An Open Pilot Trial of BHV-4157 in Adult Subjects With Cerebellar Ataxia
Phase: PHASE3
Conditions: Spinocerebellar Ataxias, Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 2, Spinocerebellar Ataxia 3, Spinocerebellar Ataxia Type 6, MSA-C
Sponsor: University of California, Los Angeles

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PROTOCOL 
Project No.: 
Biohaven study number: BHV4157-Open, under IND 137551 
Title: 
An Open  Trial of BHV-4157 in Adult Subjects with Cerebellar Ataxia 
Objectives: 
a) 
Primary Objectives 
• 
To assess  the efficacy of BHV-4157 (140 mg orally  once 
daily) on ataxia symptoms in subjects with Cerebellar 
Ataxia after 12 weeks of treatment as measured by the 
total score on the Scale for the Assessment and Rating of 
Ataxia [SARA] 
b)    Secondary Objectives 
• 
To assess of the safety and tolerability of BHV-4157 in 
subjects with Cerebellar Ataxia; including safety 
measures-- Beck Depression Inventory(BDI), Beck 
Anxiety Inventory (BAI), and Sheehan Suicidality 
Tracking Scale Sheehan (STS). 
• 
To assess the efficacy of BHV-4157 on the 8- meter Timed 
Walk test 
c) 
Exploratory Objectives 
• 
To assess the efficacy of BHV-4157 on non- ataxia 
symptoms in subjects with Cerebellar Ataxia after 12 weeks 
of treatment, via assessment on the INAS 
• 
To assess the efficacy of BHV-4157 on the 9- hole peg test 
• 
To assess the efficacy of BHV-4157 on health outcome 
assessment, EQ-5D 
• 
To assess the efficacy of BHV-4157 on patient impression 
via use of the PGIC 
• 
To assess the efficacy of BHV-4157 on clinician impression 
via use of the CGIC 
• 
In the subgroup with SCA3/dizziness-predominant, to 
add preliminary assessments on effects of BHV-4157 on 
selected patient reported measures of dizziness and its impact 
on quality of life. There are 4 that have been used in most 
studies of dizziness/vertigo posted on ClinicalTrials.gov. 
1. 
Vertigo Symptom Scale 15 item short form. 
2. 
Dizziness Handicap Inventory (© AMA) 
3. 
Vestibular Disorders ADL Scale (© AMA) 
4. 
Activities-specific Balance Confidence Scale 

