A Phase IIb/III, Randomized, Double-blind, Placebo-controlled Trial of BHV-4157 in Adult Subjects with Spinocerebellar Ataxia
- UT Southwestern Ambulatory Services
BHV4157-201 is a Phase iib/iii, multicenter, randomized, double-blind, 2-arm placebo controlled parallel-group study designed to assess safety, tolerability, and efficacy in a population of patients with Spinocerebellar ataxia. Subjects will be randomized to receive placebo (QD) or BHV-4157 (140 mg QD), stratified by diagnosis (known or presumed genotype) and baseline severity (Gait item of the SaRa of [LessThanorequalTo] 4 and [Greater Than]4). Subjects with SCa3 genotype will be limited to comprise up to approximately 10% so that this most common type of SCa is not over-represented. Dosing will continue for 8 weeks. Subjects will return to the clinic two weeks after discontinuing study medication for a follow-up safety visit. in addition, subjects completing the Randomization Phase will be offered approximately 48 weeks of open-label treatment as long as the Pi believes open-label treatment offers an acceptable risk-benefit profile. Subjects who agree to enter the extension Phase will not complete the follow-up safety visit and should continue dosing as specified. Subjects entering the extension Phase would have their first extension Visit four weeks after the Week 8 Randomization Phase visit. if there is a delay of two weeks or more in dosing between the Randomization Phase and the extension Phase, subjects would be required to complete an extension Baseline Visit. Thereafter, subjects will undergo visits every fourth week through Week 12 of this phase. Then subjects will undergo visits every 12 weeks up to Week 48 of this phase. all subjects will undergo a termination visit two weeks after the last dose of study drug. Subjects will be assessed at clinic visits per the Schedule of assessments/Time and events.
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 Population
a. Subjects with a known or suspected diagnosis of the following specific hereditary ataxias: SCA1, SCA2, SCA3, SCA6, SCA7, SCA8 and SCA10;
i. Subjects should have confirmed genotypic diagnosis from a CLIA certified lab or a family member that has had such testing.
ii. 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 (that
includes copy repeat number)
b. Ability to ambulate 8 meters without assistance (canes and other devices allowed);
c. Screening total SARA total score >=8;
d. Score of >= 2 on gait subsection of the SARA;
e. 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;
f. Minimum of 6 years of education and fluent in English;
g. Subjects must have adequate hearing, vision, and language skills to perform neuropsychiatric testing and interviews as specified in the protocol;
h. Subjects must be able to understand and agree to comply with the prescribed dosage regimens and procedures; report for regularly scheduled office visits reliably communicate with study personnel about adverse events and concomitant medications;
i. 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 days after the last dose of investigational product in such a manner that risk of pregnancy is minimized. Oral estrogen and progestin hormonal contraceptives as a sole method of contraception are
therefore prohibited. It is required that all WOCBP who are sexually active 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 (e.g. diaphragm with spermicide, condom with spermicidal gel, intrauterine devices, cervical cap) and one other method. The other method could include oral contraceptives or another barrier method (Section 5.5);
j. Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 72 hours of dosing
k. It is required that men who are sexually active with WOCBP agree to use two methods of contraception for the duration of the study (beginning at first treatment and extending to 90 days after the last dose of study drug).