Conditions: Healthy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 9
Healthy volunteers: yes

Brief summary:
Approximately 9 participants will be enrolled in the study in a single cohort. Participants will be randomized to 3 g IXT-m200 or placebo at 7:2. Each will receive their dose as a 30-min intravenous infusion, then remain at the study site overnight to complete Day 1 and Day 2 assessments (e.g., electrocardiogram (ECG), laboratory assessments, blood draws, and vital signs). Following discharge on Day 2, participants will return to the clinic for follow-up pharmacokinetic (PK) and safety assessments on Day 8, then every 1-3 weeks thereafter until Day 127.

Detailed description:

Arms:
arm 1: 3 g of IXT-m200 given once by 30-min intravenous infusion arm 2: Normal saline

Interventions: intervention 1: IXT-m200 intervention 2: Placebo
Intervention descriptions: intervention 1: Anti-methamphetamine chimeric monoclonal antibody (mAb) intervention 2: Normal saline

Protocol document:
ICF_002.pdf: 
A Phase 1, Double-Blind, Randomized, Placebo-Controlled, 
Single-Dose Intravenous Study to Evaluate the Safety, 
Tolerability, and Pharmacokinetics of IXT-m200 in Healthy 
Participants 
Protocol Number: M200C-2102 
IND Sponsor: InterveXion Therapeutics, LLC 
Funded by: NIH/NIDA U01 DA045366 
Version Number:  1 
04 Oct 2021 
NCT05027451


InterveXion Therapeutics, LLC / Protocol Number M200C-2102 
Page 1 of 14  
Magdy L. Shenouda, M.D. 
Advarra IRB Approved Version 4 Oct 2021 
INFORMED CONSENT FORM 
AND 
AUTHORIZATION TO USE AND DISCLOSE PROTECTED HEALTH INFORMATION 
Sponsor / Study Title: 
InterveXion Therapeutics, LLC / “A Phase 1, Double-Blind, 
Randomized, Placebo-Controlled, Single-Dose Intravenous 
Study to Evaluate the Safety, Tolerability, and 
Pharmacokinetics of IXT-m200 in Healthy Participants” 
Protocol Number: 
M200C-2102 
Principal Investigator: 
(Study Doctor) 
Magdy L. Shenouda, M.D. 
Telephone: 
(646) 215-6422 (24 Hours)
Address: 
Clinilabs Inc4 Industrial Way West 
2nd floor 
Eatontown, NJ    07724 
KEY INFORMATION 
You are being asked to participate in this research study as a healthy participant. There is no 
known benefit from your participation in this study. Information learned from the study may 
help other people in the future.  Since there is no direct medical benefit to participation, your 
other option is not to participate.   
This consent form will review the question the study is trying to answer which is the safety and 
tolerability of the study drug (IXT-m200). It will review the information that will be collected 
from you prior to and during the course of the study as well as the study related activities.   
An investigational drug is one that is not approved by the United States Food and Drug 
Administration (FDA). This study is trying to determine the potential safety and tolerability of 
the study drug after a single administration in comparison with placebo (inactive substance, 
purified saline water that looks like study drug).  You will receive the study drug/placebo as a 
short intravenous (IV) infusion.  In addition, you will have a series of screening and medical 
assessments as outlined in this consent form which will give you a greater sense of your general 
health.  As part of the study, these assessments will be conducted at no cost to you.    
Your health will be closely monitored by the study team while on study site as well as 
throughout the duration of the study.  Please note, your participation is completely voluntary.  
You may withdraw from participation at any time.   


InterveXion Therapeutics, LLC / Protocol Number M200C-2102 
Page 2 of 14   
 
 
Magdy L. Shenouda, M.D. 
Advarra IRB Approved Version 4 Oct 2021 
 
 
Introduction 
You are invited to take part in a research study. This research study is studying IXT-m200, which 
is a possible treatment for methamphetamine, or METH, use disorder.  InterveXion 
Therapeutics, LLC is sponsoring this research study, and it is being funded by a grant from the 
National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA).  IXT-m200 is 
believed to work by directly binding to METH and keeping it from entering the brain, which may 
help people who want to stop using METH to overcome their addiction.  
 
Please read this form carefully. Take your time to ask the study doctor or study staff as many 
questions about the study as you would like. The study doctor or study staff can explain words 
or information that you do not understand. Reading this form and talking to the study doctor or 
study staff may help you decide whether to take part or not. If you decide to take part in this 
study, you must sign your name at the end of this form and date it.  
 
PURPOSE OF CONSENT FORM  
You are being asked to participate in a research study. It is important that you read the 
following explanation of the proposed procedures. This form describes the purpose, 
procedures, benefits, risks, discomforts, and precautions of the study. It also describes your 
right to withdraw from the study at any time. A qualified member of the study staff will go 
through the consent with you and discuss all the information. When you understand the study, 
you will then be asked if you agree to take part. If you agree, you will be asked to sign and date 
this consent form. Once you sign and date it, we will give you a signed and dated copy to keep. 
 
BACKGROUND AND PURPOSE 
You are being asked to participate in this research study as a healthy volunteer. 
 
The purpose of this research study is to:  
• Test the safety and tolerability of the study drug, IXT-m200. 
• Investigate the pharmacokinetic (PK) properties (how the study drug moves in the body) 
of IXT-m200 
 
This is a research study to test a new investigational drug.  An investigational drug is one that is 
not approved by the United States Food and Drug Administration (FDA). This study is to 
determine the potential safety and tolerability of study drug after a single administration in 
comparison with placebo (purified saline water that looks like study drug but has no active drug 
in it). Throughout the study, blood will be collected for pharmacokinetic (PK) analysis to 
evaluate elimination of IXT-m200 after a single administration of study drug. 
 
What will happen during this study 
There will be approximately 9 healthy adults randomized into the study. Participants will be 
randomized (like the flip of a coin) to 3 grams IXT-m200 or placebo (saline water).  Each will 
receive their dose as a 30 minute IV (intravenous) infusion, then remain at the study site 
overnight to complete Day 1 and Day 2 assessments (Electrocardiogram [ECG], laboratory 
assessments, blood draws, and vital signs).  Following discharge on Day 2, participants will 


InterveXion Therapeutics, LLC / Protocol Number M200C-2102 
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Magdy L. Shenouda, M.D. 
Advarra IRB Approved Version 4 Oct 2021 
 
 
return to the clinic for follow up PK and safety assessments on Day 8, then every 1-3 weeks 
thereafter until Day 127.    
 
Your participation in this study will begin with a screening period to assess eligibility of 
participation, which could last up to 30 days prior to IXT-m200 administration.  If you agree to 
participate in this study, you will be asked to refrain from the following during the study period: 
 
• Ingesting or using any other investigational drug or device.  
• Donating blood, plasma, platelets, eggs or sperm.  
 
You will be asked to limit your alcohol consumption to approximately 1 drink per day (women) 
and 2 drinks per day (men) while in the study.  Participants are required to practice an 
adequate method of birth control, including intrauterine device (IUD); oral, dermal ("patch"), 
implant or injected contraceptives; tubal ligation; barrier methods with spermicide; or 
vasectomized partner throughout the study. 
 
IXT-m200 may also bind to drugs that are similar to METH. You should refrain from taking such 
drugs during the study period, including methamphetamine, amphetamine (including 
Adderall®, Dexedrine®, or Evekeo®) and MDMA (also known as ecstasy). 
 
Visit Schedule/Duration of Inpatient Stay: (The total length of the study is up to 127 days) 
• One outpatient screening visit.  
• After Screening, you will return to check-in to the inpatient unit for 2 days/1 night (Days 
1 and 2), and 10 outpatient visits will occur on Days 8, 15, 22, 29, 36, 43, 64, 85, & 106.  
Final Study visit is Day 127 
 
Screening Visit:  
Before any procedures are performed, you will be asked to sign and date this informed consent 
form to participate in the study.  Screening procedures are intended to take one day, but may 
take additional days. 
 
The following screening tests and procedures will then be performed to determine if you 
qualify to take part in this study: 
 
• Review of demographics such as age, gender, race, etc.; 
• Review of requirements and verifying inclusion/exclusion criteria for study participation; 
• Review of your medical and psychiatric history including any medications you are taking 
or have taken recently; 
• Height, and weight measurements and body mass index (BMI) calculation; 
• A complete physical examination; 
• Measurement of vital signs to check your heart rate, blood pressure, oral body 
temperature, SaO2 (oxygen levels), and respiratory rate. Blood pressure will be taken in 
Seated and semi-recumbent positions; 


InterveXion Therapeutics, LLC / Protocol Number M200C-2102 
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Magdy L. Shenouda, M.D. 
Advarra IRB Approved Version 4 Oct 2021 
 
 
• Clinical laboratory tests of blood chemistry, hematology, and urinalysis.  Also drug and 
alcohol levels; 
• All testing results will be kept confidential and disclosed only as required by law. You will 
be notified and given information on counseling services if you have positive results. The 
study doctor may be required by law to report the results of these tests to the local 
health authority; 
• A urine pregnancy test for females to determine if you are pregnant. The result of the 
pregnancy test must be negative for you to qualify to participate in this study; 
• A Verified Clinical Trials (VCT) assessment to ensure study participation is valid; 
 
If you qualify to take part in this study and go on to receive the study treatment, you will 
undergo the following study visits and procedures: 
 
Check in procedure: Day 1: 
 
Once your eligibility has been confirmed by the study doctor, you will be asked to check into 
the Clinic on Day 1 (Admission) until Day 2.  
The following procedures will be completed on Day 1: 
• A targeted physical examination; 
• Participants will be asked to eat a light meal prior to arriving at the study center but not 
have anything but clear liquids to eat or drink for 1 hour before appointment time. 
Participants will be offered a light meal after dosing completion;  
• Urine pregnancy tests (females only); the result must be negative to continue in the 
study;  
• Check for adverse events (side effects); 
• Confirm prior and concomitant medications;  
• Inclusion/exclusion criteria; 
• Admission to Inpatient Unit 
• Measurement of vital signs to check your heart rate, blood pressure, oral body 
temperature, SaO2 (oxygen levels), and respiratory rate. Blood pressure will be taken in 
Seated and semi-recumbent positions; 
 
• Blood samples are to be taken pre-dose for cytokines, PK, and Human anti-chimeric 
antibodies (HACA) 
• Randomization and then administration of IXT-m200 or placebo 
Study Treatment: 
You will receive the study drug as a short (approximately 30 minutes) IV infusion. 


InterveXion Therapeutics, LLC / Protocol Number M200C-2102 
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Magdy L. Shenouda, M.D. 
Advarra IRB Approved Version 4 Oct 2021 
 
 
You will be assigned by chance (like a flip of a coin) to receive either IXT-m200 or placebo 
(inactive substance).  This is a double-blind study, which means neither you nor the study 
doctor will know to which of these study drug groups you are assigned. In case of an 
emergency, however, the study doctor can get this information.  
 
The following assessments are to be performed at Day 1 following dose administration: 
• Multiple triplicate 12-Lead Electrocardiogram (ECG) will be taken at 30 min post-dose. 
• Measurement of sitting or semi-recumbent   l signs to check your heart rate, blood 
pressure, body temperature, SaO2, and respiratory rate will be taken at 0.25, 0.5, 1, 2 
and 4 hours (+/- 5 min) after dosing starts, and as needed afterward until normalization.    
• Laboratory tests (blood and urine sampling) Samples are to be taken at screening, pre-
dose and 2 hours post dose completion; also a urine drug screen.  
• Additional blood samples may be taken two more times if you have an infusion reaction. 
• PK samples are to be taken at 1, 4, and 8 hours after dosing. 
• Check for adverse events and concomitant medications. 
 
Day 2: 
• 
Laboratory Tests- blood and urine samples will be obtained 
• 
Wellness Check- update medical history, update medications, vital signs and physical 
exam 
• 
Blood for PK 
  
Days 8, 15, 22, 29, 36, 43, 64, 85, 106 
• 
Laboratory Tests- blood and urine samples will be obtained on Days 8, 29, and 64  
• 
Wellness Check- update medical history, update medications, vital signs and physical 
exam 
• 
Blood for PK 
Day 127: 
• 
Wellness Check- update medical history, update medications, vital signs and physical 
exam 
• 
Urine pregnancy check 
• 
Blood for PK 
• 
Blood for HACA 
 
After Study Treatment: Because this is a research study, the study drug will be given to you 
only during this study and not after the study is over.  
 


InterveXion Therapeutics, LLC / Protocol Number M200C-2102 
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Magdy L. Shenouda, M.D. 
Advarra IRB Approved Version 4 Oct 2021 
 
 
Risks, Side Effects, and Discomforts 
IXT-m200 had been given to over 65 human study participants in two different studies when 
this study started. Though we don’t yet know all the risks of taking IXT-m200, we do believe 
that it is generally safe.  
 
There were no serious adverse events in the previous studies. One participant had an infusion 
reaction halfway through the IXT-m200 infusion. The participant had a brief period of 
bronchospasm and wheezing. Bronchospasm is a sudden constriction of the muscles in the 
walls of the bronchioles (airway). The infusion was stopped and the participant was treated. 
The participant fully recovered from the incident. 
 
IXT-m200 is a monoclonal antibody. Risks of taking a monoclonal antibody may include allergic 
reactions such as hives or itching, flu-like symptoms including chills, fatigue, fever, and muscle 
aches and pains, nausea, vomiting, diarrhea, skin rashes, or low blood pressure. 
 
As with taking any drug, there is a risk of allergic reaction. Allergic reactions can be serious 
and/or life threatening and sometimes lead to death. Some symptoms of allergic reactions are 
rash, difficulty breathing, and wheezing, sudden drop in blood pressure, swelling around the 
mouth, throat or eyes, a fast heart rate, and sweating.  Seek treatment and alert the study 
doctor and study staff immediately if you have any of these symptoms. 
 
If you have any side effects or concerns, you should tell the study doctor or study staff 
immediately. If you don’t tell the study doctor and/or study staff the truth about any side 
effects or concerns, you may harm yourself by being in this study. If it is an emergency or if you 
cannot contact the study staff or study doctor, you should call 911 immediately. 
 
Unforeseen Risks  
Since the study drug is investigational, there may be other risks that are unknown. 
 
Risks of Study Procedures 
• Electrocardiogram (ECG):  Skin irritation is rare but could occur during an ECG from the 
electrodes or gel that is used. 
• Blood Draw Risks: Risks from the PK sample collection and clinical safety phlebotomy 
(blood drawing) procedures include infection, bleeding, bruising, blood clot formation, 
discomfort at the injection site, and (rarely) fainting. Phlebotomy will be conducted 
using careful, sterile technique to minimize these risks.  
o The total blood volume withdrawn from any single participant will not exceed 
150 mL (about 10 tablespoons). If additional blood sample analysis is needed, it 
is possible that more than one attempt to obtain a blood sample may be 
necessary.  


InterveXion Therapeutics, LLC / Protocol Number M200C-2102 
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Magdy L. Shenouda, M.D. 
Advarra IRB Approved Version 4 Oct 2021 
 
 
• IV Catheter Risks: Blood samples may be drawn from an intravenous catheter or needle 
in order to aid with the blood draws. A catheter is a thin tube inserted into your vein 
temporarily that will enable the study staff to draw blood at the various time points 
without inserting a needle directly into your vein multiple times. Procedure risks include 
bleeding, bruising, discomfort at the injection site, and rarely infection and fainting.  
• If you are having suicidal thoughts call the study doctor at the telephone number on the 
first page of this form. If you feel in crisis, you can call 911 and/or a Nationwide Suicide 
Hotline that is answered 24 hours a day with a skilled, trained counselor. One example is 
the national Suicide Prevention Lifeline at 1-800-273-TALK (8255). 
• Nasal / Nasopharyngeal Swab: You may experience discomfort, eyes watering, 
sneezing, or bleeding. 
 
Birth Control Restrictions  
Taking the study drug may involve risks to a pregnant woman, an embryo, fetus (unborn baby) 
or nursing infant. Therefore, if you are pregnant, planning to become pregnant, planning to 
father a child, or are breastfeeding a child, you cannot participate in this study. 
 
Females: 
In order to reduce the risk of pregnancy, participants are required to practice an adequate 
method of birth control, including intrauterine device (IUD); oral, dermal ("patch"), implant or 
injected contraceptives; tubal ligation (tubes tied); barrier methods with spermicide; or 
vasectomized partner throughout the study (until day 127). 
 
If you become pregnant after you have received study drug, tell your study doctor or study staff 
immediately. You will still be asked to come in for follow-up visits and to continue all study 
assessments, however you will not receive study drug anymore. If you become pregnant, the 
study staff will collect information about the pregnancy, its outcome, and the health of the 
child after birth. Generally, follow-up will be no longer than 6 to 8 weeks after the 
estimated delivery date. 
 
Males:  
In order to reduce the risk of pregnancy, you must be willing to use a condom or remain 
abstinent while you are participating in this study.  
 
Benefits 
There is no known benefit from your participation in this study. Information learned from the 
study may help other people in the future.  
 
Alternatives to Participation 
This research study is for research purposes only. The only alternative is to not participate in 
this study. 
 


InterveXion Therapeutics, LLC / Protocol Number M200C-2102 
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Magdy L. Shenouda, M.D. 
Advarra IRB Approved Version 4 Oct 2021 
 
 
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 provided to you. 
 
Compensation for Injury 
If you become ill or are injured while you are in the study, get the medical care that you need 
right away. You should inform the healthcare professional treating you that you are 
participating in this study. If you tell the study staff that you think you have been injured then 
they will help you get the care you need.  
If you are injured as a result of taking the study drug(s) or from procedures done for the 
purpose of this study, the sponsor will pay for those medical expenses necessary to treat your 
injury that are not covered by your medical insurance or any other third-party coverage. By 
signing and dating this document, you will not lose any of your legal rights or release anyone 
involved in the research from responsibility for mistakes. 
To pay medical expenses, the sponsor will need to know some information about you like your 
name, date of birth, and Medicare Beneficiary Identifier (MBI). This is because the sponsor has 
to check to see if you receive Medicare and if you do, report the payment it makes to Medicare.  
 
Cost of Study to Participant 
There will be no charge for any of the study drug, study related procedures and study visits to 
you or your insurance company during your participation in the study.  
 
Compensation for Study Participation 
You will be paid up to a total of up to $2175 if you complete this study. You will be paid for the 
visits you complete according to the following schedule: 
• Visit Screening - $150 
• Travel - Up to $80 roundtrip 
• Visits:  
Day 1 $350 (inpatient stay), Day 2 $150, Day 8 $150, Day 15 $150, Day 22 $150,  
Day 29 $150, Day 36 $150, Day 43 $150, Day 64 $150, Day 85 $150, Day 106 $150, 
• End of Study Visit: Day 127 $150 
 
If you do not complete the study, for any reason, you will be paid for each study visit you do 
complete.  
 
You will be paid for all completed study visits at the end of each visit. 
 
If you have any questions regarding your compensation for participation, please contact the 
study staff.   


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Magdy L. Shenouda, M.D. 
Advarra IRB Approved Version 4 Oct 2021 
 
 
 
We will reimburse you up to a total of $80 roundtrip for the cost of traveling to your study 
visits. If there is a need for you to come in for additional Screening visits or Follow-up visits you 
will be reimbursed for each visit up to $80 round trip.    
 
Please note/Payment Schedule: 
Study compensation will be paid according to a specified schedule for administrative purposes. 
Payment will be divided into 3 parts. First, you will be paid $80 for round trip travel on the day 
of your screening visit.  
On Day 2 of the study (day of discharge), you will receive $80 roundtrip for travel and if you 
complete all procedures that are required from Day 1 through Discharge Day, you will receive 
$350 for Day 1 and $150 for Day 2.  All subsequent visits will be paid as followed: Day 8 $150, 
Day 15 $150, Day 22 $150, Day 29 $150, Day 36 $150, Day 43 $150, Day 64 $150, Day 85 $150, 
Day 106 $150, end of study visit: Day 127 $150.  All payments will be paid via Clincard (a debit 
card that will be provided to you on which your stipends will be deposited). 
 
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. However, please 
note that the FDA requires that any information collected up to the point of your withdrawal 
cannot be removed from the study. 
 
Your study doctor may end your participation in this study at any time, with or without your 
consent for any of 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. 
 
If you leave the study for any reason, the study doctor may ask you to have some end-of-study 
tests for your safety. 
 