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Study Rationale: 
BHV-4157 is a glutamate modulating drug that is being developed for eventual 
commercial use in the treatment of spinocerebellar ataxia (SCA).  There is a 
current Phase IIb/3, double-blind, placebo-controlled study being 
performed in 140 ambulatory patients with SCA 1, 2, 3, 6, 7, 8, and 
10 (ClinicalTrials.gov Identifier: NCT0296089; IND/FDA Orphan Designation 16-
5200; Compassionate IND for this proposed study—pending).  
There is currently no approved medication indicated for SCA. 
BHV-4157 is a novel tripeptide prodrug of the glutamate modulating agent 
riluzole.  While BHV-4157 has yet to be fully studied in clinical populations, 
studies with riluzole in populations with ataxia provide support for the 
therapeutic potential of BHV-4157.  Relevant pharmacologic activities of 
riluzole, such as increasing glutamate transporters (Cvetanovic et al. 2015; Custer 
et al. 2006) or potential activation of small-conductance calcium-activated 
potassium channels (Shakkottai e t  a l .  2011) prompted clinical testing. Two 
well-designed clinical trials (Ristori et al. 2010) and (Romano et al. 2015) 
demonstrated preliminary safety and robust efficacy of riluzole 50 mg twice a 
day in patients with SCA. Since BHV-4157 is a prodrug of riluzole, it is expected 
to have similar therapeutic potential in SCA. 
BHV-4157 was developed to advance upon the limitations of riluzole that have 
restricted its broader clinical application.  Riluzole tablets have 60% 
bioavailability, attributed to high first-pass metabolism in the liver. This is 
thought to be related to metabolism by the heterogeneously expressed CYP1A2 
enzyme, which also contributes to the high PK variability associated with 
riluzole (Greonveld et al. 2001; Sanderink et al. 1997; Martinet et al. 1997).  In 
addition, riluzole is associated with reduced exposure when taken with meals 
(i.e., a negative food effect), resulting in the guideline to take riluzole within a 
three hour fasting window (one hour before or two hours after a meal).  Riluzole 
is also dosed twice a day, has dose-dependent effects on liver function tests, and 
the drug substance itself has other intrinsic limitations including: very low 
solubility in water, poor oral palatability, pH dependent chemical stability, and 
intense oral numbness if administered directly to the oral mucosa. 
In an effort to mitigate the aforementioned limitations of riluzole, several 
classes of prodrugs were designed, synthesized, and evaluated in multiple in 
vitro stability assays to predict in vivo drug levels (McDonnell et al. 2012). 
BHV-4157 is a third generation of prodrug development representing 
multiple years of chemistry effort with optimized in vivo and in vitro features 
based on stability while transiting the digestive system, enhanced 
gastrointestinal absorption, avoidance of first pass metabolism, favorable 
safety pharmacology, metabolic cleavage in the plasma, enhanced 
pharmacokinetic properties, and good oral palatability. 
Based on the preclinical features of BHV-4157, we anticipate the clinical 
pharmacology to offer favourable properties as compared to commercially 
available riluzole: 
• 
BHV-4157 is expected to have better oral bioavailability; 
• 
BHV-4157 is designed to release riluzole after bypassing first-pass 
metabolism and thus lowers the overall drug burden to the liver, which 
may translate into a better safety and tolerability profile, and reduces 
pharmacokinetic variability. 

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• 
BHV-4157 is expected to allow for once daily dosing, thus improving 
regimen compliance; 
• 
BHV-4157 is expected to be readily absorbed in both the fasting and 
fed states; thus, the prodrug is not anticipated to require any special 
meal restrictions.  In contrast, oral riluzole tablets require a 3-hour 
window of fasting around the two daily doses. 
• 
BHV-4157 will ultimately be formulated as an orally dispersible tablet 
(Zydis). 
This formulation will be amenable to patients who have difficulty 
swallowing. BHV-4157 is expected to have good oral tolerability 
and palatability when administered sublingually. 
Study Design: 
BHV4157-Open is a single center, open study designed to assess safety, 
tolerability, and efficacy signals in a population of subjects with Cerebellar 
Ataxia. Subjects will receive oral BHV-4157 (140 mg QD). 
Dosing will continue for 12 weeks, with subjects being seen every 4 weeks. Subjects 
will return to the clinic two weeks after discontinuing study medication for a follow-
up safety visit. Subjects will be offered an additional 36 weeks  of extension treatment  
(as  allowed  by  the  FDA)  as  long  as  the  PI believes the extension treatment offers 
an acceptable risk-benefit profile. 
Subjects entering the Compassionate Extension Phase will undergo visits every 
12 weeks up to Week 48.  All subjects will undergo a termination visit two weeks 
after the last dose of study drug. 
Subjects: 
Up to 24 male and female outpatient subjects between the ages of 18 – 75, 
inclusive, with a known or suspected diagnosis of the following specific ataxias:  
SCA3/dizziness predominant (up to 4 subjects); SCA1, SCA2, SCA3, 
or SCA6 already taking Riluzole for more than 8 weeks (up to 4 subjects, who will 
directly switch to BHV4157 at Baseline visit); non-genetic pure cerebellar ataxia 
(up to 4 subjects); MSA-C (up to 12 subjects). 

