIM III self-care and mobility scale, GRASSP, 
Modified Ashworth Scale, and autonomic evaluations as per ISAFSCI.  Subjects will also be 
administered several questionnaires at this visit, including: 
• BPI (Appendix 9) 
• SF-36 v2 (Appendix 6) 
• Neuro-QOL (Appendix 7). 
A magnetic resonance imaging scan will be obtained as described (Appendix 12).  The MRI 
must be completed and results known and made available to the principal investigator prior to 
the subject’s admittance to the clinic on Visit 2 (Pre-Dose).  Results from the MRI will be read 
by a sponsor-arranged expert. 
Subjects who fail to meet any entry criterion that can be assessed at that time are considered to 
be screen failures and are not required to return for additional visits (although a subject can be 
seen at any time for safety reasons).  Subjects who are screen failed due to lab values can be re-
screened as determined by the principal investigator in consultation with the study medical 
monitor.  Subjects who rescreen will be assigned a new screening number. 
Serious AEs will be recorded and monitored starting at the time of subject signing the ICF. 


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Upon completion of the Screening Visit (Visit 1), subjects will be given an appointment 
reminder card that contains the date and time for their next visit.  
See the schedule of events (Table 5) for details on the assessments on each Study Day. 
11.1.2. 
In-Clinic Treatment, Visit 2 (Study Days 1 to 4 [Pre-Dose and Post-Dose]) 
Eligible subjects will be admitted to the clinical site on the evening prior to or morning of the 
scheduled dosing depending on site’s requirements. If during this visit and prior to dosing a 
subject is determined to no longer be eligible to continue in the study, the appropriate Screening 
eCRFs will be completed and the subject deemed a Screen Failure and will not be required to 
return for additional visits (although a subject can be seen at any time for safety reasons.) 
All inclusion and exclusion criteria, medical and surgical history, and prior medications will be 
reviewed for a second time to confirm eligibility.  New SAEs and concomitant medications 
reported by the subject since the Screening Visit (Visit 1) will be recorded on the eCRF.  A urine 
pregnancy test will be performed on all women of childbearing potential.  
Results obtained during the Screening Visit (Visit 1) including the results of the MRI scan must 
be reviewed by the investigator prior to subject treatment with study drug to ensure subject 
remains eligible for the study.  
Vital signs (blood pressure, pulse rate, respiratory rate or pulse oximetry, and oral body 
temperature) will be obtained after the patient has been in a sitting position for 5 minutes. 12-
lead pre- and post-dose ECG will be taken in triplicate, 5 minutes apart, after the patient has been 
in a supine (resting) position for at least 5 minutes.  An abbreviated physical exam should be 
performed. 
If the subject remains eligible for study participation, the EDC will be accessed to enroll the 
subject, visit information will be entered, and the required eCRFs completed.  The research 
pharmacist will be contacted regarding the subject’s enrollment and for specifics about the 
timing of the scheduled lumbar puncture as well as preparation and availability of study drug 
necessary for the intrathecal administration of AXER-204.  
During the lumbar puncture, an amount of CSF approximately equivalent to the amount of study 
drug to be injected into the intrathecal space (~9-20 mL) will be obtained pre-dose for CSF/PK 
assessment, spinal cord injury biobanking, and potentially biomarker analysis.  For the 20 mL 
maximum dose, at least 15 mL of CSF should be collected immediately prior to administration. 
If at least 15 mL cannot be collected, the principal investigator may elect to discontinue the 
subject from the trial or to ask the subject to return on the following day for a second attempt 
after additional hydration.  In this situation, the subject may be directed to remain at a nearby 
overnight accommodation or home (if within a reasonable distance) and report the next morning 
for examination or to remain in the hospital overnight.  Note that, under these circumstances, 
there is no requirement for an overnight hospital stay; if a decision is made to keep the patient 
overnight for convenience (e.g. travel issues), this hospitalization should not initiate a serious 
adverse event report (e.g. local alternate accommodations not readily available).  Study Drug 
AXER-204 will be administered via slow bolus infusion intrathecal administration.  Details 
including dose and quantity administered, physician administering the study drug, and date and 
time of administration will be recorded on the eCRF and in the subject’s record.  Post lumbar 
puncture and post-dose subjects are to be monitored for any adverse events.   


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If a lumbar puncture fails to return CSF after two attempts, it is recommended that fluoroscopy 
be scheduled to assist in achieving successful LP.  Likewise, it is recommended that the lumbar 
puncture procedure be suspended if the CSF sample is bloody or turbid.  Decisions regarding the 
lumbar puncture procedure are at the discretion of the site principal investigator.  
The subject is to be confined to the clinic on Study Days 2, and 3, and discharged on Study Day 
4 after all required assessments have been completed.  See the schedule of events (Table 5) for 
details on the assessments on each Study Day. 
Prior to discharge from the clinical unit on Study Day 4, subjects will be given an appointment 
reminder card that contains the date and time of their next visit.  
11.1.3. 
Post-Treatment Follow-up Phone Calls, Study Days 5, 6, and 7 
Subjects do not have to visit the clinic for Post-treatment follow-up on Days 5, 6, and 7 unless 
necessary to follow-up on adverse events.  Subjects will receive a telephone call from study site 
personnel inquiring as to their general health.  Any reported adverse events experienced by a 
subject will be documented in the subject’s records and on the eCRF.  Subjects will also be 
reminded about their next visit to the study site. 
11.1.4. 
Post Treatment Follow-up Visits 3 & 4 (Study Days 8 and 15) 
At Visit 3, Study Day 8, subjects’ vital signs (BP, pulse, respiratory rate or pulse oximetry, and 
oral body temperature) will be obtained. Subjects will undergo a lumbar puncture and will have 
CSF collected for PK assessments.  Blood samples will be collected and serum samples for PK 
assessments and presence of ADA will be obtained.  Information on changes or newly 
administered concomitant medications as well as any new or ongoing AEs will be collected.    
Subjects will be given instructions to return to the study site for the next visit and provided an 
appointment reminder card. 
During Visit 4, Study Day 15, blood samples will be collected for clinical laboratory testing and 
serum samples obtained for PK analysis.  Information on changes to ongoing and any new 
concomitant medication as well as any new or ongoing AEs will be recorded on the eCRF and in 
the patient’s record.   
At the completion of the visit, subjects will be given an appointment reminder card that contains 
the date and time of their next visit to the study site. 
11.1.5. 
Post Treatment Follow-up Visit 5 (Study Day 29/ET) 
Visit 5 (Study Day 29/ET) is to be conducted on subjects who will be completing the study as 
well as those who terminate early or are withdrawn from the study.   
At this visit, a full physical exam will be performed.  The subject will be weighed and weight 
recorded on the eCRF.  Vital signs (BP, pulse, respiratory rate or pulse oximetry, and oral body 
temperature) will be obtained.  A urine pregnancy test will be obtained on all females of 
childbearing potential. 
Subjects will undergo lumbar puncture for CSF collection for PK assessments.  Blood sampling 
for laboratory testing including viral serology will also be obtained. Serum for PK and the 
presence of ADA will be analyzed.  Urine sample will be obtained for urinalysis.   


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Information on changes or newly administered concomitant medications as well as any new or 
ongoing AEs will be recorded on the eCRF.  
All scales should, if possible, be administered by the same clinician who administered the scales 
during the Screening period.  These shall be completed in the order as noted in 11.2 and include 
the full ISNCSCI scale, SCIM III self-care and mobility scale, GRASSP, Modified Ashworth 
Scale, and autonomic evaluations as per ISAFSCI.  Subjects will also be administered several 
questionnaires at this visit, including:  
• BPI (Appendix 9) 
• SF-36 v2 (Appendix 6) 
• Neuro-QOL (Appendix 7) 
Subjects’ completion or termination from the study (in the case of subjects who terminate early 
from the study or who are withdrawn) will be recorded on the eCRF and in the subjects’ record. 
11.2. 
Part 2 
Each investigator will be assigned a unique site code. This site code will be concatenated with 
the screening number to assure that each subject will be uniquely identified in the clinical 
database. Site numbering will begin with 01 preceded by the number 2, and screening numbers 
will begin with 001. As subjects are screened, the next subject qualified chronologically at a site 
will be assigned the next number in ascending numerical order.  Thus, the subject identification 
number for the first subject screened at the first site will be 201-001.  The first subject enrolled at 
the second site will be 202-001 and so on. 
Subjects will participate in the study for a total duration of up to approximately 337 days.  Visits 
will be scheduled at Screening Visit 1 (Study Days -84 to -1), Treatment Phase with Visit 2 
occurring on Study Day 1 and subsequent dosing visits occurring approximately every 21 days 
encompassing Visits 3-7 (Study Days 21 through 104).  There will be telephone calls to assess 
status regarding any adverse events on Study Day 8 and Study Day 137.  Post-treatment follow-
up visits will occur at Visits 8 and 9 (Study Days 169 and 253). 
Refer to the Schedule of Events (Table 6) for all the procedures and assessments performed 
during the study.  The following sections provide important details of the procedures.  Where 
possible, the order that the key measures are to be performed is as follows.   
• ISNCSCI 
• Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) 
Note: GRASSP prehension ability and prehension performance testing will be video 
recorded.   
• Modified Ashworth Scale, fingers and thumb excluded 
• SCIM III Self-Care & Mobility subscores 
• Brief Pain Inventory 
• Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL) 
• SF-36 v2 


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• CUE-Q 
• PGIC – Chronic SCI 
• International Standards to document remaining Autonomic Function after Spinal 
Cord Injury (ISAFSCI) 
11.2.1. 
Screening Period, Visit 1 (Study Days -84 through -1) 
Subjects will sign an ICF before any screening-related procedures are performed. The Screening 
Visit (Visit 1) should occur between Study Days -84 to -1.  
Subjects will also be presented with a separate biobank ICF for review. If a subject agrees, 
samples of his/her CSF, blood, MRI scans and data collected in the study, will be stored for 
future research.  A subject does not have to agree or sign the biobank ICF in order to be eligible 
participate in this main study.   
Once the subject has consented to participate in the study (including PK and CSF sampling) and 
has signed the ICF, the subject should be registered in the EDC system and a 6-digit subject 
identification number will be assigned.  This number will be used to identify each subject 
throughout the study and will be entered on all documentation for a subject and into the EDC.   
• Note: At any time during Visit 1 or Visit 2, if a subject is not eligible to receive 
investigational product, or if the subject withdraws or is discontinued from the study, 
their subject identification number cannot be reissued or assigned to another subject. 
The inclusion and exclusion criteria should be carefully assessed. The subject’s demographics, 
medical and disease history, and prior and concomitant medications will be recorded.  
Each subject will undergo a full physical examination including height and weight. The physical 
examination may be performed by the investigator, a sub-investigator who is a medical doctor, or 
a qualified nurse practitioner or physician’s assistant in accordance with the site’s current 
practice and in accordance with local requirements as applicable.  
Blood samples will be obtained for biochemistry, hematology laboratory tests, and viral 
serology. A urine sample for urinalysis will be collected.  A serum pregnancy test will be 
obtained on all female subjects. (Section 8).  Note:  The screening laboratory assessments must 
be completed within 28 days of enrollment. 
Urine testing for drugs of abuse will include the standard 9-drug panel (amphetamines, cocaine, 
marijuana, opiates, phencyclidine, barbiturates, benzodiazepines, methadone, and 
propoxyphene).  Subjects using marijuana /THC-CBD preparations, opiates, sedative hypnotics, 
or tranquilizers may be permitted to participate in the trial provided the dosage and frequency of 
use are not considered likely to interfere with evaluation of safety and efficacy endpoints in the 
trial.  Determination of exclusion due to use of a specific medication from these classes of 
medications will be made by the Principal Investigator in conjunction with the Medical Monitor 
and sponsor physician based on medical assessment of factors including the dosage, frequency of 
use, and medical condition being treated.   
Vital signs (blood pressure, pulse rate, pulse oximetry, and oral body temperature) will be 
obtained after the patient has been in a sitting position for 5 minutes. A 12-lead pre-dose ECG 


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will be taken in triplicate, 5 minutes apart, after the patient has been in a supine (resting) position 
for at least 5 minutes.  
Subjects will be assessed by ISNCSCI and GRASSP and their UEMS and GRASSP prehension 
ability scores will be used to assess eligibility. 
An MRI scan will be scheduled and must be completed and results known and made available to 
the Principal Investigator prior to the subject check in to the clinic on Visit 2 (Pre-Dose).  Results 
from the MRI scan will be run locally and findings read by sponsor arranged expert. 
Subjects who fail to meet any entry criterion that can be assessed at that time are considered to 
be screen failures and are not required to return for additional visits (although a subject can be 
seen at any time for safety reasons).  Subjects may be re-screened as determined by the Principal 
Investigator in consultation with the Study Medical Monitor. 
Serious AEs will be recorded and monitored starting at the time of subject signing the ICF. 
Upon completion of the Screening Visit (Visit 1), subjects will be given an appointment 
reminder card that contains the date and time for their next visit.   
11.2.2. 
Treatment Phase, Visits 2 through 7 (Study Days 1 through 104) 
At Visit 2, Study Day 1, eligible subjects will visit the clinical site to undergo the scheduled 
lumbar puncture. Subject will be randomized in the EDC at this visit.  
If prior to randomization during this visit a subject is determined to no longer be eligible to 
continue in the study, the appropriate Screening eCRFs will be completed and the subject 
deemed a Screen Failure. 
All inclusion and exclusion criteria, medical and surgical history, and prior medications will be 
reviewed for a second time. New SAEs and concomitant medications reported by the subject 
since the Screening Visit (Visit 1) will be recorded on the eCRF. A urine pregnancy test will be 
performed on all women of childbearing potential. 
Results obtained during the Screening Visit (Visit 1) including the results of the MRI scan must 
be reviewed by the investigator prior to subject treatment with investigational product to ensure 
subject remains eligible for the study. Subjects who do not continue to be eligible to participate 
in the study are screen failures and are not required to return for additional visits (although a 
subject can be seen at any time for safety reasons). 
At Visit 2, Study Day 1 the following baseline assessments will be performed in the following 
order prior to dosing: 
• ISNCSCI 
• Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP).  
Note: GRASSP prehension ability and prehension performance testing will be video 
recorded.   
• Modified Ashworth Scale, fingers and thumb excluded 
• SCIM III Self-Care & Mobility subscores 
• Brief Pain Inventory 


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• Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL) 
• SF-36 v2 Health Survey 
• CUE-Q 
• PGIC – Chronic SCI 
• International Standards to document remaining Autonomic Function after Spinal 
Cord Injury (ISAFSCI) 
Note:  Baseline ISNCSCI UEMS and GRASSP prehension ability scores may fall outside of the 
lower and upper bounds of the inclusion criteria for these measures by up to 3 points without 
impacting eligibility (i.e. bilateral UEMS must be 1-39 and bilateral GRASSP prehension ability 
may be 1-20 at baseline).  Subjects with scores at baseline (Visit 2, Study Day 1) that fall outside 
of the UEMS and GRASSP prehension ability inclusion criteria by more than 3 points will not be 
eligible to continue in the study.    
Vitals will be taken pre-dose, post dose, then every 2 hours until subject leaves the unit.  Vital 
signs (blood pressure, pulse rate, respiratory rate or pulse oximetry, and oral body temperature) 
will be obtained after the patient has been in a sitting position for 5 minutes. A 12-lead pre-dose 
ECG will be taken in triplicate, 5 minutes apart, after the patient has been in a supine (resting) 
position for at least 5 minutes. The ECG will be read locally.  An abbreviated physical exam will 
be performed. 
The randomization page in the EDC will be accessed to randomize the subject, visit information 
will be entered, and the required eCRFs completed.  The research pharmacist will be contacted 
regarding the subject’s randomization and for specifics about the timing of the scheduled lumbar 
puncture and preparation and availability of study drug or placebo necessary for the intrathecal 
administration of investigational product.   
Serum will be collected for PK and ADA analysis as detailed in Section 13.2.  
If a lumbar puncture fails to return CSF after two attempts, it is recommended that fluoroscopy 
be scheduled to assist in achieving successful LP.  Likewise, it is recommended that the lumbar 
puncture procedure be suspended if the CSF sample is bloody or turbid.  Decisions regarding the 
lumbar puncture procedure are at the discretion of the site principal investigator.  Additionally, 
investigators may make an assessment based on a given patient that all LPs will be conducted 
under fluoroscopy.  
During the lumbar puncture, an amount of CSF approximately equivalent to the amount of 
investigational product to be injected into the intrathecal space (~9-20 mL) will be obtained pre-
dose for CSF/PK assessment, spinal cord injury biobanking, and potentially biomarker analysis.  
For the 20 mL maximum dose, at least 15 mL of CSF should be collected immediately prior to 
administration. If at least 15 mL cannot be collected, the principal investigator may elect to skip 
dosing for the visit or to ask the subject to return on the following day for a second attempt after 
additional hydration.  In this situation, the subject may be directed to remain at a nearby 
overnight accommodation or home (if within a reasonable distance) and report the next morning 
for examination or to remain in the hospital overnight.  Note that, under these circumstances, 
there is no requirement for an overnight hospital stay; if a decision is made to keep the patient 
overnight for convenience (e.g. travel issues), this hospitalization should not initiate a serious 


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adverse event report (e.g. local alternate accommodations not readily available).  Investigational 
product will be administered via slow bolus infusion intrathecal administration.  Details 
including dose and quantity administered, physician administering the investigational product, 
and date and time of administration will be recorded on the eCRF and in the subject’s record.  
Post lumbar puncture and post-dose subjects are to be monitored for any adverse events.   
The Site Principal Investigator may discontinue a subject from the study due to unsuccessful 
collection of CSF to allow for isovolumetric dose administration if the subject has not received 
any doses and they consider it unlikely that further dosing attempts will be successful.  Subjects 
who received at least one dose of investigational product should complete the remaining visits to 
monitor for safety and efficacy as per the schedule of events. Under this circumstance, further 
per-protocol LP attempts should not be made.  Conducting all LPs under fluoroscopy should be 
considered if difficulties in obtaining adequate CSF collection is encountered.  
For dosing visits that include neurological exams and questionnaires (e.g. ISNCSCI, GRASSP, 
SCIM III self-care and mobility), these assessments should be performed prior to dosing. 
Depending on scheduling considerations, subjects may be asked to return the following day for 
dose administration.  Under this circumstance, nearby overnight accommodations will be 
arranged for the subject upon request. 
Following dosing, patients will remain under the observation of study personnel in the hospital 
setting (eg, may include infusion center, PACU, recovery suite, observation unit, short stay 
center) for 4 hours for safety monitoring. Thereafter, if deemed clinically stable by the 
Investigator, patients may leave the hospital setting.  If further safety observation is directed by 
the investigator, the subject may be directed to remain at a nearby overnight accommodation or 
home (if within a reasonable distance) and report the next morning for examination or to remain 
in the hospital overnight.  Note that, under these circumstances, there is no requirement for an 
overnight hospital stay; if a decision is made to keep the patient overnight for convenience (e.g. 
travel issues), this hospitalization should not initiate a serious adverse event report (e.g. local 
alternate accommodations not readily available).  Upon completion of the visit, subjects will be 
given an appointment reminder card that contains the date and time of the follow-up telephone 
call and for their next visit.  
A telephone call to assess status regarding any adverse events will be conducted on Study Day 8.   
At Study Visits 3 through 7 (Study Days 21 through 104), subjects will receive either AXER-204 
or placebo via slow bolus infusion intrathecal administration.   
At Study Visits 3 through 7, (Study Days 21 through 104), 12-Lead ECGs, abbreviated physical 
examinations vitals will be obtained.  Vitals will be taken pre-dose, post dose, then every 2 hours 
until subject leaves the unit.  Serum collection for PK will be obtained pre-dose and 4 hours post-
dose, CSF will be collected pre-dose (as part of the dosing procedure), urine pregnancy tests will 
be administered on all women of childbearing potential.  Changes to concomitant medication 
will be assessed and recorded as well as adverse events and serious adverse events.   
At Visit 3 (Study Day 21) the following efficacy assessments will be performed prior to dosing: 
• ISNCSCI 
At Visits 5 and 7 (Study Days 63 and 104), the following efficacy assessments will be performed 
prior to dosing in the order listed: 


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• ISNCSCI 
• GRASSP. Note: GRASSP prehension ability and prehension performance testing will 
be video recorded.   
• SCIM III self-care and mobility subscores 
Upon completion of the visit, subjects will be given an appointment reminder card that contains 
the date and time when they will receive a telephone call and the date and time of their next visit.   
11.2.3. 
Follow-up on Study Day 137 
Study Day 137 will consist of a telephone Study personnel will conduct telephone call to assess 
status regarding any adverse events.  Depending on the results, the subject may be asked to come 
to the clinic for evaluation. 
11.2.4. 
Follow-up Visits 8 and 9 (Study Days 169 and 253) 
At Visits 8 and 9 (Study Days 169 and 253), 12-Lead ECGs, physical examinations (abbreviated 
at Visit 8; full exam at Visit 9, with height/weight), vitals will be performed. Serum samples will 
be collected for PK and ADA analysis as detailed in Section 13.2.  Blood will be collected for 
laboratory testing and viral serology, and urine collected for urinalysis.  Urine pregnancy tests 
will be conducted for women of childbearing potential.  Changes to concomitant medication will 
be assessed and recorded as well as AEs and SAEs.  CSF will be collected at Visit 9 (Study Day 
253). 
In Study Visits 8 and 9, subjects will have all efficacy and QoL assessments performed (see the 
Schedule of Events for specifics, Table 6), in the following order: 
• ISNCSCI 
• GRASSP.  Note: GRASSP prehension ability and prehension performance testing 
will be video recorded.   
• Modified Ashworth Scale, fingers and thumb excluded 
• SCIM III Self-Care & Mobility subscores 
• Brief Pain Inventory 
• Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL)  
• SF-36 v2 Health Survey 
• CUE-Q 
• PGIC – Chronic SCI 
• International Standards to document remaining Autonomic Function after Spinal 
Cord Injury (ISAFSCI) 
GRASSP prehension ability and prehension performance testing will be video recorded.  
 


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12. 
INVESTIGATIONAL PRODUCT MATERIALS AND 
MANAGEMENT 
Investigational product will be provided to the clinical sites. 
12.1. 
Study Drug 
Single-use vials with labels and an outer fiberboard carton with a single panel label will have the 
following information: 
• LEI - hNgR(310)-Fc Drug Product 
• Concentration: 10 mg/mL  
• Volume: 5 mL 
• Storage: ≤ - 65° C 
• Caution: Filter Before Use - New Drug-Limited by United States Law to 
Investigation Use Only 
• Manufactured by 
 
The clinical trial supply label will be in accordance with ICH GCP and local requirements for 
investigational product labelling. 
12.2. 
Investigational Product Packaging and Labeling 
Investigational products are for investigational use only and the products supplied for this study 
are intended for use only within the context of this study.  The investigational product supplied 
for this study should be stored in a secure, temperature controlled, locked place with restricted 
access, maintained under adequate security until dispensed for subject use or returned to the 
sponsor.   
For all shipments of study drug, site study personnel shall note a 6-month use limit date based on 
the date of thaw of the vials.  A label will be supplied to record the thaw date and storage use 
limit date on the box containing the vials.  Placebo expiry shall be defined in a memo included 
with the shipment and will be extended as warranted via memo when new stability data becomes 
available.  A label will be supplied to record the expiry date on the box containing the vials.  The 
label shall be updated if the expiry is extended before the placebo in the box is fully depleted.   
12.3. 
Investigational Product Storage 
AXER-204 is formulated as an isotonic solution in Phosphate Buffered Saline and is provided in 
5 mL vials. It will be shipped to sites frozen at -80 °C (on dry ice).  Upon receipt it shall be 
placed in the refrigerator at 2-8 °C in a secure location and allowed to thaw for a minimum of 16 
hours prior to use in dose preparation.  Once thawed, AXER-204 shall be kept stored in the 
refrigerator at 2-8 °C for up to 6 months prior to use.  After thawing, the vials containing AXER-
204 should NOT be shaken or vigorously agitated as this may result in generation of foam and 
particles.  Contact the sponsor for instructions in the event there is a deviation from the required 
storage conditions. 