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 Investigator, 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 


InterveXion Therapeutics, LLC / Protocol Number M200C-2102 
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Magdy L. Shenouda, M.D. 
Advarra IRB Approved Version 4 Oct 2021 
 
 
means that absolute confidentiality cannot be guaranteed. If the results of this study are 
published or presented at meetings, you will not be identified. 
 
This research is covered by a Certificate of Confidentiality from the National Institutes of 
Health. This means that the researchers cannot release or use information, documents, or 
samples that may identify you in any action or suit unless you say it is okay. They also cannot 
provide them as evidence unless you have agreed.  This protection includes Federal, state, or 
local civil, criminal, administrative, legislative, or other proceedings. An example would be a 
court subpoena. 
 
There are some important things that you need to know.  The Certificate DOES NOT stop 
reporting that federal, state or local laws require. Some examples are laws that require 
reporting of child or elder abuse, some communicable diseases, and threats to harm yourself or 
others.  The Certificate CANNOT BE USED to stop a sponsoring United States Federal or state 
government agency from checking records or evaluating programs. The Certificate DOES NOT 
stop disclosures required by the Federal Food and Drug Administration (FDA). The Certificate 
also DOES NOT prevent your information from being used for other research if allowed by 
Federal regulations. 
 
Researchers may release information about you when you say it is okay. For example, you may 
give them permission to release information to insurers, medical providers or any other 
persons not connected with the research. The Certificate of Confidentiality does not stop you 
from willingly releasing information about your involvement in this research. It also does not 
prevent you from having access to your own information. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov. 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 this Web site at any time. 
 
Future Research Studies 
Your private information or biospecimens collected during this study will not be used or 
distributed for future research studies, even if identifiers are removed. 
 
Your specimens (even if identifiers are removed) will be transferred to a commercial 
organization for testing and may be used for commercial profit. You will not share in this 
commercial profit. 
 
Questions or Concerns about the Study 
You can ask questions about this consent form or the study (before you decide to start the 
study, at any time during the study, or after completion of the study). Questions may include: 
• Who to contact in the case of a research-related injury or illness; 
• Payment or compensation for being in the study, if any; 
• Your responsibilities as a study participant; 


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Magdy L. Shenouda, M.D. 
Advarra IRB Approved Version 4 Oct 2021 
 
 
• Eligibility to participate in the research; 
• The study doctor’s or study site’s decision to exclude you from participation; 
• Results of tests and/or procedures; 
• Other questions, concerns, or complaints. 
 
Whom to Contact About This Study 
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 the first page of this consent document.  If you seek emergency 
care or hospitalization is required, alert the physician that you are participating in this research 
study.  
 
An Institutional Review Board (IRB) is an independent committee established to help protect 
the rights of research participants.  If you have any questions about your rights as a research 
participant, and/or concerns or complaints regarding this research study contact: 
 
• By mail: 
Study Subject Adviser 
 Advarra IRB 
6100 Merriweather Dr., Suite 600 
Columbia, MD 21044 
• or call toll free: 877-992-4724 
• or by email: adviser@advarra.com  
 
Please reference the following number when contacting the Study Subject Adviser: 
Pro00057374.  
 
Health Care Provider Notification Option 
I consent to having my family doctor or primary health care provider notified by the study site 
of my participation in this study and/or any significant findings related to my health (please 
check yes or no). 
YES (If yes, please complete the information below) 
NO  
Name and address of family 
doctor or primary health care 
provider: 
Name: 
Address: 
 
Telephone and Fax Number: 
Tel: 
Fax: 


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Magdy L. Shenouda, M.D. 
Advarra IRB Approved Version 4 Oct 2021 
 
 
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 and dating this consent document. I will receive a copy of this signed and 
dated consent document. 
 
________________________________________ 
 
 
Participant’s Printed Name  
 
 
________________________________________ 
 
___________  
Participant’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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Magdy L. Shenouda, M.D. 
Advarra IRB Approved Version 4 Oct 2021 
 
 
AUTHORIZATION TO USE AND DISCLOSE 
PROTECTED HEALTH INFORMATION 
 
If you decide to be in this study, the study doctor and research team will use and share health 
data about you to conduct the study. Health data may include: 
• Your name. 
• Address. 
• Phone number. 
• Date of birth. 
• Medical history. 
• Information from your study visits, including all test results.  
 
Health data may come from your study records or from existing records kept by your doctor or 
other health care workers.  
 
For this study, the research team may share health data about you with authorized users. 
Authorized users may include: 
• Representatives of InterveXion Therapeutics, LLC.   
• Representatives of Clinilabs 
• Representatives of Advarra IRB (an Institutional Review Board that reviews this study). 
• The Food and Drug Administration (FDA) and other US Federal and state agencies. 
• The National Institute on Drug Abuse who funded this study. 
• Government agencies to whom certain diseases (like HIV, hepatitis, and STDs) must be 
reported. 
• Governmental agencies of other countries. 
• Outside individuals and companies, such as laboratories and data storage companies, 
that work with the researchers and sponsor and need to access your information to 
conduct this study. 
• A data safety monitoring board which oversees this research  
 
Your health data will be used to conduct and oversee the research, including for instance:  
• To see if IXT-m200 is safe. 
• To compare IXT-m200 to placebo. 
 
Once your health data has been shared with authorized users, it may no longer be protected by 
Federal privacy law and could possibly be used or disclosed in ways other than those listed 
here.  
 
Your permission to use and share health data about you will end in 50 years unless you revoke 
it (take it back) sooner.  
 


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Magdy L. Shenouda, M.D. 
Advarra IRB Approved Version 4 Oct 2021 
 
 
You may revoke (take back) your permission to use and share health data about you at any time 
by writing to the study doctor at the address listed on the first page of this form. If you do this, 
you will not be able to stay in this study. No new health data that identifies you will be gathered 
after your written request is received. However, health data about you that has already been 
gathered may still be used and given to others as described in this form.  
 
Your right to access your health data in the study records will be suspended during the study to 
keep from changing the study results. When the study is over, you can access your study health 
data. 
 
If you decide not to sign and date this form, you will not be able to take part in the study. 
 
STATEMENT OF AUTHORIZATION 
I have read this form and its contents were explained. My questions have been answered. I 
voluntarily agree to allow study staff to collect, use and share my health data as specified in this 
form. I will receive a signed and dated copy of this form for my records. I am not giving up any 
of my legal rights by signing and dating this form.  
 
__________________________________ 
Printed Name of Participant 
 
 
__________________________________ 
 
 
__________ 
Signature of Participant 
 
 
 
 
Date 
 
________________________________________ 
 
 
Printed Name of the Person Obtaining the  
Authorization 
 
________________________________________ 
 
___________ 
Signature of the Person Obtaining the  
 
 
Date 
Authorization  
 

Prot_000.pdf: 
A Phase 1, Double-Blind, Randomized, Placebo-Controlled, 
Single-Dose Intravenous Study to Evaluate the Safety, 
Tolerability, and Pharmacokinetics of IXT-m200 in Healthy 
Participants 
Protocol Number: M200C-2102 
IND Sponsor: InterveXion Therapeutics, LLC 
Funded by: NIH/NIDA U01 DA045366 
Version Number:  1 
25 Aug 2021 
NCT05027451


  
 ii
TABLE OF CONTENTS 
 
TABLE OF CONTENTS ................................................................................................................ ii 
SPONSOR APPROVAL AND SIGNATURE PAGE .................................................................... 1 
STATEMENT OF COMPLIANCE ................................................................................................ 2 
1 PROTOCOL SUMMARY ........................................................................................................ 3 
1.1 Synopsis ........................................................................................................................... 3 
1.2 Schema ............................................................................................................................. 4 
1.3 Schedule of Activities ...................................................................................................... 5 
2 INTRODUCTION .................................................................................................................... 6 
2.1 Background ...................................................................................................................... 6 
2.1.1 
Study Agent ........................................................................................................ 6 
2.1.2 
Nonclinical IXT-m200 Effectiveness Summary ................................................ 6 
2.1.3 
Nonclinical Safety Summary of IXT-m200 ....................................................... 6 
2.1.4 
Clinical Research Summary ............................................................................... 6 
2.2 Risk/Benefit Assessment ................................................................................................. 7 
2.2.1 
Known Potential Risks ....................................................................................... 7 
2.2.2 
Known Potential Benefits .................................................................................. 8 
2.2.3 
Assessment of Potential Risks and Benefits ...................................................... 8 
3 OBJECTIVES AND ENDPOINTS .......................................................................................... 9 
4 STUDY DESIGN...................................................................................................................... 9 
4.1 Overall Design ................................................................................................................. 9 
4.2 Justification for Dose ....................................................................................................... 9 
4.3 End of Study Definition ................................................................................................... 9 
5 STUDY POPULATION ......................................................................................................... 10 
5.1 Inclusion Criteria ........................................................................................................... 10 
5.2 Exclusion Criteria .......................................................................................................... 10 
5.3 Rationale for the Selected Population ............................................................................ 11 
5.4 Lifestyle Considerations ................................................................................................ 11 
5.5 Screen Failures ............................................................................................................... 11 
5.6 Strategies for Recruitment and Retention ...................................................................... 11 
6 STUDY INTERVENTION ..................................................................................................... 12 
6.1 Study Intervention(s) Administration ............................................................................ 12 
6.1.1 
Study Intervention Description ........................................................................ 12 
6.1.2 
Dosing and Administration .............................................................................. 12 
6.2 Preparation/Handling/Storage/Accountability ............................................................... 12 
6.2.1 
Acquisition and accountability ......................................................................... 12 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ....................................... 12 
6.2.3 
Product Storage and Stability ........................................................................... 13 
6.2.4 
Preparation ....................................................................................................... 13 
6.3 Measures to Minimize Bias: Randomization and Blinding ........................................... 13 
6.4 Study Intervention Compliance ..................................................................................... 14 
6.5 Concomitant Therapy .................................................................................................... 14 
7 STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL............................................................................... 14 
7.1 Discontinuation of Study Intervention ........................................................................... 14 
7.2 Participant Discontinuation/Withdrawal from the Study ............................................... 14 


  
 iii
7.3 Lost to Follow-Up .......................................................................................................... 15 
8 STUDY ASSESSMENTS AND PROCEDURES .................................................................. 15 
8.1 Safety and Other Assessments ....................................................................................... 15 
8.1.1 
Eligibility Criteria ............................................................................................ 15 
8.1.2 
Medical and Medication History ...................................................................... 16 
8.1.3 
Vital Signs ........................................................................................................ 16 
8.1.4 
Physical Exam .................................................................................................. 16 
8.1.5 
Psychiatric Evaluation ...................................................................................... 16 
8.1.6 
Pregnancy Test ................................................................................................. 16 
8.1.7 
Laboratory Tests .............................................................................................. 16 
8.1.8 
Electrocardiograms .......................................................................................... 17 
8.1.9 
Blood for PK/HACA and Cytokines ................................................................ 17 
8.2 Adverse Events and Serious Adverse Events ................................................................ 17 
8.2.1 
Definition of Adverse Events (AE) .................................................................. 17 
8.2.2 
Definition of Serious Adverse Events (SAE) .................................................. 18 
8.2.3 
Classification of an Adverse Event .................................................................. 18 
8.2.4 
Time Period and Frequency for Event Assessment and Follow-Up ................ 19 
8.2.5 
Adverse Event Reporting ................................................................................. 20 
8.2.6 
Serious Adverse Event Reporting .................................................................... 20 
8.2.7 
Reporting Events to Participants ...................................................................... 21 
8.2.8 
Events of Special Interest ................................................................................. 21 
8.2.9 
Reporting of Pregnancy ................................................................................... 21 
8.3 Unanticipated Problems ................................................................................................. 21 
8.3.1 
Definition of Unanticipated Problems (UP) ..................................................... 21 
8.3.2 
Unanticipated Problem Reporting .................................................................... 21 
8.3.3 
Reporting Unanticipated Problems to Participants .......................................... 22 
9 STATISTICAL CONSIDERATIONS.................................................................................... 22 
9.1 Statistical Hypotheses .................................................................................................... 22 
9.2 Sample Size Determination ........................................................................................... 22 
9.3 Populations for Analyses ............................................................................................... 23 
9.4 Statistical Analyses ........................................................................................................ 23 
9.4.1 
General Approach ............................................................................................ 23 
9.4.2 
Safety Analyses ................................................................................................ 23 
9.4.3 
Baseline Descriptive Statistics ......................................................................... 23 
9.4.4 
Tabulation of Individual participant Data ........................................................ 23 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ......... 24 
10.1 Regulatory, Ethical, and Study Oversight Considerations ............................................ 24 
10.1.1 Informed Consent Process ............................................................................... 24 
10.1.2 Study Discontinuation and Closure .................................................................. 24 
10.1.3 Confidentiality and Privacy ............................................................................. 25 
10.1.4 Future Use of Stored Specimens and Data ....................................................... 25 
10.1.5 Key Roles and Study Governance ................................................................... 26 
10.1.6 Safety Oversight ............................................................................................... 26 
10.1.7 Clinical Monitoring .......................................................................................... 26 
10.1.8 Quality Assurance and Quality Control ........................................................... 26 
10.1.9 Data Handling and Record Keeping ................................................................ 27 
10.1.10 Protocol Deviations .......................................................................................... 28 


  
 iv
10.1.11 Publication and Data Sharing Policy ............................................................... 28 
10.1.12 Conflict of Interest Policy ................................................................................ 28 
10.2 Abbreviations ................................................................................................................. 29 
10.3 Protocol Amendment History ........................................................................................ 30 
11 REFERENCES ....................................................................................................................... 31 
 


Phase I Safety, Tolerability, and Pharmacokinetics oflXT-m200 in Healthy Volunteers 
M200C-2102 
Sl'O\SOR 
Al'l'RO\'AL 
A\D SIG\:\ n11u: PAGE 
Chief Medical Officer 
Chief Operating Officer 
Version I 
25 Aug2021 


Phase 1 Safety, Tolerability, and Pharmacokinetics of IXT-m200 in Healthy Volunteers 
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25 Aug 2021 
 
 
 
 2
STATEMENT OF COMPLIANCE 
 
The trial will be conducted in accordance with International Conference on Harmonisation Good Clinical 
Practice (ICH GCP), applicable United States (US) Code of Federal Regulations (CFR), and the National 
Institute on Drug Abuse (NIDA) Terms and Conditions of Award. The Investigator will assure that no 
deviation from, or changes to the protocol will take place without prior agreement from InterveXion 
Therapeutics and documented approval from the Institutional Review Board (IRB), except where 
necessary to eliminate an immediate hazard(s) to the trial participants. All personnel involved in the 
conduct of this study have completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must 
be obtained before any participant is enrolled. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form 
will be IRB approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent using a previously approved consent form. 
 
 
 
 
Investigator Signature/Date: _____________________________________________________________ 


Phase 1 Safety, Tolerability, and Pharmacokinetics of IXT-m200 in Healthy Volunteers 
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1 
PROTOCOL SUMMARY 
 
1.1 
SYNOPSIS  
Title: 
A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Single-Dose 
Intravenous Study to Evaluate the Safety and Pharmacokinetics of IXT-
m200 in Healthy Participants 
Study Description: 
This Phase 1 study will evaluate the safety and pharmacokinetics of a single 
3-g dose of IXT-m200 given by intravenous infusion to healthy 
participants. 
Objectives: 
 
Primary Objective: To evaluate the safety and tolerability of a single 3-g 
intravenous dose of IXT-m200 in healthy participants via physical 
examinations and adverse event, vital sign, ECG, and clinical laboratory 
testing. 
 
Secondary Objectives: To characterize the pharmacokinetics of IXT-m200 
following a single 3-g intravenous dose of IXT-m200 in healthy 
participants by measurement of IXT-m200 concentrations. 
Endpoints: 
Primary Endpoint:   
• 
Number of participants with treatment-related AEs assessed by 
physical examinations and vital sign, AE, ECG, and clinical 
laboratory testing. 
Secondary Endpoints: 
• 
Time course of IXT-m200 concentrations 
Study Population: 
Approximately 9 healthy adults will be randomized into the study. 
Phase: 
1 
Description of Sites: 
Approximately 1 site in the US will enroll participants 
Description of Study 
Intervention: 
IXT-m200 is a high-affinity chimeric anti-METH monoclonal antibody that 
is well-tolerated in healthy volunteers and in non-intoxicated participants 
with METH use disorder when administered up to 20 mg/kg 
(approximately 1.5 g). It will be administered at a dose of 3 g 
(approximately 40 mg/kg) in this study. IXT-m200 or placebo treatment 
will be given by intravenous infusion over 30 minutes.  
Study Duration: 
Approximately 5 months 
Participant Duration: 
18 weeks 
 
 


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1.2 
SCHEMA 
 
 
 
 
Screening Visit
Day -30 to -1
Inpatient
Days 1 and 2
Subject 
participation 
concluded
•Laboratory tests and wellness check
•ECG and pregnancy test
•Blood samples for cytokines, PK, and HACA
•Randomization and dosing
•Informed consent
•Initial evaluations
•Laboratory tests
Follow-up 
Days 8, 15, 22, 29, 
36, 43, 64, 85, & 106
•Laboratory tests (Days 8, 28, and 63 only)
•Wellness check 
•Blood samples for PK
Final Study Visit
Day 127
•Wellness check 
•Pregnancy test
•Blood samples for PK and HACA
Follow for AEs


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1.3 
SCHEDULE OF ACTIVITIES 
 
Assessment a 
Screening 
Inpatient 
Follow-up (±1 day) 
Follow-up (±3 days) 
ET 
Study Week 
≤-1 
1 
2 
3-17 
18 
NA 
Study Day 
-30 to -1 
1b 
2 
8 
15, 22, 29, 36, 43, 
64, 85, 106 
127 
NA 
Informed consent 
X 
 
 
 
 
 
 
Initial evaluations 
Eligibility criteria 
Demographics 
Medical history and 
medications 
Vital signs c  
Physical exam  
Psychiatric evaluation 
Urine pregnancy test 
X 
 
 
 
 
 
 
Laboratory tests d 
X 
X 
X 
X 
X (29 and 64 only) 
 
X 
Urine drug screen 
 
X 
 
 
 
 
 
Wellness check 
Update medical history 
Update medications 
Vital signs c 
Targeted physical exam 
 
X 
X 
X 
X 
X 
X 
ECG e 
 
X 
 
 
 
 
 
Urine pregnancy test 
 
X 
 
 
 
X 
X 
Blood for cytokines f 
 
X 
 
 
 
 
 
Blood for PK g  
 
X 
X 
X 
X 
X 
X 
Blood for HACA h 
 
X 
 
 
 
X 
X 
Randomization 
 
X 
 
 
 
 
 
Dose administration i 
 
X 
 
 
 
 
 
AE monitoring 
 
Continuous 
X 
Abbreviations: ECG – electrocardiogram; ET – early termination visit; HACA – human anti-chimeric antibodies; 
NA – not applicable; PK – pharmacokinetic 
 
a Descriptions of assessments are in Section 8.1. 
b Study Day -1 is the day prior to the first dose. Study Day 1 is the day of the first dose. 
c Vital sign measurements will be taken on Day 1 starting with a pre-dose measurement (≤30 min prior), then 0.25, 
0.5, 1, 2, and 4 hours (±5 min) after dosing starts, and as needed afterward until normalization. Measurements will 
be obtained once on each non-dosing day. Each test may be repeated once at each time point if the initial result is 
out of range.  
d Laboratory tests require blood and urine sampling for hematology, serum chemistry, and urinalysis. Samples are to 
be taken at screening, pre-dose and 2-hr post-dose completion (±10 min) on Day 1, and once on Days 2, 8, 29, and 
64. 
e ECGs are to be done pre-dose (up to 2 hr prior) and 30-min post-dose completion (±15 min) on Day 1.   
f Cytokine samples are to be taken pre-dose (≤60 min prior) on Day 1. If a participant has an infusion reaction, 
cytokine sampling at 1- and 4-hours post-dose (±10 min) should be performed. If no infusion reaction is observed, 
pre-dose samples will not be analyzed. 
g PK samples are to be taken pre-dose (≤30 min prior), then 1, 4, and 8 hr (±10 min) and 24 hr (±30 min) after the 
start of the infusion on Day 1. All other PK samples are to be collected once each visit.  
h HACA samples are to be taken pre-dose (≤60 min prior) on Day 1 and once on Day 126.  
i Doses will be given over 30 min by IV infusion. 
 