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Inclusion criteria: 
1. 
Informed Consent 
a. 
Subjects (or legally acceptable representative as required by the 
IRB/IEC) must provide a written signed informed consent 
form/forms (IRB/EC specific) prior to the initiation of any 
protocol required procedures. 
2. 
Age and Sex 
a. 
Male and female outpatient subjects between the ages of 18 - 
75, inclusive 
3. 
Target Populations 
a. 
Subjects with (1) a known or suspected diagnosis of a 
specific hereditary ataxia:  SCA3/dizziness-
predominant or SCA1, SCA2, SCA3, SCA6, already 
taking Riluzole for more than 8 weeks; (2) other genetic or 
non-genetic pure cerebellar ataxia; (3) MSA-C: 
i.   SCA subjects should have confirmed genotypic 
diagnosis from a CLIA-certified lab or a family 
member that has had such testing. 
ii.   Alternatively, subjects must be willing to undergo 
genetic testing from a CLIA-certified lab if testing 

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has not been previously done on the study subject and 
a copy of results is not available for verification. 
b. 
Ability to ambulate 8 meters without assistance (canes and 
other devices allowed); 
c. 
Determined by the investigator to be medically stable at 
Baseline/randomization as assessed by medical history, 
physical examination, laboratory test results, and 
electrocardiogram testing. Subjects must be physically able 
and expected to complete the trial as designed; 
d. 
Minimum of 6 years of education; 
e. 
Subjects must have adequate hearing, vision, and language 
skills to perform interviews as specified in the protocol; 
f. 
Subjects must be able to understand and agree to comply with 
the prescribed dosage regimens and procedures; report for 
regularly scheduled office visits; and reliably communicate with 
study personnel about adverse events and concomitant 
medications; 
g. 
Women of childbearing potential (WOCBP) and men must be 
using an acceptable method of contraception to avoid pregnancy 
throughout the study and for up to 30 day after the last dose of 
investigational product in such a manner that risk of pregnancy 
is minimized. The requisite drug interaction studies to determine 
the interaction of BHV-4157 with oral contraceptives have not 
been performed to date. It is therefore not possible to determine 
the efficacy of oral contraceptives as an effective method of 
contraception for WOCBP who participation this study. Oral 
estrogen and progestin hormonal contraceptives as a sole method 
of contraception are therefore prohibited. It is required that all 
WOCBP use two methods of contraception for the duration of 
the study (i.e. beginning at first treatment to 30 days after the 
last dose of study drug).The two methods should include one 
barrier method (ex. condom with spermicidal gel, intrauterine 
devices, cervical cap etc.) and one other method. The other 
method could include oral contraceptives or another barrier 
method. 
h. 
Women of childbearing potential must have a negative serum 
pregnancy test at screening and a negative urine pregnancy test 
within 72 hours prior to first dosing. 
i.    SCA subjects (SCA3/dizziness predominant; SCA1, 2, 3, 6 on 
Riluzole for more than 8 weeks) will not be limited to Inclusion 
Criteria of Screening SARA score ≥8 or Score of ≥ 2 on gait 
subsection of the SARA. 
Exclusion criteria: 
1. 
Target Disease Exceptions 
a. 
Any medical condition other than one of the hereditary 
ataxias specified in the inclusion criteria that could 
predominantly explain or contribute significantly to the 
subjects’ symptoms of ataxia (for example, alcoholism, 
vitamin deficiencies, multiple sclerosis, vascular disease, 
tumors, paraneoplastic disease, head injury, idiopathic late 
onset ataxia, multisystem atrophy) or that can confound 
assessment of ataxia symptoms (for example, stroke, 
arthritis); 
b. 
MMSE score < 24; 
c. 
Subjects with prominent spasticity or dystonia that meet 