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Placebo consists of Phosphate Buffered Saline and is provided in 5 mL vials.  It will be shipped 
to sites at a temperature of 2-8 °C.  Upon receipt it shall be placed in the refrigerator at 2-8 °C.   
12.4. 
Investigational Product Preparation 
Refer to the dose preparation appendix in the Pharmacy Manual describing the details regarding 
dose preparation.  
12.5. 
Investigational Product Management 
The pharmacist or their designee will verify that investigational product supplies are received 
intact and in the correct amounts by signing and dating the investigational product receipt section 
at the bottom of the packing list.  The person receiving the supplies must verify that the shipment 
contains all the items noted in the shipment inventory.  Any damaged or unusable investigational 
product in a given shipment will be documented in the study files.  The pharmacist must notify 
the sponsor or designee of any damaged or unusable investigational product supplied to the site. 
The site will maintain a Study Drug and Placebo Inventory Log (includes, but not limited to, the 
following: lot number, number of units received, expiry date, and number of vials and syringes 
dispensed.  The site will also maintain patient-specific investigational product dispensing logs. 
An overall accountability of investigational product will be performed and verified throughout 
the study and at the site closeout visit.  Upon completion of the study, copies of the 
investigational product accountability records will be returned to the sponsor.  All used and 
unused study investigational product supplies will be inventoried and accounted, and any used or 
unused supplies which have not been destroyed locally shall be returned to the sponsor or 
designee at the end of the study.  By signing the Investigator Agreement page of this protocol, 
the investigator agrees not to supply investigational product to any person(s) not enrolled in the 
study. 
12.6. 
Investigational Product Accountability 
Subjects will be treated at the clinical site, in-patient clinical unit, or other approved location and 
therefore the Pharmacist or other investigational staff via documentation of receipt of the 
investigational product and dosing/treatment given will perform/maintain accountability.   
12.7. 
Investigational Product Handling and Disposal 
Records of receipt, dispensing records and inventory forms, as applicable, will be examined and 
reconciled during and at the end of the study.  Both the investigational product that is used 
during the study, as well as any remaining unused investigational product, must be accounted for 
on study drug and placebo accountability records provided to the PI by the sponsor or their 
designee or documented per site SOPs.   
At the end of the study or when instructed by the sponsor or designee, all used and unused 
investigational product vials, accompanied by a packing slip, must be returned to the designated 
clinical supplies vendor for disposal or destroyed per site SOPs.  If used investigational product 
vials and/or unused but expired investigational product vials were destroyed locally per site 
policies or procedures, destruction should be documented on the accountability log. 


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In addition, a copy of all completed investigational product accountability records must be 
retained in the Investigators’ Study Files, with a copy sent to the sponsor or their designee. 
The product is to be stored in a safe place (locked facility) at the appropriate temperature. 


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13. 
ASSESSMENT OF EFFICACY AND PHARMACOKINETICS 
13.1. 
Efficacy 
Site personnel will be trained and certified to perform the efficacy assessments.  The same raters 
will be used for evaluation of a given subject insofar as possible.  Raters will be blinded to 
treatment for Part 2 of the trial. 
13.1.1. 
Part 1 
Part 1 is focused on safety, tolerability, and pharmacokinetics.  However, a subset of efficacy 
assessments are included, as follows: 
• ISNCSCI.  ISNCSCI is a comprehensive clinician-administered neurological exam 
for SCI. It is widely used for research and clinical (neurologic) description to fully 
assess sensory and motor functioning and level of injury in traumatic SCI.  The 
UEMS will be calculated from the full ISNCSCI and evaluated separately. 
• GRASSP [Kalsi-Ryan 2012a, Kalsi-Ryan 2012b].  GRASSP is a clinician 
administered test with three subset scores that assesses strength in 10 key muscles in 
the upper extremity as well as dexterity and fine motor skills. 
• SCIM III self-care and mobility scores [Catz 2007, Itzkovich 2007].  SCIM III 
measures functional outcomes in three sections:  self-care, respiration and sphincter 
management, and mobility.  The current study will employ the self-care and mobility 
subscores. 
13.1.2. 
Part 2 
The primary objective of Part 2 is to evaluate the safety, tolerability, and pharmacokinetics of 
repeat dosing.  In addition, a number of efficacy assessments are included as secondary 
endpoints.  The key secondary efficacy endpoint for Part 2 will be within-subject change from 
pre-treatment baseline and slope for UEMS as compared to placebo.  The UEMS is collected as 
part of the ISNCSCI (Appendix 3). 
Additional secondary efficacy endpoints will include changes from pre-treatment baseline and 
slope for: 
• Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) 
prehension performance scores.  GRASSP is a clinician administered test with three 
subset scores that assesses strength in 10 key muscles in the upper extremity as well 
as dexterity and fine motor skills (Appendix 4). 
• Version III of the Spinal Cord Independence Measure (SCIM III) self-care.  SCIM III 
measures functional outcomes in three sections:  self-care, respiration and sphincter 
management, and mobility.  The current study will employ the self-care and mobility 
subscores.  The evaluation will be administered by a clinician (Appendix 8). 
Exploratory functional endpoints will include within-subject changes from pre-treatment 
baseline and slope for: 
• ISNCSCI lower extremity motor and sensory scores  


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• GRASSP strength, sensation and prehension ability scores 
• SCIM III mobility scores 
• Patient Reported Outcomes 
− CUE-Questionnaire (CUE-Q) [Marino 2012, Marino 2015].  Assesses subject-
reported upper limb function (Appendix 2). 
− SF-36 v2 - Provides an investigator-evaluated Quality of Life (QoL) assessment 
for subjects.  SF-36 will provide data on the subjects' perceived health and well-
being over the course of the study (Appendix 6). 
− Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL) - 
(Appendix 7). 
− PGIC – Chronic SCI (Appendix 10) – Provides a patient-reported global 
impression of change in the symptoms, activity limitations, emotions and overall 
quality of life with chronic spinal cord injury since beginning the trial. 
• ISAFSCI [Krassioukov 2012].  The ISAFSCI will be used to document autonomic 
control of the heart, blood pressure, sweating and temperature regulation.  Lower 
urinary tract function, bowel function, and sexual function will be scored 
(Appendix 1). 
Exploratory biomarkers of target engagement and axonal growth may be assessed.   
Since the mechanism of action entails enhanced axonal growth and plasticity, changes attained 
through Study Day 169 are anticipated to be most relevant to assessing on-target effects of 
therapy.   
13.2. 
Pharmacokinetics 
Both serum and cerebrospinal fluid samples will be collected for analysis, as shown in Table 10 
and Table 11.   
In Part 1, a window relative to the nominal timepoint is allowed for sample collection as follows: 
• Blood serum pharmacokinetic samples will be collected at 0 hour (immediately pre-
dose), and 1 h (±10 min), 6 h (±10 min), 12 h (±10 min), and 24 h (±10 min) post-
dose, as well as at Study Day 4 (72h ± 10 min), 8 (±1d), 15 (±3d), and 29 (±4d).   
• Cerebrospinal fluid samples (CSF) will be collected via lumbar puncture at 0 hour 
(immediately pre-dose), 24 h (±2h) Study Day 4 (72 h ±4h), and Study Days 8 (±1d), 
and 29 (±4d).  
The timing for serum and CSF sample collection may be adjusted for subsequent cohorts based 
on pharmacokinetic data from the preceding cohorts.  Serum PK samples collected at pre-dose 
and on Study Days 8 and 29 will be analyzed for the presence of anti-drug antibodies (ADA). 
In Part 2 , Visits 3-7 (Study Days 21, 42, 63, 84, 104) will have a window of ±5 days and Visits 
8 and 9 (Study Days 169 and 253) will have a window of ±7 days.  CSF samples will be 
collected for PK analysis pre-dose on Study Days 1, 21, 42, 63, 84, and 104.  The CSF sample 
collected on Study Day 253 will also be analyzed for PK.  Serum samples will be collected for 


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PK analysis pre-dose and 4 h post-dose on Study Days 1, 21, 42, 63, 84, and 104.  Serum will 
also be collected for PK analysis on Study Days 169 and 253.  Pre-dose serum will be collected 
for ADA analysis on Study Days 1, 21, 42, 63, 84, and 104.  Serum will also be collected for 
ADA analysis on Study Days 169 and 253.  A subset of the CSF samples may also be analyzed 
for ADAs depending on development and presence of ADAs in the serum.  Part 2 serum and 
CSF from subjects receiving placebo will be collected but will not be analyzed for PK and 
ADAs. 
In Part 2 on Study Days 1, 21, 42, 63, 84, and 104 a window relative to the nominal timepoint is 
allowed for sample collection as follows: 
• Serum pharmacokinetic samples will be collected at 0 hour (within 4 h pre-dose), and 
4 h (±10 min) post-dose 
• Cerebrospinal fluid samples (CSF) will be collected via lumbar puncture at 0 hour 
(immediately pre-dose) 


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Table 10: 
Part 1 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) 
 
Day 1 (Dosing day)  
Day 2 (24 hours post-
dose) 
Day 4 (72 hours post-
dose)  
Day 
8 
Day 
15 
Day 
29 
Cerebrospinal Fluid  
Pre-Dose 
X 
X 
X 
 
X 
Serum  
Pre-Dose, and post-dose at Hours 1, 6, 
12 
X 
X 
X 
X 
X 
Serum aliquot for ADA 
testing 
X (Pre-dose) 
 
 
X 
 
X 
Table 11: 
Part 2 Pharmacokinetic Sampling Schedule (Study RNX-AX204-101) 
 
Study Phase 
Treatment Phase 
Window at Visits  3-7 ± 5 days 
Follow-Up 
± 7 days 
Study Day 
Month 
1 
21 
 
42 
63 
 
84 
 
104 
 
169 
Month 6 
253/ET 
Month 9 
Visit Number 
2 
3 
4 
5 
6 
7 
8 
9 
Cerebrospinal Fluid 
X 
X 
X 
X 
X 
X 
X 
Serum  
X 
X 
X 
X 
X 
X 
X 
X 
Serum aliquot for ADA 
testing 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations:  M = month, ET = Early Termination.  
 
 
 


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13.2.1. 
Serum 
Serum samples will be prepared for shipment according to the detailed procedure supplied. For 
research subjects that provided consent, the required quantity will be removed and processed into 
aliquots for inclusion in the spinal cord injury biobank.  Study personnel are required to verify 
that a subject provided the required separate biobank informed consent permitting sample 
inclusion in the biobank before a portion of the serum is removed and processed for this purpose. 
13.2.2. 
Cerebrospinal Fluid 
Cerebrospinal fluid samples will be prepared for shipment according to the detailed procedure 
supplied.  For research subjects that provided consent, from 9 to 20 mL will be removed and 
processed into aliquots for inclusion in the spinal cord injury biobank.  Study personnel are 
required to verify that a subject provided the required biobank separate informed consent 
permitting sample inclusion in the biobank before a portion of the serum is removed and 
processed for this purpose. 
13.2.3. 
Shipment of Pharmacokinetic Samples 
Serum and CSF samples will be packed on dry ice and shipped to the designated lab for 
processing at pre-determined intervals.  Specific instructions will be given to the site personnel. 


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14. 
ASSESSMENT OF SAFETY 
The Schedule of Events for Part 1 given in Table 5, and for Part 2 in Table 6 provide the timing 
for assessments starting with the Screening Visits. 
14.1. 
Safety Parameters 
Safety will be evaluated similarly for both Parts, through the collection of data from: 
• Physical examinations 
• Vital signs 
• 12-lead electrocardiograms 
• Laboratory parameters (hematology, blood chemistry, and urinalysis) 
• Treatment-emergent adverse events (TEAEs).   
− TEAEs will be defined as any AE occurring during or after the injection of 
investigational product.   
− TEAEs will be limited to those events occurring within 28 days after the last visit. 
Condition-specific safety outcomes will include: 
• 
ISNCSCI, GRASSP and all of the neurological measures evaluated for efficacy 
• Spasticity (Modified Ashworth Scale) [Pandyan 1999].  A clinician administered 
examination for spasticity which measures muscle tone changes.  A score of 0-4 is 
assigned to each muscle group evaluated (Appendix 5).  Notes: Testing will exclude 
fingers and thumb.  Scores are to be recorded for left and right sides for each muscle 
group tested. 
• Pain (BPI) [Cleeland 1994].  A self-administered questionnaire used to assess the 
severity of a subject's pain and the impact of this pain on the subject's daily 
functioning.  
14.1.1. 
Demographic/Medical History 
Demographic information and medical history will be collected at Screening for determination of 
eligibility. 
14.1.2. 
Vital Signs 
Vital signs, including blood pressure, pulse rate, respiratory rate or pulse oximetry, and oral body 
temperature, will be measured after the patient has been in a sitting/recumbent position for 5 
minutes.   
Height and weight will be captured as per the Schedule of Events.  BMI will be derived. 


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14.1.3. 
Physical Examination 
Physical examinations will be conducted and abnormalities will be described.  At certain visits, 
as indicated in the Schedule of Events, only symptom-driven examinations (abbreviated physical 
examinations) will be performed.   
Clinically significant changes, in the judgment of the investigator, in physical examination 
findings (abnormalities) will be recorded as adverse events. 
14.1.4. 
Electrocardiogram (ECG) 
A 12-lead ECG will be obtained on all subjects.  The electrocardiogram will precede other 
evaluations in the sequence of operations at each timepoint as scheduled.   
The screening ECG will be evaluated by a physician for the presence of abnormalities.  Subjects 
with clinically significant abnormalities may not enter the study.  The timing of these evaluations 
may be adjusted and additional evaluation times may be added, if indicated.   
The 12-lead ECGs will be taken in triplicate.  To minimize variability, patients should be in a 
supine (resting) position for at least 5 minutes prior to each ECG recording, 5 minutes between 
each ECG. If findings from the ECG performed at the Screening Visit (Visit 1) are clinically 
significant and would potentially prevent the subject from safely participating in the study 
(taking into account the patient’s overall status, as well as the medication profile), the patient 
should not be enrolled (or randomized) and should be withdrawn from the study.  
Triplicate ECGs will be performed twice during the Treatment/In-Clinic Visit (Visit 2) just prior 
to the lumbar puncture and within 60 minutes following administration of investigational product 
(and, for Part 2, at each subsequent dosing time point). Clinically significant abnormalities noted 
after investigational product administration are to be recorded as AEs.  All ECGs will be read 
locally by appropriately trained staff. 
14.1.5. 
Laboratory Assessments 
The results of all laboratory tests required by the protocol will be recorded in the subject's eCRF.  
All clinically important abnormal laboratory tests occurring during the study will be repeated at 
appropriate intervals until they return either to baseline or to a level deemed acceptable by the 
Site Principal Investigator and the sponsor, or until a diagnosis that explains them is made.  
Abnormal laboratory test results that result in a change in study drug dosage or in 
discontinuation of the drug, or require intervention or diagnostic evaluation to assess the risk to 
the patient/subject, should be recorded as adverse events in the case report form.  Investigators 
should review the CTCAE toxicity criteria that can be found at the following URL:  
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_8.5x11.pdf 
All laboratory assessments will be collected as per the schedule of events (Table 5, Table 6). 
The clinical laboratory tests analyzed in this study are provided in Table 12.  The INRPTT, urine 
pregnancy testing and in-clinic safety laboratory tests requiring stat analysis will be processed 
locally.  In addition, laboratory samples taken during Study Days 1-4 will be processed locally.  
All other laboratory tests will be analyzed by a central laboratory, 
.  All 
CSF, blood, and urine samples will be collected and sent to the central laboratory on the day of 


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collection unless otherwise instructed.  INR/PTT is required prior to the Day 1 lumbar puncture 
procedure with repeat INR/PTT tests on subsequent Study Days only if directed by the Principal 
Investigator.  Clinical laboratory results will be reviewed by the study investigator when results 
are known prior to enrollment/randomization, and results available for each collection during the 
study including prior to discharge from the in-patient clinic in Part 1 of the study.  During the 
course of the study, abnormal laboratory values should be repeated and subjects interviewed for 
evidence of clinical signs and symptoms consistent with the laboratory abnormality. Subjects 
with abnormal laboratories at screening can be rescreened (ie, lab repeated) for inclusion into the 
study within the 28-day screening window specified for labs.  A Laboratory Manual will be 
provided separately for processing and shipping procedures.  
Table 12: 
Laboratory Parameters to be Assessed (Study RNX-AX204-101) 
Hematology 
Serum Chemistry 
Hemoglobin 
Glucose 
Albumin 
Hematocrit 
Blood urea nitrogen 
 
Platelet count (or estimate) 
Creatinine 
Creatine kinase 
White blood cell count including 
differential (absolute values only) 
Total bilirubin 
Calcium 
Alkaline phosphatase 
Total Cholesterol 
Alanine transaminase (ALT) 
 
Red blood cell (RBC) count 
Aspartate transaminase (AST) 
Direct bilirubin 
Mean corpuscular volume (MCV)  
RBC morphology 
MCH 
MCHC 
RDW 
 
Sodium 
Total protein 
 
Phosphorous 
Triglycerides 
Urinalysis 
Potassium 
Uric acid 
pH 
Chloride 
 
Specific gravity 
Bicarbonate 
 
Blood 
Lactate dehydrogenase 
 
Glucose 
 
 
Protein 
Coagulation 
 
Ketones 
Prothrombin time (PT) 
 
Urine Bilirubin  
Activated partial thromboplastin time 
(PTT) 
 
International normalized ratio (INR) 
 
CSF Analysis 
 
 
Cell counts 
Pregnancy tests 
 
Total protein 
Serum pregnancy 
 
Glucose 
Urine pregnancy 
 
Table 13: 
Moderate and Marked Liver Function Abnormality Thresholds (Study 
RNX-AX204-101) 
 
AST/ALT 
Alkaline Phosphatase  Total Bilirubin 


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Moderate 
≥1.5 x ULN 
≥1.2 x ULN 
≥1.5 x ULN 
Marked 
≥3 x ULN 
≥3 x ULN 
≥2 x ULN 
ULN is defined as the upper limit of normal if the pretreatment Baseline was normal, or the 
pretreatment baseline if it was abnormal.   
Moderate abnormal liver function tests should be repeated within 1 to 2 days.  If they are 
confirmed, they should be repeated at intervals determined in consultation with the sponsor and 
medical monitor until they resolve. 
Subjects with an AST/ALT elevation between >3x and 5x ULN must have this test repeated 
upon receipt of this value and the sponsor notified.  If repeat analysis cannot be performed within 
24 hours or if an AST/ALT value >3x ULN is confirmed, the subject must discontinue treatment 
immediately and the sponsor must be notified.  The abnormal tests should be repeated within 48 
hours of receipt of this value and then at 3 to 7-day interval until they resolve.  In consultation 
with the sponsor, additional evaluation of the subject may be arranged.  The additional 
evaluation may include GI consultation and additional laboratory tests (eg, HBV, HAV, and 
CMV serology, CPK, reticulocyte count). 
14.1.5.1. Other Laboratory Tests 
A serum pregnancy test will be performed at scheduled time points (see the Schedules of Events) 
on all women in both Parts 1 and 2.  Serum tests are required at the Screening Visit (Visit 1) for 
Part 1 and Part 2.  Urine pregnancy tests are required at the Dose Visits for Part 1 and Part 2 for 
women of childbearing potential and for Visits 8 and 9 for Part 2.  
14.1.5.2. Virus Serology 
Infectious disease testing will include:  HIV-1/HIV-2 antibody, hepatitis B surface antigen, 
hepatitis C antibody. 
14.1.5.3. Drug Screen 
A urine sample for drug screening will minimally include amphetamines, cocaine, marijuana, 
opiates, phencyclidine, barbiturates, benzodiazepines, methadone, and propoxyphene. 
14.2. 
Adverse and Serious Adverse Events 
14.2.1. 
Definition of Adverse Events 
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
product or medical device; the event need not necessarily have a causal relationship with the 
treatment or usage. Examples of AEs include but are not limited to:   
• clinically significant symptoms and signs 
• abnormal test findings 
• changes in physical examination findings 
• hypersensitivity 
• progression/worsening of underlying disease 


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Additionally, AEs may include the signs or symptoms resulting from: 
• drug overdose 
• drug misuse 
• drug interactions 
• exposure in utero 
Diagnostic and therapeutic non-invasive and invasive procedures should not be reported as AEs. 
For example, an acute appendicitis that begins during the AE reporting period should be reported 
as the AE, and the resulting appendectomy should be recorded as treatment of the AE. 
14.2.2. 
Abnormal Test Findings 
The criteria for determining whether an abnormal objective test finding should be reported as an 
AE are as follows:  
• test result is associated with accompanying symptoms, and/or 
• test result requires additional diagnostic testing or medical/surgical intervention, 
and/or 
• test result leads to a discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy, and/or 
• test result is considered to be an AE by the investigator or sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE. Any abnormal test result that is determined to be an error does not require 
reporting as an AE. 
14.2.3. 
Adverse Events of Special Interest (AESI) 
Adverse Events of Special Interest (AESI) for this study include possible allergic/immune 
reactions to administration of a protein therapeutic, AEs generally associated with lumbar 
puncture, and theoretical AEs arising from axon growth.  No AESI have been identified from 
non-clinical toxicology studies with AXER-204.  The following are considered AEs of Special 
Interest for this study: 
• Immune/Allergic reactions:  fever, rash, arthralgia, myalgia, hematuria, proteinuria, 
serositis, central nervous system complications, and hemolytic anemia.  Injection site 
reactions may occur 
• Events relating to the lumbar puncture procedure: infection, postdural puncture 
headache, bleeding, brainstem herniation, meningitis, back pain, excessive CSF 
leakage requiring blood patch 
• Complicating infections: discitis and vertebral osteomyelitis 
• Neurological symptoms or injuries: low back pain, radicular injury, abducens palsy 
• Other: late onset of epidermoid tumors of the thecal sac, increased pain, increased 
spasticity 