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2 
INTRODUCTION 
 
2.1 
BACKGROUND  
 
2.1.1 STUDY AGENT 
 
IXT-m200, also called ch-mAb7F9, binds METH with high selectivity and affinity. The product contains 
a murine METH-binding variable region and the constant domains of a human immunoglobulin G 
(IgG) 2κ. This antibody isotype was chosen because of the lower risk of immune response compared to an 
IgG1 or IgG3. IXT-m200 targets METH, does not rely on binding to any endogenous target for its action, 
and has been well-tolerated in previous clinical studies (see below). 
  
Through the binding of METH in the bloodstream, it is anticipated that IXT-m200 will alter the 
pharmacokinetics (PK) of METH and decrease concentrations of METH reaching its active sites in the 
brain. The presence of IXT-m200 should therefore decrease the perceived pleasurable effects of METH. 
Over the longer term, when combined with behavioral therapy, IXT-m200 should reduce the frequency of 
METH use over time. 
  
2.1.2 NONCLINICAL IXT-M200 EFFECTIVENESS SUMMARY 
 
A significant body of nonclinical work in rats indicates that IXT-m200 may be effective as a treatment for 
METH use disorders by altering METH CNS effects. The potential human efficacy of IXT-m200 is 
demonstrated by multiple in vivo preclinical studies using the murine version of the antibody, called 
mAb7F9. The studies and results are summarized in the Investigator’s Brochure (IB). 
 
2.1.3 NONCLINICAL SAFETY SUMMARY OF IXT-M200 
 
InterveXion has performed multiple nonclinical safety studies with IXT-m200 which support dosing in 
humans, and the results of these studies are summarized in the IB. Briefly, a single-dose GLP toxicology 
study was performed in rats at doses up to 400 mg/kg. No test article-related mortality or evidence of 
systemic toxicity was observed and no target organs were identified (No Observed Adverse Effect Level 
(NOAEL) > 400 mg/kg). High titers of anti-IXT-m200 antibodies were detected in the serum of 1 rat each 
dosed at 50 mg/kg, 150 mg/kg, and 400 mg/kg. Furthermore, a  repeat-dose GLP toxicology study was 
performed in rats using weekly dosing at doses up to 300 mg/kg/week for 26 weeks. No test-article 
related mortality or evidence of systemic toxicity was observed and no target organs were identified 
(NOAEL > 300 mg/kg). No animals in this study were confirmed positive for anti-IXT-m200 antibodies. 
 
Additional nonclinical safety studies have also been performed in combination with METH to evaluate 
the potential interaction of IXT-m200 and METH. Results from these studies are also summarized in the 
IB, and there were no adverse effects, as measured by cardiovascular parameters or body 
temperature/activity, attributed to IXT-m200 administration when followed by high doses of METH.  
 
2.1.4 CLINICAL RESEARCH SUMMARY 
 
A Phase 1 study of the safety of single doses of IXT-m200 in healthy humans has been completed1. In this 
first clinical study, 42 participants (17 females) were dosed in 5 groups (0.2, 0.6, 2, 6, or 20 mg/kg 
IXT-m200), with 10 participants receiving placebo (saline). Pharmacokinetic results indicated that 
IXT-m200 is similar to other IgGs, with an elimination half-life of ~18 days, volume of distribution (Vd) 
of ~5 L and clearance of ~200 mL/d. The disposition of IXT-m200 did not appear to be affected by dose. 


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There were no serious adverse events (SAEs) or serious adverse reactions during the conduct of the study. 
There were 3 adverse events in 2 subjects that were attributed to IXT-m200. A mild infusion reaction 
(Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 Grade 3) and bronchospasm (Grade 
2) occurred in the same subject. The symptoms included a brief period of bronchospasm with no drop in 
oxygen saturation that resolved with stopping the infusion. A separate subject experienced an AE of mild 
proteinuria (Grade 1). Both subjects were in the same dose group (2 mg/kg IXT-m200).  
  
Samples from all participants were tested for immunogenicity, ie, anti-IXT-m200 antibodies. Samples 
from only 4 (12.5%) IXT-m200 treated participants were confirmed to have low titers. One of these 4 
participants also provided a pre-dose sample that screened positive for anti-IXT-m200 antibodies. The 
development of anti-IXT-m200 antibodies did not appear to be dose-related. 
  
Overall, there were no apparent safety or tolerability concerns identified when IXT-m200 was dosed over 
the range from 0.2 to 20 mg/kg. Therefore, a maximum tolerated dose was not reached. 
  
Following the Phase 1 study, a Phase 2 study of IXT-m200 was conducted (STAMPOUT: Study of 
Antibody for Methamphetamine Outpatient Therapy, NCT03336866). This was a parallel-group, placebo-
controlled, double-blind study in otherwise healthy, non-treatment seeking participants who use METH. 
Participants were required to discriminate METH (30 mg, intravenous) from placebo with a drug effects 
questionnaire (DEQ) to qualify. Those who qualified received single doses of IXT-m200 (6 or 20 mg/kg) 
or placebo followed by weekly METH challenges for up to 4 weeks. The challenges consisted of METH 
(30 mg, intravenous) and placebo, separated by 4 hours. Safety, METH and IXT-m200 PK, and DEQ data 
were collected for up to 126 days. 
 
56 participants were included in the pharmacokinetic and safety sets, with 20 receiving the placebo, 18 
receiving 6 mg/kg IXT-m200, and 18 receiving 20 mg/kg IXT-m200. IXT-m200 was well-tolerated. 
There were no SAEs and all AEs were grades 1 or 2; all resolved as expected. Importantly, IXT-m200 did 
not result in substantial hemodynamic changes when compared with METH alone. IXT-m200 met the 
primary study endpoint, and significantly (p<0.001) altered METH AUC and Cmax with all METH 
challenges, up to 30-fold and 8-fold respectively, without altering METH renal elimination . IXT-m200 
decreased METH Vd over 9-fold after the first METH challenge. Though the study was not powered for 
pharmacodynamic changes, there were favorable trends in DEQ data, suggesting that IXT-m200 has 
favorable effects on the reinforcing effects of METH use. This study is discussed further in the IB. 
 
2.2 
RISK/BENEFIT ASSESSMENT   
 
2.2.1 KNOWN POTENTIAL RISKS  
2.2.1.1 GENERAL MAB POTENTIAL RISKS 
 
Given that there are more than 50 Food and Drug Administration (FDA)-approved mAb medications, and 
several with non-endogenous targets that have been approved (Anthim®, Abthrax®, Synagis®, 
Zinplava®) or are in late-stage clinical trials, risks may be predicted and strategies developed to mitigate 
these risks based on an understanding of the pharmacology of these approved medications. These are 
outlined in the IB along with a summary of the nonclinical toxicology studies of IXT-m200 in absence 
and presence of high-dose METH in rats.  
 


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2.2.1.2 SPECIFIC IXT-M200 POTENTIAL RISKS 
 
During the Phase 1 study of IXT-m200, there were no SAEs or discontinuations due to treatment-
emergent AEs. Overall, 90% of participants experienced at least 1 AE, but there were no apparent trends 
in the frequency, relatedness, or severity of AEs with increased dose or between active- and placebo-
treated participants1. 
  
There were 3 adverse events in 2 subjects that were attributed to IXT-m200. A mild infusion reaction 
(CTCAE v.4.0 Grade 3) and bronchospasm (Grade 2) occurred in the same subject. The symptoms 
included a brief period of bronchospasm with no drop in oxygen saturation that resolved with stopping 
the infusion. A separate subject experienced an AE of mild proteinuria (Grade 1). Both subjects were in 
the same dose group (2 mg/kg IXT-m200). 
  
The most frequently reported AEs were increased blood creatine phosphokinase, upper respiratory tract 
infection, decreased hemoglobin, headache, increased aspartate aminotransferase (AST) and alanine 
aminotransferase (ALT), proteinuria, decreased white blood cell (WBC) count, and nasal congestion. 
  
Because IXT-m200 is a mouse-human chimeric antibody, the potential for a human anti-chimeric 
antibody (HACA) response exists. Following single doses of IXT-m200, only 4 of 32 participants were 
confirmed positive for HACA in the Phase 1 study. The development of HACA did not appear to be dose-
related. 
 
In the Phase 2a STAMPOUT study, all AEs were grade 1 or grade 2. Common AEs included palpitations, 
tachycardia, dry mouth, nausea, injection site pain, headache, euphoria, hypervigilance, and 
hyperhidrosis. All of these AEs are expected in people receiving METH, and all participants in this study 
received METH. Of these, only blurred vision, nausea, feeling abnormal, and dry mouth were probably 
related to IXT-m200; each AE was reported by only one subject who received IXT-m200. Furthermore, 
none of the AEs associated with METH appeared to be exacerbated by IXT-m200. For example, an 
analysis of heart rate changes following METH administration demonstrated that average percent heart 
rate increase, and average peak heart rates were not changed in the presence of IXT-m200. Plus, the 
individual maximum attained heart rate in each group was 139 (placebo), 142 (6 mg/kg), and 144 
(20 mg/kg).  
 
Finally, as in the Phase 1 study, samples from all participants were tested for HACA. Only one participant 
in each IXT-m200 dose group had notable titers of anti-IXT-m200 antibodies, and the PK of IXT-m200 
in these participants did not differ from other participants in the dose group. 
 
2.2.2 KNOWN POTENTIAL BENEFITS  
 
IXT-m200 is an investigational product which has no pharmacologic activity beyond binding METH, and 
will convey no benefit to participants who do not use METH.  
 
2.2.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
The risks of exposing the participants to IXT-m200 are justified to determine its safety at this increased 
dose level of 3 g.  
 


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3 
OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
Primary 
 
To evaluate the safety and tolerability of a single 
3-g intravenous dose of IXT-m200 in healthy 
participants.  
Number of participants with treatment-related AEs 
assessed by physical examinations and vital sign, 
ECG, and clinical laboratory testing. 
Secondary 
 
To characterize the pharmacokinetics of IXT-
m200 following a single 3-g intravenous dose of 
IXT-m200 in healthy participants.  
Time course of IXT-m200 concentrations 
 
4 
STUDY DESIGN  
 
4.1 
OVERALL DESIGN 
 
Approximately 9 participants will be enrolled in the study in a single cohort. Participants will be 
randomized to 3 g IXT-m200 or placebo at 7:2. Each will receive their dose as a 30-min IV infusion, then 
remain at the study site overnight to complete Day 1 and Day 2 assessments (e.g., ECG, laboratory 
assessments, blood draws, and vital signs). Following discharge on Day 2, participants will return to the 
clinic for follow-up PK and safety assessments on Day 8, then every 1-3 weeks thereafter until Day 127. 
 
4.2 
JUSTIFICATION FOR DOSE 
 
The IXT-m200 dose of 3 g was selected for this study because it is potentially effective in reducing 
METH effects for several weeks, and will be used in an upcoming repeat-dose Phase 2 clinical study in 
patients with METH use disorder. Prior to this Phase 2 study, safety and pharmacokinetics of a single 3-g 
dose in healthy volunteers will be established.  
 
IXT-m200 will be administered via IV infusion over 30 min. This is necessary because it is a protein 
medication and would be metabolized to inactive components in the gastrointestinal tract if administered 
orally. The volume that must be given is too large to allow for intramuscular or subcutaneous 
administration based on the current formulation. This will result in a rate of 40 mg/kg/hr in a 75-kg 
person, which is significantly lower than doses given during a multiple-dose GLP toxicology study in 
which the slowest rate for the high dose was 1800 mg/kg/hr.  
 
4.3 
END OF STUDY DEFINITION 
A participant is considered to have completed the study if s/he has completed all phases of the study 
including the last visit or last scheduled procedure shown in 1.3. The end of the study is defined as 
completion of the last visit or procedure in the trial globally. 
Participants who have an ongoing AE at the time of study completion will be followed as described in 
8.2.5. 


Phase 1 Safety, Tolerability, and Pharmacokinetics of IXT-m200 in Healthy Volunteers 
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5 
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
 
Eligible participants will:  
1. Be at least 18 years of age at the time of study consent; 
2. Be able and willing to read, comprehend, and give Authorization for Use/Disclosure of Health 
Information (HIPAA) and informed consent; 
3. Be healthy, based on the pre-study medical evaluation (medical history and physical exam, vital 
signs, ECG, and clinical laboratory evaluations); 
4. Be willing to comply with study instructions and dosing, agree to make all appointments, and 
complete the entire course of the study; 
5. Be of nonchildbearing potential or agree to use protocol-specified method(s) of birth control 
throughout study participation; 
6. Agree to adhere to Lifestyle Considerations throughout study duration (see section 5.3). 
 
5.2 
EXCLUSION CRITERIA 
 
Eligible participants will NOT:  
1. Have a history of treatment with a monoclonal antibody in the past year; 
2. Have a known contraindication or sensitivity to IXT-m200 based on known allergies to other mAbs, 
any inactive ingredient of IXT-m200, or any other products required for the study procedures; 
3. Have a history of alcohol and/or drug use disorder, as determined by DSM-5 criteria; 
4. Have a history of stimulant use, including methamphetamine and amphetamine; 
5. Be currently taking certain other drugs and medications, including: “designer drugs” (e.g., 3,4-
methylenedioxyMETH (MDMA, Ecstasy, Adam, XTC) and its N-dimethyl metabolite 
methylenedioxyamphetamine (MDA), anti-orexigenic drugs (including over-the-counter medications 
for weight loss), or be chronic users of phenethylamine compounds (e.g., phenylpropanolamine, 
ephedrine, pseudoephedrine, amphetamine, phentermine, phenmetrazine, methylphenidate, 
diethylpropion, and propylhexedrine); 
6. Have a positive drug screen for any psychoactive substances (legal or nonlegal) on Day 1 prior to 
dosing; 
7. Have a history of severe allergy (rash, hives, breathing difficulty, etc) to any medications; 
8. Have a history of allergic or environmental bronchial asthma within the past 3 years; 
9. Have a clinically significant history of or current abnormality or disease of any organ system, 
including renal, hepatic, gastrointestinal, cardiovascular, pulmonary (including chronic asthma), 
endocrine (eg, diabetes), central nervous, or hematologic systems, or recent clinically significant 
surgery, 
10. Have a history of seizure, epilepsy, severe head injury, multiple sclerosis, or other known 
neurological conditions,  
11. Have a planned or scheduled surgical procedure during the study; 
12. Have recently donated blood or plasma (within 30 days of study drug dose); 
13. Have a current diagnosis of anorexia nervosa or bulimia disorder; 
14. Be currently participating or has participated within the last 30 days prior to the start of this study in a 
drug, device, or other interventional research study; 
15. Be pregnant or lactating; 
16. In the Investigator’s or Sponsor’s (or designee) opinion, be inappropriate for the study. 


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5.3 
RATIONALE FOR THE SELECTED POPULATION 
 
Phase 1 PK and safety studies have frequently been done in healthy subjects with many chimeric mAbs, 
including IXT-m2001. This study is designed to increase the dose level tested in healthy participants prior 
to testing in patients that use METH. 
 
5.4 
LIFESTYLE CONSIDERATIONS 
 
IXT-m200 may alter the pharmacokinetics of molecules that are structurally similar to METH; therefore, 
participants should not take drugs such as amphetamine (including Adderall®, Dexedrine®, or Evekeo®) 
or MDMA (also known as ecstasy) for the duration of study participation. 
 
Participants are prohibited from the following during the study period: 
• 
Ingesting or using any other investigational drug or device. 
• 
Donating blood, plasma, platelets, eggs or sperm. 
 
Participants will be encouraged to limit their ethanol consumption to approximately 1 drink per day for 
women and 2 drinks per day for men while in the study. 
 
Participants are required to practice an adequate method of birth control, including intrauterine device 
(IUD); oral, dermal ("patch"), implant or injected contraceptives; tubal ligation; barrier methods with 
spermicide; or vasectomized partner throughout the study. 
 
5.5 
SCREEN FAILURES 
 
Screen failures are defined as participants who consent to participate in the clinical trial but are not 
subsequently randomly assigned to the study intervention or entered in the study. A minimal set of screen 
failure information is required to ensure transparent reporting of screen failure participants, to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to respond to 
queries from regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any serious adverse event (SAE). 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) because of a short 
term or temporary medical issue may be rescreened (≥30 days later).  
 
5.6 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
Traditional advertising methods will be utilized to ensure recruitment goals are met. This will be 
accomplished by using advertising such as print, electronic, and/or digital newspapers, flyers, mailers, 
billboards, television, radio, online, social networking, and other means of communicating with potential 
participants  that are IRB-approved. The site subject database may also be searched to identify potential 
participants. 
  
All recruitment materials will refer interested persons to a contact email, website, or telephone number, 
and they will be approached by a study staff member trained to provide the caller with information about 
the study and to schedule interested persons for an in-person interview. Participants will undergo an initial 
screening and those who pass the initial screen will undergo informed consent procedures. 
  


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To address retention, we will incorporate standard procedures used in previous Phase 1 trials, which 
include financial compensation for study participation.  
 
6 
STUDY INTERVENTION 
 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
 
6.1.1 STUDY INTERVENTION DESCRIPTION 
 
The study drug, IXT-m200, is a chimeric mAb that binds METH with high affinity. The product contains 
a murine METH-binding variable region and the constant domains of a human IgG 2κ. This antibody 
isotype was chosen because of the lower risk of immune response compared to an IgG1 or IgG3. 
IXT-m200 specifically targets METH and does not rely on binding to any endogenous target for its 
action. 
  
6.1.2 DOSING AND ADMINISTRATION 
 
Participants will only be randomized and dosed with study drug if they have passed all screening 
requirements before or on Day 1. Participants will be randomized on Day 1 to receive 3 g IXT-m200 or 
placebo (7:2). Each participant will receive 1 dose of assigned study drug on Day 1.   
 
Participants should lie supine or semi-reclined during dose administration. Each dose will be given with 
an infusion pump over 30 minutes with a 50-mL saline flush dispensed after each dose to ensure the entire 
dose is flushed through the infusion set. The study drug infusion start/stop time, infusion rate, infusion 
volume, whether the infusion was completed, if it was stopped, or stopped and restarted will be recorded.  
 
Participants will be asked to eat a light meal prior to arriving at the study center but not have anything but 
clear liquids to eat or drink for 1 hour before appointment time. Participants will be offered a light meal 
after dosing completion. 
 
All study drug doses will be administered in a blinded manner by the Investigator or designee. 
 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
 
Study Drug: All required IXT-m200 vials will be shipped by Sponsor to the study site prior to study 
initiation. All unused supplies will be checked against the drug accountability records during the study 
and/or at the end of the study. All unused study drug must be disposed of in accordance with applicable 
requirements.  
  
Placebo: An unblinded member of the site staff will be responsible for acquiring commercially available 
normal saline for use as placebo for IXT-m200. 
 
6.2.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
 
Study Drug: IXT-m200 is formulated as a solution containing approximately 20 mg/mL IXT-m200 in 10 
mM sodium phosphate, pH 6.5, 150 mM sodium chloride, and 0.05% w/v polysorbate 80. The product is 


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a clear solution packaged in glass vials with stoppers and flip-off seals. Catalent Pharma Solutions 
manufactures the formulated active pharmaceutical ingredient.  
 
Labels will be similar to the following: 
  
InterveXion Therapeutics® 
Anti-methamphetamine IXT-m200 
18.5-21.5 mg/mL 
Manufactured: DD MMM YYYY 
DP Lot: XXXXXXX 
Catalent Lot: XXXXX 
10 mM sodium phosphate, 150 mM sodium chloride, pH 6.5, with 0.05% Tween 80 
Store refrigerated at 2 to 8°C 
CAUTION: New Drug – Limited by Federal (or United States) law to investigational use only. 
InterveXion Therapeutics, LLC 
4301 W. Markham, Slot 831, Little Rock, AR 72205 
 
Placebo: Normal saline (0.9% sodium chloride) should be a clear solution for injection. Packaging and 
labeling will be appropriate for use. 
 
Only unblinded study staff will have access to the labeled study drugs.   
 
6.2.3 PRODUCT STORAGE AND STABILITY 
 
IXT-m200 vials are single-use and should be stored refrigerated at 2 to 8°C. The stability of the product is 
still under investigation and stability protocols will run concurrent to the study. A previous lot of 
IXT-m200 remained stable after 48 months of refrigerated storage when the stability protocol was 
terminated. 
 
