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

NCT04475549 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: C6463-201
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 5

Brief Summary

This is a single-arm study to evaluate safety and tolerability of oral IW-6463 in adults diagnosed with MELAS.

Conditions

MELAS

Keywords

mitochondrial disease

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Study Drug Dose Reductions or Discontinuations Due to ≥ 1 Treatment Emergent Adverse Event (TEAE)

  A TEAE is defined as an adverse event (AE) with an onset that occurs between the first dose of study drug and the end of study period. AEs are defined as an untoward medical occurrence that does not necessarily have a causal relationship with study drug treatment.

  From first dose date to Day 43 (±4)

• Number of Participants Who Experienced ≥1 AE, TEAE, Serious AE (SAE), or TEAE of Special Interest (AESI)

  AEs are defined as an untoward medical occurrence that does not necessarily have a causal relationship with study drug treatment. A TEAE is defined as an AE with an onset that occurs from the first dose of study drug up until the end of study period. An SAE is an AE that fulfills 1 or more of the following: results in death; is immediately life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; is an important medical event that may jeopardize the participant or may require medical intervention to prevent 1 of the outcomes listed above. Events were categorized as mild, moderate, or severe and as related or unrelated to study drug. AESIs include bleeding events, symptomatic hypotensive events and/or tachycardia, dizziness, syncope, and TEAEs related to change of neurobehaviors (ie, suicidality or euphoria).

  From first dose date to Day 43 (±4)

Study Arms (1)

IW-6463

EXPERIMENTAL

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

Drug: IW-6463 Tablets

Interventions

IW-6463 Tablets DRUG

IW-6463 tablets administered orally (daily)

Also known as: CY6463, zagociguat

IW-6463

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior genetic confirmation of a known mitochondrial disease mutation
• Neurological features of MELAS (can be based on medical history)
• Elevated plasma lactate levels at Screening Visit (≥1.0 mmol/L)
• 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.
• 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.

You may not qualify if:

• Positive pregnancy test at Screening or on Day 1
• Hypotension defined as systolic blood pressure (BP) ≤90 mmHg or diastolic BP ≤60 mmHg at Screening or predose at Day 1
• Hypertension defined as systolic BP \>160 mmHg or diastolic BP \>100 mmHg, at Screening or predose at Day 1
• Uncontrolled diabetes
• Severe gastrointestinal dysmotility as determined by the investigator that may impact compliance and/or oral drug administration, absorption and exposure.
• Unable to fast for 3-4 hours after a meal
• 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.
• Current or past history of clinically significant cardiomyopathy and/or cardiac conduction abnormality
• Used any nicotine-containing products (eg, cigarettes, e-cigarettes, vape pens, cigars) within 1 month of enrollment

Sponsors & Collaborators

• Tisento Therapeutics: lead

Study Sites (5)

Children's National Hospital of DC

Washington D.C., District of Columbia, 20010, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

MELAS Syndrome; Mitochondrial Diseases

Condition Hierarchy (Ancestors)

Mitochondrial Encephalomyopathies; Mitochondrial Myopathies; Muscular Diseases; Musculoskeletal Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Neuromuscular Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Cyclerion Clinical Development
• Organization: Cyclerion Therapeutics, Inc.

info@cyclerion.com

1-857-327-8778

Study Officials

• Chad Glasser, PharmD

  Cyclerion Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: July 17, 2020
• Study Start: November 13, 2020
• Primary Completion: January 23, 2022
• Study Completion: January 23, 2022
• Last Updated: August 29, 2024
• Results First Posted: November 15, 2023

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)