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14.2.4. 
Serious Adverse Event (SAE) 
An SAE or serious adverse drug reaction is any untoward medical occurrence that at any dose: 
• results in death 
• is life-threatening (immediate risk of death) 
• requires inpatient hospitalization or prolongation of existing hospitalization, except 
overnight hospital stays as outlined in Section 11.2.2 Treatment Phase, Visits 2 
through 7 (Study Days 1 through 104) whereby a decision is made to keep the patient 
overnight for convenience (e.g. travel issues, local alternate accommodations not 
readily available). 
• results in persistent or significant disability/incapacity, or 
• results in congenital anomaly/birth defect. 
Medical and scientific judgment should be exercised in determining whether an event is an 
important medical event. An important medical event may not be immediately life-threatening 
and/or result in death or hospitalization. However, if it is determined that the event may 
jeopardize the subject and/or may require intervention to prevent one of the other AE outcomes, 
the important medical event should be reported as serious. 
14.2.4.1. Hospitalization 
Adverse events associated with hospitalization or prolongations of hospitalization are considered 
serious. Any initial admission (even if less than 24 hours) to a healthcare facility meets these 
criteria. Admission also includes transfer within the hospital to an acute/intensive care unit (eg, 
from the psychiatric wing to a medical floor, medical floor to a coronary care unit, neurological 
floor to a tuberculosis unit).  Exception: overnight hospital stays as outlined in Section 11.2.2 
Treatment Phase, Visits 2 through 7 (Study Days 1 through 104) whereby a decision is made to 
keep the patient overnight for convenience (e.g. travel issues, local alternate accommodations not 
readily available). 
Hospitalization does not include the following: 
• rehabilitation facilities 
• hospice facilities 
• respite care (eg, caregiver relief) 
• skilled nursing facilities 
• nursing homes 
• routine emergency room admissions 
• same day surgeries (as out-subject/same day/ambulatory procedures). 
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical AE is 
not in itself an SAE. Examples include:  


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• admission for treatment of a preexisting condition not associated with the 
development of a new adverse event or with a worsening of the preexisting condition 
(eg, for work-up of persistent pre-treatment lab abnormality) 
• social admission (eg, subject has no place to sleep) 
• administrative admission (eg, for yearly physical exam) 
• protocol-specified admission during a study (eg, for a procedure required by the study 
protocol) 
• optional admission not associated with a precipitating clinical adverse event (eg, for 
elective cosmetic surgery) 
• preplanned treatments or surgical procedures should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject. 
14.2.5. 
Adverse Event Reporting 
The investigator is to record all directly observed AEs and all AEs spontaneously reported by the 
subject in the source documents and eCRFs. 
All observed or volunteered AEs regardless of treatment arm or suspected causal relationship to 
the investigational product(s) will be reported as described in the following sections.  
For all AEs, the investigator must pursue and obtain information adequate both to determine the 
outcome of the AE and to assess whether it meets the criteria for classification as an SAE 
requiring immediate notification to the sponsor or its designated representative. For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of the 
AE. The investigator is required to assess causality.  For AEs with a causal relationship to the 
investigational product, follow-up by the investigator is required until the event or its sequelae 
resolve or stabilize at a level acceptable to the investigator, and the sponsor concurs with that 
assessment.   
In order to ascertain if headaches are secondary to the lumbar puncture per se, the clinical 
characteristics of the headache, including positional exacerbations will be assessed and reported.  
For Part 1, adverse events should be recorded and monitored from the time of first dose through 
subject completion of the study up to 28 days post-dose, or until the investigator deems the AE 
as resolved or stable (unchanging).  Serious AEs should be recorded and monitored from the 
time of signing of the informed consent form (ICF) through subject completion of the study up to 
28 days after completion of the study, or until investigator deems the SAE as resolved or stable 
(unchanging). 
For Part 2, adverse events should be recorded and monitored from the time of first dose up to 28 
days after completion of the study (28 days after Month 9 visit or ET), or until the investigator 
deems the AE as resolved or stable (unchanging).  Serious AEs should be recorded and 
monitored from the time of signing of the informed consent form (ICF) through subject 
completion of the study (28 days after Month 9 visit or ET), or until investigator deems the SAE 
as resolved or stable (unchanging). 


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14.2.5.1. Severity Assessment 
The investigator will use the Common Terminology Criteria for Adverse Events (CTCAE) to 
determine the toxicity grade of AEs, found at the following URL:  
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_8.5x11.pdf 
Note the distinction between the severity and the seriousness of an AE. A severe event is not 
necessarily a serious event. For example, a headache may be severe (interferes significantly with 
subject's usual function) but would not be classified as serious unless it met one of the criteria for 
SAEs, listed above. 
14.2.5.2. Causality Assessment 
For all collected AEs, the investigator will determine each AE’s causality based on temporal 
relationship and his/her clinical judgement.  For each AE, relatedness will be assessed with 
respect to 1) investigational product and 2) the LP procedure.  The degree of certainty about 
causality will be graded using the categories below and the investigator must record the causal 
relationship on the eCRF, as appropriate, and report such an assessment in accordance with the 
SAE reporting requirements if applicable. 
Table 14: 
Relatedness Definitions (Study RNX-AX204-101) 
Definitely related 
There is clear evidence to suggest a causal relationship, and other 
possible contributing factors can be ruled out.  The clinical event, 
including an abnormal laboratory test result, occurs in a plausible 
time relationship to study product intake and cannot be explained 
by concurrent disease or other drugs or chemicals.  The response 
to withdrawal of the study product (dechallenge) should be 
clinically plausible. 
Probably related 
There is evidence to suggest a causal relationship, and the 
influence of other factors is unlikely.  The clinical event, 
including an abnormal laboratory test result, occurs within a 
reasonable time after intake of the study product, is unlikely to be 
attributed to concurrent disease or other drugs or chemicals and 
follows a clinically reasonable response on withdrawal 
(dechallenge). 
Possibly related 
There is some evidence to suggest a causal relationship (eg, the 
event occurred within a reasonable time after intake of the study 
product).  However, other factors may have contributed to the 
event (eg, the subject’s clinical condition, other concomitant 
events).  Although an AE may rate only as “possibly related” 
soon after discovery, it can be flagged as requiring more 
information and later be upgraded to “probably related” or 
“definitely related”, as appropriate. 
Unlikely to be related 
A clinical event, including an abnormal laboratory test result, 
whose temporal relationship to study product makes a causal 
relationship improbable (eg, the event did not occur within a 
reasonable time after intake of the study product) and in which 
other drugs, or chemicals, or underlying diseases provide 


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plausible explanations (eg, the subject’s clinical condition, other 
concomitant treatments). 
Not Related 
The AE is completely independent of study product intake, and/or 
evidence exists that the event is definitely related to another 
etiology.   
14.2.5.3. Exposure in Utero 
An exposure in-utero occurs if: 
1. A female becomes, or is found to be, pregnant either while receiving or having been 
directly exposed to (eg, environmental exposure) the investigational product, or the 
female becomes, or is found to be, pregnant after being directly exposed to the 
investigational product (maternal exposure). 
2. A male has been exposed, either due to treatment or environmental, to the investigational 
product prior to or around the time of conception and/or is exposed during his partner’s 
pregnancy (paternal exposure). 
If any subject becomes or is found to be pregnant during the study subject’s treatment with the 
investigational product, the investigator must submit this information to the sponsor on an 
Exposure in Utero Form.  In addition, the investigator must submit information regarding 
environmental exposure to the sponsor’s product in a pregnant woman (eg, a nurse reports that 
she is pregnant and has been exposed to the investigational product by contact or spillage) using 
the Exposure in Utero Form.  This must be done irrespective of whether an adverse event has 
occurred and within 24 hours of awareness of the pregnancy.  The information submitted should 
include the anticipated date of delivery (see below for information related to induced termination 
of pregnancy). 
Follow-up is conducted to obtain pregnancy outcome information on all Exposure in Utero 
reports with an unknown outcome.  The investigator will follow the pregnancy until completion 
or until pregnancy termination (ie, induced abortion) and then notify the sponsor of the outcome. 
The investigator will provide this information as a follow-up to the initial Exposure in Utero 
Form.  The reason(s) for an induced abortion should be specified. An Exposure in Utero report is 
not created when an ectopic pregnancy report is received since this pregnancy is not usually 
viable.  Rather, a SAE case is created with the event of ectopic pregnancy. 
If the outcome of the pregnancy meets the criteria for immediate classification as a SAE (ie, 
spontaneous abortion, stillbirth, neonatal death, or congenital anomaly [including that in an 
aborted fetus, stillbirth or neonatal death]), the investigator should follow the procedures for 
reporting SAEs. 
In the case of a live birth, the “normality” of the newborn can be assessed at the time of birth (ie, 
no minimum follow-up period of a presumably normal infant is required before an Exposure in 
Utero Form can be completed).  The “normality” of an aborted fetus can be assessed by gross 
visual inspection, unless pre-abortion test findings are suggestive of a congenital anomaly. 
Additional information regarding the exposure in utero may be requested by the investigator. 
Further follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  In the case of paternal exposure, the 


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investigator must obtain permission from the subject’s partner in order to conduct any follow-up 
or collect any information. 
14.2.5.4. Reporting Requirements 
14.2.5.4.1. Serious Adverse Reporting Requirements 
Each AE is to be assessed to determine if it meets the criteria for an SAE. If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate.  
If an SAE occurs, the sponsor is to be notified within 24 hours of awareness of the event by the 
investigator.  In particular, if the SAE is fatal or life-threatening, notification to the sponsor must 
be made immediately, irrespective of the extent of available AE information.  This timeframe 
also applies to additional new information (follow-up) on previously forwarded SAE reports as 
well as to the initial and follow-up reporting of Exposure in Utero cases (Section 14.2.5.3). 
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study patient initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time of 
his/her first awareness of the AE.  
To report the SAE, complete the SAE form electronically in the eCRF for the study. When the 
form is completed, 
 will be notified electronically and will retrieve the 
form.  If the event meets serious criteria and it is not possible for you to access the internet, fax a 
paper copy to 
.  As soon as internet service has been restored, send an email to 
 at 
.  
 Safety personnel are available for 
SAE reporting on a 24-hour basis. Incoming reports are reviewed during normal business hours.”  
For all SAEs, the investigator is obligated to pursue and provide information to the sponsor in 
accordance with the timeframes for reporting specified above.  In addition, an investigator may 
be requested by the sponsor to obtain specific additional follow-up information in an expedited 
fashion.  This information may be more detailed than that captured on the AE page of the eCRF.  
In general, this will include a description of the AE in sufficient detail to allow for a complete 
medical assessment of the case and independent determination of possible causality. Information 
on other possible causes of the event, such as concomitant medications and illnesses must be 
provided. In the case of a patient death, a summary of available autopsy findings must be 
submitted as soon as possible to the sponsor or its designated representative. 
14.2.5.5. Non-Serious Adverse Event Reporting Requirements 
All AEs will be reported on the Adverse Event page(s) of the eCRF. It should be noted that the 
form for collection of SAE information is not the same as the Adverse Event eCRF.  Where the 
same data are collected, the forms must be completed in a consistent manner.  For example, the 
same AE term should be used on both forms.  Adverse events should be reported using concise 
medical terminology on the eCRFs as well as on the form for collection of SAE information. 
A non-serious AESI will be promptly entered in the eCRF and reported on expedited basis 
(within 24 hours) to the sponsor (or designee) to facilitate real-time review of patterns of 
toxicity. Investigators are to report AESIs in accordance with the SAE reporting process noted in 


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Section 14.2.5.4.1 within 24 hours of becoming aware of all AEs of Special Interest.  All AESIs 
must be promptly assessed by the Medical Monitor within 24 hours of receipt. 
14.2.5.6. Sponsor Reporting Requirements to Regulatory Authorities 
Adverse events reporting, including serious unexpected serious adverse reactions (SUSAR), will 
be carried out in accordance with applicable local regulations. 


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15. 
STATISTICS 
15.1. 
Sample Size 
The Part 1 sample size was derived empirically from experience with previous single ascending 
dose clinical studies in other disorders and is deemed appropriate to achieve the study objectives. 
The Part 2 sample size was selected to ensure adequate power for detecting treatment-related 
change in bilateral UEMS (Score from 0 to 50). 
A 5-point difference, between the treated and placebo groups, in the change from baseline to 6 
months in bilateral UEMS is considered clinically meaningful. Analysis of historical data for 
cervical SCI patients for the period between ~6-12 months following acute SCI indicates a 
standard deviation of bilateral UEMS change over 6 months to be around 3 to 4 points. 
With a sample size of 12 subjects per active and placebo group, Part 2 of the study has 80% 
power with Type I error of α=0.05 (two sided), assuming a 5-point difference as indicated above, 
and with a common standard deviation within each treatment group of approximately 4 in the 
change from baseline to 6 months in bilateral UEMS.  
Accounting for uncertainties in the assumptions based upon historical data used to extrapolate 
for estimating the sample size in this study and the need for estimation of missing data a sample 
size of approximately 16 subjects per treatment arm (32 total) will be randomized.    
15.2. 
Stages of Analysis 
The analysis for this study will be performed in three stages, with the first analysis performed 
upon completion of the clinical portion of Part 1, the second analysis (including the core efficacy 
assessment) performed upon completion Day 169 of Part 2 (ie, after all subjects have completed 
through Study Day 169), and the final analysis performed upon completion of the post-treatment 
follow-up phase of Part 2 (Day 253).  The methods applied to each analysis will be consistent 
with the objectives of the study.   
The blind will be maintained for all blinded study personnel (including investigators and 
subjects) through the completion of Day 169 of Part 2. After completion of Day 169, designated 
sponsor staff and external consultants/contractors required to perform the analysis will be 
unblinded to the treatment allocations in order to complete data analysis though Day 169. The 
blind will be maintained for site investigators and subjects through completion of Day 253 unless 
the blind must be broken sooner for safety or regulatory reasons. 
15.3. 
General Methods 
Data will be tabulated using both descriptive and inferential statistics where specified.   
• For Part 1, data will be tabulated by dosing cohort as well as pooled (all subjects 
combined), and no inferential statistics are planned. 
• For Part 2, data will be tabulated for each treatment group separately (placebo and 
AXER-204) to allow for visual inspection of outcomes between the arms.  Inferential 
comparison of the treatment groups is planned. 
For both Parts, all data collected will be included in by-domain data listings, sorted by subject 
number and time point, or as appropriate. 


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No hypothesis testing will be performed for demographics, background, or safety data.  
Continuous data will be summarized by presenting the number of subjects (n), means, mean 
changes from baseline, mean % changes from baseline (where appropriate), standard deviations, 
minimum, First quartile (Q1), median, third quartile (Q3), and maximum values. The number of 
subjects with missing data will be indicated. 
Categorical data will be summarized by presenting the number of subjects (n), the number of 
subjects with missing data as well as counts and percentages in each of the categories. 
Percentages will be based upon the number of subjects with available data. 
When inferential testing is applied to all efficacy assessments, dichotomous/binary categorical 
efficacy endpoints will be assessed via a 2-sided Fisher’s Exact test or Chi-square test as 
appropriate.  Continuous efficacy endpoints will also present least-squares means and p-values 
from hypothesis testing of efficacy endpoints using mixed-effects model for repeated measures 
(MMRM). 
Additional details will be included in the statistical analysis plan (SAP) which will be finalized 
prior to unblinding Part 2 of the study and any amendments to it made prior to locking the 
database and unblinding the study.   
15.4. 
Handling of Missing Data 
Every attempt will be made to collect all protocol required data at each time point.     
Imputations will only be performed for efficacy data and for missing or partial dates, missing 
severity or relationship to investigational product. Missing AE or CM dates and missing severity 
or relationship to investigational product will always use a conservative approach. Details will be 
included in the SAP.  
For subjects who discontinue treatment (for any reason), subjects will continue to be followed 
and key efficacy endpoints and safety data collected where possible. 
The primary analyses for change in bilateral UEMS will use a mixed model repeated measures 
which automatically accounts for the missing data based upon the covariate structure assumed. 
To evaluate robustness of results, sensitivity analyses will be performed with imputation 
methods for missing data. 
15.5. 
Subgroups 
The sample size precludes analysis by-subgroup.  However, exploratory assessment of any trends 
among subgroups (eg, by pre-treatment AIS grade) may be performed, after initial review if the 
data warrant. 
15.6. 
Analysis Populations 
Safety Population:  Safety outcomes will be assessed for all subjects who are given at least one 
dose of investigational product.  
Full Analysis Set (FAS) Population:  Efficacy outcomes will be evaluated using the FAS, 
defined as all subjects randomized, treated with at least 1 dose of investigational product, and 
with at least one post-baseline assessment of efficacy. 


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Per Protocol Population: The per protocol population will be a subset of FAS and include 
subjects who received at least 80% of study drug and have no major protocol deviations that 
would impact efficacy assessment.  
15.7. 
Alpha Level Considerations 
All inferential testing will be performed using two-sided 5% Type I error (α), and therefore 2-
sided p-values ≤ 0.05 will be considered statistically significant in this study. 
The first hypothesis test will be the key secondary efficacy endpoint of change in bilateral 
UEMS from baseline to Study Day 169 using the MMRM model as detailed below. Additional 
secondary efficacy endpoints tested will be the change in GRASSP prehension performance from 
baseline to Study Day 169 and of change in SCIM self-care from baseline to Study Day 169.  
15.8. 
Subject Disposition and Exposure 
The numbers of subjects randomized (Part 2 only), completing or withdrawing, along with 
reasons for withdrawal, will be summarized by dose (Part 1) and treatment group (Part 2).  
Tabulation of the number of doses of investigational product, duration of treatment as well as 
total dose given will be provided. 
15.9. 
Demographics and Baseline Characteristics Analyses 
Demographic variables (age, sex, race, and ethnicity) as well as height (cm), weight (kg), Body 
Mass Index (BMI), temperature, heart rate, blood pressure and respiratory rate or pulse oximetry 
(from the vital signs) at baseline will be summarized using descriptive statistics.  All 
demographic data will be provided in a data listing. 
15.10. 
Efficacy Endpoints 
For Part 1 efficacy, outcomes will be presented by each dosing cohort, with no inferential 
assessments among cohorts planned.  Thus, for Part 1, efficacy will be presented only 
descriptively. 
For Part 2, changes from pre-treatment to each on-treatment time point will be calculated, with 
the primary time point at Day 169.  Shifts over time in ordinal endpoints will be presented, with 
comparisons between treatment groups assessed using a CMH row mean scores statistic at each 
time point.  Slope of change will also be evaluated.  Part 2 efficacy analysis is described in the 
following sections. 
15.10.1. 
Part 2 Efficacy Endpoints 
 Change in bilateral UEMS from baseline to Day 169 will be evaluated as a key secondary 
endpoint for the trial. 
Baseline bilateral UEMS is defined as the last non-missing bilateral UEMS prior to first 
treatment in Part 2. 
The null and alternative hypothesis for this study are as follows: 
H0: μA= μP 
HA: μA≠ μP 


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Where H0 and HA refer to the Null and alternative hypothesis to be tested in this study, μA and μP 
refers to the mean change in bilateral UEMS from baseline to Study Day 169 for subjects 
randomized to AXER-204 and Placebo groups respectively.  
Analysis to compare the change in bilateral UEMS from baseline to each post baseline visit will 
be based upon a mixed-effects model for repeated measures (MMRM) for the double-blind 
period using the FAS population. 
Additional secondary efficacy endpoints will include change from baseline to Day 169 in the 
total GRASSP prehension performance score and change from baseline to Day 169 in SCIM III 
self-care score. The analyses for these scores will be handled the same way as the key secondary 
endpoint. 
Exploratory efficacy endpoints will include changes from baseline to each post baseline value in 
each of the following endpoints. 
• Change from baseline to each post baseline value for bilateral UEMS, GRASSP 
prehension performance, and SCIM III self-care scores. 
• Bilateral ISNCSCI sensory and lower extremity motor scores 
• Bilateral GRASSP strength, sensation and prehension ability scores 
• Patient Reported Outcomes 
− CUE-Questionnaire (CUE-Q) 
− PGIC – Chronic SCI 
− SF-36 v2 Health Survey 
− Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine Motor, ADL)  
• ISAFSCI.  The ISAFSCI will be used to document autonomic control of the heart, 
blood pressure, sweating and temperature regulation.  Lower urinary tract function, 
bowel function, and sexual function will be scored. 
Responder analyses may be performed to compare the proportion of responders in each treatment 
group. Details of responder analyses with thresholds used to define clinically meaningful 
improvements will be defined in the SAP.  
Sensitivity analyses of the secondary and exploratory endpoints may be performed if the 
outcomes warrant further analysis. 
15.11. 
Safety Endpoints 
The safety analysis will be descriptive in nature.  All safety data will be listed, and data will be 
tabulated by dose (Part 1) and treatment group (Part 2) where the data warrant.  Safety data 
include: 
• AEs, including assessment of lumbar infusion site  
− Events occurring prior to the first dose of investigational product or placebo will 
be defined as pre-treatment events. 


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− For Part 1, TEAEs will be defined as any AE occurring during or after the 
injection of study drug.  This will therefore include all events occurring through 
Day 29/ET. 
− For Part 2, TEAEs will be limited to those events occurring within 28 days after 
the last visit.   
Incidence of AEs will be summarized for each treatment group/cohort by MedDRA system 
organ class (SOC) and preferred term, sorted in descending frequency by SOC, and then by 
preferred term within SOC.  These summaries will be given by treatment in separate tables for 
each of the following TEAE event sets: 
• All events 
• Treatment related events (defined by a relationship to study drug of possible, 
probable, or definite). 
• Serious adverse events 
• Events leading to premature discontinuation from study 
• Events by maximum severity 
• AEs of Special Interest, ie, events relating to the lumbar puncture procedure (eg, 
infection, headache, back pain, excessive CSF leakage requiring blood patch). 
Other safety outcomes will include: 
• Clinical laboratory tests, including hematology, chemistry, metabolic, and urinalysis.  
Changes over time will be presented.  Potentially clinically significant (PCS) ranges 
will be defined and used to determine the incidence of subjects experiencing new-
onset PCS laboratory values, where new-onset is defined as a PCS value for a subject 
following initiation of study treatment for which the subject did NOT have a PCS 
value for that analyte PRIOR to initiation of study treatment. 
• Vital signs including: respiratory rate or pulse oximetry, heart rate, temperature, and 
blood pressure, as per the schedule of events.  BMI will be assessed, with height 
collected only at screening.   
• Physical examination  
• 12-lead ECG.  ECG parameters will be analyzed in a fashion similar to that of clinical 
laboratory parameters. 
Condition-specific safety outcomes will include: 
• ISNCSCI, GRASSP and all of the neurological measures evaluated for efficacy 
• Spasticity (Modified Ashworth Scale).  A clinician administered examination for 
spasticity which measures muscle tone.  A score of 0-4 is assigned to each muscle 
group evaluated. Note: Testing will exclude fingers and thumb. 
• Pain (BPI).  A self-administered questionnaire used to assess the severity of a 
subject's pain and the impact of this pain on the subject's daily functioning. 


