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

MELAS Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04475549
• Other study ID #: C6463-201
• Secondary ID: CY6463
• Status: Terminated
• Phase: Phase 2
• Start date: November 13, 2020
• Est. completion date: January 23, 2022

Study information

• Verified date: November 2023
• Source: Tisento Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: January 23, 2022
• Est. primary completion date: January 23, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acidosis
• Acidosis, Lactic
• MELAS
• MELAS Syndrome
• Mitochondrial Encephalomyopathies

Intervention

Drug:
• IW-6463 Tablets
IW-6463 tablets administered orally (daily)

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Columbia University	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's National Hospital of DC	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Tisento Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)