6.2.4 PREPARATION 
 
An unblinded staff member (e.g., pharmacist) will prepare the study drugs for administration. The 
appropriate amount of IXT-m200 should be administered over 30 min.  Since IXT-m200 is a clear 
solution, it will appear similar to saline placebo. 
  
Placebo: Normal saline requires no preparation prior to administration. 
 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
Each potential participant will be assigned a unique number in the screening process (screening number). 
This number will be used to identify the participant throughout the study.  
 
Participants who qualify will be randomized on Day 1 to 3 g IXT-m200 or placebo (7:2). 
 
Unblinding of treatment assignment during the study is discouraged and should occur only if it is 
absolutely necessary for the Investigator, Sponsor, or participant to know what he or she received for 
safety reasons. If the Sponsor or the Investigator deems identification of the study drug to the participant 
as necessary for the purpose of providing urgent care, the pharmacy will inform the Investigator of the 
assignment, who will notify the Sponsor and participant. The process of unblinding will be appropriately 
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possible, the Sponsor should be notified prior to unblinding; otherwise, they must be notified within 24 
hours after unblinding. 
 
6.4 
STUDY INTERVENTION COMPLIANCE 
 
Study drug is administered by intravenous infusion by qualified personnel who are blinded to the 
treatment assignment of the participant. Compliance with dosing will be verified by reference to the CRF 
documentation of dosing. 
 
6.5 
CONCOMITANT THERAPY 
 
All concomitant medications (i.e., prescription medications, over-the-counter medications, 
non-prescription medications, and supplements) taken during study participation will be recorded on the 
CRF. For this protocol, a prescription medication is defined as a medication that can be prescribed only 
by a properly authorized/licensed clinician.  
 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
 
The criteria outlined in section 8.2.3.1 will be used to categorize the severity of all AEs. The Sponsor, in 
consultation with the Investigator, will suspend enrollment until a full safety review is performed if any 1 
of the following events occurs, unless the event was clearly unrelated to study drug administration: 
 
• 
Two (2) participants experience a Grade 3 AE; or, 
• 
One (1) participant experiences a Grade 4 AE; or, 
• 
A death occurs.  
 
Events unrelated to study drug administration include those that are temporally unrelated to study drug 
administration, such as events occurring prior to dosing; or events in which the participant is a passive 
victim, such as a passenger in a motor vehicle crash. 
 
A decision to reinitiate enrollment will be made by the Sponsor following any necessary consultation with 
the appropriate authorities based on the results of the safety review. All other study procedures will 
continue per protocol during any study pause. 
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
 
Participants who withdraw consent for future study visits (following early termination assessments) will 
be considered ‘withdrawn’. Participants are free to withdraw at any time upon request; they will be asked 
to complete early termination assessments as soon as possible. 
 
Participants that receive less than the complete single dose of study drug but agree to continue 
participation in other study procedures and assessments will be considered ‘discontinued’. Participants are 
free to discontinue at any time during dosing upon request. Participants will be encouraged to complete 
study visits and assessments, even if they elect to discontinue study drug administration. In this case, all 
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The Investigator may discontinue a participant from study drug administration for the following reasons: 
• 
the participant meets an exclusion criterion (either newly developed or not previously recognized) 
that precludes further study participation, such as an infusion reaction, 
• 
any clinical AE, laboratory abnormality, or other medical condition or situation occurs such that 
continued participation in the study would not be in the best interest of the participant,  
• 
significant non-compliance by the participant, 
• 
if, in the Investigator’s opinion, continuation with study drug administration would be detrimental to 
the participant’s well-being,   
• 
at the specific request of InterveXion (Sponsor) or the Investigator.  
 
In all cases, the reason for withdrawal or discontinuation must be recorded in the CRF and in the 
participant’s medical records. If the reason is not known, an attempt must be made to follow up with the 
participant to establish whether the reason was an AE, and, if so, this AE must be reported. Once the 
participant has been contacted and expresses their decision to withdraw from further participation in the 
study, the research staff will cease to try to make further contact. 
 
Participants who withdraw or are discontinued may be replaced at Sponsors discretion until there are 6 
participants who have completed the protocol through Day 63. 
 
7.3 
LOST TO FOLLOW-UP 
 
A participant will be considered lost to follow-up if he or she fails to return for the final scheduled visit, 
including an early term visit, and is unable to be contacted by the study site staff.  
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
• 
The site will attempt to contact the participant and reschedule the missed visit, counsel the 
participant on the importance of maintaining the assigned visit schedule, and ascertain if the 
participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the Investigator or designee will make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if necessary, a 
certified letter to the participant’s last known mailing address or local equivalent methods). These 
contact attempts should be documented in the participant’s medical record or study file.  
• 
Should the participant continue to be unreachable, he or she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 
SAFETY AND OTHER ASSESSMENTS 
 
Assessments are to be performed at the time points described in the Schedule of Activities (1.3).  
 
8.1.1 ELIGIBILITY CRITERIA 
 
• 
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria checklist 
should be used to assess participants for Substance Use Disorders (including METH, opioids, 
alcohol, nicotine, marijuana, etc.) 


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• 
Urine drug screen to include illicit substances (barbiturates, benzodiazepines, cocaine, opiates, 
phencyclidine, MDMA, METH, or amphetamine) on Day 1 (a positive test for 
tetrahydrocannabinol may be acceptable if the subject is not intoxicated at the discretion of the 
Investigator). 
 
8.1.2 MEDICAL AND MEDICATION HISTORY 
 
• 
A complete medical history will be obtained by interview and any available medical records at 
screening. Interim medical history will be obtained at all subsequent time points. 
• 
A complete medication history will be obtained by interview and any available medical records at 
screening, with particular attention to any medications taken in the previous 12 months. The 
medication history, including concomitant medications, will be updated at all subsequent visits. 
 
8.1.3 VITAL SIGNS 
 
• 
Vital sign measurements (heart rate, blood pressures [systolic and diastolic], respiratory rate, 
temperature [oral], and pulse oximetry readings) will be obtained after the participant has been 
resting for at least 5 minutes. 
 
8.1.4 PHYSICAL EXAM 
 
• 
Physical examination (excluding rectal/genital and breast examination) will consist of an 
examination of the following: general appearance, neurological, skin, head, eyes, ears, nose, throat, 
neck, lymph nodes, chest, heart, abdomen, and extremities.  
• 
Targeted physical exams will include heart, lungs, abdomen, skin, and site of injection. Additional 
areas may be targeted if AEs or other complaints require appropriate and more detailed exams. 
• 
Height and weight will be recorded at screening; weight will be recorded at subsequent visits. 
 
8.1.5 PSYCHIATRIC EVALUATION 
 
• 
A psychiatric history will be obtained at screening evaluating for (but not limited to) the following: 
major current depression, psychosis, bipolar illness, organic brain disorder, anorexia nervosa or 
bulimia disorder or dementia, which require ongoing medication or which would make study 
compliance difficult in the opinion of the Investigator.  
 
8.1.6 PREGNANCY TEST 
 
• 
Urine pregnancy tests will be performed on all females at designated visits. 
 
8.1.7 LABORATORY TESTS  
 
The below laboratory tests will be centrally assessed: 
• 
Hematology 
o Erythrocytes: red blood cell (RBC) count, hematocrit, hemoglobin, mean corpuscular 
hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, red cell 
distribution width, and reticulocyte count as an absolute value. 
o Leukocytes: WBC and differential (basophils, eosinophils, lymphocytes, monocytes, and 
neutrophils) reported as absolute values. 


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o Coagulation: platelet count, prothrombin time measured as international normalized ratio, 
activated partial thromboplastin time. 
• 
Serum Chemistry 
o Liver: alkaline phosphatase, ALT, AST (serum glutamic-oxaloacetic transaminase), bilirubin 
(total, direct, and indirect), gamma-glutamyl transferase, and lactic dehydrogenase. 
o Renal: blood urea nitrogen, creatinine, and uric acid. 
o Electrolytes, sodium, potassium, chloride, and carbon dioxide. 
o General: CPK, albumin, calcium, magnesium, glucose (fasting), phosphate, protein (total), 
amylase, and lipase. 
• 
Urinalysis 
o Microscopic: pH, specific gravity, glucose, ketones, leukocyte esterase, nitrites, occult blood, 
and protein, RBCs/hpf, WBCs/hpf, bacteria, casts, epithelial cells, mucous threads, and 
crystals. 
o Quantitative: protein and creatinine if microscopic is positive for protein. 
 
8.1.8 ELECTROCARDIOGRAMS 
 
• 
Electrocardiograms (12-lead) will be recorded after the participants have been supine for 5 minutes. 
Standard ECG parameters including heart rate, QRS, PR, QT, and QTc intervals will be measured. 
The ECGs will be read by a study physician to assess for any abnormalities. Abnormal ECG 
parameters include, but are not limited to ventricular hypertrophy, left axis deviation, atrial or 
ventricular arrhythmias other than sinus, and prolonged QTc (greater than 500 ms). ECGs may be 
repeated if data quality is compromised due to poor lead placement or machine error.  
• 
Confirmed ECG anomalies will be referred for appropriate medical follow-up. 
 
8.1.9 BLOOD FOR PK/HACA AND CYTOKINES 
 
• 
PK of IXT-m200: A validated enzyme linked immunosorbent assay procedure will be used to 
quantitate IXT-m200 in serum samples. Approximately 1 mL per sample is required. 
• 
HACA: A validated electrochemiluminescent procedure has been developed to quantitate HACA in 
serum samples. Approximately 1 mL per sample is required. These samples may be analyzed after 
the completion of this study. 
• 
Cytokine panel to include at a minimum IL-6, IL-8, and TNFα levels will be determined only if any 
study drug infusion reaction occurs.  
 
8.2 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.2.1 DEFINITION OF ADVERSE EVENTS (AE) 
 
An AE is any untoward medical occurrence in a person administered study drug, whether or not 
considered intervention-related. An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, 
whether or not related to the IXT-m200 dose.   
 
The AE may be: 
• 
a new illness; 
• 
worsening of a sign or symptom of the condition under treatment or of a concomitant illness; 
• 
an effect of the study medication, including comparator; or 
• 
a combination of 2 or more of these factors. 


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No causal relationship with IXT-m200 or with the clinical study itself is implied by the use of the term 
“AE”. Pre-existing conditions will not be reported as an AE unless there has been a substantial increase in 
the severity or frequency of the problem which has not been attributed to natural history. 
 
Surgical procedures themselves are not AEs; they are therapeutic measures for conditions that require 
surgery. The condition for which the surgery is required may be an AE. Planned surgical measures 
permitted by the clinical study protocol and the condition(s) leading to these measures are not AEs. 
 
Adverse events fall into the categories “nonserious” or “serious”. 
 
8.2.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
 
An SAE is an AE that at any dose: 
 
• 
results in death; 
• 
is life-threatening; 
• 
requires hospitalization or prolongation of existing hospitalization; 
• 
results in persistent or significant disability/incapacity; or 
• 
is a congenital anomaly/birth defect.  
 
The term “life-threatening” in the definition of “serious” refers to an event in which the person was at 
immediate risk of death at the time of the SAE; it does not refer to an SAE which hypothetically might 
have caused death if it were more severe. 
 
Medical and scientific judgment will be exercised in deciding whether other AEs, such as important 
medical events that may not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the person or may require intervention to prevent one of the other outcomes listed above. 
These will also usually be considered serious.  
 
8.2.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.2.3.1 SEVERITY OF EVENT 
 
The general approach outlined by the Club Phase 1 working group in the British Journal of Clinical 
Pharmacology2 will be used to categorize the severity of all AEs. The stopping rules outlined in Section 
7.1 will apply.  
 
The following criteria will be used:  
• 
Grade 1: Transient or mild discomfort; does not interfere with daily activity; no medical 
intervention/treatment required,  
• 
Grade 2: Mild to moderate limitation in activity, some assistance may be needed; no or minimal 
intervention/treatment required, including but not limited to mild analgesics, antacids or 
antibiotics,  
• 
Grade 3: Marked limitation in activity, some assistance usually required; medical 
intervention/treatment required,  
• 
Grade 4: Extreme limitation in activity, significant assistance required; significant medical 
intervention/treatment, likely requiring hospitalization.  
 


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For example, if hypotension is not immediately responsive to medications, this will constitute a Grade 3 
reaction and it will be documented as such. Similarly, if bronchospasm (SaO2 < 93% on oxygen) occurs 
and requires medications, this will constitute a Grade 3 reaction, and will be documented as such.  
 
8.2.3.2 RELATIONSHIP TO STUDY INTERVENTION 
 
All adverse events (AEs) must have their relationship to study intervention assessed by the clinician who 
examines and evaluates the participant based on temporal relationship and his/her clinical judgment. The 
degree of certainty about causality will be graded using the categories below. In a clinical trial, the study 
product must always be suspect.  
 
DEFINITELY – The AE:  
• 
is clearly related to the investigational agent or research intervention;  
• 
has a temporal relationship to the administration of the study drug;  
• 
follows a known pattern of response;  
• 
occurs in the absence of an alternative cause.  
 
PROBABLY – The AE:  
• 
follows a reasonable temporal sequence from study drug administration;  
• 
abates upon discontinuation of the drug;  
• 
cannot be reasonably explained by the known characteristics of the participant’s clinical state.  
 
POSSIBLY – The AE:  
• 
follows a reasonable temporal sequence from study drug administration;  
• 
could have been produced by the participant’s clinical state or by other modes of therapy 
administered to the participant.  
 
UNLIKELY – The AE:  
• 
does not follow a reasonable temporal sequence from study drug administration;  
• 
is readily explained by the participant’s clinical state or by other modes of therapy administered 
to the participant.  
 
UNRELATED – The AE:  
• 
is definitely produced by the participant’s clinical state or by other modes of therapy administered 
to the participant.  
 
8.2.3.3 EXPECTEDNESS  
 
The Sponsor will be responsible for determining whether an AE is expected or unexpected. An AE will be 
considered unexpected if the nature, severity, or frequency of the event is not consistent with the risk 
information previously described for the study agent. 
 
8.2.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-
UP 
 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and 
interviews of a study participant presenting for medical care, during engagement of the participant with 
the smartphone app, or upon review by a Study Monitor. All AEs including local and systemic reactions 
not meeting the criteria for SAEs will be captured on the appropriate CRF. Information to be collected 


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includes event description, time of onset, clinician’s assessment of severity, relationship to study product 
(assessed only by those with the training and authority to make a diagnosis), and time of 
resolution/stabilization of the event. All AEs occurring while on study must be documented appropriately 
regardless of relationship. All AEs will be followed to adequate resolution.  
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any time 
during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity. All AEs characterized as intermittent require documentation of onset and 
duration of each episode.  
 
The Investigator will record all reportable events with start dates occurring any time after informed 
consent is obtained until the last day of study participation. At each study visit, the Investigator will 
inquire about the occurrence of AE/SAEs since the last visit. Events will be followed for outcome 
information until resolution or stabilization. 
 
8.2.5 ADVERSE EVENT REPORTING  
 
All AEs (whether serious or nonserious) that occur after the participant has been randomized into a 
treatment group must be documented on the appropriate pages of the CRF. For all AEs, the Investigator 
will provide an assessment of the AE, its treatment and resolution, and its relationship to IXT-m200. 
Every attempt should be made to describe the AE in terms of a diagnosis. If appropriate, component 
symptoms should also be listed below the diagnosis. If only nonspecific signs or symptoms are present, 
then these should be recorded as a diagnosis. 
 
All participants who have AEs, whether considered associated with the use of IXT-m200 or not, will be 
monitored to determine the outcome. The clinical course of the AE will be followed up according to 
accepted standards of medical practice, even after the end of the period of observation to a maximum of 
30 days following the end of study visit. Should the AE result in death, a full pathologist’s report should 
be supplied, if possible. 
 
8.2.6 SERIOUS ADVERSE EVENT REPORTING  
 
The Investigator will complete an SAE form within the following timelines:  
• 
All deaths and immediately life-threatening events, whether related or unrelated, will be recorded 
on the designated SAE form and submitted to the Sponsor within 24 hours of site awareness.  
• 
Other SAEs regardless of relationship, will be submitted to the Sponsor within 72 hours of site 
awareness.  
 
All SAEs will be followed until satisfactory resolution or until the site Investigator deems the event to be 
chronic or the adherence to be stable. Other supporting documentation of the event may be requested by 
the Sponsor and should be provided as soon as possible.  
 
Information not available at the time of the initial report will be documented on a follow-up SAE form. 
SAE information previously sent to the Sponsor will not be duplicated. When a nonserious event becomes 
serious, details will be forwarded immediately to the Sponsor on the designated SAE report form. 
 


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The study Sponsor will be responsible for notifying the Food and Drug Administration (FDA) of any 
unexpected fatal or life-threatening suspected adverse reaction as soon as possible, but in no case later 
than 7 calendar days after the sponsor's initial receipt of the information.  In addition, the Sponsor must 
notify FDA and all participating Investigators in an Investigational New Drug (IND) safety report of 
potential serious risks, from clinical trials or any other source, as soon as possible, but in no case later 
than 15 calendar days after the sponsor determines that the information qualifies for reporting. 
 
The NIDA Project Officer (PO) will be notified by the Sponsor within 72 hours of the SAE occurrence, 
and also via NIDA’s online Serious Adverse Event Tracking and Reporting System (SAETRS).  
 
8.2.7 REPORTING EVENTS TO PARTICIPANTS  
 
It is not anticipated that safety updates, including AEs or SAEs, will be reported to study participants. 
 
8.2.8 EVENTS OF SPECIAL INTEREST  
 
Not applicable. 
 
8.2.9 REPORTING OF PREGNANCY  
 
If a participant is found to be pregnant after they have received study drug, they should complete the 
study, with no further study drug doses administered, and be followed to determine the outcome of the 
pregnancy if the participant is willing. Generally, follow-up will be no longer than 6 to 8 weeks after the 
estimated delivery date. While pregnancy itself is not considered an AE or SAE, any pregnancy 
complications will be recorded as an AE or SAE. 
 
Pregnancies should be reported by the Investigator to the Sponsor within 2 days of identification.  
 
8.3 
UNANTICIPATED PROBLEMS 
 
8.3.1 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
 
Unanticipated problems involving risks to participants or others will include, in general, any incident, 
experience, or outcome that meets all of the following criteria:  
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and 
informed consent document; and (b) the characteristics of the participant population being 
studied;  
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and  
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized.  
 
8.3.2  UNANTICIPATED PROBLEM REPORTING  
 
Investigators will adhere to the following guidelines for prompt reporting: 
• 
Unanticipated problems that are SAEs should be reported to the IRB within 1 week of the 
Investigator becoming aware of the event. 


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• 
Any other unanticipated problem should be reported to the IRB within 2 weeks of the Investigator 
becoming aware of the problem. 
 
All unanticipated problems should be reported by the Sponsor to the supporting Department of Health and 
Human Services (DHHS) agency head (or designee), and Office for Human Research Protections (OHRP) 
within one month of the IRB’s receipt of the report of the problem from the Investigator. 
 
In some cases, the requirement for prompt reporting may be met by submitting a preliminary report to the 
IRB, the supporting DHHS agency head (or designee), and OHRP, with a follow-up report submitted at a 
later date when more information is available.  Determining the appropriate time frame for reporting a 
particular unanticipated problem requires careful judgment by persons knowledgeable about human 
participant protections.  The primary consideration in making these judgments is the need to take timely 
action to prevent avoidable harms to other participants. 
 
8.3.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
 
It is not expected that unanticipated problems will be reported to study participants, although appropriate 
study-related actions may be undertaken if determined necessary. 
 
9 
STATISTICAL CONSIDERATIONS  
 
A statistical analysis plan (SAP) will be prepared after the protocol is approved. This document will 
provide further details regarding the definition of analysis variables and analysis methodology to address 
all study objectives. The SAP will serve as a complement to the protocol and supersedes it in case of 
differences. 
 
9.1 
STATISTICAL HYPOTHESES 
 
This is primarily a PK and safety study that is not evaluating any formal hypotheses. 
 
Primary: 
1) To evaluate the safety and tolerability of a single 3-g intravenous dose of IXT-m200 in healthy 
participants. 
 
Secondary: 
1) To characterize the pharmacokinetics of IXT-m200 following a single 3-g intravenous dose of IXT-
m200 in healthy participants. 
 
9.2 
SAMPLE SIZE DETERMINATION 
 
The sample size chosen for this study is not based on statistical considerations. The number of subjects 
within each dose group was chosen based on historical experience with safety and tolerance trials and to 
match the study design used in the previous Phase 1 study with IXT-m200 which provided adequate 
safety and pharmacokinetic data. The sample size falls within the range of those used in other studies of 
this nature. 
 