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Concomitant treatments will be assessed according to the timing of their start/stop dates as they 
relate to the study drug treatment, as follows: 
• Prior.  Medications with start AND stop date before date of first dose of study drug or 
placebo. 
• Concomitant.  Medications with subject exposure that includes at least one dose of 
study drug or placebo. 
• New-onset medications.  Concomitant medications with a start date AFTER the first 
dose of study drug or placebo.  New-onset medications are a subset of the full set of 
concomitant medications. 
• Post-treatment medications.  Medications with a start date at least 28 days AFTER the 
last dose of study drug or placebo. 
Changes from pre-treatment will be calculated in a similar fashion as for the efficacy endpoints, 
but no inferential statistics will be provided for safety endpoints.  Shifts from baseline in ECG 
will be tabulated for heart rate and QTcF.  Other endpoints will be assessed according to the 
scale of the variable. 
15.12. 
Pharmacokinetic Endpoints 
Concentration data in both blood serum and in cerebrospinal fluid will be assessed descriptively 
over time.  Correlation with efficacy and safety outcomes may be performed, as the data warrant. 


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16. 
QUALITY CONTROL AND QUALITY ASSURANCE 
During study conduct, the sponsor or its agent will conduct periodic monitoring visits to ensure 
that the protocol and good clinical practices (GCPs) are being followed. The monitors will 
review source documents to confirm that the data recorded on eCRFs are accurate. The 
investigator and institution will allow the sponsor monitors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification. 
The study site may be subject to review by IRB/IEC, and/or to quality assurance audits 
performed by the sponsor, or companies working with or on behalf of the sponsor, and/or to 
inspection by appropriate regulatory authorities. 
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process. 


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17. 
ETHICS 
17.1. 
Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, ICFs, and other relevant documents, eg, subject instructions, recruitment 
advertisements, if applicable, from the IRB/IEC. All correspondence with the IRB/IEC should be 
retained in the Investigator Site File. Copies of IRB/IEC approvals should be forwarded to the 
sponsor. 
The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects. In that 
event, the investigator must notify the IRB/IEC and the sponsor in writing immediately after the 
implementation. 
17.2. 
Ethical Conduct of the Study 
The study will be conducted in accordance with the Declaration of Helsinki on Ethical Principles 
for Medical Research Involving Human Subjects, adopted by the General Assembly of the World 
Medical Association (2008). 
In addition, the study will be conducted in accordance with the protocol, the International 
Conference on Harmonisation (ICH) guideline on Good Clinical Practice (GCP), and applicable 
local regulatory requirements and laws. 
17.3. 
Subject Information and Consent 
All parties will ensure protection of subject personal data and will not include subject names on 
any sponsor forms, reports, publications, or in any other disclosures, except where required by 
laws. In case of data transfer, the sponsor will maintain high standards of confidentiality and 
protection of subject personal data. 
The ICF must be in compliance with ICH GCP, local regulatory requirements, and legal 
requirements. 
The ICF used in this study, and any changes made during the course of the study, must be 
prospectively approved by both the IRB/IEC and the sponsor before use. 
The investigator must ensure that each study subject, or his/her legally acceptable representative, 
is fully informed about the nature and objectives of the study and possible risks associated with 
participation.  The investigator, or a person designated by the investigator, will obtain written 
informed consent from each subject or the subject's legally acceptable representative before any 
study-specific activity is performed.  The investigator will retain the original of each subject's 
signed ICF and a copy provided to each subject. 


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17.4. 
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP 
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
Competent Authority in any area of the World, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, the sponsor should be informed immediately.   
In addition, the investigator will inform the sponsor immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of any 
serious breaches of this protocol or of ICH GCP that the investigator becomes aware of. 


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18. 
DATA HANDLING AND RECORDKEEPING 
18.1. 
Case Report Forms 
As used in this protocol, the term eCRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study. 
An eCRF is required and should be completed for each included subject.  The completed original 
eCRFs are the sole property of the sponsor and should not be made available in any form to third 
parties, except for authorized representatives of the sponsor or appropriate regulatory authorities, 
without written permission from the sponsor. 
The investigator has ultimate responsibility for the accuracy, authenticity, and timely collection 
and reporting of all clinical, safety, laboratory data entered on the eCRFs and any other data 
collection forms.  The eCRFs must be signed by the investigator to attest that the data contained 
on the eCRFs is true.  Any corrections to entries made on the eCRFs must be dated, initialed, and 
explained (if necessary) and should not obscure the original entry. 
In most cases, the source documents are the hospital's or the physician's subject chart. In these 
cases, data collected on the eCRFs must match the data in those charts.  
In some cases, the eCRF, or part of the eCRF, may also serve as source documents. In these 
cases, a document should be available at the investigator’s site as well as at the sponsor and 
clearly identify those data that will be recorded on the eCRF, and for which the eCRF will stand 
as the source document. 
18.2. 
Record Retention 
To enable evaluations and/or audits from regulatory authorities or the sponsor, the investigator 
agrees to keep records, including the identity of all participating subjects (sufficient information 
to link records, eg, eCRFs and hospital records), all original signed ICFs, copies of all eCRFs, 
SAE forms, source documents, and detailed records of treatment disposition, and adequate 
documentation of relevant correspondence (eg, letters, meeting minutes, telephone calls reports). 
The records should be retained by the investigator according to ICH, local regulations, or as 
specified in the Clinical Study Agreement, whichever is longer. 
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), the sponsor should be prospectively notified. The 
study records must be transferred to a designee acceptable to the sponsor, such as another 
investigator, another institution, or to the sponsor.  The investigator must obtain the sponsor's 
written permission before disposing of any records, even if retention requirements have been 
met. 


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19. 
PUBLICATION POLICY 
Publication of study results is discussed in the Clinical Study Agreement. 
19.1. 
Publications by Investigators 
All information concerning the product, as well as any matter concerning the operation of the 
sponsor or its delegate, such as clinical indications for the drug, its formula, methods of 
manufacture, and other scientific data relating to it, that have been provided by the sponsor or its 
delegate and are unpublished, are confidential and must remain the sole property of the sponsor 
or its delegate.  The Investigator will agree to use the information only for the purposes of 
carrying out this study and for no other purpose unless prior written permission from the sponsor 
or its delegate is obtained.  The sponsor has full ownership of the eCRFs completed as part of the 
study. 
All publications and presentations of the results of the Study are governed by the applicable 
provisions of the Clinical Trial Agreement between the sponsor (or its delegate) and the 
institution.  By signing the study protocol, the investigator agrees that the results of the study 
may be used for the purposes of national and international registration, publication, and 
information for medical and pharmaceutical professionals by the sponsor or its delegate.  If 
necessary, the authorities will be notified of the Investigator’s name, address, qualifications, and 
extent of involvement.  The Investigator may not publish or present any information on this 
study without the express written approval of the sponsor or its delegate.  Additionally, the 
sponsor or its delegate may, for any reason, withhold approval for publication or 
presentation.  Such manuscript or materials should be provided for sponsor/delegate review only 
after the final database, is available. 
 


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20. 
LIST OF REFERENCES (ALPHABETICAL) 
AXER-204 [Investigator’s Brochure] Version #2.0. New Haven, CT: ReNetX Bio, Inc. 2020 
Brinker T, Stopa E, Morrison J, Klinge P. A new look at cerebrospinal fluid circulation. Fluids 
Barriers CNS. 2014;11:10. 
Cafferty WB, Duffy P, Huebner E, Strittmatter SM. MAG and OMgp synergize with Nogo-A to 
restrict axonal growth and neurological recovery after spinal cord trauma. J Neurosci. 
2010;30(20):6825–6837. 
Catz A, Itzkovich M, Tesio L, et al. A multicenter international study on the Spinal Cord 
Independence Measure, version III: Rasch psychometric validation. Spinal Cord. 
2007;45(4):275–291. 
Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med 
Singapore. 1994;23(2):129–38. 
Cockcroft DW, Gault H. Prediction of creatinine clearance from serum creatinine. Nephron 
1976;16(1): 31-41. 
Fawcett JW, Curt A, Steeves JD, et al. Guidelines for the conduct of clinical trials for spinal cord 
injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and 
statistical power needed for therapeutic clinical trials. Spinal Cord. 2007;45(3):190–205. 
Guidance for industry on estimating the maximum safe starting dose in initial clinical trials for 
therapeutics in adult healthy volunteers. US Department of Health and Human Services, Food 
and Drug Administration, Center for Drug Evaluation and Research Web site. 
https://www.fda.gov/downloads/Drugs/Guidances/UCM078932.pdf%23search=%27guidekines+
for+industry+sfe+starting%27 Updated July 2005. Accessed Aug 10, 2018.  
Harvey PA, Lee DHS, Qian F, Weinreb PH, Frank E. Blockade of Nogo receptor ligands 
promotes functional regeneration of sensory axons after dorsal root crush. J Neurosci. 
2009;29(19):6285–6295. 
Hladky SB, Barrand MA. Mechanisms of fluid movement into, through and out of the brain: 
evaluation of the evidence. Fluids Barriers CNS. 2014;11(1):26. 
Itzkovich M, Gelernter I, Biering-Sorensen F, et al., The Spinal Cord Independence Measure 
(SCIM) version III: reliability and validity in a multi-center international study. Disabil Rehabil. 
2007;29(24):1926–1933. 
Ji B, Li M, Budel S, et al. Effect of combined treatment with methylprednisolone and soluble 
Nogo-66 receptor after rat spinal cord injury. Eur J Neurosci. 2005;22(3):587–594. 
Kalsi-Ryan S, Beaton D, Curt A, et al. The Graded Redefined Assessment of Strength Sensibility 
and Prehension: reliability and validity. J Neurotrauma. 2012;29(5):905–1014. 
Kalsi-Ryan S, Curt A, Verrier MC, Fehlings MG. Development of the Graded Redefined 
Assessment of Strength, Sensibility and Prehension (GRASSP): reviewing measurement specific 
to the upper limb in tetraplegia. J Neurosurg Spine. 2012;17(1 Suppl):65–76. 
Krassioukov A, Biering-Sørensen F, Donovan W, et al., International standards to document 
remaining autonomic function after spinal cord injury. J Spinal Cord Med. 2012;35(4):201–310. 


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Kroin JS. Intrathecal drug administration. Present use and future trends. Clin Pharmacokinet. 
1992;22(5):319–326. 
Kuttler A, Dimke T, Kern S, Helmlinger G, Stanski D, Finelli LA. Understanding 
pharmacokinetics using realistic computational models of fluid dynamics: biosimulation of drug 
distribution within the CSF space for intrathecal drugs. J Pharmacokinet Pharmacodyn. 
2010;37(6):629–644. 
Lee JK, Kim JE, Sivula M, Strittmatter SM. Nogo receptor antagonism promotes stroke recovery 
by enhancing axonal plasticity. J Neurosci. 2004;24(27):6209–6217. 
Li S, Liu BP, Budel S, et al. Blockade of Nogo-66, myelin-associated glycoprotein, and 
oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting 
and recovery after spinal injury. J Neurosci. 2004;24(46):10511–10520. 
Liu BP, Cafferty WBJ, Budel SO, Strittmatter SM. Extracellular regulators of axonal growth in 
the adult central nervous system. Philos Trans R Soc Lond B Biol Sci. 
2006;361(1473):1593-1610. 
Marino RJ, Kern SB, Leiby B, Schmidt-Read M, Mulcahey MJ. Reliability and validity of the 
capabilities of upper extremity test (CUE-T) in subjects with chronic spinal cord injury. J Spinal 
Cord Med. 2015;38(4):498–504. 
Marino RJ, Patrick M, Albright W, et al., Development of an objective test of upper-limb 
function in tetraplegia: the capabilities of upper extremity test. Am J Phys Med Rehabil. 
2012;91(6):478–486. 
Masserman JH. Cerebrospinal hydrodynamics: IV. clinical experimental studies. Arch Neur 
Psych. 1934;32(3):523–553. 
NSCISC Spinal Cord Injury, Facts and Figures at a Glance. National Spinal Cord Injury 
Statistical Center Web site. https://www.nscisc.uab.edu/Public/Facts%20and%20Figures%20-
%202018.pdf Accessed Aug 10, 2018.  
Ohtake Y, Li S. Molecular mechanisms of scar-sourced axon growth inhibitors. Brain Res. 
2015:1619:22–35. 
OMNIPAQUE™ (iohexol) Injection Drug Approval Package. US Department of Health and 
Human Services, Food and Drug Administration Web site. 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/018956s095,020608s031lbl.pdf. 
Updated July 1993. Accessed Aug 10, 2018.  
Pandyan AD, Johnson GR, Price CI, Curless RH, Barnes MP, Rodgers H. A review of the 
properties and limitations of the Ashworth and modified Ashworth Scales as measures of 
spasticity. Clin Rehabil. 1999;13(5):373–383. 
Papisov MI, Belov VV, Gannon KS. Physiology of the intrathecal bolus: the leptomeningeal 
route for macromolecule and particle delivery to CNS. Mol Pharm. 2013;10(5):1522–1532. 
https://www.rand.org/health/surveys_tools/mos/36-item-short-form.html Updated 2018. 
Accessed Aug 10, 2018.  
Rieselbach RE, Di Chiro G, Freireich EJ, Rall DP. Subarachnoid distribution of drugs after 
lumbar injection. N Engl J Med. 1962;267:1273–1278. PubMed PMID:  13973811 


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Rieselbach RE, Morse EE, Rall DP, Frei E 3rd, Freireich EJ. Treatment of Meningeal leukemia 
with intrathecal aminopterin. Cancer Chemother Rep. 1962 Feb;16:191-6. PubMed PMID: 
14492194. 
Rieselbach RE, Morse EE, Rall DP, Frei E 3rd, Freireich EJ. Intrathecal aminopterin therapy of 
meningeal leukemia. Arch Intern Med. 1963 May;111:620-30.  PubMed PMID: 13973810. 
Sakka L, Coll G, Chazal J. Anatomy and physiology of cerebrospinal fluid. Eur Ann 
Otorhinolaryngol Head Neck Dis. 2011;128(6):309–316. 
Schwab ME, Strittmatter SM. Nogo limits neural plasticity and recovery from injury. Curr Opin 
Neurobiol. 2014;27:53–60. 
Sharma K, Selzer ME, Li S. Scar-mediated inhibition and CSPG receptors in the CNS. Exp 
Neurol. 2012;237(2):370–378. 
SPINRAZATM (nusinersen) injection, for intrathecal use. US Department of Health and Human 
Services, Food and Drug Administration Web site. 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/209531lbl.pdf, Updated 2016. 
Accessed Aug 10, 2018.  
Thorne RG, Frey WH 2nd. Delivery of neurotrophic factors to the central nervous system: 
pharmacokinetic considerations. Clin Pharmacokinet. 2001;40(12):907–946. 
Wang X, Baughman KW, Basso DM, Strittmatter SM. Delayed Nogo receptor therapy improves 
recovery from spinal cord contusion. Ann Neurol. 2006;60(5):540–549. 
Wang X, Duffy P, McGee AW, et al., Recovery from chronic spinal cord contusion after Nogo 
receptor intervention. Ann Neurol. 2011;70(5):805–821. 
Wang X, Yigitkanli K, Kim CY, et al. Human NgR-Fc decoy protein via lumbar intrathecal 
bolus administration enhances recovery from rat spinal cord contusion. J Neurotrauma. 
2014;31(24):1955–1966. 
Wang X, Zhou T, Maynard GD, et al. Nogo receptor decoy promotes recovery and corticospinal 
growth in non-human primate spinal cord injury. Brain. 2020 Jun 1;143(6):1697-1713. 
 


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21. 
INVESTIGATORS AGREEMENT 
 
I have read the protocol, RNX-AX204-101 and agree to conduct this trial in accordance with all 
stipulations of the protocol and in accordance with International Conference on Harmonisation 
(ICH) and all applicable local Good Clinical Practice (GCP) guidelines, including the 
Declaration of Helsinki.  I agree to maintain the confidentiality of all information received or 
developed in connection with this protocol.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical Institution 
 
 
 
 
 
 
 
 
Date 

SAP_001.pdf: 
 CONFIDENTIAL 
Statistical Analysis Plan 
A Multicenter, Two Part (Open-Label Single-
Ascending Dose Followed by Double-Blind, Placebo-
Controlled Repeat Dose) Study to Evaluate the 
Safety, Tolerability, Pharmacokinetics, and Efficacy 
of AXER-204 in Subjects with Chronic Spinal Cord 
Injury (the RESET* Study) 
*RESET- Chronic SCI Study. ReNetX Safety Efficacy and
Tolerability of AXER-204 for Chronic SCI 
ReNetX Bio, Inc 
PROTOCOL RNX-AX204-101  
 Study ID: 000000169744 
Document Version: Version 5.0 Final 
Document Date: 05AUG2022
NCT03989440


Statistical Analysis Plan 
Sponsor Name: ReNetX Bio, Inc 
Sponsor Protocol ID: RNX-AX204-101 
 
 Study ID: 000000169744 
 
 CONFIDENTIAL 
Document Date: 05 August 2022 
 
Page 2 of 56 
 
 
ST-AD-008 version 04 
 
Table of Contents 
 
Glossary of Abbreviations ................................................................................ 7 
1. 
Source Documents ................................................................................. 8 
2. 
Protocol Details ..................................................................................... 8 
2.1 
Study Objectives................................................................................. 8 
2.1.1 
Part 1 Single Ascending Dose ................................................................................................ 9 
2.1.2 
Part 2 Placebo-Controlled Repeat Dose ................................................................................ 9 
2.2 
Overall Study Design ......................................................................... 10 
2.2.1 
Part 1 ................................................................................................................................... 11 
2.2.2 
Part 2 ................................................................................................................................... 12 
2.3 
Sample Size ..................................................................................... 13 
2.3.1 
Part 1 ................................................................................................................................... 13 
2.3.2 
Part 2 ................................................................................................................................... 13 
3. 
Efficacy and Safety Variables................................................................. 14 
3.1 
Efficacy Variables .............................................................................. 14 
3.1.1 
Part 1 ................................................................................................................................... 14 
3.1.2 
Part 2 ................................................................................................................................... 15 
3.2 
Safety Variables................................................................................ 28 
4. 
Pharmacokinetic variables ..................................................................... 28 
5. 
Immunogenicity variables ..................................................................... 29 
6. 
Analysis Population .............................................................................. 29 
6.1 
All Randomized Set (Part 2) ............................................................... 29 
6.2 
Safety Population (Part 1 and Part 2) .................................................. 29 
6.3 
Full Analysis Set (Part 1) ................................................................... 29 
6.4 
Modified Intent to Treat Analysis set (Part 2) ........................................ 29 
6.5 
PK Analysis Set (Part 1 and Part 2) ..................................................... 29 
6.6 
Antidrug Antibody Analysis Set (Part 1 and Part 2) ................................ 30 
6.7 
Per Protocol Set (Part 2 only) ............................................................. 30 


Statistical Analysis Plan 
Sponsor Name: ReNetX Bio, Inc 
Sponsor Protocol ID: RNX-AX204-101 
 
 Study ID: 000000169744 
 
 CONFIDENTIAL 
Document Date: 05 August 2022 
 
Page 3 of 56 
 
 
ST-AD-008 version 04 
 
7. 
DATA Handling .................................................................................... 30 
7.1 
Time points ...................................................................................... 30 
7.2 
Visit Window (Part 2) ........................................................................ 30 
7.3 
Handling of Dropouts and Missing Data ................................................ 31 
7.3.1 
Handling of Missing or Incomplete Dates ........................................................................... 31 
7.3.2 
Handling of Missing Efficacy Endpoints .............................................................................. 32 
7.4 
Handling of Randomization Error (Part 2) ............................................. 32 
8. 
Statistical Methods ............................................................................... 32 
8.1 
General Principles ............................................................................. 32 
8.2 
Subject Disposition and Data Sets Analyzed ......................................... 33 
8.3 
Protocol Deviations ........................................................................... 34 
8.4 
Demographics and Other Baseline Characteristics ................................. 34 
8.4.1 
Demographic and baseline characteristics ......................................................................... 34 
8.4.2 
Medical History ................................................................................................................... 35 
8.4.3 
Previous and Concomitant Medications ............................................................................. 35 
8.5 
Efficacy ............................................................................................ 36 
8.5.1 
Part 1 ................................................................................................................................... 36 
8.5.2 
Part 2 ................................................................................................................................... 37 
8.6 
Pharmacokinetic Assessment .............................................................. 41 
8.6.1 
Pharmacokinetic Analysis ................................................................................................... 41 
8.6.2 
Presentation of Pharmacokinetic Data ............................................................................... 45 
8.7 
Immunogenicity Analysis ................................................................... 45 
8.8 
Safety ............................................................................................. 46 
8.8.1 
Extent of Exposure .............................................................................................................. 46 
8.8.2 
Adverse Events .................................................................................................................... 46 
8.8.3 
Laboratory Evaluations ....................................................................................................... 48 
8.8.4 
Vital Signs ............................................................................................................................ 49 
8.8.5 
Electrocardiograms ............................................................................................................. 50 
8.8.6 
Physical Examination ........................................................................................................... 51 


Statistical Analysis Plan 
Sponsor Name: ReNetX Bio, Inc 
Sponsor Protocol ID: RNX-AX204-101 
 
 Study ID: 000000169744 
 
 CONFIDENTIAL 
Document Date: 05 August 2022 
 
Page 4 of 56 
 
 
ST-AD-008 version 04 
 
8.8.7 
Condition-specific Safety Variables (Part 1 and Part 2) ...................................................... 51 
8.9 
Interim Analysis................................................................................ 51 
9. 
Changes from the Protocol Specified Statistical Analyses .......................... 52 
9.1 
Secondary efficacy endpoint ............................................................... 52 
9.2 
Exploratory efficacy endpoint ............................................................. 52 
9.3 
Analysis population ........................................................................... 52 
10. 
Changes in the Planned Statistical Analyses ............................................ 52 
10.1 Post Hoc Exploratory Analysis for Efficacy Endpoints to Study Day 169 .... 53 
10.2 Post Hoc Exploratory Analysis for Efficacy Endpoints to Study Day 253 .... 54 
10.3 Clarifications to Pre Hoc Slope Analysis ................................................ 54 
11. 
References .......................................................................................... 55 
 
 
 
 


Statistical Analysis Plan 
Sponsor Name: ReNetX Bio, Inc 
Sponsor Protocol ID: RNX-AX204-101 
 
 Study ID: 000000169744 
 
 CONFIDENTIAL 
Document Date: 05 August 2022 
 
Page 5 of 56 
 
 
ST-AD-008 version 04 
 
Approvals  
The undersigned agree that all required reviews of this document are complete, and 
approve this Statistical Analysis Plan as final.  Programming of the tables, figures and 
listings based upon the specifications within this document can proceed. 
Approved by 
 Lead Statistician Approval 
 
 
 
 
 
Signature 
 
Date 
 
 Biostatistician 2 
Printed Name/Title 
 
 Pharmacokineticist Approval 
 
 
 
 
 
Signature 
 
Date 
 
 Director, Pharmacokinetics 
Printed Name/Title 
 
ReNetX Approval: 
 
 
 
 
 
Signature 
 
Date 
 
George D. Maynard, President and Chief Scientific Officer, ReNetX Bio, Inc. 
Printed Name/Title 
 
 
 
Digitally signed by George D. Maynard 
Date: 2022.08.05 12:00:19 -04'00'


