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

Primary Purpose

MELAS

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

IW-6463 Tablets

About this trial

This is an interventional treatment trial for MELAS focused on measuring mitochondrial disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
Other inclusion criteria per protocol

Exclusion Criteria:

Positive pregnancy test at Screening or on Day 1
Hypotension defined as systolic 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
Other exclusion criteria per protocol

Sites / Locations

Children's National Hospital of DC
Johns Hopkins University
Massachusetts General Hospital
Columbia University
Children's Hospital of Philadelphia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IW-6463

Arm Description

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

Outcomes

Primary Outcome Measures

Number (or %) of participants who discontinue or dose reduced the study drug due to a treatment-emergent adverse event (TEAE)

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)

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

TEAE is defined as an adverse event with an onset that occurs after receiving the study drug, until the end of study period

Secondary Outcome Measures

Full Information

NCT ID

NCT04475549

First Posted

July 14, 2020

Last Updated

January 20, 2023

Sponsor

Cyclerion Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT04475549

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)

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Terminated

Why Stopped

Study terminated due to enrollment challenges.

Study Start Date

November 13, 2020 (Actual)

Primary Completion Date

January 23, 2022 (Actual)

Study Completion Date

January 23, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cyclerion Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

MELAS

Keywords

mitochondrial disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

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

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

IW-6463

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

IW-6463 Tablets

Other Intervention Name(s)

CY6463

Intervention Description

IW-6463 tablets administered orally (daily)

Primary Outcome Measure Information:

Title

Number (or %) of participants who discontinue or dose reduced the study drug due to a treatment-emergent adverse event (TEAE)

Description

TEAE is defined as an adverse event with an onset that occurs after receiving the study drug, until the end of study period

Time Frame

From first dose date to Day 43 (±4)

Title

Number (or %) of participants who experience at least one treatment-emergent adverse event (TEAE)

Description

TEAE is defined as an adverse event with an onset that occurs after receiving the study drug, until the end of study period

Time Frame

From first dose date to Day 43 (±4)

Title

Number (or %) of participants who experience at least one treatment-emergent adverse event (TEAE) by severity

Description

TEAE is defined as an adverse event with an onset that occurs after receiving the study drug, until the end of study period

Time Frame

From first dose date to Day 43 (±4)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Other inclusion criteria per protocol Exclusion Criteria: 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 Other exclusion criteria per protocol

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chad Glasser, PharmD

Organizational Affiliation

Cyclerion Therapeutics, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Children's National Hospital of DC

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20010

Country

United States

Facility Name

Johns Hopkins University

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21205

Country

United States

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Columbia University

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

Children's Hospital of Philadelphia

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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