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9.3 
POPULATIONS FOR ANALYSES 
 
The study analysis populations will consist of: 
 
Population 
Description 
Pharmacokinetic 
All participants who receive study drug and have at least one measured IXT-m200 
concentration at a scheduled PK time point after start of dosing. If participants do 
not receive a complete dose or have incomplete data, a decision will be made on a 
case-by-case basis as to their inclusion in the analysis. This population will be used 
for all PK summaries. 
Safety 
All participants who receive at least a dose of study drug, including placebo. This 
population will be used for all demographic and safety summaries. 
 
9.4 
STATISTICAL ANALYSES 
 
9.4.1 GENERAL APPROACH 
 
Safety and tolerability results will be summarized using descriptive statistics. Continuous variables will 
be summarized using appropriate summary statistics (e.g., the number of non-missing observations (n), 
mean, standard deviation, median, 25th and 75th percentiles, minimum, and maximum; geometric mean, 
coefficient of variation (CV%), and 95% CIs may also be presented, as appropriate). Categorical variables 
will be summarized with the frequency count and percentage of participants with non-missing data.  
 
The results of this study will be reported using summary tables, figures, and data listings. All summaries 
will be by treatment group. 
 
9.4.2 SAFETY ANALYSES 
 
All safety analyses will be performed on the Safety population. Descriptive statistics will be used to 
summarize AEs, serious AEs, AEs causing withdrawal or discontinuation from the study, AEs judged by 
the Investigator as potentially related to study drug, changes in laboratory and vital signs, and immune 
response by measurement of anti-IXT-m200 antibody levels. AEs will be tabulated by Medical Dictionary 
for Regulatory Activities (MedDRA) system organ class (SOC) and preferred term.  
 
9.4.3 BASELINE DESCRIPTIVE STATISTICS 
 
Demographic and baseline characteristics (age, sex, race, ethnicity, body weight, height, and BMI) will be 
summarized by treatment group using descriptive statistics for the Safety population. 
 
9.4.4 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
 
Participant-level listings will include collected data by treatment group and timepoint. 
 


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10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 INFORMED CONSENT PROCESS 
 
10.1.1.1 CONSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting the screening 
process, and subsequently administering study intervention. Other information may be provided to 
potential participants to help describe the nature and objectives of the study and clinical research in 
general, including access to web-based material describing the study. All such participant-facing 
information will be approved in advance by the study’s IRB. 
  
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study 
and continues throughout the individual’s study participation. Extensive discussion of risks and possible 
benefits of participation will be provided to the participants. Consent forms will be IRB-approved and the 
participant will be asked to read and review the document. The Investigator or designee will explain the 
research study to the participant and answer any questions that may arise. All participants will receive a 
verbal explanation in terms suited to their comprehension of the purposes, procedures, and potential risks 
of the study and of their rights as research participants. Participants will have the opportunity to carefully 
review the written consent form and ask questions prior to signing. The participants should have the 
opportunity to discuss the study with advisors or think about it prior to agreeing to participate. The 
participant will sign the Informed Consent Form (ICF) prior to any procedures being done specifically for 
the study. The participants may withdraw consent at any time throughout the course of the trial. A copy of 
the ICF will be given to the participants for their records. The rights and welfare of the participants will 
be protected by emphasizing to them that the quality of their medical care will not be adversely affected if 
they decline to participate in this study. 
 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
 
This study may be temporarily suspended or prematurely terminated at the sole discretion of the Sponsor. 
Written notification, documenting the reason for study suspension or termination, will be provided by the 
Sponsor to Investigators, NIDA, and, if necessary, FDA. Investigators will notify participants and the 
IRB. Sponsor will provide the reason(s) for the termination or suspension. Participants will be contacted, 
as applicable, and informed of changes to the study visit schedule. 
  
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants either related to the 
study intervention or unrelated events (such as a national health emergency); 
• 
Demonstration of efficacy that would warrant early termination; 
• 
Insufficient compliance to protocol requirements; 
• 
Data that are not sufficiently complete and/or evaluable; 
• 
Determination that the primary endpoint has been met; 


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• 
Determination of futility. 
 
At the discretion of the Sponsor, if temporarily suspended, the Study may resume once any relevant 
concerns have been addressed.  
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
 
Participant confidentiality is held strictly in trust by the participating Investigators, their staff, and the 
Sponsor and their agents. This confidentiality is extended to cover testing of biological samples in 
addition to the clinical information relating to participants. All personal details of participants will be 
treated as confidential by the Investigator and staff, and handling of personal data will be in compliance 
with the Health Insurance Portability and Accountability Act of 1996 and any applicable state laws 
governing the individual study sites. The study participants’ contact information will be securely stored at 
each clinical site for internal use during the study. At the end of the study, all records will continue to be 
kept in a secure location for as long a period as dictated by the reviewing IRB, institutional policies, or 
Sponsor requirements. 
  
The study protocol, documentation, data, and all other information generated will be held in strict 
confidence. No information concerning the study or the data will be released to any unauthorized third 
party without prior written approval from the Sponsor. The Study Monitor or other authorized 
representatives of the Sponsor, IRB or regulatory agencies may inspect any documents maintained by the 
Investigator, such as available medical records (office, clinic, or hospital) and pharmacy records for the 
participants in this study. The clinical study site will permit access to such records. 
  
Certificate of Confidentiality (COC): To further protect the privacy of study participants, a COC is 
granted by the National Institutes of Health (NIH) to all awardees conducting research that collects or 
uses identifiable, sensitive information. This certificate protects identifiable research information from 
forced disclosure. It allows the Investigator and others who have access to research records to refuse to 
disclose identifying information on research participation in any civil, criminal, administrative, 
legislative, or other proceeding, whether at the federal, state, or local level. By protecting researchers and 
institutions from being compelled to disclose information that would identify research participants, 
Certificates of Confidentiality help achieve the research objectives and promote participation in studies by 
helping assure confidentiality and privacy to participants. 
 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
 
Data collected for this study will be analyzed and stored as described above. After the study is completed, 
the de-identified, archived data will be maintained as long as regulations require, and will be made 
available by the Sponsor for use by other researchers including those outside of the study via a data 
sharing agreement.  
 
Blood and urine specimens remaining after clinical safety assessments are performed will be stored only 
until the clinical study report is completed. 
  
Blood specimens remaining after PK assessments are performed will be stored for at least 12 months for 
future drug metabolism and PK analysis if needed. 
 
No genetic analysis will be performed. 
 


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10.1.5 KEY ROLES AND STUDY GOVERNANCE 
 
Sponsor Contact 
Principal Investigator 
W. Brooks Gentry, MD 
Magdy L Shenouda, MD 
InterveXion Therapeutics, LLC  
Clinilabs 
4301 W. Markham St. #831 
Little Rock, AR 72205 
4 Industrial Way West, 2nd Floor 
Eatontown, NJ 07724 
501-320-7601 
212-994-4569 
gentrywilliamb@uams.edu 
mshenouda@clinilabs.com 
 
10.1.6 SAFETY OVERSIGHT 
 
As a Phase 1 study specifically designed to determine safety of a single 3-g dose of IXT-m200, robust 
evaluation of safety parameters and safety oversight will be conducted. The clinical site has been selected 
based on its track record as a Phase 1 safety unit, with all available resources for detection and 
management of any observed adverse events during the study. The Investigator will directly monitor 
participant safety and make real-time recommendations for any necessary interventions or study 
modifications to the Sponsor’s Medical Liaison. 
 
10.1.7 CLINICAL MONITORING 
 
Clinical site monitoring is conducted to ensure that the rights and well-being of study participants are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct of the 
trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with applicable 
regulatory requirement(s). 
  
Data at clinical sites will be monitored by one or more Study Monitors. Throughout the course of the 
study, the Study Monitor will make frequent contact with the Investigator. This will include telephone 
calls and on-site visits. During the on-site visits, the Study Monitor will perform source data verification 
(a comparison of the data in the electronic data capture systems with the participant’s medical records 
including verification of informed consent). This will require direct access to all original records for each 
participant (e.g., clinic charts). 
 
The Study Monitor will also perform drug accountability checks and will request to perform a review of 
the Investigator’s study file to assure completeness of documentation in all respects of clinical study 
conduct. 
  
Upon completion of the study, the Study Monitor will arrange for a final review of the study files, after 
which the files should be secured for the appropriate time period. The Investigator, or appointed delegate, 
will meet with the Study Monitor during the on-site visits and will cooperate in providing the documents 
for inspection and responding to inquiries. In addition, the Investigator will permit inspection of the study 
files by authorized representatives of the Sponsor or regulatory agencies. 
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
 
The clinical site will perform internal quality management of study conduct, data and biological specimen 
collection, documentation, and completion. Quality control (QC) procedures will be implemented 
beginning with the data entry system and data QC checks that will be run on the database will be 
generated. Any missing data or data anomalies will be communicated to the site(s) for clarification and 
resolution. 


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Following written Standard Operating Procedures (SOPs), the Study Monitor will verify that the clinical 
trial is conducted and data are generated and biological specimens are collected, documented (recorded), 
and reported in compliance with the protocol, GCP, and other applicable regulatory requirements.  
 
The investigational site will provide direct access to all source data/documents and reports for the purpose 
of monitoring and auditing by the Sponsor, and inspection by local and regulatory authorities. 
 
10.1.9 DATA HANDLING AND RECORD KEEPING  
 
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data collection is the responsibility of the clinical trial staff at each site under the supervision of the site 
Investigator. The Investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. All source documents should be completed in a neat, legible manner to 
ensure accurate interpretation of data.   
 
Data recorded in the CRF(s) derived from source documents should be consistent with the data recorded 
on the source documents. Hardcopies of any source document(s) used for recording data for each 
participant enrolled in the study will be filed at the investigative site to be reviewed by the Study Monitor 
for accuracy.  
 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical 
laboratory data will be entered into a 21 CFR Part 11-compliant data capture system. The data system 
includes password protection and internal quality checks, such as automatic range checks, to identify data 
that appear inconsistent, incomplete, or inaccurate. Clinical data will be entered directly from the source 
documents. 
 
10.1.9.2 STUDY RECORDS RETENTION  
 
Study documents should be retained for a minimum of 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing applications in an 
ICH region, or until at least 2 years have elapsed since the formal discontinuation of clinical development 
of the investigational product. These documents should be retained for a longer period, however, if 
required by local regulations. No records will be destroyed without the written consent of the Sponsor, if 
applicable. It is the responsibility of the Sponsor to inform the Investigator when these documents no 
longer need to be retained.  
 
The following records must be retained by the Investigator:  
• 
Signed ICFs for all participants 
• 
Screening log (if applicable), and enrollment log 
• 
Record of official communications between the site and the IRB 
• 
Composition of the IRB or other applicable statement  
• 
Record of all significant communications between the site and Sponsor  
• 
List of sub-Investigators and other appropriately qualified persons to whom the Investigator has 
delegated significant trial-related duties, together with their roles in the study and their signatures 
• 
Copies of CRFs and of documentation of corrections for all participants 
• 
Drug accountability records 
• 
Record of any body fluids or tissue samples retained 


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• 
All other source documents (medical records, hospital record copies, laboratory records, etc) 
• 
All other documents as listed in Section 8 of the ICH consolidated guideline on GCP (Essential 
Documents for the Conduct of a Clinical Trial) 
 
If the Investigator is unable to continue to store the study records, s/he must contact the Sponsor to make 
alternative arrangements. Details of these arrangements should be documented. 
 
10.1.10 
PROTOCOL DEVIATIONS  
  
A protocol deviation is any change, divergence, or departure from the study design or procedures defined 
in the protocol; or any noncompliance with the clinical trial protocol, GCP, or manual of procedures 
requirements. The noncompliance may be either on the part of the participant, an Investigator, or study 
site staff. As a result of deviations, corrective actions are to be developed by the site and implemented 
promptly. All deviations will be compiled in a centralized location. 
  
These practices are consistent with ICH E6: 
• 
4.5 Compliance with Protocol, Sections 4.5.1, 4.5.2, and 4.5.3 
• 
5.1 Quality Assurance and Quality Control, Section 5.1.1 
• 
5.20 Noncompliance, Sections 5.20.1, and 5.20.2. 
 
It is the responsibility of the site to use continuous vigilance to identify and report deviations in a timely 
manner. The Investigator will document and explain any deviation from the approved protocol in the 
study source documents and notify the Sponsor. Protocol deviations may need to be sent to the reviewing 
IRB, depending on the nature of the deviation and the IRB guidelines. The Investigators and study staff 
are responsible for knowing and adhering to the IRB requirements. 
 
Deviations will be classified by whether or not they meet the definition of important protocol deviations. 
Important protocol deviations are a subset of deviations that might significantly affect the completeness, 
accuracy, and/or reliability of the study data or that might significantly affect a participant's rights, safety, 
or well-being. Deviations will be categorized by type and will be reviewed on an ongoing basis. 
 
10.1.11 
PUBLICATION AND DATA SHARING POLICY 
 
This study will comply with the NIH Public Access Policy, which ensures that the public has access to the 
published results of NIH-funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
  
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-
Funded Clinical Trial Information and the Clinical Trials Registration and Results Information 
Submission rule. As such, this trial will be registered at www.clinicaltrials.gov, and results information 
from this trial will be submitted to www.clinicaltrials.gov. In addition, every attempt will be made to 
publish results in peer-reviewed journals.   
 
10.1.12 
CONFLICT OF INTEREST POLICY 
 
Any conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any 
aspect of this trial will be disclosed and managed. Furthermore, persons who have a perceived conflict of 
interest will be required to have such conflicts managed in a way that is appropriate to their participation 


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in the trial. The Sponsor has established policies and procedures to disclose all conflicts of interest and 
will establish a mechanism for the management of all reported dualities of interest. 
 
10.2 ABBREVIATIONS 
 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
BMI 
Body Mass Index 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
COC 
Certificate of Confidentiality 
CONSORT 
Consolidated Standards of Reporting Trials 
CPK 
Creatine Phosphokinase 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Coefficient of Variation 
DHHS 
Department of Health and Human Services 
DSM-5 
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition 
ECG 
Electrocardiogram 
ET 
Early termination visit 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
HACA 
Human Anti-Chimeric Antibodies 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation  
ICF 
Informed Consent Form 
IgG 
Immunoglobulin G 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
IV 
Intravenous 
MedDRA 
Medical Dictionary for Regulatory Activities 
METH 
Methamphetamine 
MDA 
Methylenedioxyamphetamine 
MDMA 
MethylenedioxyMETH 
NIH  
National Institutes of Health 
NIDA 
National Institute on Drug Abuse 
NOAEL 
No Observed Adverse Effect Level 
OHRP 
Office for Human Research Protections 
PK 
Pharmacokinetics 
PO 
Program Officer 
QC 
Quality Control 
RBC 
Red Blood Cell 
SAE 
Serious Adverse Event 
SAETRS 
Serious Adverse Event Tracking and Reporting System 
SAP 
Statistical Analysis Plan 


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SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
STAMPOUT 
Study of Antibody for Methamphetamine Outpatient Therapy 
UP 
Unanticipated Problem 
US 
United States 
Vd 
Volume of Distribution 
WBC 
White Blood Cell 
 
 
10.3 PROTOCOL AMENDMENT HISTORY 
 
Version - Date 
Description of Change  
Brief Rationale 
1 - 25 Aug 2021 
Not applicable 
New protocol 
 
 
 
 
 


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11 REFERENCES  
 
1. Stevens MW, Henry RL, Owens SM, Schutz R, Gentry WB. First human study of a chimeric 
anti-methamphetamine monoclonal antibody in healthy volunteers. mAbs 2014; 6:1649–56. 
2. Sibille M, Patat A, Caplain H, Donazzolo Y. A safety grading scale to support dose escalation 
and define stopping rules for healthy subject first-entry-into-man studies. Br J Clin Pharmacol 
2010; 70:736–48. 
  
 

SAP_001.pdf: 
InterveXion Therapeutics, LLC 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
Clinical Study Report 
Confidential 
16.1.9 
Documentation of Statistical Methods, Pharmacokinetic Analysis
Statistical Analysis Plan, Version 1.0: 15 December 2021 
WinNonlin Supplemental Appendix 16.1.9 


InterveXion Therapeutics, LLC 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
Statistical Analysis Plan 
Confidential 
Version 1.0 – 15 December 2021 
PROTOCOL M200C-2102
A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Single-Dose 
Intravenous Study to Evaluate the Safety, Tolerability, and 
Pharmacokinetics of IXT-m200 in Healthy Participants 
STATISTICAL ANALYSIS PLAN – V1.0 
December 15, 2021 
CONFIDENTIAL 
Submitted to: 
InterveXion Therapeutics, LLC 
Address: 4301 W. Markham #831 
Little Rock, Arkansas 72205 
NCT05027451


InterveXion Therapeutics, LLC 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
Statistical Analysis Plan 
 
Confidential 
 
Version 1.0 – 15 December 2021 
 
 
Signature Page 
 
Prepared by: 
 
 
 
______________________________________ 
________________ 
Chao Chen, Ph. D.                                                       Date 
Sr. Director, Biostatistics 
 
           
Symbiance, Inc. 
500 College Road, Suite 220 
Princeton, NJ 08540 
 
 
Approved by: 
 
 
 
______________________________________ 
________________ 
Misty Stevens, Ph.D.   
 
Date 
Chief Operating Officer 
InterveXion Therapeutics, LLC 
 
 
 


InterveXion Therapeutics, LLC 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
Statistical Analysis Plan 
 
Confidential 
 
Version 1.0 – 15 December 2021 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Abbreviation 
Definition 
AE  
Adverse Event  
AUCinf 
Area under the serum concentration-time curve from zero (start of the 
infusion) extrapolated to infinity 
AUClast 
Area under the serum concentration-time curve from zero (start of the 
infusion) to last quantifiable time point 
CL 
Clearance 
Clast 
Serum concentration at last measurable time point (observed) 
Cmax 
Maximum serum concentration (observed) 
CRF  
Case Report Form  
CTCAE  
Common Terminology Criteria for Adverse Events  
CV  
Coefficient of Variation  
DSM-5  
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition  
ECG  
Electrocardiogram  
ET  
Early termination visit  
GLP  
Good Laboratory Practices  
HACA  
Human Anti-Chimeric Antibodies  
HIPAA  
Health Insurance Portability and Accountability Act  
IgG  
Immunoglobulin G  
IV  
Intravenous  
IXT-m200 
InterveXion investigational medicinal product, a high-affinity chimeric 
anti-METH monoclonal antibody 
Kel 
Elimination rate constant associated with the terminal elimination 
phase (also referred to as λz) 
MedDRA  
Medical Dictionary for Regulatory Activities  
METH  
Methamphetamine  
MDA  
Methylenedioxyamphetamine  
MDMA  
MethylenedioxyMETH 
MRTinf 
Mean residence time extrapolated to infinity 
MRTlast 
Mean residence time from zero to last quantifiable time point 
PK  
Pharmacokinetics  
SAE  
Serious Adverse Event  
SAP  
Statistical Analysis Plan  
SOC  
System Organ Class  
SOP  
Standard Operating Procedure  
STAMPOUT 
Study of Antibody for Methamphetamine Outpatient Therapy 
T½ 
Terminal elimination half-life 


InterveXion Therapeutics, LLC 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
Statistical Analysis Plan 
 
Confidential 
 
Version 1.0 – 15 December 2021 
Abbreviation 
Definition 
TEAE 
Treatment Emergent Adverse Event 
Tlast 
Time to last measurable serum concentration (observed) 
Tmax 
Time to maximum serum concentration (observed) 
Vd  
Volume of Distribution 
Vz 
Volume of distribution based on the terminal phase 
Vss 
An estimate of volume of distribution at steady-state 


InterveXion Therapeutics, LLC 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
Statistical Analysis Plan 
 