Statistical Analysis Plan 
Sponsor Name: ReNetX Bio, Inc 
Sponsor Protocol ID: RNX-AX204-101 
 
 Study ID: 000000169744 
 
 CONFIDENTIAL 
Document Date: 05 August 2022 
 
Page 6 of 56 
 
 
ST-AD-008 version 04 
 
Reviewers 
The following reviews of the SAP were conducted: 
 
Version History  
Version # 
Description of Changes 
Version Date 
V1.0 
Initial 
31Jan2020 
V2.0 
Updated Section 5 and 8.7 to include 
ADA analysis  
09Jun2020 
V3.0 
Updated to include analysis for part 2 of 
the study 
09Sep2021 
V4.0 
Updated to move random coefficients 
model as secondary efficacy analysis, to 
include intercurrent events strategy for 
primary and secondary efficacy 
endpoints, and Section 7.4 for handling 
of randomization error 
08Mar2022 
V5.0 
Updated Section 10 for changes in the 
planned statistical analyses 
 
05Aug2022 
 
 
 
Name and Title  
 Role 
Version Last 
Reviewed 
Company/ 
Organization 
, Associate 
Director, Biostatistics 
Peer Review 
Statistician 
Version 4/5 
 
, Director, Biostatistics 
Peer Review 
Statistician 
Version 1/2 
 
, Principal 
Statistical Programmer 
Lead Programmer 
Version 
1/2/4/5 
 
 
Director, 
Pharmacokinetics 
Version 1/4 
 
 
Senior Medical Director Version 2/4 
 
George Maynard 
Study Director 
Version 
1/2/4/5 
ReNetX 
Gilbert Block 
Chief Medical Officer 
Version 2/4/5 
ReNetX 
Stephen Strittmatter 
Medical Consultant 
Version 1 
ReNetX 


Statistical Analysis Plan 
Sponsor Name: ReNetX Bio, Inc 
Sponsor Protocol ID: RNX-AX204-101 
 
 Study ID: 000000169744 
 
 CONFIDENTIAL 
Document Date: 05 August 2022 
 
Page 7 of 56 
 
 
ST-AD-008 version 04 
 
Glossary of Abbreviations 
Abbreviation 
Term 
ADA 
Anti-drug antibody 
ADL 
Activities of daily living 
AE 
Adverse event 
AIS 
American spinal injury association (ASIA) impairment scale 
AR(1) 
Autoregressive 
ARH(1) 
Autoregressive with heterogeneity 
ASIA 
American spinal injury association 
ATC 
Anatomical therapeutic chemical 
BMI 
Body mass index 
bpm 
Beats per minute 
BP 
Blood pressure 
BPI 
Brief pain inventory 
CGIC 
Clinical Global Impression of Change 
CI 
Confidence interval 
CS 
Compound symmetry 
CSCI 
Chronic spinal cord injury 
CSF 
Cerebrospinal fluid 
CTCAE 
Common terminology criteria for adverse events 
CUE-Q 
Capabilities of upper extremity questionnaire 
CV 
Coefficient of variation 
DSMB 
Data and safety monitoring board 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
ET 
Early termination 
FAS 
Full analysis set population 
FDA 
Food and drug administration 
GRASSP 
Graded redefined assessment of strength sensation and prehension 
HR 
Heart rate 
ICH 
International Conference on Harmonization 
ISAFSCI 
International standards to document remaining autonomic function after 
spinal cord injury 
ISNCSCI 
International standards for neurological classification of SCI 
LEMS 
Lower extremity motor score 
LS 
Least squares 
MAR 
Missing at random 
MAS 
Modified Ashworth scale 
MedDRA 
Medical dictionary for regulatory activities  
mITT 
Modified Intent to Treat 
MMRM 
Mixed-effects model for repeated measures 
MNAR 
Missing not at random 
msec 
Millisecond 
MTD 
Maximum tolerated dose 
NCA 
Non-compartmental approach 
Neuro-QOL 
Quality of life in neurological disorders 


Statistical Analysis Plan 
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Sponsor Protocol ID: RNX-AX204-101 
 
 Study ID: 000000169744 
 
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Document Date: 05 August 2022 
 
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Abbreviation 
Term 
NLI 
Neurological level of injury 
PA 
Prehension ability 
PCS 
Potentially clinically significant 
PGIC 
Patient Global Impression of Change 
PK 
Pharmacokinetics 
PP 
Prehension performance 
PPS 
Per Protocol Set 
PT 
Preferred term 
QoL 
Quality of life 
QTcF 
QT interval using Fridericia correction formula 
ROM 
Range of motion 
SAE 
Serious Adverse Event 
SCI 
Spinal cord injury  
SCIM III 
Version III of the spinal cord independence measure 
SD 
Standard deviation 
SF-36 
Short form - 36 v2 health survey 
SF-6D 
Short form six-dimension 
SF-6D_R2 
Short form six-dimension release 2 
SOC 
System organ class 
TEAE 
Treatment-emergent adverse event 
TOEP 
Toeplitz 
TOEPH 
Toeplitz with heterogeneity 
TFLs 
Tables, figures and listings 
UEMS 
Upper extremity motor score 
WHO 
World health organization 
ZPP 
Zone of Partial Preservation 
1. Source Documents 
The Statistical Analysis Plan was written based on the following documentation: 
Document 
Date 
Version 
Protocol 
01Oct2020 
V4.0 
eCRF 
21JAN2021 
V3.0 
2. Protocol Details 
2.1 
Study Objectives 
Study RNX-AX204-101 is a two-part (Parts 1 and 2) study that will be run 
sequentially. Each part has unique objectives. The start of Part 2 will also be 
contingent on Data and Safety Monitoring Board (DSMB) review of data from Part 
1.  


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2.1.1 Part 1 Single Ascending Dose 
2.1.1.1 
Primary Objective  
To evaluate the safety, tolerability, and pharmacokinetics (PK) of ascending, single 
intrathecal lumbar slow bolus infusions of AXER-204 in subjects with chronic spinal 
cord injury (CSCI). 
2.1.2 Part 2 Placebo-Controlled Repeat Dose 
2.1.2.1 
Primary Objective  
x 
To evaluate the safety and tolerability of repeat intrathecal lumbar slow bolus 
infusions of AXER-204 compared to placebo in subjects with CSCI. 
x 
To evaluate the PK of repeat doses of AXER-204 in subjects with CSCI. 
2.1.2.2 
Secondary Objectives  
x 
To assess the efficacy of repeat dose therapy of AXER-204 compared to placebo 
on function and activities of daily living (ADL) measures as assessed by: 
o Primary Efficacy Objective:  
 
International Standards for Neurological Classification of SCI 
(ISNCSCI) Upper Extremity Motor Score (UEMS) 
o Secondary Efficacy Objectives: 
 
Graded Redefined Assessment of Strength, Sensation and 
Prehension (GRASSP) prehension performance 
 
Version III of the Spinal Cord Independence Measure (SCIM III) 
self-care 
 
Patient Global Impression of Change (PGIC) – Chronic SCI  
2.1.2.3 
Exploratory Objectives 
x 
To evaluate the efficacy of repeat dose therapy of AXER-204 compared to 
placebo as assessed by the following: 
o ISNCSCI UEMS for the side with the higher baseline score and the side 
with the lower baseline score 
o ISNCSCI total motor and sensory scores   
o GRASSP strength, sensation and prehension ability scores 
o SCIM III mobility scores 
o International Standards to document remaining Autonomic Function after 
Spinal Cord Injury (ISAFSCI) 
o Patient Reported Outcomes 
 
CUE-Questionnaire (CUE-Q). Assesses subject-reported upper limb 
function. 


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 
SF-36 v2. Provides a patient-reported Quality of Life (QoL) 
assessment. SF-36 will provide data on the subjects' perceived 
health and well-being over the course of the study. 
 
Neuro-QOL Item Bank v1.0 – Upper Extremity Function (Fine 
Motor, ADL) 
 
Clinical Global Impression of Change (CGIC) from GRASSP 
Prehension Performance Video Recordings 
o Modified Ashworth Scale (MAS) for spasticity. 
o Brief Pain Inventory (BPI) mean Pain score and mean activity interference 
score 
x 
Exploratory biomarkers of target engagement and axonal growth may be 
assessed.  
2.2 
Overall Study Design 
Study RNX-AX204-101 is a two-part study that will be run sequentially. Each Part 
will be conducted at approximately 5 centers in the United States.  
For each Part, eligible subjects will be between the ages of 18 to 65 years inclusive, 
male or female, with a traumatic spinal cord injury that occurred at least 1 year 
prior to the screening date, and with significant neurologic impairment of the hands 
and arms. Subjects who participated in Part 1 may be evaluated for enrollment in 
Part 2 provided at least 6 months will have elapsed between the dose received in 
Part 1 and the initiation of dosing in Part 2. 
The study will be analyzed separately for Part 1 and Part 2 as illustrated in Figure 1. 
All Part 1 outputs will be created when Part 1 is finished and database for Part 1 is 
locked. For Part 2, when all enrolled patients have completed the 6-month visit, 
data will be cleaned and locked and then unblinded to be analyzed for the primary 
and secondary efficacy endpoints to compare treatment effects from baseline to 
Study Day 169. Although the data will be unblinded for 
 and ReNetX staff, 
the raters, patients and primary investigators will remain blinded until final 
database lock following Study Day 253.  All safety summaries will also be created. 
When all patients have completed Study Day 253 visits, the database will be locked 
and all outputs including analysis for treatment effect on study day 253 will be 
created including all data points from start of the Part 2 to end of study for patients 
enrolled in Part 2.  
 
 


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Figure 1 
Sequence of Data Analyses 
 
2.2.1 Part 1 
Part 1 is a multicenter, open-label, single ascending dose study in subjects with 
CSCI. Four cohorts of 6 subjects each are planned, with subjects within each cohort 
expected to receive the same dose of AXER-204. Up to 24 subjects will be enrolled 
in Part 1. If the Maximum Tolerated Dose (MTD) is reached prior to the fourth 
cohort, the sponsor may enroll the remaining subjects (up to a total enrollment of 
24 for the study) to obtain further data at the tolerated dose levels. The sponsor in 
conjunction with the investigators and medical monitor will determine dose 
escalation.  
The starting dose is 3 mg. Dose escalation will proceed to 30 mg, 90 mg, 200 mg 
contingent on safety and tolerability. Dosing volumes will be given as follows: 
x 
Cohort 1: 3 mg, 10 mL 
x 
Cohort 2: 30 mg, 10 mL 
x 
Cohort 3: 90 mg, 9 mL 
x 
Cohort 4: 200 mg, 20 mL 
Study participation for each subject in Part 1 is expected to be up to 16 weeks in 
duration, with up to an 84-day screening period, a 3-day in-clinic treatment period, 
and a follow-up period through 29 days post-dose:  
x 
Screening (up to 84 days prior to Study Day 1). Subjects have 84 days from 
the time of signing informed consent to complete their screening 
assessments and, if needed, their washout period for prohibited concomitant 
medications.   However, clinical laboratory tests required for screening must 
be completed within 28 days prior to Study Day 1. 


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x 
Treatment period: Check-in Day 1, administration of study drug, 3-night in-
clinic stay, and discharge on Day 4 following the completion of all scheduled 
procedures.  
x 
Follow-up: Subjects will have follow-up visits for up to 29 days post-dose as 
follows: subjects will receive a phone call on Study Days 5, 6 and 7 to inquire 
about their general health and will return to the clinic for visits on Study Day 
8 (± 1 day), Study Day 15 (±3 days) and Study Day 29 or Early Termination 
(ET) (± 4 days).  
2.2.2 Part 2 
Part 2 is a multicenter, randomized, double-blind, placebo-controlled, repeat dose 
study in CSCI subjects. Approximately 32 subjects will be randomized (ratio 1:1) to 
receive AXER-204 or placebo (an isotonic phosphate buffered saline formulation). 
Subject to review of the safety, tolerability, and pharmacokinetic data from Part 1 
and DSMB approval, the dose will be 200 mg given once every 3 weeks for 15 
weeks as outlined in the schedule of events. Subject to DSMB approval, the dose 
may be reduced to 90 mg and the dose interval may be modified based on data 
from Part 1 but is not expected to be less than once every 14 days or more than 28 
days. Subject to DSMB approval, the dose and dose frequency may also be 
adjusted during Part 2 based on emergent safety and tolerability data. 
Study participation for each subject in Part 2 is expected to be up to 337 days in 
duration, with up to an 84-day screening period, a 104-day treatment period, and 
then post treatment follow-ups at Study Days 137, 169, and 253: 
x 
Screening (within 84 days prior to Day 1). Subjects have 84 days from the 
time of signing informed consent to complete their screening assessments 
and, if needed, their washout period for prohibited concomitant medications. 
The screening laboratory tests must be completed within 28 days prior to 
Study Day 1. 
x 
Treatment Period (15 weeks). Investigational product given approximately 
every 21 days for up to 104 days per subject. A telephone call to assess 
status regarding any adverse events will be conducted on Study Day 8 (±3 
days). 
o Eligible subjects will be randomized to either AXER-204 or to placebo. 
The randomization will be stratified based on pre-treatment American 
Spinal Injury Association Impairment Scale (AIS) grade (AIS A,B vs. 
AIS C,D) and prior receipt of study drug in Part 1 (Received AXER-204 
in Part 1 vs. Did not receive AXER-204 in Part 1). The pre-treatment 
AIS grade is determined on Visit 2, Day 1. 


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x 
Follow-up (21 weeks). Following the last Treatment Period dose of 
investigational product or Early Termination of dosing, a telephone call to 
assess status regarding any adverse events will be conducted on Study Day 
137 (± 7 days) and two follow-up visits will occur at Study Days 169 (± 7 
days) and 253 (± 7 days). 
2.3 
Sample Size  
2.3.1 Part 1 
The Part 1 sample size of 24 (6 subjects per dose) was derived empirically from 
experience with previous single ascending dose clinical studies in other disorders 
and is deemed appropriate to achieve the study objectives, with adequate exposure 
to assess safety for dose selection in Part 2.  
2.3.2 Part 2 
The Part 2 sample size of approximately 32 subjects was selected with the goal of 
ensuring adequate power for detecting meaningful treatment-related change in 
bilateral Upper Extremity Motor Score, UEMS (Score from 0 to 50).  Little or no 
spontaneous improvement in motor score is expected in people with chronic SCI, 
more than one year from injury (i.e. 'UEMS = 0) (Fawcett et al. 2007). As shown 
in Table 1, we have targeted detection of 5-point improvement in UEMS (and 
possibly less) as functionally relevant in the chronic cervical SCI patients recruited 
to this study. The potential impact of missing data and a correction for non-normal 
distribution of the data are not included in these estimates. 
Table 1 
Estimated power as a function of enrollment, effect size, and 
normal variability of the outcome measure (' UEMS) 
' UEMS = 5 
' UEMS = 4 
' UEMS = 3 
Enrollment 
SD = 3 
SD = 4 
SD = 3 
SD = 4 
SD = 3 
SD = 4 
32 
99% 
96% 
95% 
78% 
78% 
53% 
26 
98% 
92% 
90% 
68% 
68% 
45% 
20 
94% 
85% 
80% 
56% 
56% 
35% 
SD = Standard deviation of the change in UEMS 
Based on 2 sided D = 0.05 using NQuery (Version 4.0).  
 
' UEMS: A smaller improvement in 'UEMS (e.g. 2 points) could be clinically 
meaningful if it occurred in a muscle group essential for a particular activity of daily 
living such as grasping in the chronic SCI population.  A 3-point improvement in 


Statistical Analysis Plan 
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UEMS has been identified as the minimum clinically important difference in acute 
cervical SCI patients (Scivoletto et al. 2013).  Although a minimum clinically 
important difference in UEMS has not been determined for chronic SCI patients, 
chronic SCI patients may have greater awareness of personal benefit resulting from 
changes due to their stable baseline function (Wu et al. 2015).   
Standard Deviation (SD):  Although we estimated SD of 3 and 4, the data from the 
23 patients evaluated at screening and Day 29 in Part 1 of this trial yielded a SD for 
'UEMS of 2.0 which may be more representative of variability in our patient 
population and the rater consistency attained in the trial that may provide us with 
even higher power. 
3. Efficacy and Safety Variables 
3.1 
Efficacy Variables 
3.1.1 Part 1 
3.1.1.1 
Primary Efficacy Endpoints 
Not applicable. 
3.1.1.2 
Secondary Efficacy Endpoints 
Not applicable. 
3.1.1.3 
Other Efficacy Endpoints 
In Part 1, the following efficacy assessments will be collected in eCRF and will be 
summarized descriptively: 
x 
International Standards for Neurological Classification of SCI (ISNCSCI) motor 
and sensory scores. The ISNCSCI scale includes a motor and sensory 
examination for each side of the body (left/right). Higher values indicate better 
function with the maximum scores corresponding to normal function. 
The following 4 subscores will be summarized:  
o Upper Extremity Motor Score (UEMS) with scores ranging from 0-50; 
o Lower Extremity Motor Score (LEMS) with scores ranging from 0-50; 
o Pin Prick Sensory Score with scores ranging from 0-112; 
o Light Touch Sensory Score with scores ranging from 0-112. 
x 
Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) 
scores (Kalsi-Ryan et al. 2012a, Kalsi-Ryan et al. 2012b). The GRASSP is a 
clinical impairment measure for the upper limbs through three domains 


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(strength, sensation and prehension) that are important in describing arm and 
hand function. Higher scores indicate better function.  
The following 4 subscores will be summarized:  
o Strength total scores (left and right) with scores ranging from 0-50 for 
each side; 
o Sensation total scores (left and right) with scores ranging from 0-12 for 
each side; 
o Prehension Ability total scores (left and right) with scores ranging from 0-
12 for each side; 
o Prehension Performance total scores (left and right) with scores ranging 
from 0-20 for each side.     
x 
Spinal Cord Independence Measure (SCIM III) self-care and mobility domain 
scores (Catz et al. 2007, Itzkovich et al. 2007). The SCIM III is a questionnaire 
evaluating activities of daily living (ADL) regarding self-care, mobility, and 
respiration and sphincter management. Higher scores correspond to better 
ability to carry out ADL. The current study will employ the self-care and mobility 
subscores. 
The following 2 subscores will be summarized:  
o Self-care with scores ranging from 0-20;  
o Mobility with scores ranging from 0-40. 
The following efficacy assessments collected in eCRF will be listed: 
x 
Additional items from the ISNCSCI: neurological level for sensory and motor for 
right and left, neurological level of injury, American Spinal Injury Association 
(ASIA) impairment scale, and zone of partial preservation for right and left;  
x 
Data collected for the following additional measures: SF-36 Health Survey, 
Neuro-QOL Upper Extremity Function, International standards to document 
remaining autonomic function after spinal cord injury (ISAFSCI).   
3.1.2 Part 2 
The ICH E9 (R1) addendum on estimands and sensitivity analysis in clinical trials to 
the guideline on statistical principles for clinical trials came into effect on 30 July 
2020. This section addresses the construction of estimands for the primary and 
secondary efficacy objectives. Each estimand is defined according to the following 
five attributes: 
x 
The treatment condition of interest, and as appropriate, the alternative 
condition to which comparison will be made. 
x 
The population of subjects targeted by the clinical question. 


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x 
The variable (or endpoint) to be obtained for each subject that is required to 
address the clinical question. 
x 
The clinical question of interest in respect of other intercurrent events not 
covered through the precise specifications of treatment, population and 
variable. 
x 
A population-level summary for the variable providing a basis for 
comparison between treatment conditions. 
The primary efficacy and secondary efficacy endpoints were selected as the best 
available to provide assessments of changes in motor function, ability to carry out 
activities of daily living, and any important changes related to the patient’s 
condition of chronic SCI.  A brief description and rationale for each is as follows: 
3.1.2.1 
Estimand for the Primary Efficacy Endpoint: Bilateral Upper 
Extremity Motor Score (UEMS) 
The primary estimand is the change from baseline in ISNCSCI Bilateral Upper 
Extremity Motor Score (UEMS) to Study Day 169 between AXER-204 and placebo in 
patients with chronic spinal cord injury (CSCI). 
UEMS is the primary efficacy measure and represents the upper extremity 
component of the International Standards for Neurological Classification of Spinal 
Cord Injury (ISNCSCI) motor exam.  Although historically a total motor score of 
100 for all extremities was calculated, for the last decade it has not been 
recommended to add the upper limb and lower limb scores together. Examination 
of the metric properties of the motor score indicates that it should be separated 
into two scales, one composed of the 5 upper limb muscle functions on left and 
right, and one of the 5 lower limb muscle functions left and right, with a maximum 
score of 50 each (Marino and Graves 2004, Graves et al. 2006).   
Based on the expected mechanism of action of AXER-204 and the focus on subjects 
with cervical cord injury, the upper limb score has been selected as the primary 
endpoint measure. The overall motor score remains part of the exploratory 
analyses.  Similarly, other recent SCI therapeutic intervention clinical trials have 
included change in UEMS as the primary efficacy endpoint (Fehlings et al. 2018, 
Levi et al. 2019). 
The ISNCSCI is the most well-established and validated scale of motor and sensory 
function in spinal cord injury treatment and rehabilitation. ISNCSCI assessments 
are standardized by the governing body American Spinal Injury Association in 
conjunction with the International Spinal Cord Society. The UEMS portion of the 
ISNCSCI evaluates muscle strength controlled by five myotomes on each side of 


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the body. The muscles tested, the corresponding levels, and the expected 
functional relevance of each level are illustrated in Table 2.  
Table 2 
UEMS:  Neurological Levels, Muscles, Functional Importance for 
Activities of Daily Living 
Spinal Level   Muscle 
group 
Personal 
Independence 
Wheelchair 
Management 
Transfers 
C5  
Elbow 
flexors  
Type, feed 
Manipulate brake, 
push on the flat 
 
C6  
Wrist 
extensors 
Drink, wash, shave, 
dress upper body 
Remove 
armrests/ 
footplates 
From chair to 
bed or car 
C7  
Elbow 
extensors 
Turn in bed, dress 
lower body 
Wheel over 
uneven ground 
From chair to 
toilet or chair 
or bath 
C8  
Finger 
flexors 
Bladder and bowel 
care 
Negotiate curbs 
From chair to 
bath 
T1  
 
Small finger 
abductors 
 
Balance on rear 
wheels 
From chair to 
floor 
Adapted from van Hedel and Curt (van Hedel and Curt 2006). 
 
Scoring: Each muscle is given a score between 0 and 5 as follows (Rupp et al. 
2021): 
0 = Total paralysis 
1 = Palpable or visible contraction 
2 = Active movement, full range of motion (ROM) with gravity eliminated 
3 = Active movement, full ROM against gravity 
4 = Active movement, full ROM against moderate resistance in a muscle specific 
position 
5 = (Normal) active movement, full ROM against full resistance in a muscle-
specific position expected from an otherwise unimpaired person 
Figure 2 is provided to visually show the impact of each neurological level and the 
muscle groups impacted.  The inclusion criteria for the trial selects a functionally 
homogenous group of patients in terms of impaired arm and hand function 
controlled by spinal cord nerves at the C5-T1 levels (UEMS =4-36, GRASSP PP = 4-
17). Of note, this means that the trial enrolls subjects with cervical level injury with 
neurologically complete and incomplete injuries and spanning all ASIA impairment 
scale grades (A, B, C, D) for patients with SCI.   