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either of the following criteria: 
i.   In the opinion of the investigator will compromise 
the ability of the SARA instrument to assess 
underlying ataxia severity; or, 
ii.   Are associated on the INAS instrument at screening 
with moderate or severe scores on dystonia (at least 
3 of 5 items) or spasticity (at least 2 of 3 items) or 
rigidity (at least 2 of 3 items) 
d. 
SARA total score of > 30 points at screening; 
e. 
Subjects may not have started physical or occupational 
therapy within one month of screening and are not expected 
to start such therapy during the randomization phase. 
Subjects with ongoing occupational or physical therapy may 
be allowed to continue as long as the intensity remains 
unchanged from two months prior to screening throughout the 
randomization period. 
2. 
Medical History Exclusions 
a. 
Clinical history of stroke. Note: Subjects with a history of 
transient ischemic attack (TIA) may be enrolled, if it occurred 
at least 3 months prior to screening and the subject is 
prescribed appropriate treatment [e.g., platelet aggregation 
inhibitors]; 
b. 
Immunocompromised  subjects. Note: Subjects taking a 
systemic immunosuppressive  agent may be randomized only 
if they are on a stable dose, have no clinically relevant 
immunosuppression,  and have a white blood count (WBC) 
within normal limits; 
c. 
Active liver disease or a history of hepatic intolerance to 
medications that in the investigator’s judgment, is medically 
significant; 
d. 
History of medically significant gastrointestinal (GI) illnesses 
including: 
i.   A current diagnosis of active, peptic ulceration or 
gastrointestinal bleeding within the last 6 months 
and/or chronic inflammatory bowel disease at 
screening; 
ii.   A history of any gastrointestinal surgery that impacts 
the absorption of study drug; 
iii.   Chronic or frequent episodes of loose stools; bowel 
movements; 
e. 
Vitamin B12 or folate deficiency Note: Subjects with a B12 
deficiency can participate in the study if they are on stable 
Vitamin B12 replacement for at least 3 months prior to 
randomization and their B12 levels are within normal limits 
prior to randomization; 
f. 
Hematologic or solid malignancy diagnosis within 5 years 
prior to screening. (Note: Subjects with a history of localized 
skin cancer, basal cell or squamous cell carcinoma, may be 
enrolled in the study as long as they are cancer free prior to 
randomization. Subjects with other localized cancers (without 
metastatic spread) who have previously completed their 
course of treatment more than 2 years prior to baseline, are 
not currently receiving treatment and have been in remission 
may be enrolled only if, in the opinion of the investigator, 
there is no expectation for recurrence or further cancer 

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treatment during the study period. Antihormonal therapy (e.g., 
tamoxifen) is allowed if the subject's cancer is in remission 
and the subject is on maintenance therapy to reduce their risk 
of recurrence; 
g. 
Any unstable cardiovascular (includes uncontrolled 
hypertension), pulmonary, gastrointestinal, or hepatic disease 
30 days prior to screening; 
h. 
End-stage cardiovascular disease (e.g., Congestive Heart 
Failure New York Heart Association/CHF NYHA Class III or 
IV or unstable angina); 
i. 
Treated for, or have had a lifetime diagnosis of, schizophrenia 
or bipolar disorder; 
j. 
Active major depressive episode within the past 6 months. 
Note: Subjects on a stable maintenance dose of a non- 
tricyclic, non-monoamine oxidase inhibitor (MAOI) 
antidepressant medication (e.g., serotonin reuptake inhibitor, 
bupropion) with symptoms in remission may be eligible; 
k. 
History of neurosyphilis (as indicated by a positive rapid 
plasma reagin [RPR] test and a positive confirmatory test); 
l. 
History of drug or alcohol abuse within 12 months as defined 
by DSM-IV-TR-TR criteria; 
m.   History or evidence of any medical, neurological or 
psychological condition that would expose the subject to an 
undue risk of a significant adverse event or interfere with 
assessments of safety and efficacy during the course of the 
trial as determined by the clinical judgment of the 
investigator; 
n. 
History of chronic pulmonary disease or chronic pulmonary 
symptoms. 
 