Confidential 
 
Version 1.0 – 15 December 2021 
Table of Contents 
1. 
Introduction ......................................................................................................................... 7 
1.1 
Background ................................................................................................................... 7 
1.2 
IXT-m200 Pharmacokinetics in Healthy Volunteers ......................................................... 7 
1.3 
IXT-m200 Safety and Tolerability .................................................................................... 7 
1.4 
Justification for IXT-m200 Dose ...................................................................................... 8 
2. 
Trial Design and Methods .................................................................................................... 9 
2.1 
Study Objectives ............................................................................................................ 9 
2.1.1 
Primary Objectives .............................................................................................................................. 9 
2.1.2 
Secondary Objectives .......................................................................................................................... 9 
2.2 
Study Overview ............................................................................................................. 9 
2.3 
Sample Size Considerations ............................................................................................ 9 
2.4 
Selection and Withdrawal of Participants ....................................................................... 9 
2.4.1 
Inclusion Criteria ................................................................................................................................. 9 
2.4.2 
Exclusion Criteria ...............................................................................................................................10 
2.5 
Criteria for Individual Participant Discontinuation of Protocol Therapy ...........................10 
2.6 
Criteria for Individual Participation Discontinuation from the Trial .................................11 
2.7 
Handling of Participant Withdrawals or Discontinuation of Study Intervention ...............11 
2.8 
Replacement of Participants..........................................................................................11 
2.9 
IXT-m200 Dosing and Administration.............................................................................11 
2.10 
Schedule of Events ........................................................................................................12 
2.11 
Study Endpoints ............................................................................................................13 
2.11.1 
Primary Endpoints ........................................................................................................................13 
2.11.2 
Secondary Endpoints ....................................................................................................................13 
3. 
Efficacy Assessments ......................................................................................................... 13 
4. 
Pharmacokinetic Assessments ........................................................................................... 13 
5. 
Safety Assessments ............................................................................................................ 14 
6. 
Data Analysis and Statistical Considerations ..................................................................... 15 
6.1 
General Considerations .................................................................................................15 
6.2 
Analysis Populations .....................................................................................................15 
6.3 
Safety Population: All participants who receive exposure to study drug, including placebo 
comprise the Safety Population. This population will be used for all demographic and safety 
summaries.Safety Analyses .......................................................................................................15 


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6.4 
Pharmacokinetic Analyses .............................................................................................15 
6.4.1 
Serum Concentrations.......................................................................................................................16 
6.4.2 
Pharmacokinetic Parameters ............................................................................................................16 
6.5 
Immunogenicity and Cytokines Analyses .......................................................................17 
7. 
Data Handling .................................................................................................................... 17 
7.1 
Handling of Missing Data...............................................................................................17 
7.2 
Drop-outs, Withdrawals, Replacement Policy ................................................................17 
8. 
Changes to the Planned Analyses ...................................................................................... 17 
9. 
Revision History ................................................................................................................. 17 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1. 
Introduction 
This Statistical Analysis Plan (SAP) is based on study procedures and analyses described in the 
protocol Number: M200C-2102 dated August 25, 2021. Table/Figure shells and mock listings 
corresponding to the contents of this document will be in a separate file.  
1.1 
Background 
IXT-m200, also called ch-mAb7F9, binds METH with high selectivity and affinity. The 
product contains a murine METH-binding variable region and the constant domains of a 
human immunoglobulin G (IgG) 2κ. This antibody isotype was chosen because of the lower 
risk of immune response compared to an IgG1 or IgG3. IXT-m200 targets METH, does not 
rely on binding to any endogenous target for its action, and has been well-tolerated in previous 
clinical studies (see below). 
 
Through the binding of METH in the bloodstream, it is anticipated that IXT-m200 will alter 
the pharmacokinetics (PK) of METH and decrease concentrations of METH reaching its active 
sites in the brain. The presence of IXT-m200 should therefore decrease the perceived 
pleasurable effects of METH. Over the longer term, when combined with behavioral therapy, 
IXT-m200 should reduce the frequency of METH use over time. 
 
1.2 
IXT-m200 Pharmacokinetics in Healthy Volunteers 
A Phase 1 study of the safety of single doses of IXT-m200 in healthy humans has been 
completed1. In this first clinical study, 42 participants (17 females) were dosed in 5 groups 
(0.2, 0.6, 2, 6, or 20 mg/kg IXT-m200), with 10 participants receiving placebo (saline). 
Pharmacokinetic results indicated that IXT-m200 is similar to other IgGs, with an elimination 
half-life of ~18 days, volume of distribution (Vd) of ~5 L and clearance of ~200 mL/d. The 
disposition of IXT-m200 did not appear to be affected by dose. 
1.3 
IXT-m200 Safety and Tolerability 
There were no serious adverse events (SAEs) or serious adverse reactions during the conduct 
of the Phase 1 study. There were 3 adverse events in 2 participants that were attributed to IXT-
m200. A mild infusion reaction (Common Terminology Criteria for Adverse Events (CTCAE) 
v.4.0 Grade 3) and bronchospasm (Grade 2) occurred in the same participant. The symptoms 
included a brief period of bronchospasm with no drop in oxygen saturation that resolved with 
stopping the infusion. A separate participant experienced an AE of mild proteinuria (Grade 1). 
Both participants were in the same dose group (2 mg/kg IXT-m200).  
 
Samples from all participants were tested for immunogenicity, i.e., anti-IXT-m200 antibodies. 
Samples from only 4 (12.5%) IXT-m200 treated participants were confirmed to have low 
titers. One of these 4 participants also provided a pre-dose sample that screened positive for 
 
1 Stevens MW, Henry RL, Owens SM, Schutz R, Gentry WB. First human study of a chimeric anti-
methamphetamine monoclonal antibody in healthy volunteers. mAbs 2014; 6:1649–56. 


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anti-IXT-m200 antibodies. The development of anti-IXT-m200 antibodies did not appear to be 
dose-related. Overall, there were no apparent safety or tolerability concerns identified when 
IXT-m200 was dosed over the range from 0.2 to 20 mg/kg. Therefore, a maximum tolerated 
dose was not reached. 
 
Following the Phase 1 study, a Phase 2 study of IXT-m200 was conducted (STAMPOUT: 
Study of Antibody for Methamphetamine Outpatient Therapy, NCT03336866). This was a 
parallel-group, placebo-controlled, double-blind study in otherwise healthy, non-treatment 
seeking participants who use METH. Those who qualified received single doses of IXT-m200 
(6 or 20 mg/kg) or placebo followed by weekly METH challenges for up to 4 weeks. The 
challenges consisted of METH (30 mg, intravenous) and placebo, separated by 4 hours. Safety, 
METH and IXT-m200 PK, and pharmacodynamic data were collected for up to 126 days. 
 
In the STAMPOUT study, all AEs were grade 1 or grade 2. Common AEs included 
palpitations, tachycardia, dry mouth, nausea, injection site pain, headache, euphoria, 
hypervigilance, and hyperhidrosis. All of these AEs are expected in people receiving METH, 
and all participants in this study received METH. Of these, only blurred vision, nausea, feeling 
abnormal, and dry mouth were considered by the investigator as probably related to IXT-
m200; each AE was reported by only one participant who received IXT-m200. Furthermore, 
none of the AEs associated with METH appeared to be exacerbated by IXT-m200. For 
example, an analysis of heart rate changes following METH administration demonstrated that 
average percent heart rate increase, and average peak heart rates were not changed in the 
presence of IXT-m200. Plus, the individual maximum attained heart rate in each group was 
139 (placebo), 142 (6 mg/kg), and 144 (20 mg/kg). Finally, as in the Phase 1 study, samples 
from all participants were tested for HACA. Only one participant in each IXT-m200 dose 
group had notable titers of anti-IXT-m200 antibodies, and the PK of IXT-m200 in these 
participants did not differ from other participants in the dose group. 
 
1.4 
Justification for IXT-m200 Dose 
The IXT-m200 dose of 3 g was selected for this study because it is potentially effective in 
reducing METH effects for several weeks, and will be used in an upcoming repeat-dose Phase 
2 clinical study in patients with METH use disorder. Prior to this Phase 2 study, safety and 
pharmacokinetics of a single 3-g dose in healthy volunteers will be established. IXT-m200 will 
be administered via IV infusion over 30 min. This is necessary because it is a protein 
medication and would be metabolized to inactive components in the gastrointestinal tract if 
administered orally. The volume that must be given is too large to allow for intramuscular or 
subcutaneous administration based on the current formulation. This will result in a rate of 
40 mg/kg/hr in a 75-kg person, which is significantly lower than doses given during a multiple-
dose GLP toxicology study in which the slowest rate for the high dose was 1800 mg/kg/hr. 


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2. 
Trial Design and Methods 
2.1 
Study Objectives  
2.1.1 Primary Objectives 
• To evaluate the safety and tolerability of a single 3-g intravenous dose of IXT-m200 in 
healthy participants. 
2.1.2 Secondary Objectives 
• To characterize the pharmacokinetics of IXT-m200 following a single 3-g intravenous dose 
of IXT-m200 in healthy participants. 
2.2 
Study Overview  
Approximately 9 participants will be enrolled in the study in a single cohort. Participants will 
be randomized to 3 g IXT-m200 or placebo at a 7:2 ratio. Each will receive their dose as a 30-
min IV infusion, then remain at the study site overnight to complete Day 1 and Day 2 
assessments (e.g., ECG, laboratory assessments, blood draws, and vital signs). Following 
discharge on Day 2, participants will return to the clinic for follow-up PK and safety 
assessments on Day 8, then every 1-3 weeks thereafter until Day 127. 
2.3 
Sample Size Considerations 
Nine healthy adults will be randomized into the study. The sample size chosen for this study is 
not based on statistical considerations. The number of participants within each dose group was 
chosen based on historical experience with safety and pharmacokinetic trials and to match the 
study design used in the previous Phase 1 study with IXT-m200 which provided adequate 
safety and pharmacokinetic data. The sample size falls within the range of those used in other 
studies of this nature. 
2.4 
Selection and Withdrawal of Participants 
2.4.1 Inclusion Criteria 
Participants must meet the following inclusion criteria:  
1. Be at least 18 years of age at the time of study consent; 
2. Be able and willing to read, comprehend, and give Authorization for Use/Disclosure of 
Health Information (HIPAA) and informed consent; 
3. Be healthy, based on the pre-study medical evaluation (medical history and physical 
exam, vital signs, ECG, and clinical laboratory evaluations); 
4. Be willing to comply with study instructions and dosing, agree to make all 
appointments, and complete the entire course of the study; 
5. Be of nonchildbearing potential or agree to use protocol-specified method(s) of birth 
control throughout study participation; 


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6. Agree to adhere to Lifestyle Considerations throughout study duration (see protocol 
section 5.3). 
2.4.2 Exclusion Criteria  
Participants meeting any of the following criteria will be excluded from the study:  
1. Have a history of treatment with a monoclonal antibody in the past year; 
2. Have a known contraindication or sensitivity to IXT-m200 based on known allergies to 
other mAbs, any inactive ingredient of IXT-m200, or any other products required for the 
study procedures; 
3. Have a history of alcohol and/or drug use disorder, as determined by DSM-5 criteria; 
4. Have a history of stimulant use, including methamphetamine and amphetamine; 
5. Be currently taking certain other drugs and medications, including: “designer drugs” 
(e.g., 3,4-methylenedioxyMETH (MDMA, Ecstasy, Adam, XTC) and its N-dimethyl 
metabolite methylenedioxyamphetamine (MDA), anti-orexigenic drugs (including over-
the-counter medications for weight loss), or be chronic users of phenethylamine 
compounds (e.g., phenylpropanolamine, ephedrine, pseudoephedrine, amphetamine, 
phentermine, phenmetrazine, methylphenidate, diethylpropion, and propylhexedrine); 
6. Have a positive drug screen for any psychoactive substances (legal or nonlegal) on Day 
1 prior to dosing; 
7. Have a history of severe allergy (rash, hives, breathing difficulty, etc.) to any 
medications; 
8. Have a history of allergic or environmental bronchial asthma within the past 3 years; 
9. Have a clinically significant history of or current abnormality or disease of any organ 
system, including renal, hepatic, gastrointestinal, cardiovascular, pulmonary (including 
chronic asthma), endocrine (e.g., diabetes), central nervous (e.g., psychiatric 
conditions), or hematologic systems, or recent clinically significant surgery, 
10. Have a history of seizure, epilepsy, severe head injury, multiple sclerosis, or other 
known neurological conditions, 
11. Have a planned or scheduled surgical procedure during the study; 
12. Have recently donated blood or plasma (within 30 days of study drug dose); 
13. Have a current diagnosis of anorexia nervosa or bulimia disorder; 
14. Be currently participating or has participated within the last 30 days prior to the start of 
this study in a drug, device, or other interventional research study; 
15. Be pregnant or lactating; 
16. In the Investigator’s or Sponsor’s (or designee) opinion, be inappropriate for the study. 
2.5 
Criteria for Individual Participant Discontinuation of Protocol 
Therapy 
The Investigator may discontinue a participant from study drug administration for the 
following reasons: 


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• the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation, such as an infusion reaction, 
• any clinical AE, laboratory abnormality, or other medical condition or situation occurs such 
that continued participation in the study would not be in the best interest of the participant, 
• significant non-compliance by the participant, 
• if, in the Investigator’s opinion, continuation with study drug administration would be 
detrimental to the participant’s well-being, 
• at the specific request of InterveXion (Sponsor) or the Investigator. 
In all cases, the reason for withdrawal or discontinuation must be recorded in the CRF and in 
the participant’s medical records. If the reason is not known, an attempt must be made to 
follow up with the participant to establish whether the reason was an AE, and, if so, this AE 
must be reported. Once the participant has been contacted and expresses their decision to 
withdraw from further participation in the study, the research staff will cease to try to make 
further contact. 
2.6 
Criteria for Individual Participation Discontinuation from the Trial 
Participants who withdraw consent for future study visits (following early termination 
assessments) will be considered ‘withdrawn’. Participants are free to withdraw at any time 
upon request; they will be asked to complete early termination assessments as soon as possible. 
Participants that receive less than the complete single dose of study drug but agree to continue 
participation in other study procedures and assessments will be considered ‘discontinued’. 
Participants are free to discontinue at any time during dosing upon request.  
2.7 
Handling of Participant Withdrawals or Discontinuation of Study 
Intervention 
Participants will be encouraged to complete study visits and assessments, even if they elect to 
discontinue study drug administration. In this case, all study activities will be completed per 
protocol with the exception of dose administration. 
2.8 
Replacement of Participants 
Participants who withdraw or are discontinued may be replaced at the Sponsor’s discretion 
until there are 6 participants who have completed the protocol through Day 63. 
2.9 
IXT-m200 Dosing and Administration 
Participants will only be randomized and dosed with study drug if they have passed all 
screening requirements before or on Day 1. Participants will be randomized on Day 1 to 
receive 3 g IXT-m200 or placebo (7:2).  
 
Each participant will receive 1 dose of assigned study drug on Day 1. Participants should lie 
supine or semi-reclined during dose administration. Each dose will be given with an infusion 


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pump over 30 minutes with a 50-mL saline flush dispensed after the dose to ensure the entire 
dose is flushed through the infusion set. The study drug infusion start/stop time, infusion rate, 
infusion volume, whether the infusion was completed, if it was stopped, or stopped and 
restarted will be recorded.  
2.10 Schedule of Events 
Table 2-1 Schedule of Events 
Assessment a 
Screening 
Inpatient 
Follow-up (±1 day) 
Follow-up (±3 days) 
ET 
Study Week 
≤-1 
1 
2 
3-17 
18 
NA 
Study Day 
-30 to -1 
1b 
2 
8 
15, 22, 29, 36, 43, 
64, 85, 106 
127 
NA 
Informed consent 
X 
 
 
 
 
 
 
Initial evaluations 
Eligibility criteria 
Demographics 
Medical history and 
medications 
Vital signs c  
Physical exam  
Psychiatric evaluation 
Urine pregnancy test 
X 
 
 
 
 
 
 
Laboratory tests d 
X 
X 
X 
X 
X (29 and 64 only) 
 
X 
Urine drug screen 
 
X 
 
 
 
 
 
Wellness check 
Update medical history 
Update medications 
Vital signs c 
Targeted physical exam 
 
X 
X 
X 
X 
X 
X 
ECG e 
 
X 
 
 
 
 
 
Urine pregnancy test 
 
X 
 
 
 
X 
X 
Blood for cytokines f 
 
X 
 
 
 
 
 
Blood for PK g  
 
X 
X 
X 
X 
X 
X 
Blood for HACA h 
 
X 
 
 
 
X 
X 
Randomization 
 
X 
 
 
 
 
 
Dose administration i 
 
X 
 
 
 
 
 
AE monitoring 
 
Continuous 
X 
 
Abbreviations: ECG – electrocardiogram; ET – early termination visit; HACA – human anti-chimeric antibodies; 
NA – not applicable; PK – pharmacokinetic  
 
a) Descriptions of assessments are in Section 8.1 of the Protocol.  
b) Study Day -1 is the day prior to the first dose. Study Day 1 is the day of the first dose.  
c) Vital sign measurements will be taken on Day 1 starting with a pre-dose measurement (≤30 min prior), 
then 0.25, 0.5, 1, 2, and 4 hours (±5 min) after dosing starts, and as needed afterward until normalization. 
Measurements will be obtained once on each non-dosing day. Each test may be repeated once at each 
time point if the initial result is out of range.  
d) Laboratory tests require blood and urine sampling for hematology, serum chemistry, and urinalysis. 
Samples are to be taken at screening, pre-dose and 2-hr post-dose completion (±10 min) on Day 1, and 
once on Days 2, 8, 29, and 64.  


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e) ECGs are to be done pre-dose (up to 2 hr prior) and 30-min post-dose completion (±15 min) on Day 1.  
f) 
Cytokine samples are to be taken pre-dose (≤60 min prior) on Day 1. If a participant has an infusion 
reaction, cytokine sampling at 1- and 4-hours post-dose (±10 min) should be performed. If no infusion 
reaction is observed, pre-dose samples will not be analyzed.  
g) PK samples are to be taken pre-dose (≤30 min prior), then 1, 4, and 8 hr (±10 min) and 24 hr (±30 min) 
after the start of the infusion on Day 1. All other PK samples are to be collected once each visit.  
h) HACA samples are to be taken pre-dose (≤60 min prior) on Day 1 and once on Day 127.  
i) 
Doses will be given over 30 min by IV infusion 
 
 
2.11 Study Endpoints 
2.11.1 
Primary Endpoints 
The primary endpoint for the study is number of participants with treatment-related AEs 
assessed by physical examinations and vital sign, ECG, and clinical laboratory testing. 
2.11.2 
Secondary Endpoints 
The secondary endpoint is the time course of IXT-m200 concentrations. This will be examined 
by determining the IXT-m200 serum pharmacokinetic (PK) parameters derived from the serial 
serum concentrations following single-dose IV administration, including Cmax, Tmax, Kel (λz), 
AUClast, AUCinf, MRT, CL, and Vd and other PK parameters as data permit. 
3. 
Efficacy Assessments 
Not Applicable. 
 
4. 
Pharmacokinetic Assessments 
Serum IXT-m200 PK parameters will be calculated from serum concentration data determined 
using a validated bioanalytical method. Pharmacokinetic parameters will be calculated using 
noncompartmental analysis methods suitable for intravenous infusion. Pharmacokinetic 
parameters that will be calculated if data permit are presented in Table 4-1. 
 
Table 4-1 Pharmacokinetic Parameters 
Parameter 
Description 
Method of Determination 
Cmax 
Maximum serum concentration (observed) 
Observed directly from data 
 
Tmax 
Time to maximum serum concentration 
(observed) 
Observed directly from data 
 
Clast 
Serum concentration at last measurable time 
point (observed) 
Observed directly from 
data 


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5. 
Safety Assessments 
All safety analyses will be performed on the Safety population. Descriptive statistics will be 
used to summarize AEs, serious AEs, AEs causing withdrawal or discontinuation from the 
study, AEs judged by the Investigator as potentially related to study drug, changes in 
laboratory and vital signs, and immune response by measurement of anti-IXT-m200 antibody 
levels. AEs will be tabulated by Medical Dictionary for Regulatory Activities (MedDRA) 
system organ class (SOC) and preferred term. 
 
Other safety observations and measurements will include vital signs, physical exam, pregnancy 
test, laboratory tests, and ECG.  Descriptive statistics will be used to summarize continuous 
variables and change from baseline. Frequency and shift tables will be created for categorical 
variables.  
 
