Keywords: Huntington's Disease (HD) , Chorea , SD-809 , First-HD , Movement Disorder
IRB Number: 00067316
Specialty: Neurology, Neurology, Neurology
Sub Specialties: Movement Disorders, Chorea, Huntington Disease
This is a randomized, double blind, placebo controlled parallel group study in which subjects with chorea associated with HD who have never been exposed to tetrabenazine will be invited to participate. Subjects will undergo an independent evaluation by a qualified healthcare provider to determine their capacity to provide informed consent. Subjects who qualify for the study will be randomized to receive either SD-809 ER or placebo in a 1:1 (SD-809 ER to placebo) ratio. Subjects will be titrated to an optimal dose level of study drug, followed by maintenance therapy at that dose. The overall treatment period will be 12 weeks in duration. The titration period will last 8 weeks, the maintenance period will be 4 weeks, followed by a washout period of 1 week. To provide a systematic examination for independent rating of chorea, a limited motor examination will be video recorded using a standard protocol at Screening, Baseline and at Weeks 9 and 12.
Approximately 90 subjects will be randomized (1:1) into the study, with approximately 45 subjects receiving SD-809 ER and 45 subjects receiving placebo. The study will be conducted at approximately 30 centers in the U.S. and Canada. The study is divided into a screening period, a titration period, a maintenance period and a post-treatment safety follow up period. For subjects who complete the study, overall study participation will be up to 20 weeks.
The objectives of this study are:
• To evaluate the efficacy of SD-809 ER to reduce the chorea associated with HD
• To evaluate the safety and tolerability of titration and maintenance therapy with SD-809 ER
Screening period (up to 4 weeks): Subjects will undergo an independent evaluation by a qualified healthcare provider to determine their capacity to provide informed consent. After informed consent is obtained, subjects who are stable from a medical and psychiatric standpoint will undergo a screening evaluation, including medical history, physical and neurological examination, laboratory testing, 12-lead ECG, and scales to evaluate HD. Subjects will return to the clinic for a Baseline evaluation on Day 0 to re-confirm eligibility. Subjects who remain eligible for participation in the study will be randomized and will initiate therapy with either SD-809 ER or placebo on the day after the Baseline visit (Day 1). For all visits in the screening period, subjects will be required to be accompanied by a caregiver. If the capacity assessment deems the subject not able to sign consent, the legally authorized representative will also need to accompany the subject at the visit requiring signing of consent and subject assent.
Titration period (8 weeks): All subjects and caregivers will interact weekly with the clinical site, either by telephone contact or clinic visit, through Week 8 of the titration period, in order to evaluate safety and establish a dose of study drug that adequately controls chorea and is well tolerated. Safety evaluations during titration include Unified Huntington Disease Rating Scale (UHDRS) motor examination, laboratory testing, ECGs, monitoring for adverse events and rating scales for depression, cognitive function, akathisia, swallowing disturbance and somnolence. Subjects on allowed doses of citalopram (Celexa®) or escitalopram (Lexapro®, Cipralex®) will have additional ECGs during the titration period as specified in the Schedule of Events. See protocol for SoE (p. 12-13) .
In person study visits will be scheduled at Weeks 2, 4, and 6 after initiating therapy and telephone contacts will be scheduled for Weeks 1, 3, 5, 7 and 8 after initiating therapy. The investigator, in consultation with the subject and caregiver, will determine when an adequate level of chorea control has been achieved. The dose of SD-809 ER may be increased on a weekly basis until there is adequate control of chorea, the subject experiences a protocol defined “clinically significant” adverse event (defined as related to study medication and either a) moderate or severe in intensity or b) meets the criteria for a Serious Adverse Event [SAE])1, or adequate control of chorea has been achieved, the dose of study drug should not be increased further. If a subject experiences a “clinically significant” AE that is attributed to study drug, the investigator will use his or her judgment to determine if a dose reduction or suspension is necessary. Dose adjustments should be made based on all available information including the subject and caregiver’s reports of adverse events and chorea control, the clinical assessment of safety and efficacy by the investigator, as well as information from rating scales including the Unified Huntington Disease Rating Scale (UHDRS), the Hospital Anxiety and Depression Scale (HADS), the Swallowing Disturbance Questionnaire (SDQ), the Unified Parkinson’s Disease Rating Scale (dysarthria item) (UPDRS [dysarthria]), the Barnes Akathisia Rating Scale (BARS), the Epworth Sleepiness Scale (ESS), and the Columbia Suicide Severity Rating Scale (C-SSRS). At the end of the titration period, the subject’s dose will be established for the maintenance period.
Maintenance period (4 weeks): Subjects will continue to receive their maintenance dose over the next 4 weeks (dose reductions for adverse events are allowed) and will return for in person visits at Weeks 9 and 12 for evaluation of safety, efficacy and pharmacokinetics. In addition, there will be a telephone contact at Week 10 to evaluate safety. At the end of the maintenance period (Week 12), subjects will undergo a complete evaluation, including physical and neurological exam, safety labs and 12-lead ECG and performance of all rating scales. If a subject requires a dose reduction based on a telephone contact during the maintenance period, an unscheduled clinic visit should be conducted.
Washout (1 week): All subjects will discontinue study drug after the Week 12 visit and will return at Week 13 for evaluation of safety, chorea and motor function. Subjects who complete the study and were tolerating study drug may be eligible to participate in a long term safety study of SD-809 ER.
Subjects not participating in the long term safety study of SD-809 ER will have a follow up telephone contact at Week 16, four weeks after their last dose of study drug.
Principal Investigator: David Shprecher