3. 
Physical and Laboratory Test Findings 
a. 
Uncontrolled hypertension at screening (e.g., repeated 
diastolic measurements ≥ 96 mmHg); 
b. 
Diagnosis of hypothyroidism by a screening thyroid 
stimulating hormone (TSH) value > the upper limit of normal 
(ULN) and free thyroxine (T4) index < the lower limit of 
normal (Note: Subjects with history of hypothyroidism may 
participate in the study, provided they are euthyroid on stable 
thyroid replacement therapy for at least 3 months prior to 
screening, and therapy is expected to remain stable during the 
course of the study; 
c. 
Hepatic test abnormalities at screening: 
i.   Aspartate Aminotransferase (AST), Alanine 
Aminotransferase (ALT) or GGT > 2 times the 
upper limit of normal; or 
ii.   Total bilirubin > 2 times the upper limit of normal 
(ULN); 
d. 
P-Amylase or Lipase values greater than 2 times the upper 
limit of normal at screening (ULN); 
e. 
HbA1C > 7.5% at screening; 
f. 
Pathologic renal findings at screening as defined by the 
presence of either of the following criteria: 
i.   Estimated glomerular filtration rate (eGFR) 
according to the re-expressed abbreviated (four- 
variable) Modification of Diet in Renal Disease 

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(MDRD) Study equation < 30 ml/min/ 1.73m2; The 
MDRD estimation is calculated as follows: eGFR 
(mL/min/1.73m2) = 175 x (standardized Scr)-1.154 x 
(Age)-0.203 x (0.742 if female) x (1.212 if Black). 
[Scr: Standardized serum creatinine] 
g. 
Hematologic abnormalities at screening: 
i.   Hemoglobin < 10 g/dL; or 
ii.   WBC < 3.0 x 103/mm3; or 
iii.   Platelet count < 100,000/mm3; 
h. 
Human Immunodeficiency Virus (HIV) positive at screening 
(indicated by positive confirmatory Western Blot); 
i. 
HBsAg or  HCV positive at screening; 
j. 
QTc (Bazett’s) and QTc (Fridericia) interval > 480 msec at 
screening and confirmed by repeat measurement or 
uncontrolled arrhythmia or frequent premature ventricular 
contraction (PVCs) (> 5/minute) or Mobitz Type II second or 
third degree atrioventricular (AV) block or evidence of acute or 
sub-acute myocardial infarction or ischemia. [Note: Subjects 
with MRI compatible pacemakers or bundle branch block 
(BBB) and a paced QTc (Fridericia) < 480 msec and a stable 
cardiac status may be enrolled after obtaining a cardiology 
consult. It must be determined by the consulting cardiologist 
that the subject’s cardiac status is stable and does not pose a 
risk for participation in the trial.] 
k.    Screening laboratory testing can be done at patient’s primary 
care physician’s office up to 6 weeks prior to Screening visit, 
provided that results are available at time of Screening visit. 
4. 
Prohibited Treatments and/or Therapies 
a. 
History of not tolerating treatment with riluzole for any 
reason 
b. 
Treatment with riluzole in the 30 days prior to screening 
and/or during the study; [with the exception of the switch 
group of SCA subjects]. 
c. 
Prior trial of riluzole treatment of at least 8 weeks 
duration ;  [with the exception of the switch group of 
SCA subjects]. 
d. 
Use of chlorzoxazone is prohibited 30 days prior to screening 
and during the study; 
e. 
Use of aminopyridine is prohibited 30 days prior to screening 
and during the study; 
f. 
Use of tricyclic antidepressants and mono-amine-oxidase 
(MAO) inhibitors are prohibited 30 days prior to screening 
and during the study; 
g. 
Use of any approved treatments for Alzheimer’s Disease 
(AD). Subjects should be free of such medications (donepezil, 
galantamine, rivastigmine and memantine) for at least 3 months 
prior to Baseline with no plans to start such medications during 
the study; or, subjects should be on stable doses of these 
medications for at least 3 months prior to the baseline visit; 
h. 
Use of memantine is prohibited 30 days prior to screening 
and during the study; 
i. 
A new anxiolytic or sleep medication not taken at a stable 
dose within 30 days prior to screening. Note: Low dose 
anxiolytic pre-medications prior to diagnostic testing (e.g., 
MRI) as well as sleep medications taken prn (as needed) are   

