An Open Pilot Trial of BHV-4157

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) 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 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 as assessed by
medical history, physical examination, laboratory test results available in medical
record, and electrocardiogram testing available in medical record. 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 of 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.

j. Non-genetic pure cerebellar and MSA-C subjects will 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 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 initial 12 week treatment 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 enter treatment phase 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
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. 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 Baseline, 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.
If diabetic, HbA1C > 7.5% within 3 months of screening; e. Pathologic renal findings
at screening as defined by the presence of either of the following criteria within 3
months of screening: i. Estimated glomerular filtration rate (eGFR) according to the
re-expressed abbreviated (four- variable) Modification of Diet in Renal Disease (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] ii. Quantitative urine
protein/creatinine ratio greater than 0.2. This test may be repeated if clinically
indicated. In the event of a urinary tract infection (UTI), the test may be repeated
after the UTI has resolved; f. Hematologic abnormalities within 3 months of screening:
i. Hemoglobin < 10 g/dL; or ii. WBC < 3.0 x 103/mm3; or iii. Platelet count <
100,000/mm3; g. QTc (Bazett's) and QTc (Fridericia) interval > 480 msec within 3
months of 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.]

4. Prohibited Treatments and/or Therapies

1. History of not tolerating treatment with riluzole for any reason

2. 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].

3. Prior trial of riluzole treatment of at least 8 weeks duration ; [with the
exception of the switch group of SCA subjects].

4. Use of chlorzoxazone is prohibited 30 days prior to screening and during the
study;

5. Use of aminopyridine is prohibited 30 days prior to screening and during the
study;

6. Use of tricyclic antidepressants and mono-amine-oxidase (MAO) inhibitors are
prohibited 30 days prior to screening and during the study;

7. 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;

8. Use of memantine is prohibited 30 days prior to screening and during the study;

9. 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
allowed;

10. Chronic NSAID use (e.g., naproxen, acetylsalicylic acid, ibuprofen) should be
treated with proton pump inhibitors unless otherwise clinically prohibited;

11. Medical marijuana use within 30 days of baseline visit (and subjects will be
expected to refrain from use during the period of the study).