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Figure 2 
Illustration of Muscles Tested in UEMS and Controlling Spinal 
Neurologic Levels 
 
The minimum clinically important change for bilateral UEMS has been estimated to 
be 3-points for acute and subacute SCI patients with a mean time from injury of 
52 days (Scivoletto et al. 2013). In general, cervical SCI patients with a clinically 
important change in UEMS also improved functionally.  This correlation between 
change in UEMS and function may be anticipated given the muscle groups 
evaluated in the test and their utility for carrying out activities of daily living.    
UEMS typically remains stable for chronic SCI patients, it is anticipated that even 
small changes may be considered significant from the perspective of patients (Wu 
et al. 2015).   
Thus, change in ISNCSCI UEMS provides a robust and well-established measure of 
muscle function with relevance to functional changes for patients. 
3.1.2.1.1 
Treatment Condition of Interest 
The treatment condition of interest is AXER-204 administered every 21 days, and is 
compared against the alternative treatment condition of placebo administered every 
21 days. 


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3.1.2.1.2 
Population 
The population is subjects with chronic spinal cord injury (CSCI) defined through 
the inclusion and exclusion criteria as part of the clinical trial protocol version 4.0. 
3.1.2.1.3 
Endpoint 
The endpoint is the change from baseline in ISNCSCI Bilateral Upper Extremity 
Motor Score (UEMS) to Study Day 169. 
3.1.2.1.4 
Handling of Intercurrent Events 
The following intercurrent events are anticipated during the study. Table 3 
describes how intercurrent events will be collected and handled within the analysis. 
Table 3  
Handling of Intercurrent Events for the Primary Estimand 
Intercurrent event 
Data collection and analysis 
Important protocol deviation, 
including use of prohibited 
medication, prior to assessment 
scheduled on Study Day 169 
Patients will be followed and data 
collected after the intercurrent event will 
be used in analysis in line with the 
treatment policy strategy, i.e. regardless 
of the intercurrent event. 
Did not receive at least 5 doses 
(~80%) of the planned cumulative 
number of doses of treatment 
Did not perform at least one post-
baseline assessment 
Patients who experienced the 
intercurrent event will be excluded from 
analysis in line with a principal stratum 
strategy. 
Discontinuation from the study prior 
to assessment scheduled on Study 
Day 169 
Patient’s measurements up until the time 
of the intercurrent event will be used in 
analysis in line with the while on 
treatment policy, i.e. the endpoint is only 
evaluable in patients who complete the 
assessment scheduled on Study Day 169. 
 
3.1.2.1.5 
Population-level Summary for Comparison between 
Treatment Conditions 
The treatment effect will be the difference between AXER-204 and placebo in 
estimated least squares means of change from baseline in ISNCSCI Bilateral UEMS 
at Study Day 169 as estimated through a mixed-effects model for repeated measures 
(MMRM) as defined in section 8.5.2.1. 


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3.1.2.1.6 
Sensitivity Estimand for the Primary Efficacy Objective 
The robustness of the assumptions of the primary estimand will be evaluated 
through the use of a sensitivity estimand through the following alternative approach 
to intercurrent events (Table 4). 
Table 4  
Handling of Intercurrent Events for the Sensitivity Estimand for 
the Primary Efficacy Objective 
Intercurrent event 
Data collection and analysis 
Important protocol deviation, 
including use of prohibited 
medication, prior to assessment 
scheduled on Study Day 169 
Patients who experienced the 
intercurrent event will be excluded from 
analysis in line with a principal stratum 
strategy. 
Did not receive at least 5 doses 
(~80%) of the planned cumulative 
number of doses of treatment 
Did not perform at least one post-
baseline assessment 
Discontinuation from the study prior 
to assessment scheduled on Study 
Day 169 
Patient’s measurements up until the time 
of the intercurrent event will be used in 
analysis in line with the while on 
treatment policy, i.e. the endpoint is only 
evaluable in patients who complete the 
assessment scheduled on Study Day 169. 
 
3.1.2.2 
Estimand for 1st Secondary Efficacy Endpoint: Bilateral 
Prehension Performance (PP) 
One of the secondary estimands is change from baseline in GRASSP Bilateral 
prehension performance (PP) total score to Study Day 169 between AXER-204 and 
placebo in patients with chronic spinal cord injury (CSCI). 
The Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP 
V2) prehension performance sub-scale assesses performance of four tasks that 
mimic everyday activities of daily living.  Patients are asked to 1) pour water from a 
bottle into a cup, 2) pull 9 pegs one-by-one out of holes on one side of a board and 
insert them into holes on the opposite side, 3) pick up a key, insert it into a lock 
and turn the key, and 4) pick up 4 nuts, one-by-one, and screw them onto 
matching screws.  The required grasping pattern for each of the four tasks is 
illustrated in Figure 3. 


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Figure 3 
GRASSP Prehension Performance Illustration   
 
Scores are assigned as follows: 
0: The task cannot be conducted at all 
1: The task cannot be completed, (less than 50% of the task) 
2: The task is not completed, (50% or more of the task) 
3: The task is conducted (completed) using tenodesis or an alternative grasp 
other than the expected grasp. 
4: The task is conducted using the expected grasp with difficulty (lack of 
smooth movement or difficult slow movement) 
5: The task is conducted without difficulties using the expected grasping 
pattern and unaffected hand function 
 
Each task must be completed within 75 seconds and the number of drops is 
recorded.  Each side is tested and the scores combined to obtain the bilateral score.  
There is a substantial concurrence between GRASSP prehension performance and 
activities of daily living from a patient perspective (Kalsi-Ryan et al. 2019). 
Accordingly, GRASSP prehension performance provides an objective, clinician-
evaluated measure of function in performing activities of daily living. 
3.1.2.2.1 
Treatment Condition of Interest 
The treatment condition of interest is the same as section 3.1.2.1.1. 
3.1.2.2.2 
Population 
The population is the same as section 3.1.2.1.2. 


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3.1.2.2.3 
Endpoint 
The endpoint is the change from baseline in GRASSP Bilateral prehension 
performance (PP) score to Study Day 169. 
3.1.2.2.4 
Handling of Intercurrent Events 
The intercurrent events strategy is the same as section 3.1.2.1.4. 
3.1.2.2.5 
Population-level Summary for Comparison between 
Treatment Conditions 
The treatment effect is the same as section 3.1.2.1.5, except the endpoint is as 
described in section 3.1.2.2.3. 
3.1.2.2.6 
Sensitivity Estimand for the 1st Secondary Efficacy 
Objective 
The sensitivity estimand is the same as section 3.1.2.1.6. 
3.1.2.3 
Estimand for 2nd Secondary Efficacy Endpoint: SCIM III Self 
Care 
One of the secondary estimands is change from baseline in SCIM III Self Care score 
to Study Day 169 between AXER-204 and placebo in patients with chronic spinal 
cord injury (CSCI). 
The Spinal Cord Independence Measure, Version III (SCIM III) questionnaire has 
been widely used to assess performance of activities of daily living. It relies on 
patient responses to 17 questions across three domains: self-care, respiration and 
sphincter management, and mobility. This study is collecting data for self-care and 
mobility and self-care has been selected as a secondary efficacy measure based on 
the expectation that the change in this domain will be most reflective of changes in 
arm and hand function being measured with the primary efficacy measure of 
change in ISNCSCI UEMS. 
The self-care sub-scale is comprised of four questions to determine the level of 
independence in feeding, bathing (upper body, lower body), dressing (upper body, 
lower body), and grooming with a possible score of 0-20 points. 
The SCIM III minimal clinically important difference has not been determined for 
patients with chronic SCI.   
3.1.2.3.1 
Treatment Condition of Interest 
The treatment condition of interest is the same as section 3.1.2.1.1. 


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3.1.2.3.2 
Population 
The population is the same as section 3.1.2.1.2. 
3.1.2.3.3 
Endpoint for the Secondary Estimand 
The endpoint is the change from baseline in SCIM III Self Care score to Study Day 
169. 
3.1.2.3.4 
Handling of Intercurrent Events 
The intercurrent events strategy is the same as section 3.1.2.1.4. 
3.1.2.3.5 
Population-level Summary for Comparison between 
Treatment Conditions 
The treatment effect is the same as section 3.1.2.1.5, except the endpoint is as 
described in section 3.1.2.3.3. 
3.1.2.3.6 
Sensitivity Estimand for the 2nd Secondary Efficacy 
Objective 
The sensitivity estimand is the same as section 3.1.2.1.6. 
3.1.2.4 
Estimand for 3rd Secondary Efficacy Endpoint: Patient Global 
Impression of Change (PGIC) 
One of the secondary estimands is Patient Global Impression of Change (PGIC) 
responder rate at Study Day 169 between AXER-204 and placebo in patients with 
chronic spinal cord injury (CSCI). 
 
The PGIC instrument captures the patient’s overall evaluation of response to 
treatment. Specifically, the PGIC asks: “Since beginning this clinical trial, how 
would you describe the overall change (if any) related to your chronic spinal cord 
injury?” The patient is asked to report the degree to which they have changed since 
entering the treatment period using a 7-point Likert scale (1= ‘Much worse’, 
2=‘Worse’, 3=‘ A little worse’, 4=‘No change’, 5=‘A little better’, 6=‘Better, 
7=‘’Much better’) and “If better or worse, what has changed?”. Patients that have 
evaluation results including “Much better”, “Better”, or “A little better” at Study Day 
169 are considered Responders.  This provides a global assessment from the 
patient’s perspective and may capture anticipated and unanticipated changes that 
occur during the study. 
 
Overall, these scales administered by trained raters in this double blinded, placebo-
controlled study will provide a reliable assessment of treatment-related changes 
from baseline in upper extremity motor function, including performance of activities 
of daily living, and capture any changes related to the patient’s own assessment of 
their chronic SCI.   


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Rater Training:  Given the importance of these measures to assess functional 
changes, activities of daily living and clinical relevance, ReNetX established a 
comprehensive training for raters across all measures including certification directly 
from the groups that developed and standardized these measures.   
3.1.2.4.1 
Treatment Condition of Interest 
The treatment condition of interest is the same as section 3.1.2.1.1. 
3.1.2.4.2 
Population 
The population is the same as section 3.1.2.1.2. 
3.1.2.4.3 
Endpoint 
The endpoint is the Patient Global Impression of Change (PGIC) responder rate at 
Study Day 169. Patients that have evaluation results including “Much better”, 
“Better”, or “A little better” are considered Responders, whereas patients that have 
evaluation results including “Much worse”, “Worse”, “A little worse”, or “No change” 
are considered Non-Responders. 
3.1.2.4.4 
Handling of Intercurrent Events 
The intercurrent events strategy is the same as section 3.1.2.1.4. 
3.1.2.4.5 
Population-level Summary for Comparison between 
Treatment Conditions 
The treatment effect will be the difference between AXER-204 and placebo in 
percentages of PGIC responder rate at Study Day 169 as estimated through a Fisher’s 
Exact Test as defined in section 8.5.2.2. 
3.1.2.4.6 
Sensitivity Estimands for the 3rd Secondary Efficacy 
Objective 
The first sensitivity estimand is the same as section 3.1.2.1.6. Another sensitivity 
estimand will follow an alternative approach to intercurrent events (Table 5). 
 
 


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Table 5  
Handling of Intercurrent Events for the Sensitivity Estimand for 
the 3rd Secondary Efficacy Objective 
Intercurrent event 
Data collection and analysis 
Important protocol deviation, 
including use of prohibited 
medication, prior to assessment 
scheduled on Study Day 169 
Patients will be followed and data 
collected after the intercurrent event will 
be used in analysis in line with the 
treatment policy strategy, i.e. regardless 
of the intercurrent event. 
Did not receive at least 5 doses 
(~80%) of the planned cumulative 
number of doses of treatment 
Did not perform at least one post-
baseline assessment 
Patients who experienced the 
intercurrent event will be excluded from 
analysis in line with a principal stratum 
strategy. 
Discontinuation from the study prior 
to assessment scheduled on Study 
Day 169 
Among patients who experienced the 
intercurrent event, the intercurrent event 
will be integrated in the response 
variable in line with the composite 
variable strategy, i.e. considered to be 
Non-Responder (4=‘No change’). 
 
3.1.2.5 
Exploratory Efficacy Endpoints 
3.1.2.5.1 
Change from baseline to Study Day 169 
o ISNCSCI Unilateral UEMS of the side with higher baseline scores ranging 
from 0-25. For each patient, choose the side with higher baseline 
unilateral UEMS score and all post-baseline value and change from 
baseline values for the same side will be analyzed.  If the baseline scores 
for each side are equal, then the right side will be grouped with the higher 
baseline UEMS scores for analysis. 
o ISNCSCI Unilateral UEMS of the side with lower baseline scores ranging 
from 0-25. If the baseline scores for each side are equal, then the left 
side will be grouped with the lower baseline UEMS scores for analysis. The 
analysis will be similar to the one with higher baseline UEMS scores as 
described above. 
o ISNCSCI Bilateral Motor score (including both upper and lower extremity 
for both left and right sides) with scores ranging from 0-100.  
o ISNCSCI Bilateral Sensory score - light touch (sum of right total and left 
total) with scores ranging from 0-112.  


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o ISNCSCI Bilateral Sensory score – pin prick (sum of right total and left 
total) with scores ranging from 0-112.  
o GRASSP Bilateral Strength score (sum of score from left and right) with 
scores ranging from 0-100.  
o GRASSP Bilateral Sensation total score (sum of score from left and right) 
with scores ranging from 0-24.  
o GRASSP Bilateral Prehension Ability (PA) total scores (sum of score from 
left and right) with scores ranging from 0-24.  
o SCIM III mobility score (see section 3.1.1 for details) with scores ranging 
from 0-40.  
o CUE – Questionnaire (CUE-Q) total score with scores ranging from 0-128. 
CUE-Q contain 17 questions each on a scale of 0 to 4 to assess subject 
reported upper limb function for both arms or hands including Ability to 
reach or lift, Ability to pull and push with arms, Moving and positioning 
arm and wrist, and Using hands and fingers.   
o Neuro-QoL upper extremity function t-score, with overall raw score 
ranging from 20-100. Neuro-QoL upper extremity function questionnaire 
consist 20 questions to assess upper extremity function (fine motor or 
ADL). All questions are rated on a 1- to 5-point verbal rating scale with 
higher score associated with better function.   
o SF-36 score. SF-36 V2 provides a patient-reported QoL assessment on 
subjects’ perceived health and well-being over the course of the study. 
The following derived scales will be determined (Optum PRO CoRE): 
x 
Bodily Pain  
x 
General Health 
x 
Mental Health 
x 
Mental Component  
x 
Physical Component 
x 
Physical Functioning 
x 
Social Functioning 
x 
Role Emotional  
x 
Role Physical 
x 
Vitality 
x 
SF-6D (Utility Index)  
x 
SF-6D_R2 (Utility Index Release 2)  
 


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3.1.2.5.2 
Other exploratory efficacy endpoints 
x 
ISNCSCI ASIA impairment scale (AIS) with scales including A, B, C, D, E 
(protocol Appendix 3) at Study Day 169. 
x 
ISNCSCI Neurological Motor level at Study Day 169. 
x 
ISNCSCI Neurological Sensory level at Study Day 169. 
x 
ISNCSCI Neurological Level of Injury (NLI) at Study Day 169. 
x 
ISAFSCI assessments at Study Day 169. The ISAFSCI documents autonomic 
control of the heart, blood pressure, sweating and temperature regulation with 
findings equal to one of the following values: Normal, Abnormal, Unknown, or 
Unable to assess. Scores for lower urinary tract, bowel or sexual function will 
also be collected whereas score 0= complete loss of control; 1= Reduced or 
Altered Neurological Function; 2 = Normal function; NT=Unable to assess. 
x 
Clinical Global Impression of Change (CGIC) from GRASSP Prehension 
Performance Video Recordings.  Details are included below as this measure has 
been added beyond specific information included in the protocol. Conducted by a 
blinded rater who is trained on the scales and also has a C5/C6 injury to provide 
the perspective of the patient population we intend to treat with our therapy:  
Given the importance of this measure for functional, ADL as well as 
patient/clinically relevant changes, the GRASSP prehension performance 
assessment is video recorded at each time point to visually document changes 
reflected in the scoring as well as changes that may or may not be captured on 
the scale.   
 
CGIC Evaluation 
 
Compared to baseline, how would you describe the overall change (if any) 
related to performance of the GRASSP prehension performance tasks? 
Choose ONE. 
  
Much worse (1) 
  
Worse (2) 
  
A little worse (3) 
  
No change (4) 
  
A little better (5) 
  
Better (6) 
  
Much better (7) 
If better or worse, what has changed?   
 


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With the exception of the CGIC, all efficacy endpoints will also be analyzed for 
Study Day 253. 
3.2 
Safety Variables 
The following safety variables will be included for both Part 1 and Part 2: 
x 
Study treatment exposure; 
x 
Treatment-emergent adverse events (TEAEs); 
x 
Clinical laboratory tests including hematology, clinical chemistry, and urinalysis; 
x 
Physical examinations; 
x 
Vital signs; 
x 
12-lead electrocardiograms (ECGs); 
x 
Condition-specific safety outcomes, including the following: 
o Spasticity. Modified Ashworth Scale (MAS) (Pandyan et al. 1999) is a 
clinician administered examination for spasticity which measures muscle 
tone around selected limb joints. The total MAS score will be calculated 
and summarized for both part 1 and part 2. In addition, for part 2, 
bilateral total scores for Elbow, Wrist, Hamstrings, Quadriceps, 
Gastrocnemius, and Soleus will be analyzed to compare between 
treatment group with control group. 
o Pain. Brief Pain Inventory (BPI) (Cleeland and Ryan 1994) is a self-
administered questionnaire used to assess the severity of a subject's pain 
and the impact of this pain on the subject's daily functioning. The 
following scores will be calculated and summarized:  
 
BPI pain severity for each of the four severity items (“worst,” 
“least,” “average,” and “now”). For part 2, mean BPI pain score at 
Study Day 169 and change from baseline will be analyzed to 
compare treatment group with control group. 
 
BPI pain interference. For part 2, mean BPI pain interference score 
at Study Day 169 and change from baseline will be analyzed to 
compare treatment group with control group. 
4. Pharmacokinetic variables 
x 
Serum and CSF samples will be collected and analyzed for concentrations of 
AXER-204 at planned time points following the schedules for Part 1 or Part 2, 
as described in the protocol.   
x 
Pharmacokinetic (PK) parameters will also be determined (section 8.6.1) 
using a non-compartmental approach (NCA) for Part 1. 


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5. Immunogenicity variables 
Pre-dose Anti-drug antibody (ADA) serum will be collected for ADA analysis for both 
Part 1 and Part 2 following the protocol defined schedule. The following 
immunogenicity variables will be analyzed: 
x 
Anti-drug antibody (ADA) incidence 
6. Analysis Population 
6.1 
All Randomized Set (Part 2) 
The All Randomized Set will consist of all randomized Part 2 subjects. Subjects will 
be analyzed according to their randomized treatment. 
6.2 
Safety Population (Part 1 and Part 2) 
The Safety Population will consist of all subjects treated with at least one dose of 
study treatment. Safety outcomes will be assessed using the Safety Population. For 
Part 2, safety outcomes, including the condition-specific safety outcomes as 
described in section 8.8.7, will be analyzed according to their actual treatment 
received. 
6.3 
Full Analysis Set (Part 1) 
The Full Analysis Set (FAS) will consist of all subjects who had at least one dose of 
study treatment and at least one post-baseline ISNCSCI assessment in Part 1. 
Efficacy outcomes in Part 1 will be summarized using FAS. 
6.4 
Modified Intent to Treat Analysis set (Part 2) 
The Modified Intent to Treat (mITT) Analysis Set consist of all Part 2 subjects who 
were randomized and had at least one dose of study treatment and at least one post-
baseline ISNCSCI assessment. Efficacy outcomes for Part 2 will be evaluated using 
the mITT analysis set. Subjects will be analyzed according to their randomized 
treatment. 
6.5 
 PK Analysis Set (Part 1 and Part 2) 
The PK Analysis Set will include all subjects who received at least 1 dose of study 
drug and had evaluable PK data.  All protocol deviations that occur during the study 
will be considered for their severity/impact and will be taken into consideration 
when subjects are assigned to the PK analysis set. PK analysis will be conducted for 
PK analysis set. Subjects will be analyzed according to their randomized treatment.   


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6.6 
Antidrug Antibody Analysis Set (Part 1 and Part 2) 
The Antidrug Antibody (ADA) Analysis Set will include all subjects who received at 
least 1 dose of study treatment and had at least one post-baseline ADA. This 
analysis set will be used to summarize ADA results. Subjects will be analyzed 
according to their randomized treatment. 
6.7 
Per Protocol Set (Part 2 only) 
The Per Protocol Set (PPS) will be a subset of mITT and consist of subjects who 
received at least 5 doses (~80%) of the planned cumulative number of doses of study 
drug and have no important protocol deviations that might impact efficacy 
assessment. 
The important protocol deviations leading to exclusion from the PPS may include but 
not limited to the following: violation of key inclusion/exclusion criteria, use of 
prohibited medications as defined by the study protocol or in discussion with the 
Sponsor and/or medical monitor, errors in treatment allocation, etc. All important 
protocol deviations leading to exclusion from the PPS will be reviewed and approved 
by the Sponsor prior to database lock and unblinding. Subjects will be analyzed 
according to their randomized treatment.    
7. DATA Handling 
7.1 
Time points  
Day 1 is defined as the day of the first study treatment administration. Relative days 
after Day 1 are calculated as (assessment date – Day 1 date) + 1. Relative days prior 
to Day 1 are calculated as (assessment date – Day 1 date). The day prior to Day 1 is 
Day -1.  
For Part 1, all data will be analyzed using nominal study visits as defined in the Study 
Schedule in the protocol and eCRF. Data collected at unscheduled visits will not be 
included in summary tables but will be listed only, unless specified otherwise. 
7.2 
Visit Window (Part 2) 
For part 2, time windows will be defined for both safety and efficacy assessments 
for summaries and values by visit as well as efficacy analysis. All data for 
unscheduled and scheduled visits have the potential to be included in the summary 
and analysis based on the actual date. The window for the visits following baseline 
will be constructed according to the following convention: the upper limit of the 
interval falls half way between the 2 visits if odd number of days exists between 
two consecutive visits. If an even number of days exists between two consecutive 


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visits then the upper limit will be taken as the midpoint value minus 1 days. For 
example, the visit windows for ISNCSCI assessment are: 
x 
Day 1, visit window NA 
x 
Day 21, visit window 2 – 42 
x 
Day 63, visit window 43 – 83 
x 
Day 104, visit window 84 – 136 
x 
Day 169, visit window 137 – 211 
x 
Day 253, visit window 212 – end of study 
If there is more than one value within a visit window then the closest value to the 
scheduled visit date will be included in the summary and analysis. If 2 events are 
equal distance from the scheduled visit date then the event with earlier date will be 
selected for analysis. For listings, all visits including unscheduled visits will be 
displayed by collected visit name. 
7.3 
Handling of Dropouts and Missing Data 
Except for the data specified below, missing data will not be imputed.  
7.3.1 Handling of Missing or Incomplete Dates 
Incomplete dates (partial or missing dates) for adverse event (AE) and 
prior/concomitant medications will be imputed. The imputed dates will be used to 
determine treatment-emergent AEs or prior/concomitant medications. The subject 
data listings will present the observed data without imputation. 
x 
For partial start dates:  
o If day is missing, then if the month and year of the event are the same 
as the month and year of treatment start date, the treatment start date 
will be imputed as the date; otherwise the first day of the month will be 
imputed;  
o If month and day are missing, then if the year of the event is the same 
as the year of treatment start date, the treatment start month and day 
will be imputed as the date; otherwise, 01JAN will be imputed. 
x 
For partial stop dates,  
o if day is missing, then if the month and year of the event are the same 
as the month and year of treatment end date, the treatment end date 
will be imputed as the date; otherwise the last day of the month is 
imputed.  
o If month and day are missing, then if the year of the event is the same 
as the year of treatment end date, the treatment end month and day 
will be imputed for the date; otherwise, 31DEC will be imputed. 
x 
For dates completely missing, no imputation will be done. 