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allowed; 
j. 
Chronic NSAID use (e.g., naproxen, acetylsalicylic acid, 
ibuprofen) should be treated with proton pump inhibitors 
unless otherwise clinically prohibited; 
k.   Medical marijuana use within 30 days of baseline visit (and 
subjects will be expected to refrain from use during the period 
of the study). 
Concomitant Medications: 
1. 
Antidepressant Use:  The use of tricyclic antidepressants and mono- 
amine-oxidase (MAO) inhibitors are prohibited 30 days prior to 
screening and during the study. Other antidepressants (e.g., bupropion, 
citalopram, escitalopram, fluoxetine, mirtazapine, paroxetine, 
sertraline, venlafaxine, and duloxetine) are permitted if the subject has 
been treated with a stable dose for 3 months prior to randomization 
and no dose changes are expected throughout the randomization phase 
of the study. 
2. 
Hypnotic Use:  New use of hypnotics should be avoided. For the 
management of persistent sleeping difficulties or insomnia, subjects 
may receive the following medications at the indicated doses (or 
equivalent doses in countries outside of the US) such as: 
• 
zolpidem tartrate (Ambien): up to 10 mg at bedtime (HS) as 
needed (prn) 
• 
zolpidem tartrate extended-release (Ambien CR
→): 12.5 mg at 
HS prn 
• 
zaleplon (Sonata): 20 mg at HS prn eszopiclone (Lunesta): 3 
mg at HS prn 
Screening Procedures: 
• 
Eligibility assessments include: Inclusion/exclusion, medical history, 
demographics, disease history, neurological exam, Mini Mental State 
Exam, and pregnancy testing for WOCBP at screening and 72 hours 
prior to first dose. 
• 
Safety assessments include: Laboratory assessments, physical exam, 
physical measurements, vital signs, 12-lead ECG, concomitant 
medication review, Beck Depression Inventory (BDI), Beck Anxiety 
Inventory (BAI), and Sheehan Suicidality Tracking Scale Sheehan 
(STS). 
• 
Clinical outcome assessments include: The Scale for the Assessment 
and Rating of Ataxia (SARA), Inventory of Non-Ataxia Symptoms 
(INAS), 9 Hole Peg Test, 8 Meter Walk, Clinical Global Impression of 
Change (CGIC), Patient Global Impression of Change Scale (PGIC); 
and dizziness assessments (SCA3/dizziness predominant subjects 
only). 
Randomization Phase: 
N/A All subjects will receive open drug during the initial 12 weeks of the study. 
Extension Phase: 
Subjects completing the initial 12 week open-label administration will be offered 
and additional 36 weeks  of  open-label  e xt ension treatment  (as  allowed  by 
the  FDA)  as  long  as  the  PI believes continued open-label treatment offers an 
acceptable risk-benefit profile. 
Drug Administrations: 
Subjects will receive oral  BHV-4157 (140 mg QD). 

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Laboratory Assessments and 
Sample Collection: 
• 
Laboratory Assessments: All laboratory testing should be done 
fasting and testing will include the following. Laboratory testing 
designated as Screening can be done up to 12 weeks prior to the 
Baseline visit: 
a) Hematology: hemoglobin, hematocrit, red blood cells, white blood 
cells, differential count and absolute platelet count [Screening, Week 
12, Week 24, Week 36, and Week 48]. 
b) Serum Chemistry: albumin, sodium, potassium, chloride, calcium, 
AST, ALT, LDH, alkaline phosphatase, GGT, CPK, total protein, total 
bilirubin, glucose, creatinine, blood urea nitrogen (BUN), uric acid, 
triglycerides, total cholesterol, HbA1C, P- Amylase or Lipase, TSH, 
T4, and urine pregnancy testing will be performed at Screening. 
Urine pregnancy testing will be repeated at Baseline (up to 72 hours 
prior) and Week 12. 
AST, ALT, LDH, alkaline phosphatase, GGT, and total bilirubin will 
be repeated at Week 12, Week 24, Week 36, and Week 48. 
c) Urinalysis: macroscopic examination, pH, specific gravity, ketones, 
nitrites, bilirubin, urobilinogen, leukocyte esterase, protein, glucose, 
and occult blood will be performed at Screening.  
d) HBsAg, HCV and HIV antibody detection will be performed at 
Screening 
Any lab value outside of the normal range must be brought to the attention of a 
physician (Investigator or Sub-Investigator) at the site. The Investigator will 
indicate whether or not a flagged value is of clinical significance. 
• 
BDNF Blood Sample Collection:  N / A  
• 
Pharmacogenetic Blood Sample Collection:  N/A 
• 
Pharmacokinetic Sample Collection: N/A 