Tlast 
Time to last measurable serum 
concentration (observed) 
Observed directly from 
data 
AUClast 
Area under the serum concentration-time 
curve from zero (start of infusion) to last 
quantifiable time point 
AUC = ∆t* (C1 + C2)/2 
AUCinf 
Area under the serum concentration-time 
curve from zero (start of infusion) 
extrapolated to infinity 
AUCinf = AUClast+ Clast/z 
Kel or z 
Elimination rate constant associated with 
the terminal elimination phase 
Kel is calculated by a linear 
regression of the log-linear 
concentration-time curve.  
t½ 
Terminal elimination half life 
t1/2 = In (2) /z 
CL 
Systemic clearance  
CL = Dose/AUCinf 
Vz 
Volume of distribution based on the terminal 
phase. 
Vz = Dose/[z(AUCinf)] 
Vss 
An estimate of the volume of distribution at 
steady-state 
Vss = MRTinf * CL 
MRTlast 
Mean residence time (MRT) from zero to 
last quantifiable time point 
AUMClast/AUClast – TI/2 
TI is the length of infusion 
MRTinf 
Mean residence time (MRT) extrapolated to 
infinity 
AUMCinf/AUCinf – TI/2 
TI is the length of infusion 


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6. 
Data Analysis and Statistical Considerations 
6.1 
General Considerations 
Sample size was selected empirically without consideration of statistical power.  As a result, no 
formal statistical hypothesis will be evaluated. Draft statistical summaries will be provided 
during the course of the study using dummy treatment code. The final report will be generated 
when all corresponding data are collected and database locked and treatment code released per 
Symbiance SOP. Statistical tables, data listings, and graphs will be prepared using SAS 
Version 9.4 or higher (SAS Institute, Cary, North Carolina, USA).  
6.2 
Analysis Populations 
Pharmacokinetic Population: All participants who receive active study drug and have at least 
one measured IXT-m200 concentration at a scheduled PK time point after start of dosing 
comprise the PK Population. If participants do not receive a complete dose or have incomplete 
data, a decision will be made on a case-by-case basis as to their inclusion in the analysis. This 
population will be used for all PK summaries. 
 
6.3 
Safety Population: All participants who receive exposure to study 
drug, including placebo comprise the Safety Population. This 
population will be used for all demographic and safety 
summaries.Safety Analyses 
Safety analyses will be presented by IXT-m200 and placebo groups and for all participants in 
the safety population. 
Treatment-emergent adverse events (TEAEs) and serious TEAEs will be summarized by SOC 
and preferred term, and by severity (Grades 1, 2, 3, or 4) and relationship to treatment for IXT-
m200 and placebo groups. The analysis of TEAEs by severity will count TEAEs by worst 
severity if an individual participant has a TEAE with more than one severity. The analysis of 
TEAEs by relationship to treatment will define treatment-related TEAEs as including all 
TEAEs assessed as definitely, probably, or possibly related to treatment, and non-treatment-
related TEAEs as including all TEAEs assessed as unlikely and unrelated to treatment. 
Vital signs, physical exam, pregnancy test, laboratory tests, and ECG will be tabulated.  
Descriptive statistics will be used to summarize continuous variables and change from 
baseline, which is defined as the most recent observation before dosing. Frequency and shift 
tables will be created for categorical variables. 
6.4 
Pharmacokinetic Analyses 
Pharmacokinetic parameters will be calculated using Phoenix WinNonlin Version 8.3 or higher 
(Certara USA, Princeton, New Jersey, USA).  
 


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6.4.1 
Serum Concentrations 
Serum concentrations of IXT-m200 will be listed with nominal sampling times for all 
participants in the PK Population. 
Serum concentrations will be summarized using descriptive statistics for each treatment. Below 
the limit of quantitation (BLQ) concentrations will be treated as zero for the computation of 
descriptive statistics. Concentrations assigned a value of missing will be omitted from the 
calculation of descriptive statistics. 
Mean and individual IXT-m200 serum concentration versus nominal time will be displayed in 
the figures (linear and semi-logarithmic scale) by dose and participant. Graphs may be 
generated in SAS or WinNonlin (or both) applications. 
6.4.2 
Pharmacokinetic Parameters 
Pharmacokinetic parameters will be derived from IXT-m200 serum concentrations using actual 
doses administered and actual sampling times of blood collection for each participant in the PK 
Population. Descriptive statistics will be summarized by dose. Descriptive statistics (mean, 
standard deviation (SD), coefficient of variation (CV%), geometric mean, geometric SD, 
geometric CV%) will be reported for all PK parameters, except for Tmax where N, median, min, 
and max will be reported.  
Predose samples that are BLQ or missing will be assigned a numerical value of zero for the 
calculation of area under the concentration-time curve (AUC). Any other BLQ concentrations 
will be assigned a value of zero if they precede quantifiable samples in the initial portion of the 
profile. A BLQ value that occurs between quantifiable data points, especially prior to Cmax, will 
be evaluated to determine if an assigned concentration of zero makes sense, or if reanalysis or 
exclusion of the data is warranted. Following Cmax, BLQ values embedded between 2 
quantifiable data points will be treated as missing when calculating AUC. If BLQ values occur 
at the end of the collection interval (after the last quantifiable concentration), these will be 
treated as missing data. If consecutive BLQ concentrations are followed by quantifiable 
concentrations in the terminal portion of the concentration curve, these quantified values will 
be excluded from the PK analysis by assigning them a value of missing, unless otherwise 
warranted by the concentration-time profile. 
The linear-log trapezoidal rule will be applied for the calculation of AUC parameters in the 
noncompartmental analysis model. Pharmacokinetic parameters presented in Table 4-1 will be 
listed by participant and summarized. Graphical presentations of PK data may be added at the 
discretion of the PK scientist. 
Pharmacokinetic parameters derived with Kel such as t1/2 and AUCinf, will be listed but 
excluded from descriptive statistics if R2_adjusted < 0.8 in Kel estimation.   
For determination of AUCinf, if the percentage of extrapolated AUC is more than 20% of 
AUCinf  from tlast to infinity, then individual AUCinf result and the PK parameters depending on 
AUCinf (CL, Vz, and MRTinf) will be listed but flagged as not reliable calculations. AUCinf and 


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the PK parameters depending on AUCinf  for these flagged participants will not be included in 
the descriptive statistics table. 
6.5 
Immunogenicity and Cytokines Analyses 
Human anti-chimeric antibody (HACA) samples are to be taken pre-dose (≤60 min prior to the 
start of the infusion) on Day 1 and once on Day 127. HACA results, including screening, 
confirmation, and titer results as available, will be summarized by group and individual and in 
a descriptive statistics table if appropriate.  
A cytokine panel including at a minimum IL-6, IL-8, and TNFα levels will be determined only 
if any study drug infusion reaction occurs. If cytokines are measured, the results will be 
presented in a listing and the participant will be presented in a narrative. 
 
7. 
Data Handling 
7.1 
Handling of Missing Data 
All missing data will be queried. With the exception of the treatment of BLQ values for the 
pharmacokinetic analyses described in section 6.4, no missing values imputation will be 
applied. Pooling of centers not required as this is a single-center study. 
7.2 
Drop-outs, Withdrawals, Replacement Policy 
Participants who withdraw or are discontinued may be replaced at the Sponsor’s discretion 
until there are 6 participants who have completed the protocol through Day 63. In case a 
discontinued participant is replaced, both the original and replacing participants will be 
included in the relevant listings and AE reporting. 
 
8. 
Changes to the Planned Analyses 
Any deviation(s) of consequence from the Statistical Analysis Plan during the data analysis 
will be documented and justified in an amended Statistical Analysis Plan and/or in the final 
study report or addressed in a separate document, as appropriate. 
9. 
Revision History 
 
Version 
Date 
Comments 
1.0 
15 December 2021 
Original Statistical Analysis Plan 
 
 
 
 
 


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Appendix 16.1.9 Supplement: WinNonlin Figures and Output 
Supplemental Summary Figure 1 – Mean (±SD) Serum IXT-m200 Concentration-Time Profile following 
IXT-m200 3 g IV infusion, Linear Plot, PK Population 
Supplemental Summary Figure 2 – Mean (±SD) Serum IXT-m200 Concentration-Time Profile following 
IXT-m200 3 g IV infusion, Semi-log Plot, PK Population 


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Figure 14.2.4.1 Individual Linear Plot of Serum IXT-m200 Concentration-Time Profiles (Subject 1002) – 
PK Population 
 
Figure 14.2.4.2 Individual Linear Plot of Serum IXT-m200 Concentration-Time Profiles (Subject 1003) – 
PK Population 
 
 
 


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Page 3 of 26 
Figure 14.2.4.3 Individual Linear Plot of Serum IXT-m200 Concentration-Time Profiles (Subject 1011) – 
PK Population 
 
Figure 14.2.4.4 Individual Linear Plot of Serum IXT-m200 Concentration-Time Profiles (Subject 1012) – 
PK Population 
 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 4 of 26 
Figure 14.2.4.5 Individual Linear Plot of Serum IXT-m200 Concentration-Time Profiles (Subject 1018) – 
PK Population 
 
Figure 14.2.4.6 Individual Linear Plot of Serum IXT-m200 Concentration-Time Profiles (Subject 1023) – 
PK Population 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 5 of 26 
Figure 14.2.4.7 Individual Linear Plot of Serum IXT-m200 Concentration-Time Profiles (Subject 1024) – 
PK Population 
 
Figure 14.2.4.8 Individual Semi-log Plot of Serum IXT-m200 Concentration-Time Profiles (Subject 1002) – 
PK Population 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 6 of 26 
Figure 14.2.4.9 Individual Semi-log Plot of Serum IXT-m200 Concentration-Time Profiles (Subject 1003) – 
PK Population 
 
Figure 14.2.4.10 Individual Semi-log Plot of Serum IXT-m200 Concentration-Time Profiles (Subject 1011) 
– PK Population 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 7 of 26 
Figure 14.2.4.11 Individual Semi-log Plot of Serum IXT-m200 Concentration-Time Profiles (Subject 1012) 
– PK Population 
 
Figure 14.2.4.12 Individual Semi-log Plot of Serum IXT-m200 Concentration-Time Profiles (Subject 1018) 
– PK Population 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 8 of 26 
Figure 14.2.4.13 Individual Semi-log Plot of Serum IXT-m200 Concentration-Time Profiles (Subject 1023) 
– PK Population 
 
Figure 14.2.4.14 Individual Semi-log Plot of Serum IXT-m200 Concentration-Time Profiles (Subject 1024) 
– PK Population 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 9 of 26 
WinNonlin Fitted Plots 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 10 of 26 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 11 of 26 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 12 of 26 
 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 13 of 26 
WinNonlin Core Output  
WinNonlin 8.3.3.33 
Subject_ID=1002,Treatment=IXT-m200,Dose=3000,Actual_Infusion_Time=0.52 
 
                                                  Date:    5/09/2022 
                                                  Time:     03:47:44 
 
 
                  WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM 
                                    8.3.3.33 
                            Core Version 06Feb2020 
 
Settings 
-------- 
Model:  Plasma Data, Constant Infusion Administration 
Number of nonmissing observations:   14 
Dose time:      0.00 
Dose amount:     3000.00 
Length of Infusion:      0.52 
Calculation method:  Linear/Log Trapezoidal 
Weighting for lambda_z calculations:  Uniform weighting 
Lambda_z method:  Find best fit for lambda_z,  Log regression 
Lambda_z Acceptance Criterion, Min Rsq_Adjusted:  0.8000 
Lambda_z Acceptance Criterion, Max AUC_%Extrap_obs:   20.00 
 
 
Summary Table 
------------- 
      Time         Conc.      Pred.    Residual      AUC       AUMC      Weight 
        day        mg/L        mg/L        mg/L    day*mg/L day*day*mg/L 
------------------------------------------------------------------------------- 
      0.000        0.000                            0.000      0.000 
    0.04236        624.0                            13.22     0.5598 
     0.1667        695.4                            95.22      9.406 
     0.3333        624.0                            205.1      36.70 
      1.000        674.4                            637.7      327.0 
      8.013        338.5                            4055.  1.436e+04 
      15.01        284.3                            6229.  3.917e+04 
      21.99        228.3                            8011.  7.191e+04 
      29.01        188.5                            9469.  1.089e+05 
      36.00        118.2                        1.052e+04  1.429e+05 
      43.01 *      97.07      97.81    -0.7463  1.127e+04  1.725e+05      1.000 
      85.04 *      14.49      14.69    -0.1956  1.310e+04  2.778e+05      1.000 
      106.0 *      6.035      5.698     0.3371  1.330e+04  2.969e+05      1.000 
      127.0 *      2.133      2.212   -0.07910  1.338e+04  3.059e+05      1.000 
 
 
*) Starred values were included in the estimation of Lambda_z. 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 14 of 26 
Final Parameters 
--------------- 
N_Samples                                                14 
Dose                                     mg            3000.0000 
Rsq                                                       0.9994 
Rsq_adjusted                                              0.9991 
Flag_Rsq_adjusted                                       Accepted 
Corr_XY                                                  -0.9997 
No_points_lambda_z                                        4 
Lambda_z                              1/day               0.0451 
Lambda_z_intercept                                        6.5234 
Lambda_z_lower                          day              43.0104 
Lambda_z_upper                          day             127.0021 
HL_Lambda_z                             day              15.3642 
Span                                                      5.4667 
Tmax                                    day               0.1667 
Cmax                                   mg/L             695.3830 
Cmax_D                              mg/L/mg               0.2318 
Tlast                                   day             127.0021 
Clast                                  mg/L               2.1327 
Clast_pred                             mg/L               2.2118 
AUClast                            day*mg/L           13380.1269 
AUClast_D                       day*mg/L/mg               4.4600 
AUCall                             day*mg/L           13380.1269 
AUCINF_obs                         day*mg/L           13427.4011 
AUCINF_D_obs                    day*mg/L/mg               4.4758 
AUC_%Extrap_obs                           %               0.3521 
Flag_AUC_%Ext_obs                                       Accepted 
Vz_obs                                    L               4.9524 
Cl_obs                               mL/day             223.4237 
AUCINF_pred                        day*mg/L           13429.1545 
AUCINF_D_pred                   day*mg/L/mg               4.4764 
AUC_%Extrap_pred                          %               0.3651 
Vz_pred                                   L               4.9517 
Cl_pred                              mL/day             223.3946 
AUMClast                       day*day*mg/L          305922.4560 
AUMCINF_obs                    day*day*mg/L          312974.2497 
AUMC_%Extrap_obs                          %               2.2532 
AUMCINF_pred                   day*day*mg/L          313235.8048 
AUMC_%Extrap_pred                         %               2.3348 
MRTlast                                 day              22.6039 
MRTINF_obs                              day              23.0486 
MRTINF_pred                             day              23.0651 
Vss_obs                                   L               5.1496 
Vss_pred                                  L               5.1526 
 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 15 of 26 
WinNonlin 8.3.3.33 
Subject_ID=1003,Treatment=IXT-m200,Dose=3000,Actual_Infusion_Time=0.5 
 
                                                  Date:    5/09/2022 
                                                  Time:     03:47:44 
 
 
                  WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM 
                                    8.3.3.33 
                            Core Version 06Feb2020 
 
Settings 
-------- 
Model:  Plasma Data, Constant Infusion Administration 
Number of nonmissing observations:   15 
Dose time:      0.00 
Dose amount:     3000.00 
Length of Infusion:      0.50 
Calculation method:  Linear/Log Trapezoidal 
Weighting for lambda_z calculations:  Uniform weighting 
Lambda_z method:  Find best fit for lambda_z,  Log regression 
Lambda_z Acceptance Criterion, Min Rsq_Adjusted:  0.8000 
Lambda_z Acceptance Criterion, Max AUC_%Extrap_obs:   20.00 
 
 
Summary Table 
------------- 
      Time         Conc.      Pred.    Residual      AUC       AUMC      Weight 
        day        mg/L        mg/L        mg/L    day*mg/L day*day*mg/L 
------------------------------------------------------------------------------- 
      0.000        0.000                            0.000      0.000 
    0.04167        967.6                            20.16     0.8399 
     0.1674        796.4                            130.7      12.17 
     0.3333        804.2                            263.5      45.44 
      1.000        775.2                            789.9      395.3 
      7.987        379.9                            4662.  1.620e+04 
      15.02        288.2                            6995.  4.266e+04 
      22.00 *      272.6      278.1     -5.508      8954.  7.884e+04      1.000 
      29.01 *      254.2      210.7      43.53  1.080e+04  1.259e+05      1.000 
      36.10 *      153.4      159.2     -5.831  1.221e+04  1.715e+05      1.000 
      43.01 *      102.8      121.1     -18.29  1.309e+04  2.059e+05      1.000 
      64.03 *      59.01      52.73      6.282  1.475e+04  2.930e+05      1.000 
      85.03 *      20.75      22.97     -2.220  1.552e+04  3.489e+05      1.000 
      106.0 *      9.117      10.02    -0.9005  1.581e+04  3.769e+05      1.000 
      127.0 *      4.904      4.364     0.5394  1.595e+04  3.933e+05      1.000 
 
 
*) Starred values were included in the estimation of Lambda_z. 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 16 of 26 
Final Parameters 
--------------- 
N_Samples                                                15 
Dose                                     mg            3000.0000 
Rsq                                                       0.9933 
Rsq_adjusted                                              0.9922 
Flag_Rsq_adjusted                                       Accepted 
Corr_XY                                                  -0.9967 
No_points_lambda_z                                        8 
Lambda_z                              1/day               0.0396 
Lambda_z_intercept                                        6.4983 
Lambda_z_lower                          day              22.0021 
Lambda_z_upper                          day             127.0160 
HL_Lambda_z                             day              17.5209 
Span                                                      5.9936 
Tmax                                    day               0.0417 
Cmax                                   mg/L             967.5700 
Cmax_D                              mg/L/mg               0.3225 
Tlast                                   day             127.0160 
Clast                                  mg/L               4.9037 
Clast_pred                             mg/L               4.3643 
AUClast                            day*mg/L           15954.9717 
AUClast_D                       day*mg/L/mg               5.3183 
AUCall                             day*mg/L           15954.9717 
AUCINF_obs                         day*mg/L           16078.9254 
AUCINF_D_obs                    day*mg/L/mg               5.3596 
AUC_%Extrap_obs                           %               0.7709 
Flag_AUC_%Ext_obs                                       Accepted 
Vz_obs                                    L               4.7162 
Cl_obs                               mL/day             186.5796 
AUCINF_pred                        day*mg/L           16065.2902 
AUCINF_D_pred                   day*mg/L/mg               5.3551 
AUC_%Extrap_pred                          %               0.6867 
Vz_pred                                   L               4.7202 
Cl_pred                              mL/day             186.7380 
AUMClast                       day*day*mg/L          393335.5205 
AUMCINF_obs                    day*day*mg/L          412212.8480 
AUMC_%Extrap_obs                          %               4.5795 
AUMCINF_pred                   day*day*mg/L          410136.2960 
AUMC_%Extrap_pred                         %               4.0964 
MRTlast                                 day              24.4028 
MRTINF_obs                              day              25.3868 
MRTINF_pred                             day              25.2793 
Vss_obs                                   L               4.7367 
Vss_pred                                  L               4.7206 
 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 17 of 26 
WinNonlin 8.3.3.33 
Subject_ID=1011,Treatment=IXT-m200,Dose=3000,Actual_Infusion_Time=0.55 
 
                                                  Date:    5/09/2022 
                                                  Time:     03:47:44 
 
 
                  WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM 
                                    8.3.3.33 
                            Core Version 06Feb2020 
 
Settings 
-------- 
Model:  Plasma Data, Constant Infusion Administration 
Number of nonmissing observations:   15 
Dose time:      0.00 
Dose amount:     3000.00 
Length of Infusion:      0.55 
Calculation method:  Linear/Log Trapezoidal 
Weighting for lambda_z calculations:  Uniform weighting 
Lambda_z method:  Find best fit for lambda_z,  Log regression 
Lambda_z Acceptance Criterion, Min Rsq_Adjusted:  0.8000 
Lambda_z Acceptance Criterion, Max AUC_%Extrap_obs:   20.00 
 
