Phase 2a Study of IW-6463 in Adults Diagnosed With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)

• ClinicalTrials.gov Identifier: NCT04475549
• Recruitment Status: Terminated
• First Posted: July 17, 2020
• Last Update Posted: January 25, 2023
• Sponsor: Cyclerion Therapeutics
• Information provided by (Responsible Party): Cyclerion Therapeutics

Tracking Information

• First Submitted Date: July 14, 2020
• First Posted Date: July 17, 2020
• Last Update Posted Date: January 25, 2023
• Actual Study Start Date: November 13, 2020
• Actual Primary Completion Date: January 23, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 14, 2020)

• Number (or %) of participants who discontinue or dose reduced the study drug due to a treatment-emergent adverse event (TEAE) [ Time Frame: From first dose date to Day 43 (±4) ]
  TEAE is defined as an adverse event with an onset that occurs after receiving the study drug, until the end of study period
• Number (or %) of participants who experience at least one treatment-emergent adverse event (TEAE) [ Time Frame: From first dose date to Day 43 (±4) ]
  TEAE is defined as an adverse event with an onset that occurs after receiving the study drug, until the end of study period
• Number (or %) of participants who experience at least one treatment-emergent adverse event (TEAE) by severity [ Time Frame: From first dose date to Day 43 (±4) ]
  TEAE is defined as an adverse event with an onset that occurs after receiving the study drug, until the end of study period

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 2a Study of IW-6463 in Adults Diagnosed With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)
• Official Title: A Phase 2a Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Individuals With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)
• Brief Summary: This is a single-arm study to evaluate safety and tolerability of oral IW-6463 in adults diagnosed with MELAS.
• Detailed Description: IW-6463 tablets will be orally administered once-daily (QD) for up to 29 days
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Open-label, single-arm study with daily dosing for up to 29 days.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: MELAS

Intervention

Drug: IW-6463 Tablets

IW-6463 tablets administered orally (daily)

Other Name: CY6463

Study Arms

Experimental: IW-6463

Open-label IW-6463 15 mg once daily (QD), with possibility to dose reduce to 10 mg.

Intervention: Drug: IW-6463 Tablets

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 13, 2022): 8
• Original Estimated Enrollment (submitted: July 14, 2020): 20
• Actual Study Completion Date: January 23, 2022
• Actual Primary Completion Date: January 23, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Prior genetic confirmation of a known mitochondrial disease mutation
2. Neurological features of MELAS (can be based on medical history)
3. Elevated plasma lactate levels at Screening Visit (≥1.0 mmol/L)
4. Women of childbearing potential must have a negative pregnancy test prior to randomization and must agree to use protocol-specified contraception from the Screening Visit through 90 days after the final dose of study drug.
5. Male participants must be surgically sterile by vasectomy (conducted ≥60 days before the Screening Visit or confirmed via sperm analysis) or must agree to use protocol-specified contraception and agree to refrain from sperm donation from the Screening Visit through 90 days after the final dose of study drug.
6. Other inclusion criteria per protocol

Exclusion Criteria:

1. Positive pregnancy test at Screening or on Day 1
2. Hypotension defined as systolic blood pressure (BP) ≤90 mmHg or diastolic BP ≤60 mmHg at Screening or predose at Day 1
3. Hypertension defined as systolic BP >160 mmHg or diastolic BP >100 mmHg, at Screening or predose at Day 1
4. Uncontrolled diabetes
5. Severe gastrointestinal dysmotility as determined by the investigator that may impact compliance and/or oral drug administration, absorption and exposure.
6. Unable to fast for 3-4 hours after a meal
7. Unable or unwilling to adhere to the study schedule, lifestyle restrictions, assessment requirements or, in the clinical judgment of the investigator, is otherwise not suitable for study participation.
8. Current or past history of clinically significant cardiomyopathy and/or cardiac conduction abnormality
9. Used any nicotine-containing products (eg, cigarettes, e-cigarettes, vape pens, cigars) within 1 month of enrollment
10. Other exclusion criteria per protocol

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04475549
• Other Study ID Numbers: C6463-201; CY6463 ( Other Identifier: Cyclerion Therapeutics )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Cyclerion Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Cyclerion Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Chad Glasser, PharmD; Cyclerion Therapeutics, Inc.

• PRS Account: Cyclerion Therapeutics
• Verification Date: January 2023