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

A Phase 2a Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Individuals With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)

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

Study Overview

• Status: Terminated
• Conditions: MELAS
• Intervention / Treatment: Drug: IW-6463 Tablets

Detailed Description

IW-6463 tablets will be orally administered once-daily (QD) for up to 29 days

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Hospital of DC
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IW-6463; Open-label IW-6463 15 mg once daily (QD), with possibility to dose reduce to 10 mg.	Drug: IW-6463 Tablets; IW-6463 tablets administered orally (daily); Other Names: CY6463; zagociguat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: Tisento Therapeutics
• Collaborators: Children's Hospital of Philadelphia
• Investigators: Study Director: Chad Glasser, PharmD, Cyclerion Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Actual): January 23, 2022
• Study Completion (Actual): January 23, 2022

Study Registration Dates

• First Submitted: July 14, 2020
• First Submitted That Met QC Criteria: July 14, 2020
• First Posted (Actual): July 17, 2020

Study Record Updates

• Last Update Posted (Actual): August 29, 2024
• Last Update Submitted That Met QC Criteria: August 13, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: mitochondrial disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Mitochondrial Diseases; Brain Diseases, Metabolic, Inborn; Cerebral Small Vessel Diseases; Acid-Base Imbalance; Mitochondrial Myopathies; MELAS Syndrome; Mitochondrial Encephalomyopathies; Acidosis; Acidosis, Lactic
• Other Study ID Numbers: C6463-201; CY6463 (Other Identifier: Cyclerion Therapeutics)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No