 
Summary Table 
------------- 
      Time         Conc.      Pred.    Residual      AUC       AUMC      Weight 
        day        mg/L        mg/L        mg/L    day*mg/L day*day*mg/L 
------------------------------------------------------------------------------- 
      0.000        0.000                            0.000      0.000 
    0.04167        536.9                            11.19     0.4661 
     0.1674        589.9                            82.00      8.076 
     0.3333        534.3                            175.2      31.28 
      1.000        568.5                            542.7      277.5 
      8.013        276.4                            3383.  1.189e+04 
      15.04        264.5                            5283.  3.374e+04 
      22.05 *      149.5      153.6     -4.116      6696.  5.947e+04      1.000 
      29.06 *      117.1      116.9     0.2140      7626.  8.311e+04      1.000 
      36.06 *      87.77      89.03     -1.253      8338.  1.062e+05      1.000 
      43.06 *      75.42      67.77      7.650      8908.  1.287e+05      1.000 
      64.10 *      28.58      29.87     -1.291      9924.  1.814e+05      1.000 
      85.08 *      13.65      13.20     0.4566  1.035e+04  2.125e+05      1.000 
      106.1 *      4.897      5.830    -0.9332  1.053e+04  2.293e+05      1.000 
      127.1 *      2.890      2.570     0.3195  1.061e+04  2.385e+05      1.000 
 
 
*) Starred values were included in the estimation of Lambda_z. 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 18 of 26 
Final Parameters 
--------------- 
N_Samples                                                15 
Dose                                     mg            3000.0000 
Rsq                                                       0.9962 
Rsq_adjusted                                              0.9956 
Flag_Rsq_adjusted                                       Accepted 
Corr_XY                                                  -0.9981 
No_points_lambda_z                                        8 
Lambda_z                              1/day               0.0389 
Lambda_z_intercept                                        5.8931 
Lambda_z_lower                          day              22.0479 
Lambda_z_upper                          day             127.0889 
HL_Lambda_z                             day              17.7993 
Span                                                      5.9014 
Tmax                                    day               0.1674 
Cmax                                   mg/L             589.8678 
Cmax_D                              mg/L/mg               0.1966 
Tlast                                   day             127.0889 
Clast                                  mg/L               2.8896 
Clast_pred                             mg/L               2.5702 
AUClast                            day*mg/L           10606.7945 
AUClast_D                       day*mg/L/mg               3.5356 
AUCall                             day*mg/L           10606.7945 
AUCINF_obs                         day*mg/L           10680.9970 
AUCINF_D_obs                    day*mg/L/mg               3.5603 
AUC_%Extrap_obs                           %               0.6947 
Flag_AUC_%Ext_obs                                       Accepted 
Vz_obs                                    L               7.2125 
Cl_obs                               mL/day             280.8727 
AUCINF_pred                        day*mg/L           10672.7935 
AUCINF_D_pred                   day*mg/L/mg               3.5576 
AUC_%Extrap_pred                          %               0.6184 
Vz_pred                                   L               7.2181 
Cl_pred                              mL/day             281.0885 
AUMClast                       day*day*mg/L          238532.8682 
AUMCINF_obs                    day*day*mg/L          249868.6319 
AUMC_%Extrap_obs                          %               4.5367 
AUMCINF_pred                   day*day*mg/L          248615.3968 
AUMC_%Extrap_pred                         %               4.0555 
MRTlast                                 day              22.2137 
MRTINF_obs                              day              23.1188 
MRTINF_pred                             day              23.0193 
Vss_obs                                   L               6.4934 
Vss_pred                                  L               6.4705 
 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 19 of 26 
WinNonlin 8.3.3.33 
Subject_ID=1012,Treatment=IXT-m200,Dose=3000,Actual_Infusion_Time=0.5 
 
                                                  Date:    5/09/2022 
                                                  Time:     03:47:44 
 
 
                  WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM 
                                    8.3.3.33 
                            Core Version 06Feb2020 
 
Settings 
-------- 
Model:  Plasma Data, Constant Infusion Administration 
Number of nonmissing observations:   15 
Dose time:      0.00 
Dose amount:     3000.00 
Length of Infusion:      0.50 
Calculation method:  Linear/Log Trapezoidal 
Weighting for lambda_z calculations:  Uniform weighting 
Lambda_z method:  Find best fit for lambda_z,  Log regression 
Lambda_z Acceptance Criterion, Min Rsq_Adjusted:  0.8000 
Lambda_z Acceptance Criterion, Max AUC_%Extrap_obs:   20.00 
 
 
Summary Table 
------------- 
      Time         Conc.      Pred.    Residual      AUC       AUMC      Weight 
        day        mg/L        mg/L        mg/L    day*mg/L day*day*mg/L 
------------------------------------------------------------------------------- 
      0.000        0.000                            0.000      0.000 
    0.04167        736.1                            15.33     0.6389 
     0.1667        721.3                            106.4      10.11 
     0.3347        587.6                            216.0      37.27 
      1.000        635.3                            622.6      310.4 
      7.955        335.1                            3887.  1.372e+04 
      15.00        266.4                            5996.  3.765e+04 
      21.96        188.1                            7562.  6.628e+04 
      28.99        145.2                            8727.  9.578e+04 
      35.97        98.44                            9567.  1.228e+05 
      43.00        74.40                        1.017e+04  1.466e+05 
      64.04        31.89                        1.123e+04  2.016e+05 
      85.04 *      9.741      9.829   -0.08753  1.162e+04  2.300e+05      1.000 
      106.0 *      4.823      4.738    0.08539  1.177e+04  2.438e+05      1.000 
      127.0 *      2.258      2.278   -0.02023  1.184e+04  2.520e+05      1.000 
 
 
*) Starred values were included in the estimation of Lambda_z. 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 20 of 26 
Final Parameters 
--------------- 
N_Samples                                                15 
Dose                                     mg            3000.0000 
Rsq                                                       0.9996 
Rsq_adjusted                                              0.9991 
Flag_Rsq_adjusted                                       Accepted 
Corr_XY                                                  -0.9998 
No_points_lambda_z                                        3 
Lambda_z                              1/day               0.0349 
Lambda_z_intercept                                        5.2490 
Lambda_z_lower                          day              85.0410 
Lambda_z_upper                          day             126.9868 
HL_Lambda_z                             day              19.8889 
Span                                                      2.1090 
Tmax                                    day               0.0417 
Cmax                                   mg/L             736.0651 
Cmax_D                              mg/L/mg               0.2454 
Tlast                                   day             126.9868 
Clast                                  mg/L               2.2581 
Clast_pred                             mg/L               2.2783 
AUClast                            day*mg/L           11836.0573 
AUClast_D                       day*mg/L/mg               3.9454 
AUCall                             day*mg/L           11836.0573 
AUCINF_obs                         day*mg/L           11900.8503 
AUCINF_D_obs                    day*mg/L/mg               3.9670 
AUC_%Extrap_obs                           %               0.5444 
Flag_AUC_%Ext_obs                                       Accepted 
Vz_obs                                    L               7.2332 
Cl_obs                               mL/day             252.0828 
AUCINF_pred                        day*mg/L           11901.4307 
AUCINF_D_pred                   day*mg/L/mg               3.9671 
AUC_%Extrap_pred                          %               0.5493 
Vz_pred                                   L               7.2328 
Cl_pred                              mL/day             252.0705 
AUMClast                       day*day*mg/L          251984.8306 
AUMCINF_obs                    day*day*mg/L          262071.8305 
AUMC_%Extrap_obs                          %               3.8489 
AUMCINF_pred                   day*day*mg/L          262162.1803 
AUMC_%Extrap_pred                         %               3.8821 
MRTlast                                 day              21.0396 
MRTINF_obs                              day              21.7713 
MRTINF_pred                             day              21.7778 
Vss_obs                                   L               5.4882 
Vss_pred                                  L               5.4895 
 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 21 of 26 
WinNonlin 8.3.3.33 
Subject_ID=1018,Treatment=IXT-m200,Dose=3000,Actual_Infusion_Time=0.5 
 
                                                  Date:    5/09/2022 
                                                  Time:     03:47:44 
 
 
                  WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM 
                                    8.3.3.33 
                            Core Version 06Feb2020 
 
Settings 
-------- 
Model:  Plasma Data, Constant Infusion Administration 
Number of nonmissing observations:   13 
Dose time:      0.00 
Dose amount:     3000.00 
Length of Infusion:      0.50 
Calculation method:  Linear/Log Trapezoidal 
Weighting for lambda_z calculations:  Uniform weighting 
Lambda_z method:  Find best fit for lambda_z,  Log regression 
Lambda_z Acceptance Criterion, Min Rsq_Adjusted:  0.8000 
Lambda_z Acceptance Criterion, Max AUC_%Extrap_obs:   20.00 
 
 
Summary Table 
------------- 
      Time         Conc.      Pred.    Residual      AUC       AUMC      Weight 
        day        mg/L        mg/L        mg/L    day*mg/L day*day*mg/L 
------------------------------------------------------------------------------- 
      0.000        0.000                            0.000      0.000 
    0.04167        636.8                            13.27     0.5528 
     0.1667        675.1                            95.26      9.244 
     0.3333        555.2                            197.5      34.52 
      1.000        486.1                            544.1      263.0 
      7.989 *      233.1      253.1     -20.00      2950.  1.006e+04      1.000 
      14.98 *      202.8      191.9      10.88      4472.  2.741e+04      1.000 
      21.99 *      145.3      145.5    -0.1663      5680.  4.952e+04      1.000 
      29.00 *      109.4      110.2    -0.8202      6567.  7.198e+04      1.000 
      36.06 *      89.21      83.39      5.818      7266.  9.461e+04      1.000 
      42.99 *      66.84      63.38      3.458      7803.  1.158e+05      1.000 
      86.17 *      9.283      11.48     -2.200      9062.  1.887e+05      1.000 
      107.0 *      5.727      5.039     0.6876      9215.  2.033e+05      1.000 
 
 
*) Starred values were included in the estimation of Lambda_z. 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 22 of 26 
Final Parameters 
--------------- 
N_Samples                                                13 
Dose                                     mg            3000.0000 
Rsq                                                       0.9942 
Rsq_adjusted                                              0.9932 
Flag_Rsq_adjusted                                       Accepted 
Corr_XY                                                  -0.9971 
No_points_lambda_z                                        8 
Lambda_z                              1/day               0.0396 
Lambda_z_intercept                                        5.8499 
Lambda_z_lower                          day               7.9889 
Lambda_z_upper                          day             106.9951 
HL_Lambda_z                             day              17.5217 
Span                                                      5.6505 
Tmax                                    day               0.1667 
Cmax                                   mg/L             675.1326 
Cmax_D                              mg/L/mg               0.2250 
Tlast                                   day             106.9951 
Clast                                  mg/L               5.7266 
Clast_pred                             mg/L               5.0389 
AUClast                            day*mg/L            9215.2150 
AUClast_D                       day*mg/L/mg               3.0717 
AUCall                             day*mg/L            9215.2150 
AUCINF_obs                         day*mg/L            9359.9739 
AUCINF_D_obs                    day*mg/L/mg               3.1200 
AUC_%Extrap_obs                           %               1.5466 
Flag_AUC_%Ext_obs                                       Accepted 
Vz_obs                                    L               8.1021 
Cl_obs                               mL/day             320.5137 
AUCINF_pred                        day*mg/L            9342.5914 
AUCINF_D_pred                   day*mg/L/mg               3.1142 
AUC_%Extrap_pred                          %               1.3634 
Vz_pred                                   L               8.1171 
Cl_pred                              mL/day             321.1101 
AUMClast                       day*day*mg/L          203338.3361 
AUMCINF_obs                    day*day*mg/L          222486.1011 
AUMC_%Extrap_obs                          %               8.6063 
AUMCINF_pred                   day*day*mg/L          220186.8568 
AUMC_%Extrap_pred                         %               7.6519 
MRTlast                                 day              21.8155 
MRTINF_obs                              day              23.5199 
MRTINF_pred                             day              23.3181 
Vss_obs                                   L               7.5385 
Vss_pred                                  L               7.4877 
 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 23 of 26 
WinNonlin 8.3.3.33 
Subject_ID=1023,Treatment=IXT-m200,Dose=3000,Actual_Infusion_Time=0.5 
 
                                                  Date:    5/09/2022 
                                                  Time:     03:47:44 
 
 
                  WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM 
                                    8.3.3.33 
                            Core Version 06Feb2020 
 
Settings 
-------- 
Model:  Plasma Data, Constant Infusion Administration 
Number of nonmissing observations:   15 
Dose time:      0.00 
Dose amount:     3000.00 
Length of Infusion:      0.50 
Calculation method:  Linear/Log Trapezoidal 
Weighting for lambda_z calculations:  Uniform weighting 
Lambda_z method:  Find best fit for lambda_z,  Log regression 
Lambda_z Acceptance Criterion, Min Rsq_Adjusted:  0.8000 
Lambda_z Acceptance Criterion, Max AUC_%Extrap_obs:   20.00 
 
 
Summary Table 
------------- 
      Time         Conc.      Pred.    Residual      AUC       AUMC      Weight 
        day        mg/L        mg/L        mg/L    day*mg/L day*day*mg/L 
------------------------------------------------------------------------------- 
      0.000        0.000                            0.000      0.000 
    0.04167        688.5                            14.34     0.5976 
     0.1667        596.5                            94.52      8.830 
     0.3333        568.3                            191.6      33.03 
     0.9944        474.8                            535.4      257.9 
      8.153        257.8                            3079.  1.097e+04 
      14.06        227.8                            4512.  2.681e+04 
      23.11        156.9                            6234.  5.832e+04 
      29.14        124.3                            7077.  8.026e+04 
      36.27        105.1                            7893.  1.069e+05 
      43.13        73.60                            8500.  1.308e+05 
      64.18 *      32.95      33.03   -0.08146      9564.  1.865e+05      1.000 
      85.14 *      17.09      17.14   -0.04422  1.007e+04  2.237e+05      1.000 
      106.0 *      9.037      8.928     0.1090  1.033e+04  2.486e+05      1.000 
      128.1 *      4.428      4.460   -0.03147  1.048e+04  2.651e+05      1.000 
 
 
*) Starred values were included in the estimation of Lambda_z. 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 24 of 26 
Final Parameters 
--------------- 
N_Samples                                                15 
Dose                                     mg            3000.0000 
Rsq                                                       0.9999 
Rsq_adjusted                                              0.9999 
Flag_Rsq_adjusted                                       Accepted 
Corr_XY                                                  -1.0000 
No_points_lambda_z                                        4 
Lambda_z                              1/day               0.0313 
Lambda_z_intercept                                        5.5060 
Lambda_z_lower                          day              64.1771 
Lambda_z_upper                          day             128.1486 
HL_Lambda_z                             day              22.1461 
Span                                                      2.8886 
Tmax                                    day               0.0417 
Cmax                                   mg/L             688.4733 
Cmax_D                              mg/L/mg               0.2295 
Tlast                                   day             128.1486 
Clast                                  mg/L               4.4282 
Clast_pred                             mg/L               4.4597 
AUClast                            day*mg/L           10477.0455 
AUClast_D                       day*mg/L/mg               3.4923 
AUCall                             day*mg/L           10477.0455 
AUCINF_obs                         day*mg/L           10618.5271 
AUCINF_D_obs                    day*mg/L/mg               3.5395 
AUC_%Extrap_obs                           %               1.3324 
Flag_AUC_%Ext_obs                                       Accepted 
Vz_obs                                    L               9.0267 
Cl_obs                               mL/day             282.5251 
AUCINF_pred                        day*mg/L           10619.5326 
AUCINF_D_pred                   day*mg/L/mg               3.5398 
AUC_%Extrap_pred                          %               1.3417 
Vz_pred                                   L               9.0258 
Cl_pred                              mL/day             282.4983 
AUMClast                       day*day*mg/L          265138.6729 
AUMCINF_obs                    day*day*mg/L          287789.6942 
AUMC_%Extrap_obs                          %               7.8707 
AUMCINF_pred                   day*day*mg/L          287950.6725 
AUMC_%Extrap_pred                         %               7.9222 
MRTlast                                 day              25.0566 
MRTINF_obs                              day              26.8526 
MRTINF_pred                             day              26.8652 
Vss_obs                                   L               7.5865 
Vss_pred                                  L               7.5894 
 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 25 of 26 
WinNonlin 8.3.3.33 
Subject_ID=1024,Treatment=IXT-m200,Dose=3000,Actual_Infusion_Time=0.5 
 
                                                  Date:    5/09/2022 
                                                  Time:     03:47:44 
 
 
                  WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM 
                                    8.3.3.33 
                            Core Version 06Feb2020 
 
Settings 
-------- 
Model:  Plasma Data, Constant Infusion Administration 
Number of nonmissing observations:   15 
Dose time:      0.00 
Dose amount:     3000.00 
Length of Infusion:      0.50 
Calculation method:  Linear/Log Trapezoidal 
Weighting for lambda_z calculations:  Uniform weighting 
Lambda_z method:  Find best fit for lambda_z,  Log regression 
Lambda_z Acceptance Criterion, Min Rsq_Adjusted:  0.8000 
Lambda_z Acceptance Criterion, Max AUC_%Extrap_obs:   20.00 
 
 
Summary Table 
------------- 
      Time         Conc.      Pred.    Residual      AUC       AUMC      Weight 
        day        mg/L        mg/L        mg/L    day*mg/L day*day*mg/L 
------------------------------------------------------------------------------- 
      0.000        0.000                            0.000      0.000 
    0.04167        910.4                            18.97     0.7903 
     0.1667        865.8                            130.0      12.29 
     0.3340        754.0                            265.3      45.91 
     0.9889        812.6                            778.0      387.1 
      8.233 *      398.1      334.0      64.15      4986.  1.799e+04      1.000 
      13.12 *      269.1      277.2     -8.055      6597.  3.494e+04      1.000 
      22.15 *      220.8      196.6      24.25      8801.  7.348e+04      1.000 
      29.15 *      148.3      150.5     -2.192  1.008e+04  1.059e+05      1.000 
      36.08 *      113.8      115.6     -1.856  1.098e+04  1.352e+05      1.000 
      41.10 *      99.04      95.51      3.532  1.151e+04  1.558e+05      1.000 
      63.16 *      34.83      41.21     -6.382  1.287e+04  2.239e+05      1.000 
      86.11 *      9.927      17.19     -7.266  1.332e+04  2.568e+05      1.000 
      107.2 *      8.825      7.709      1.116  1.352e+04  2.758e+05      1.000 
      125.1 *      5.333      3.895      1.439  1.365e+04  2.901e+05      1.000 
 
 
*) Starred values were included in the estimation of Lambda_z. 
 
 


InterveXion Therapeutics, LLC 
 
IXT-m200 for Intravenous Infusion 
Protocol M200C-2102 
 
Clinical Study Report 
 
Confidential 
 
Page 26 of 26 
Final Parameters 
--------------- 
N_Samples                                                15 
Dose                                     mg            3000.0000 
Rsq                                                       0.9776 
Rsq_adjusted                                              0.9748 
Flag_Rsq_adjusted                                       Accepted 
Corr_XY                                                  -0.9887 
No_points_lambda_z                                       10 
Lambda_z                              1/day               0.0381 
Lambda_z_intercept                                        6.1246 
Lambda_z_lower                          day               8.2333 
Lambda_z_upper                          day             125.0972 
HL_Lambda_z                             day              18.1974 
Span                                                      6.4220 
Tmax                                    day               0.0417 
Cmax                                   mg/L             910.3975 
Cmax_D                              mg/L/mg               0.3035 
Tlast                                   day             125.0972 
Clast                                  mg/L               5.3333 
Clast_pred                             mg/L               3.8947 
AUClast                            day*mg/L           13645.1032 
AUClast_D                       day*mg/L/mg               4.5484 
AUCall                             day*mg/L           13645.1032 
AUCINF_obs                         day*mg/L           13785.1184 
AUCINF_D_obs                    day*mg/L/mg               4.5950 
AUC_%Extrap_obs                           %               1.0157 
Flag_AUC_%Ext_obs                                       Accepted 
Vz_obs                                    L               5.7134 
Cl_obs                               mL/day             217.6260 
AUCINF_pred                        day*mg/L           13747.3505 
AUCINF_D_pred                   day*mg/L/mg               4.5825 
AUC_%Extrap_pred                          %               0.7438 
Vz_pred                                   L               5.7291 
Cl_pred                              mL/day             218.2239 
AUMClast                       day*day*mg/L          290143.5780 
AUMCINF_obs                    day*day*mg/L          311334.9490 
AUMC_%Extrap_obs                          %               6.8066 
AUMCINF_pred                   day*day*mg/L          305618.7579 
AUMC_%Extrap_pred                         %               5.0636 
MRTlast                                 day              21.0136 
MRTINF_obs                              day              22.3349 
MRTINF_pred                             day              21.9811 
Vss_obs                                   L               4.8606 
Vss_pred                                  L               4.7968