28-Day Study of SAGE-718 on Functioning Capacity in Participants With Huntington's Disease

Supernus Pharmaceuticals, Inc.69 enrolled

Overview

The primary purpose of this study is to assess the magnitude of the baseline difference between participants with early Huntington's Disease (HD) and healthy participants (HP) with respect to measures of cognitive performance.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Huntington Disease

Interventions

SAGE-718DRUG

SAGE-718 oral softgel lipid capsules

PlaceboDRUG

SAGE-718-matching oral capsules

Eligibility

Sex: ALLMin age: 25 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: For all 1. Agree to refrain from drugs of abuse for the duration of the study and from alcohol during the 48 hours preceding each study visit. Additional criteria for participants with HD only: 2. Be ambulatory, able to travel to the study center, and, judged by the investigator, is likely to be able to continue to travel to the study center to complete study visits for the duration of the study. 3. Have: 1. Genetically confirmed disease with cytosine, adenine, and guanine (CAG) expansion ≥36. 2. At screening, Unified Huntington's Disease Rating Scale (UHDRS) Total Functional Capacity (TFC) \>6 and \<13, suggesting no more than a moderate level of functional impairment. 3. No features of juvenile HD. 4. CAG-Age-Product (CAP) score \>70, as calculated using the CAP formula: Age × (CAG - 30) / 6.49. 5. Score of 15 to 25 (inclusive) on the Montreal Cognitive Assessment (MoCA) at screening, indicating the presence of cognitive impairment. Additional criteria for HP only: 1. Score ≥26 on the MoCA at screening. 2. Have no known family history of HD; or, have known family history of HD but have genetic test results available that show a normal CAG repeat length for both Huntingtin (HTT) alleles (\<36). Exclusion Criteria: For All 1. Receive any prohibited medications within 30 days of Screening and during participation in the study 2. Have participated in a previous clinical study of SAGE-718, have previous exposure to gene therapy; or have participated in any HD investigational drug, biologic, or device trial within 180 days, or a non-HD drug, biologic, or device trial within 30 days or 5 half-lives (whichever is longer). (Note: participants with confirmation of enrolment in the placebo arm of these trials would not be excluded.) 3. Is known to be allergic to any of SAGE-718 excipients, including soy lecithin. Additional criteria for participants with HD only: 1. Had gastric bypass surgery, has a gastric sleeve or lap band, or has had any related procedures that interfere with gastrointestinal transit. 2. Receive any prohibited medications within 30 days of Screening and during participation in the study.

Locations (14)

Sage Investigational Site

Birmingham, Alabama, United States

Sage Investigational Site

Los Alamitos, California, United States

Sage Investigational Site

Englewood, Colorado, United States

Outcomes

Primary Outcomes

Difference in Huntington's Disease Cognitive Assessment Battery (HD-CAB) Composite Score Between Participants With HD vs HP at Baseline

HD-CAB assesses cognitive function using 6 subtests:Symbol Digit Modalities Test-correctly coded items(0-110); One Touch Stockings of Cambridge(OTS)-mean time to reach correct response(range not defined); Trail Making Test Trail B (TMT-B)-time to complete task(0-240 sec); Hopkins Verbal Learning Test Revised-total correct recall trials(0-48); Paced Tapping Test-reciprocal of standard deviation(SD) of intertap intervals (range not defined); Emotion Recognition Test-negative emotions correctly identified(0-24). Values of OTS \& TMT B are multiplied by -1 to represent higher is better direction as other tests. Each of 6 subtests scores was transformed to z-score(range not defined;low negative value represents cognitive impairment), which is calculated by subtracting mean and dividing by SD of HP at baseline. HD-CAB composite=average of 6 z-scores. Negative HD-CAB of HD participants=decline in cognitive function relative to HP. Assessment is relative to reference group(healthy population).

Time frame: Baseline

Secondary Outcomes

Number of Participants With HD With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Treatment-emergent adverse events are defined as any adverse events with onset on or after the first dose of IP. A serious TEAE is any untoward medical occurrence that at any dose results in death, places the participant at immediate risk of death (a life-threatening event), requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital abnormality or birth defect.

Time frame: Up to Day 42

Number of Participants With HD With Clinically Significant Change From Baseline in Vital Sign Measurements

Vital signs including oral temperature, respiratory rate, heart rate (supine and standing), and blood pressures (supine and standing). Number of participants with clinically significant change in vital signs measurements which were deemed clinically significant by the investigator were reported.

Data from ClinicalTrials.gov

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