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Subject Safety: 
Initial 12 week open-drug administration 
• 
Review of subject eligibility before dosing; 
• 
Concomitant medication review: At Screening, Baseline, and through 
the 2-week Post Last Dose; 
• 
Physical examination at Screening, Baseline, and Week 12 
• 
Physical measurements and vital signs will be done assessed at 
Screening, B asel ine, and Week 12; 
• 
The Beck Depression Inventory (BDI) and The Beck Anxiety 
Inventory (BAI) will be assessed at Screening, Baseline, and Week 
12. The Sheehan Suicidality Tracking Scale (Sheehan STS) will be 
assessed at Screening and all visits through the 2-Weeks Post Last 
Dose Visit; 
• 
12-Lead ECG will be done at Screening and Week 12; 
• 
Hematology, serum chemistries, and urinalysis at screening. 
• 
CBC and Liver Function Tests will be done at Screening and Week 12; 
• 
Urine pregnancy testing will be performed on WOCBP at screening, 
baseline, and Week 12. Urine pregnancy testing may also be done at 
the discretion of the Investigator. 
• 
Subjects will be monitored throughout the study for adverse events. 
Extension Phase [Week 12 through Week 48] 
• 
Physical examination will be assessed at Baseline/Week 12, Week 24, 
Week 48, and 2-Weeks Post Dose; 
• 
Physical measurements and vital signs will be assessed at 
Baseline/Week 12 visit through 2-Weeks Post Last Dose; 
• 
The Beck Depression Inventory (BDI) and The Beck Anxiety 
Inventory (BAI) will be assessed at Baseline, Weeks 24, 48 and 2- 
Weeks Post Dose. The Sheehan Suicidality Tracking Scale (Sheehan 
STS) will be assessed at Baseline/Week 12 visit through 2-Weeks 
Post Last Dose; 
• 
12-Lead ECG will be done at Baseline/Week 12. 
• 
Hematology, serum chemistry, and urinalysis at Baseline/Week 12. 

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• 
CBC and Liver Function Tests will be done at Baseline/Week 12, Weeks  
24, 36,  48 and 2-Weeks Post Last Dose; 
• 
Urine pregnancy testing will be performed on WOCBP at 
Baseline/Week 12 and at the discretion of the Investigator. 
• 
Subjects will be monitored throughout the study for adverse events. 
Study Endpoints: 
• 
Primary 
The total score on the Scale for the Assessment and Rating of Ataxia 
(SARA) 
• 
Secondary / Exploratory 
a) Clinical outcomes: 
o The Inventory of Non-Ataxia Symptoms (INAS) 
o UHDRS-IV 
o 8 Meter Walk 
o 9-hole peg test 
• 
EQ-5D 
• 
Dizziness scales (for SCA3/dizziness-predominant) 
• 
Safety assessments 
a) Liver function tests 
b) CBC with differential 
c)    ECG assessments 
d)   Vital Sign Measurements 
                e)   Adverse Events will be assessed throughout the study  
                 
 
Statistical Analyses: 
TBD 

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Proposed Recruitment Groups 
 
SCA3/dizziness predominant; no SARA limitations 
Up to 4 subjects 
SCA1, 2, 3, 6 on Riluzole for >8weeks; no SARA limitations 
Up to 4subjects 
Non-genetic pure cerebellar ataxia 
Up to 4 subjects 
MSA-C 
Up to 12 subjects