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7.3.2 Handling of Missing Efficacy Endpoints  
For subjects who discontinue treatment (for any reason), subjects will continue to 
be followed and efficacy endpoints, data are collected where possible. 
In situations where the efficacy endpoints are missing, all available data will be 
analyzed with a mixed-effects model for repeated measures (MMRM) as described 
in section 8.5.2.1. To evaluate robustness of results, sensitivity analyses will be 
performed with imputation methods for missing data as described in section 
8.5.2.1.2. 
7.4 
Handling of Randomization Error (Part 2) 
Eligible Part 2 patients will be randomized to either AXER-204 or to placebo. The 
randomization will be stratified based on pre-treatment American Spinal Injury 
Association Impairment Scale (AIS) grade (AIS A,B vs. AIS C,D) and prior receipt of 
study drug in Part 1 (Received AXER-204 in Part 1 vs. Did not receive AXER-204 in 
Part 1). 
For patients who were classified differently based on AIS grade or prior receipt of 
study drug in Part 1 at pre-treatment compared to their stratified randomization 
assignment, any such inconsistencies will be documented as randomization errors 
and protocol deviations. In any such cases, pre-treatment value will be used in 
preference to the stratified randomization value for TFL reporting. 
8. Statistical Methods 
8.1 
General Principles 
x 
All data processing, summarization and analyses will be performed using 
 SAS Environment / Version 9.4 (or later) of the SAS statistical 
software package. 
x 
The following principles will be applied to all TFLs unless otherwise stated: 
Table 6 
Statistical Analysis General Principles 
Principle 
Value 
Significant tests 
 
Two sided and use a 5% significance level  
Treatment group labels and order 
presented 
Part 1: AXER-204 xx mg 
Part 2: AXER-204 200 mg; Placebo 
Tables 
Data in summary tables presented by dose 
cohort/treatment group, assessment (where 
applicable), and visit (where applicable). 


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Principle 
Value 
Listings 
All data collected presented by dose 
cohort/treatment group, subject, and visit (where 
applicable), unless otherwise specified.  
Descriptive summary statistics for 
continuous variables 
Number of subjects (N), mean, standard deviation 
(SD), median, minimum, maximum.  
Descriptive summary statistics for 
categorical variables 
Frequency counts and percentages [n (%)] 
Denominator for percentages 
Number of subjects in the analysis population, 
unless otherwise specified. 
Include “Missing” as category 
Yes, when the number missing is greater than zero 
for at least one dose cohort/treatment group. 
Display for percentage 
One decimal place, except for 100% 
Display for 0 percentages 
0 
Display to one more decimal place 
than collected value 
Mean, Median, Mean Difference 
Display to two more decimal 
places than collected value 
Standard Deviation 
Limit of precision for displays 
3 decimal places 
Date Format 
DDMMMYYYY 
TFL orientation 
Landscape 
TFL output 
For all tables and listings, 2.54 cm for the 
top/bottom/left/right margins and 8-point Courier 
New font 
 
x 
For both safety and efficacy analysis, the baseline value will be defined as the 
last non-missing value before the first dose of study treatment.  
8.2 
Subject Disposition and Data Sets Analyzed  
For Part 1, subject disposition will be listed and summarized by dose cohort and 
overall for the Safety population and will include the number and percentage of 
subjects that are included in each study population (Safety Population, FAS, PK 
analysis set, and ADA analysis set). For Part 2, subject will be listed and 
summarized by treatment group and overall for the All Randomized Set and will 
include the number and percentage of subjects included in each study population 
(Safety Population, mITT, PK analysis set, ADA analysis set, and PPS).  


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In addition, the number and percentage of subjects who complete the study and who 
discontinue early, including a breakdown of the primary reasons for discontinuation, 
will be presented. 
8.3 
Protocol Deviations 
All protocol deviations for Part 1 will be listed. 
For Part 2, Protocol deviation will be identified prior to database lock and unblinding. 
All protocol deviations will be listed. All important protocol deviations that impact the 
interpretation of efficacy outcome measures, leading to exclusion from the PPS, will 
be summarized by treatment group and overall for the mITT. Number and percentage 
of subjects with at least one important protocol deviations including a breakdown of 
type of protocol deviations will be summarized. 
8.4 
Demographics and Other Baseline Characteristics 
8.4.1 Demographic and baseline characteristics 
Demographic and baseline characteristics will be listed and summarized by dose 
cohort and overall for the Safety population. Standard descriptive statistics will be 
presented for the continuous variables of: 
x 
Age (years); 
x 
Weight (kg); 
x 
Height (cm); 
x 
Body mass index (BMI) (kg/m2); 
x 
Time from injury (months), calculated as (date of the first dose of study 
treatment – date of injury)/30.4375, date of injury will be obtained from the 
demographics eCRF page.   
BMI recorded in pounds and inches will be re-calculated as the following: BMI(kg/m2) 
= BMI(lb/in2) * 703. 
The total counts and percentages of subjects will be presented for the categorical 
variables of: 
x 
Gender (Female, Male); 
x 
Race (American Indian Or Alaska Native, Asian, African American, Native 
Hawaiian Or Other Pacific Islander, White, Other); 
x 
Ethnicity (Hispanic or Latino, Not Hispanic or Latino, Unknown); 
x 
Reproductive status (Fertile, Menopause, Sterilized, Unknown, Other); 


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x 
Injury ASIA Impairment Scale (A, B, C, D obtained from the ISNCSCI eCRF 
at screening; 
x 
Neurological level of injury (C2, C3, C4, C5, C6, C7, C8, T1, T2), obtained 
from the ISNCSCI eCRF at screening; 
x 
Cause of Spinal Cord Injury (Part 2 only) using the categories adopted by the 
National Spinal Cord Statistical Center. 
Other baseline measurements, such as vital signs, will be summarized with the post-
baseline measurements. 
For Part 2, Demographic and baseline characteristics will be listed and summarized 
by treatment group and overall for the Safety population. The same list of 
demographic and baseline characteristics as those specified for Part 1 will be 
summarized by treatment group and overall. In addition, number and percentage of 
subjects who received study drug in Part 1 will be also summarized. 
8.4.2 Medical History 
Medical history will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) [Version 22.0 (or a later version if updated during the study)].  
All medical history will be listed, and the number and percentage of subjects with any 
medical history will be summarized for the Safety population by system organ class 
(SOC) and preferred term (PT) for each dose cohort for Part 1 (or for each treatment 
group for Part 2) and overall. Subjects with more than one medical history within a 
particular SOC are counted only once for that SOC. Similarly, subjects with more than 
one medical history within a particular PT are counted only once for that PT. Tables 
will be sorted in descending overall frequency by SOC, and then in descending overall 
frequency by PT within SOC, and then alphabetically. 
8.4.3 Previous and Concomitant Medications 
Medications received prior to or concomitantly with treatment will be coded by 
 using the World Health Organization (WHO) Drug Dictionary [Version: Global 
B3-March 2019 (or a later version if updated during the study)] Anatomical 
Therapeutic Chemical (ATC) Classification codes.  
Prior medications and concomitant medications are defined as follows: 
x 
Prior medications are those with a start date and a stop date prior to the first 
dose date of study treatment;  
x 
Concomitant medications are those with a start date on or after the first dose 
date of study treatment, or those with a start date before the first dose date 
of study treatment and a stop date on or after the first dose date of study 
treatment or ongoing at the end of study;  


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x 
New-onset medications are concomitant medications with a start date after the 
first dose of study treatment. New-onset medications are a subset of the full 
set of concomitant medications. 
If a medication cannot be classified as “prior” or “concomitant” after applying 
imputation rules for missing/incomplete dates, it will be classified as concomitant. 
Prior medications and concomitant medications will be listed together and 
summarized separately for the Safety population by dose cohort for Part 1 (or by 
treatment group for Part 2) and overall. 
The number and percentage of subjects using any medication will be displayed 
together with the number and percentage of subjects using at least one medication 
within each therapeutic class (ATC-Level 2) and generic term. Tables will be sorted 
in descending overall frequency by the ATC level and in descending overall frequency 
by generic term, and then alphabetically.  
8.5 
Efficacy 
8.5.1 Part 1 
All efficacy data will be listed. The following efficacy endpoints will be summarized 
by dose cohort and overall, and by visit using standard descriptive statistics for the 
FAS, changes from baseline will be also summarized: 
x 
ISNCSCI upper extremity motor total score, obtained from eCRF;  
x 
ISNCSCI lower extremity motor total score, obtained from eCRF; 
x 
ISNCSCI pin prick sensory total score, obtained from eCRF; 
x 
ISNCSCI light touch sensory total score, obtained from eCRF; 
x 
GRASSP strength total score, calculated as the sum of the total strength 
score for the right side and the total strength score for the left side; 
x 
GRASSP sensation total score, calculated as the sum of the total sensation 
score for the right side and the total sensation score for the left side; 
x 
GRASSP prehension ability total score, calculated as the sum of the total 
prehension ability score for the right side and the total prehension ability 
score for the left side; 
x 
GRASSP prehension performance total score, calculated as the sum of the 
total prehension performance score for the right side and the total 
prehension performance score for the left side; 
x 
SCIM III self-care total score, obtained from eCRF; 
x 
SCIM III mobility total score, obtained from eCRF. 


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8.5.2 Part 2 
8.5.2.1 
Primary Efficacy Endpoint and Primary Efficacy Analysis  
The primary efficacy endpoint is the change from baseline in bilateral UEMS to 
Study Day 169. 
The null and alternative hypothesis for this endpoint are as follows: 
H0: μA= μP 
HA: μA≠ μP 
Where H0 and HA refer to the Null and alternative hypothesis to be tested, μA and μP 
refers to the mean change in bilateral UEMS from baseline to Study Day 169 for 
subjects randomized to AXER-204 and Placebo groups, respectively.  
Primary analysis to compare the change from baseline in bilateral UEMS to Study 
Day 169 will be based upon a mixed-effects model for repeated measures (MMRM) 
using the mITT. 
The MMRM model will include treatment (AXER-204 vs. Placebo), all post-baseline 
visits up until Study Day 169 (Study day 21, 63, 104, and 169), treatment-by-visit 
interaction, AIS grade (A, B vs C, D), and prior receipt of study drug in Part 1 (yes 
vs. no) as the fixed categorical effects, the baseline bilateral UEMS measurement as 
a covariate, and treatment-by-baseline UEMS interaction.   
An unstructured covariance structure will be used to model the within-patient 
errors. If this analysis fails to converge, the following covariance structures will be 
tested in order, and the first covariance structure that converges will be used: 
x 
toeplitz with heterogeneity (TOEPH) 
x 
autoregressive with heterogeneity (ARH(1) ) 
x 
compound symmetry with heterogeneous variances (CSH) 
x 
toeplitz (TOEP) 
x 
autoregressive (AR(1) ) 
x 
compound symmetry without heterogeneous variances (CS) 
The Kenward-Roger approximation will be used to estimate denominator degrees of 
freedom. Significance tests will be based on LS Means using Type III sum of 
squares. 
Based on the MMRM, analysis of comparisons between treatment groups at each 
post-randomization visit will be performed. The primary analysis will be to compare 


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treatment effect at Study Day 169. The adjusted means for each treatment group 
and the estimated treatment differences for the treatment comparisons will be 
presented for each post-randomization visit together with 95% confidence intervals 
for the differences and p-values for the treatment comparisons. The adjusted 
means and estimated treatment differences for the treatment comparisons will also 
be plotted, with corresponding 95% confidence intervals.  
Descriptive statistics (number of subjects, mean, standard deviation, median, 
minimum and maximum) will be provided for baseline, post treatment and change 
from baseline by treatment group and visit. 
8.5.2.1.1 
Primary Efficacy Endpoint and Secondary Efficacy 
Analysis 
A random coefficients model will be used to compare the rate of change (slope) in 
bilateral UEMS from start of study treatment until Study Day 169 between 
treatment group and control group. The model is similar to the MMRM model 
(section 8.5.2.1), except subject and subject by visit will be included as random 
effects. The unstructured covariance model will be used. If the computational 
algorithm fails to converge, the following covariance structures will be analyzed: 
TOEPH, ARH(1), CSH, TOEP, AR(1), CS. Reporting of model results will include the 
model estimate for the overall rate of change in bilateral UEMS and 95% CI, 
estimated treatment or control group rates and 95% CIs, and mean difference 
between treatment and control group along with the p-values. The adjusted means 
and estimated treatment differences for the treatment comparisons will also be 
plotted with corresponding 95% confidence intervals. 
8.5.2.1.2 
Sensitivity Analysis 
Three sensitivity analyses will be performed for the primary efficacy endpoint.  
x 
Multiple imputations assuming missing not at random (MNAR) 
Sensitivity analysis will be performed using multiple imputations with unobserved 
data imputed prior to fitting the linear regression. An assumption of MNAR will be 
made based upon an approach using multiple imputations with missing data for all 
subjects imputed from a regression model estimated from patients in the placebo 
group who stay on until Study Day 169. The imputation model will include the 
randomization strata and the corresponding baseline value as predictor. The 
method of multiple imputations (MI) (Ratitch et al. 2013) using Pattern Mixture 
Model (Little and Wang 1996) will be used. The amount of non-monotone missing 
data is expected to be minimal and hence any non-monotone missing bilateral 
UEMS will be imputed using the Markov Chain Monte-Carlo method. SAS PROC MI 


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and MIANALYZE will be used to generate 100 complete datasets and combine the 
results from each complete dataset analyzed using the same MMRM model as 
described above in section 8.5.2.1. 
x 
Multiple imputations assuming missing at random (MAR) 
An assumption of Missing at Random (MAR) will be made and subject’s missing 
bilateral UEMS data will be imputed using those with available data within the 
treatment group they were assigned to using an approach similar to above as 
described in section 8.5.2.1. 
x 
Excluding patients with important protocol deviations and who did not 
receive 80% of the planned treatment 
An analysis excluding patients with deviations that may affect the efficacy of the 
study treatment will be conducted in per protocol set. The same MMRM method as 
the primary analysis as described in section 8.5.2.1 will be used. This analysis will 
use the principal stratum strategy, to assess the sensitivity of the results to the 
occurrence of the intercurrent events like important protocol deviations prior to 
assessment scheduled on Study Day 169 and not receiving at least 5 doses (~80%) 
of the planned cumulative number of doses of treatment as described in section 
3.1.2.1.6. 
8.5.2.1.3 
Subgroup Analysis 
Subgroup analyses using the same methods as the primary and secondary analyses 
as described in sections 8.5.2.1 and 8.5.2.1.1 will be conducted comparing the 
primary efficacy endpoint between the treatment group and control group to assess 
consistency of treatment effects across potential prognostic factors. 
The following subgroup of mITT will be analyzed for the primary efficacy endpoint. 
x 
AIS grade (A, B vs C, D) 
x 
Received study drug in Part 1 vs. Did not receive study drug in Part 1 
x 
AIS grade (A vs. B, C, D) 
x 
Time since injury ≤5 years vs >5 years 
No adjustment to the significance level for testing will be made for subgroup 
analysis since all these subgroup analyses will be considered exploratory. 


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8.5.2.2 
Secondary Efficacy Endpoints 
x 
For Change from baseline in GRASSP Bilateral PP total score to Study Day 
169, analysis will be conducted using the same methodology as that used for 
the primary efficacy endpoint (sections 8.5.2.1 and 8.5.2.1.1).  
x 
For Change from baseline in SCIM III Self Care score to Study Day 169, 
analysis will be conducted using the same methodology as that used for the 
primary efficacy endpoint (sections 8.5.2.1 and 8.5.2.1.1).  
x 
Fisher’s exact test at two-sided significance level 0.05 will be used to test if 
there is a difference of PGIC responses (1=‘Much worse’, 2=‘Worse’, 3=‘ A 
little worse’, 4=‘No change’, 5=‘A little better’, 6=‘Better, 7=‘’Much better’)   
at Study Day 169 between patients in treatment group and control group. In 
addition, Fisher’s exact test to compare responder rate (proportion of patient 
in mITT Analysis set with responses of ‘A little better’, ‘Better’, or ‘Much 
better’) at Study Day 169 between the two treatment groups will conducted. 
A descriptive table summarizing number and percentage of patients for each 
of the seven above responses by visit and treatment group will be created. 
8.5.2.2.1 
Sensitivity Analysis 
x 
For Change from baseline in GRASSP Bilateral PP total score to Study Day 169 
and Change from baseline in SCIM III Self Care score to Study Day 169, 
sensitivity analyses will be conducted using the same methodology and model 
as that used for the primary efficacy endpoint (section 8.5.2.1.2).  
x 
For PGIC responder rate, the analysis described above will be conducted for 
the per protocol set to evaluate if deviations from protocol affect treatment 
effect assessed by PGIC. 
x 
For PGIC responder rate, the analysis described above will be repeated, 
except subjects who discontinued the study prior to the assessment 
scheduled for Study Day 169 will be assigned a response of 4=‘No change’. 
This analysis will use the composite variable strategy, to assess the sensitivity 
of the results to the occurrence of the intercurrent events like discontinuation 
from the study prior to assessment scheduled on Study Day 169 as described 
in section 3.1.2.4.6. 
8.5.2.3 
Exploratory Efficacy Endpoints 
For exploratory efficacy endpoints of changes from baseline in assessment results 
(as listed in section 3.1.2.5.1), analysis will be conducted using the same 
methodology as that used for the primary efficacy endpoint (sections 8.5.2.1 and 
8.5.2.1.1).  
 


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For other exploratory efficacy endpoints at Study Day 169: 
x 
ISNCSCI ASIA impairment scale (A, B, C, D, E) will be summarized descriptively 
as the number and percent of subjects with each response at each visit by 
treatment group.    
x 
ISNCSCI Neurological Motor level will be summarized descriptively as the 
number and percent of subjects by body part by treatment group. 
x 
ISNCSCI Neurological Sensory level will be summarized descriptively as the 
number and percent of subjects by body part by treatment group. 
x 
ISNCSCI Neurological Level of Injury (NLI) will be summarized descriptively as 
the number and percent of subjects by body part by treatment group. 
x 
ISAFSCI assessments: for each system/organ, shift table of baseline evaluation 
to Study Day 169 evaluation will be created. 
x 
Clinical Global Impression of Change (CGIC) from GRASSP Prehension 
Performance Video Recordings. Assessments of Baseline compared to Day 169 
will be completed and scores will be assigned using the 7-point Likert scale 
questions shown below and the Fisher’s exact test at two-sided significance level 
0.05 will be used to test if there is a difference in ratings (1= ‘Much worse’, 
2=‘Worse’, 3=‘ A little worse’, 4=‘No change’, 5=‘A little better’, 6=‘Better, 
7=‘’Much better’)  at Study Day 169 between patients in treatment group and 
control group. In addition, the Fisher’s exact test will be used to compare 
responder rate (proportion of patient in mITT Analysis set with responses of ‘A 
little better’, ‘Better’, or ‘Much better’) at Study Day 169 between the two 
treatment groups. A descriptive table summarizing number and percentage of 
patients for each of the seven above responses by visit and treatment group will 
be created. 
 
All efficacy endpoints will also be analyzed for Study Day 253 similar to the analysis 
conducted for Study Day 169 for each corresponding endpoint. All post treatment 
values up until Study Day 253 will be included in the analysis of treatment effect for 
Study Day 253.   
  
8.6 
Pharmacokinetic Assessment 
8.6.1 Pharmacokinetic Analysis 
In Parts 1 and 2, individual serum and CSF concentrations at each sampling time-
point for AXER-204 will be presented by listings and descriptive summary statistics. 
Individual and mean serum and CSF concentration versus time data will be plotted 


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on linear and semi-logarithmic scales.  In Part 1, all PK parameters will be 
presented by individual listings and summary statistics.  
 
Summary statistics for concentration and PK parameter data will include the 
arithmetic mean, arithmetic standard deviation, median, minimum, maximum, 
number of observations, geometric mean and geometric coefficient of variation 
(CV%). 
 
In Part 1, the following pharmacokinetic parameters will be determined where 
possible from the serum and CSF concentrations of AXER-204 using non-
compartmental methods performed using Phoenix WinNonlin (Certara, Inc., 
Version 8.1 or higher): 
Parameter Definition 
AUC0-tlast 
Area under the concentration-time curve from time zero to the time 
of the last quantifiable concentration 
AUC0-∞ 
Area under the concentration-time curve from time zero to infinity 
%AUCextrap 
Area under the concentration-time curve extrapolated from last 
quantifiable concentration to infinity as a percentage of total AUC 
Cmax 
Maximum observed concentration  
tmax 
Time of the maximum observed concentration 
t1/2 
Apparent terminal elimination half-life 
CL/F 
Apparent total serum clearance  
Vz/F 
Apparent volume of distribution during the terminal elimination 
phase (serum only) 
 
In addition, dose normalised values (suffixed DN) for AUC0-tlast, AUC0-∞ and Cmax will 
be determined by dividing the original PK parameter by mg.  
Additional pharmacokinetic parameters may be determined where appropriate. 
Pharmacokinetic analysis will, where possible, be carried out using actual post-dose 
times recorded in the raw data. If actual sampling times are missing, nominal times 
may be used. 
Concentrations are used as supplied by the analytical laboratory for PK analysis. 
The units of concentration and resulting PK parameters, with amount or 
concentration in the unit, will be presented as they are received from the analytical 
laboratory.  
Cmax and tmax will be obtained directly from the plasma concentration-time profiles.   


