A Study to Evaluate the Effect of SAGE-718 on Cognitive Function in Participants With Huntington's Disease (HD)

Supernus Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Huntington's Disease

Treatments: Drug: Placebo; Drug: SAGE-718

Study type: Interventional

Funder types: Industry

Identifiers

NCT05107128

718-CIH-201

2021-005577-16 (EudraCT Number)

Details and patient eligibility

About

The primary purpose of this study is to evaluate the effect of SAGE-718 on cognitive performance and functioning in participants with HD.

Enrollment: 189 patients

Sex: All

Ages: 25 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Meet all the following criteria for HD at Screening (Days -28 to -2):

   1. Genetically confirmed disease with huntingtin gene CAG expansion greater than or equal to (≥) 36.
   2. At screening, Unified Huntington's Disease Rating Scale (UHDRS)-Total Functional Capacity (TFC) score greater than (>) 6 and less than (<)13, suggesting no more than a moderate level of functional impairment.
   3. No features of juvenile HD.

2. Score of 15 to 25 (inclusive) on the Montreal Cognitive Assessment (MoCA) at screening indicating the presence of cognitive impairment.

3. Be willing to invite a study partner, if available, who is reliable, competent, and at least 18 years of age to participate in the study.

4. Be ambulatory (use of assistance devices such as a walker or cane is acceptable, as is occasional use of wheelchair, as judged by the investigator. Individuals requiring a wheelchair on a regular basis are excluded), able to travel to the study center, and, as 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.

5. Completion of Huntington's Disease Cognitive Assessment Battery (HD-CAB) Trail Making-B Test in less than 240 seconds at Screening (Days -28 to -2).

Exclusion criteria

1. Have participated in a previous clinical study of SAGE-718, have previous exposure to gene therapy, 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 enrollment in the placebo arm of these trials would not be excluded.)

2. Have a diagnosis of an ongoing neurodegenerative condition other than HD, including but not limited to Alzheimer's Disease, vascular dementia, dementia with Lewy bodies, or Parkinson's Disease.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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189 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants will receive SAGE-718-matching placebo, orally, once daily (QD) for up to Day 84.

Treatment:

Drug: Placebo

SAGE-718

Experimental group

Description:

Participants will receive SAGE-718, 1.2 milligrams (mg), capsules, orally, QD for Days 1 to 27, followed by 0.9 mg for the remainder of the treatment period up to Day 84.

Treatment:

Drug: SAGE-718