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For multiple peaks, the highest postdose concentration will be reported as Cmax. In 
the case that multiple peaks are of equal magnitude, the earliest Tmax will be 
reported.  
AUC will be calculated using the linear trapezoidal method when concentrations are 
increasing and the logarithmic trapezoidal method when concentrations are 
decreasing (linear up/log down rule). 
The parameters based on observed Clast will be reported. 
The following regression related pharmacokinetic parameters will be determined and 
presented in the listings:  
Parameter 
 Definition 
Oz  
 Elimination rate constant 
Oz upper 
 End of exponential fit 
Oz lower 
 Start of exponential fit 
Oz N 
 Number of data points included in the log-linear 
regression 
t1/2_interval 
ratio 
  Ratio of t1/2 relative to the Oz interval (Oz upper - Oz 
lower) 
Rsq_adj 
 Adjusted coefficient for determination of exponential fit 
 
8.6.1.1 
Criteria for Handling Concentrations Below the Limit of 
Quantification in Pharmacokinetic Analysis 
x 
Concentration values that are below the level of quantification (BLQ) will be 
set to zero, with defined exceptions as follows; 
o Any embedded BLQ value (between 2 quantifiable concentrations) and 
BLQ values following the last quantifiable concentration in a profile will 
be set to missing for the purposes of PK analysis. 
o If there are late positive concentration values following 2 BLQ 
concentration values in the apparent terminal phase, these values will 
be evaluated. If these values are considered to be anomalous, they will 
be set to missing. 
o If an entire concentration-time profile is BLQ, the profile will be excluded 
from the PK analysis. 


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8.6.1.2 
Criteria for the Calculation of an Apparent Terminal 
Elimination Half-Life 
x 
Number of Data Points 
o At least three data points will be included in the regression analysis and 
preferably should not include Cmax. 
x 
Goodness of Fit 
o When assessing terminal elimination phases, the R2 adjusted (Rsq_adj) 
value will be used as a measure of the goodness of fit of the data points 
to the determined line.  
o An elimination half-life will generally only be calculated if the R2 adjusted 
value of the regression line is greater than or equal to 0.7.  Exceptions 
can be made (e.g. CSF) for exploratory purposes. 
x 
Period of Estimation 
o Time period used for the estimation of apparent terminal elimination 
half-lives, where possible, will be over at least two half-lives 
(t1/2_interval ratio).  
o Where t1/2_interval ratio < 2 the robustness of the value(s) may be 
discussed in the study report. 
8.6.1.3 
Calculation of AUC 
x The minimum requirement for the calculation of AUC will be the inclusion of 
at least three consecutive concentrations above the lower limit of 
quantification (LLOQ), with at least one of these concentrations following 
Cmax. 
x For any partial AUC determination (i.e. AUC over a dosing interval), nominal 
time will generally be used for the end of the interval. Actual times for 
partial AUC intervals may be used at the discretion of the 
Pharmacokineticist.  
x AUC0-∞ values where the percentage extrapolation is less than 20% will be 
reported. AUC0-∞ values where the percentage extrapolation is greater than 
20% may be excluded from descriptive statistics at the discretion of 
pharmacokineticist. 
8.6.1.4 
Anomalous Values 
x If a value is considered to be anomalous due to being inconsistent with the 
expected pharmacokinetic profile, it may be appropriate to exclude this 


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point from the pharmacokinetic analysis. However, the exclusion of data 
must have strong justification and will be documented in the raw data and 
study report. 
8.6.2 Presentation of Pharmacokinetic Data 
8.6.2.1 
Presentation Pharmacokinetic Concentration Data 
x The following rules will be applied if there are values that are BLQ or if there 
are missing values (e.g., no result [NR]) in a concentration data series to be 
summarised. 
o For the calculation of summary statistics, BLQ values will be set to 
zero. 
o If an embedded BLQ value is considered anomalous within the 
concentration-time profile, this value will be excluded from the 
summary statistics. 
o Where there is NR, these will be set to missing. 
o If there are less than three values in the data series, only the min, 
max and N will be presented. The other summary statistics will be 
denoted as not calculated (NC). BLQ is considered a value. 
o If all the values are BLQ, then the arithmetic mean, arithmetic SD, 
median, min and max will be presented as zero, and the geometric 
mean and geometric CV% will be denoted as NC. 
o If the value of the arithmetic mean or median is below the lower limit 
of quantification, these values will be presented as zero and the 
geometric mean and geometric CV% will be denoted as NC. 
8.7 
Immunogenicity Analysis 
All anti-drug antibody (ADA) data collected in eCRF will be listed for the ADA 
analysis set. Positive ADA status for a sample is defined as having the screen assay 
reported as detected and the confirmatory assay reported as confirmed. Negative 
ADA status for a sample is defined as either having an assay reported as negative 
or having the screen assay reported as detected and the confirmatory assays 
reported as not confirmed. 
The number and percentage of subjects with positive or negative ADA status will be 
summarized by dose cohort for Part 1 or by treatment group for Part 2 and time 
point.  


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8.8 
 Safety 
All safety analyses will be conducted for the Safety population. 
8.8.1 Extent of Exposure 
Exposure data for the study treatment will be listed for both Part 1 and Part 2. 
For Part 2, the following variables will be summarized for each treatment group: 
x 
Treatment duration: Treatment duration (days) is defined as the date of last 
infusion – the date of first infusion +1.  
x 
Number of infusions 
x 
Cumulative dose: cumulative dose is defined as the sum of all doses taken 
during treatment period. 
x 
Type of modification including drug interrupted, withdrawn, reduced, 
delayed/not given, or rate changed. 
8.8.2 Adverse Events 
All adverse events (AEs) recorded on the eCRF will be coded using the MedDRA 
dictionary [Version 22.0 (or a later version if updated during the study)] and classified 
as pre-treat AEs, or treatment-emergent AEs as follows: 
x 
Pre-treat AEs are events that start prior to the date of first dose of study 
treatment; 
x 
TEAEs are events with start date on or after the date of first dose of study 
treatment, or with a start date prior to the date of first dose of study 
treatment whose severity worsens on or after the date of first dose of study 
treatment. TEAEs will be limited to those events occurring within 28 days 
after the last injection of study treatment, with AEs occurring after that being 
defined as post-treatment. AEs with missing start date after applying 
imputation rules will be considered as TEAEs. 
Assessment of AE severity will be based on the Common Terminology Criteria for 
Adverse Events (CTCAE, version 5.0). Missing severity will not be imputed. 
The relationship between an AE and study treatment is assessed as definitely, 
probably, possibly, unlikely, or not related. A treatment-related AE is an AE 
considered by the investigator as definitely, possibly, or probably related to study 
treatment or with unknown/missing relationship to study treatment.   
All AE data will be listed. Treatment-emergence status will be flagged in the listing. 
In addition, corresponding listings of serious AEs (SAEs), AEs leading to 
discontinuation from study, AEs of special interest, and AEs resulting in death will be 
produced. 


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Summary tables of TEAEs by dose cohort for Part 1 or by treatment group for Part 2 
and overall will be produced. 
An overview table will summarize the number and percentage of subjects with at 
least one of the following TEAEs, where subjects with more than one TEAE in a 
particular category are counted only once in that category: 
x 
Any TEAE; 
x 
TEAE by maximum severity; 
x 
Treatment-related TEAE;  
x 
TEAE leading to discontinuation from study; 
x 
TEAE of Special Interest; 
x 
Serious TEAE;  
x 
Treatment-related serious TEAE; 
x 
Serious TEAE leading to discontinuation from study; 
x 
Serious TEAE leading to death. 
The number of total TEAEs will be also included in the overview table. 
The number and percentage of subjects reporting each TEAE will be summarized by 
SOC and PT, or PT. Tables will be sorted in descending overall frequency by SOC, and 
then in descending overall frequency by PT within SOC, and then alphabetically. The 
following summaries will be produced: 
x 
TEAEs, by SOC and PT; 
x 
TEAEs, by PT; 
x 
TEAEs, by SOC and PT and maximum severity; 
x 
Treatment-related TEAEs, by SOC and PT; 
x 
Lumbar Puncture procedure related TEAEs, by SOC and PT (Part 2 only); 
x 
TEAEs leading to discontinuation from study, by SOC and PT; 
x 
TEAEs of Special Interest, by SOC and PT; 
x 
Serious TEAEs, by SOC and PT; 
x 
Treatment-related serious TEAEs, by SOC and PT; 
x 
Lumbar Puncture procedure related serious TEAEs, by SOC and PT (Part 2 
only); 
x 
Serious TEAEs leading to discontinuation from study, by SOC and PT; 
x 
Serious TEAEs leading to death, by SOC and PT. 
In the above summaries, subjects with more than one AE within a particular SOC are 
counted only once for that SOC. Similarly, subjects with more than one AE within a 
particular PT are counted only once for that PT. For summaries by maximum severity, 
subjects with multiple AEs within a particular SOC or PT will be counted under the 
category of their most severe AE within that SOC or PT.  


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8.8.3 Laboratory Evaluations 
All clinical laboratory data will be listed. Data for the following hematology, clinical 
chemistry, urinalysis and CSF laboratory (part 2 only) analytes (Table 7) will be 
summarized by dose cohort for Part 1 or treatment group for Part 2 and overall, and 
by visit. If data for any additional analytes are also recorded, then these will be listed 
only.  
Table 7  
Clinical Laboratory Tests 
 
Hematology 
Clinical Chemistry 
Urinalysis 
CSF Analysis 
(Part 2) 
Hematocrit 
Hemoglobin 
Mean corpuscular 
volume (MCV) 
Mean corpuscular 
hemoglobin (MCH) 
Mean corpuscular 
hemoglobin 
concentration (MCHC) 
Platelet count  
Red blood cell (RBC) 
count 
Red cell distribution 
width (RDW) 
White Blood Cell 
(WBC) Count 
including differential 
(neutrophils, 
lymphocytes, 
monocytes, 
eosinophils, basophils) 
 
 
Alanine transaminase 
(ALT) 
Albumin 
Alkaline phosphatase  
Aspartate transaminase 
(AST)  
Bicarbonate 
Blood urea nitrogen  
Calcium  
Chloride 
Cholesterol 
Creatine kinase  
Creatinine  
Direct bilirubin 
Gamma-Glutamyl 
transferase (GGT) 
Glucose 
Lactate dehydrogenase 
Phosphorus 
Potassium 
Sodium 
Total bilirubin  
Total protein  
Triglycerides  
Uric acid 
Blood 
Glucose 
Ketones 
pH 
Protein 
Specific gravity 
Urine bilirubin 
 
 
Total protein 
Glucose 
Red blood cells 
count 
White blood cells 
count 
Lymphocytes 
count 
Neutrophils 
count 
 
 
All laboratory data will be reported in Conventional units. Out-of-reference-range 
values will be flagged as high (H) or low (L) in the listings.  
For analysis purposes, values preceded by a “<” or a “>” sign (i.e. those below or 
above the limits of quantification) will be considered equal to the lower or upper limit 
of quantification, respectively. 
Hematology and clinical chemistry data will be summarized for each dose cohort using 
standard descriptive statistics. Changes from baseline will also be summarized. Shift 


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tables presenting movement in and out of reference range from baseline to each 
scheduled post-baseline visit will also be provided.  
Number and percentage of subjects having any clinically significant laboratory value 
during post-baseline will be summarized for hematology, clinical chemistry, and 
urinalysis analytes. In addition, number and percentage of subjects having new-onset 
potentially clinically significant (PCS) laboratory values will be summarized. A PCS 
value is defined as a value that is out-of-reference-range. New-onset value for an 
analyte is defined as a PCS value for a subject following initiation of study treatment 
for which the subject did not have a PCS value for that analyte prior to initiation of 
study treatment. The denominator for calculating the percentage is the number of 
subjects without any PCS values at baseline and with at least one post-baseline 
assessment.  
For each laboratory analyte, the baseline value will be defined as last scheduled or 
unscheduled value collected prior to the first dose of study treatment. Assessments 
carried out on day of first study treatment administration are considered to have 
taken place before the study treatment administration, if the corresponding times 
have not been recorded. For post-baseline, only data from scheduled visits will be 
included in the summary tables.  
8.8.4 Vital Signs 
The following vital signs will be listed and summarized by dose cohort and overall, 
and by visit for Part 1: 
x 
systolic and diastolic blood pressure (mmHg); 
x 
pulse rate (bpm); 
x 
Pulse Oximetry (%); 
x 
respiration rate (breaths/min); 
x 
body temperature (°C); 
x 
weight (kg); 
x 
BMI (kg/m2).  
Temperature will be displayed in degrees Celsius (°C); temperatures recorded in 
degrees Fahrenheit (°F) will be converted as: [temperature (°C) = (temperature (°F) 
– 32)×5/9]. Height will be displayed in centimeters (cm); height recorded as inches 
(in) will be converted as: [height (cm) = height (in)*2.54]. Weight will be displayed 
in kilograms (kg); weight recorded as pounds (lb) will be converted as: [weight (kg) 
= weight (lb)*0.45359237]. BMI recorded in pounds and inches will be re-calculated 
as the following: BMI(kg/m2) = BMI(lb/in2) * 703. 
All vital signs data will be listed. For Part 1, vital signs data including blood pressure, 
pulse rate, pulse oximetry, respiration rate, and temperature and changes from 
baseline for the following time points will be summarized by dose cohort and visit 
using standard descriptive statistics: 
x 
Day 1 Pre-Dose; 


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x 
Day 1 Post-Dose first measurement;  
x 
First Measurement for Days 2, 3, 4, 8, 15, and 29. 
For Part 2, same set of vital sign variables and change from baseline will be 
summarized by treatment group and the time points below. 
x 
Day 1 Pre-Dose; 
x 
Day 1 Post-Dose first measurement;  
x 
First Measurement for Days 21, 42, 63, 84, 104, 169, and 253. 
For both Part 1 and Part 2, the baseline value will be defined as last scheduled or 
unscheduled value collected prior to the first dose of study treatment. Assessments 
carried out on day of first study treatment administration are considered to have 
taken place before the study treatment administration, if the corresponding times 
have not been recorded. For post-baseline, only data from scheduled visits will be 
included in the summary tables.   
8.8.5 Electrocardiograms 
The following quantitative ECG measurements will be listed and summarized by dose 
cohort for Part 1 or by treatment group for Part 2 and overall, and by visit: 
x 
heart rate (bpm); 
x 
RR interval (msec), calculated as (60/HR)*1000; 
x 
PR interval (msec); 
x 
QRS interval (msec); 
x 
QT interval (msec); 
x 
Fridericia corrected QT (QTcF) interval (msec), calculated as QT/ඥܴܴ/1000
య
.  
Triplicate ECG will be taken in the study. Average values will be computed from 
available assessments from the triplicate ECGs to be used for data summaries. 
The ECG measurements and changes from baseline in ECG will be listed and 
summarized using standard descriptive statistics.  
An overall Investigator assessment of ECG will be listed and summarized as number 
and percentage of subjects with each assessment category by visit (categories: 
“normal”, “abnormal, not clinically significant” and “abnormal, clinically significant”). 
Shifts from baseline (normal vs. abnormal, not clinically significant vs. abnormal, 
clinically significant) to the worst post-baseline interpretation will be presented. 
The baseline value will be defined as last scheduled or unscheduled value collected 
prior to the first dose of study treatment. Assessments carried out on day of first 
study treatment administration are considered to have taken place before the study 
treatment administration, if the corresponding times have not been recorded. For 
post-baseline, only data from scheduled visits will be included in the summary tables.  


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8.8.6 Physical Examination 
Physical examination results (normal/abnormal) and details of abnormalities will be 
listed. 
8.8.7 Condition-specific Safety Variables (Part 1 and Part 2) 
The following condition-specific safety variables will be summarized by dose cohort 
for part 1 or by treatment group for part 2 and overall, and by visit using standard 
descriptive statistics, changes from baseline will be also summarized: 
x 
Total MAS score, calculated as the sum of scores of all items. The MAS score 
for each item will be re-assigned as the following: 
MAS score  
Score used in analysis 
0 
0 
1 
1 
1+ 
2 
2 
3 
3 
4 
4 
5 
x 
BPI pain severity measured at “worst”, “least”, “average”, and “now”, 
obtained from eCRF;   
x 
Mean BPI pain interference, calculated as the mean of all completed 
interference items if at least four of all seven items have been completed on 
a given administration.  
For part 2, change from baseline in Bilateral MAS total scores for Elbow, Wrist, 
Hamstrings, Quadriceps, Gastrocnemius, and Soleus; mean BPI pain score; or 
mean BPI pain interference score, to Study Day 169 will be analyzed using the 
same methodology as that used for the primary efficacy endpoint (sections 8.5.2.1 
and 8.5.2.1.1). Same statistical analysis will also be conducted for Study Day 253. 
8.9 
Interim Analysis 
No interim analysis will be performed for this study.   
 
 


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9. Changes from the Protocol Specified Statistical Analyses 
The following changes from protocol specified statistical analyses are made in this 
SAP. 
9.1 
Secondary efficacy endpoint 
Patient Global Impression of Change (PGIC) responder rate will be considered 
secondary efficacy endpoint.  
9.2 
Exploratory efficacy endpoint 
o In SAP, ISNCSCI UEMS for the side with the higher baseline score and the 
side with the lower baseline score will be analyzed as exploratory efficacy 
endpoint.  If the baseline scores for each side are equal, then the right 
side will be grouped with the higher baseline UEMS scores for analysis. 
o ISNCSCI total motor scores instead of lower extremity motor score are 
included in SAP as exploratory efficacy endpoints. 
o Clinical Global Impression of Change (CGIC) from GRASSP Prehension 
Performance Video Recordings 
9.3 
Analysis population 
PK Analysis set and ADA analysis set were added in the SAP for analysis for PK and 
ADA, respectively. In addition, mITT analysis set was added for Part 2 and all Part 
2 efficacy analysis will be conducted using mITT analysis set. 
10. Changes in the Planned Statistical Analyses 
The following changes in the planned statistical analyses indicated below are being 
made after all enrolled Part 2 patients have completed the 6-month visit, cleaning 
and unblinding of data, and completion of the 6-month top-line analysis for the 
primary, secondary and exploratory efficacy endpoints to compare treatment 
effects from baseline to Study Day 169 and prior to final database lock following 9-
month visit or Study Day 253 (as described in section 2.2). The availability of 
results of this analysis was limited to the unblinded ReNetX staff and 
 
Biostatistics and Programming team. The changes were requested by the unblinded 
ReNetX staff after review of results and approved by 
 Biostatistics and 
Programming team. 


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10.1 
Post Hoc Exploratory Analysis for Efficacy Endpoints 
to Study Day 169 
Results from the primary efficacy analysis, based upon a mixed-effects model for 
repeated measures (MMRM) as described in section 8.5.2.1, showed that there was 
no statistically significant difference at the two-sided 5% significance level between 
AXER-204 and Placebo groups in the primary efficacy endpoint. Additionally, the 
MMRM subgroup exploratory analyses (as described in section 8.5.2.1.3) did not 
show statistical significant difference between treatment and control groups in the 
primary endpoint at the unadjusted two-sided 5% significance level, but there is 
visually a potential trend toward treatment effect in the subgroups AIS grade (B, C, 
D) and no prior receipt of study drug in Part 1. 
Therefore, ReNetX performed exploratory analyses on several endpoints in these 
subgroups, which suggested that three endpoints had visually a higher change from 
baseline in AXER-204 group compared to Placebo group, and proposed additional 
post hoc analyses that may reveal treatment effect for the following efficacy 
endpoints. Similar to the subgroup analyses (section 8.5.2.1.3), the alpha from the 
primary efficacy analysis has been used, so no adjustment to the significance level 
for testing will be made because all these analyses will be considered exploratory. 
For this reason, no formal conclusions can be drawn from any differences, and p-
values will be provided for descriptive purposes only. 
o Primary efficacy endpoint: Change from baseline in bilateral UEMS to 
Study Day 169 ranging from 0-50. 
o Secondary efficacy endpoint: Change from baseline in GRASSP 
bilateral PP to Study Day 169 ranging from 0-40. 
o Exploratory efficacy endpoint: Change from baseline in ISNCSCI 
bilateral motor score (including both upper and lower extremity for both 
left and right sides) to Study Day 169 ranging from 0-100. 
x 
Including patients with AIS grade (B, C, D) 
An analysis including patients with AIS grade (B, C, D) will be conducted in the 
mITT Analysis set. The same MMRM method as the primary analysis as described in 
section 8.5.2.1 will be used. Since subgroup analysis of AIS grade (A vs. B, C, D) 
on the primary efficacy endpoint have already been performed as part of the 
planned analysis, analysis will only be done on the secondary and exploratory 
efficacy endpoints. 
 


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x 
Including patients with no prior recent of study drug in Part 1 
An analysis including patients with no prior receipt of study drug in Part 1 will be 
conducted in the mITT Analysis set. The same MMRM method as the primary 
analysis as described in section 8.5.2.1 will be used. Since subgroup analysis of 
prior receipt of study drug in Part 1 (yes vs. no) on the primary efficacy endpoint 
have already been performed as part of the planned analysis, analysis will only be 
done on the secondary and exploratory efficacy endpoints. 
x 
Including patients with AIS grade (B, C, D) and no prior receipt of study 
drug in Part 1 
An analysis including patients with AIS grade (B, C, D) and no prior receipt of study 
drug in Part 1 will be conducted in the mITT Analysis set. The same MMRM method 
as the primary analysis as described in section 8.5.2.1 will be used. 
10.2 
Post Hoc Exploratory Analysis for Efficacy Endpoints 
to Study Day 253 
All efficacy endpoints as described in section 10.1 will also be analyzed for Study 
Day 253 similar to the analysis conducted for Study Day 169 for each 
corresponding endpoint. All post treatment values up until Study Day 253 will be 
included in the analysis of treatment effect for Study Day 253. Since no subgroup 
analyses were performed for Study Day 253 as part of the planned analyses, all 
three exploratory analyses will be performed on the primary efficacy endpoint as 
well as the secondary and exploratory efficacy endpoints. 
10.3 
Clarifications to Pre Hoc Slope Analysis 
Clarifications to the secondary efficacy analysis, based upon a random coefficients 
model that compared the rate of change (slope) in the primary efficacy endpoint as 
described in section 8.5.2.1.1, was implemented prior to treatment unblinding for 
the 6-month top-line analysis (as described in section 2.2). The slope will measure 
rate of change of bilateral UEMS per month instead of per day in the interest of 
readability. Conversions from day to month will be baseline as Study month 0, 
Study day 21 as Study month 1, Study day 63 as Study month 2, Study day 104 as 
Study month 4, Study day 169 as Study month 6, and Study day 253 as Study 
month 9. 
The slope analysis is similar to the MMRM model in the primary efficacy analysis as 
described in section 8.5.2.1, but will include bilateral UEMS as the dependent 
variable; treatment, AIS grade (A,B vs C,D) and prior receipt of study drug in Part 


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1 (yes vs. no) as the fixed categorical effects; as well as visit (Study month 0, 1, 2, 
4, and 6) and treatment-by-visit interaction as the fixed continuous effects; and 
subject and subject by visit as the random effects. The unstructured covariance 
model will be used. In contrast to the primary efficacy analysis in section 8.5.2.1, if 
the computational algorithm fails to converge, the following will be tested in order, 
and the first that converges will be used: variance components covariance 
structure, removing random effect subject by visit and unstructured covariance 
structure, and removing random effect subject by visit and variance components 
covariance structure. Reporting and plotting of the model results will follow as 
described in section 8.5.2.1.1, but excluding overall rate of change in bilateral 
UEMS and 95% CI. 
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Document Date: 05 August 2022 
 
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