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EPI-743 for Mitochondrial Respiratory Chain Diseases

Primary Purpose

Mitochondrial Diseases

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
EPI-743
Sponsored by
PTC Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mitochondrial Diseases focused on measuring Leigh syndrome, MELAS, Kearns-Sayre, Alper's, Inherited mitochondrial disease, Friedreich's ataxia, POLG1 deficiency

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  1. Participants with genetic diagnosis: Genetically confirmed diagnosis of Inherited mitochondrial respiratory chain disease
  2. Participants with clinical diagnosis: Diagnosis of inherited mitochondrial disease absent genetic confirmation; Specifically, participants must meet the diagnostic criteria of "definite" or "probable" mitochondrial disease as defined by Bernier et al., 2002
  3. Deemed by principal investigator to be within 90 days of end-of-life hospice/terminal care
  4. Male or female age > one year
  5. Hematocrit within normal range for age group
  6. Agreement to use contraception if within reproductive years
  7. Participant or participant's guardian able to consent and comply with protocol requirements
  8. Presence of caregiver to ensure study compliance
  9. Abstention from use of all pill-form dietary supplements and non-prescribed medications (except as allowed by the investigator)
  10. Abstention from foods or beverages or bars fortified with Coenzyme Q10, vitamin E, super-fortified "functional" foods or beverages
  11. Abstention from use of idebenone
  12. Clinically staged with a Mitochondrial Disease Scale such as the Newcastle Score

Exclusion criteria:

  1. Allergy to EPI-743, vitamin E or sesame oil
  2. Clinical history of bleeding or abnormal prothrombin time (PT)/partial thromboplastin time (PTT) (excluding anticoagulation Rx)
  3. Hepatic insufficiency with liver function tests (LFTs) greater than two times normal
  4. Renal insufficiency requiring dialysis
  5. Fat malabsorption syndromes precluding drug absorption
  6. Any other concurrent inborn errors of metabolism
  7. Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in lactic acidosis
  8. Pregnancy

Sites / Locations

  • UCLA
  • CHOC Children's Clinic
  • Lucille Packard Children's Hospital
  • UCSD
  • Stanford Children's Health
  • Emory University
  • CUMC (Columbia University)
  • Carolinas Medical Center
  • Akron Children's Hospital
  • Cleveland Clinic
  • Children's Hospital of Philadelphia
  • MUSC
  • Baylor College of Medicine
  • UTH
  • Naval Hospital, Bremerton
  • Seattle Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

EPI-743

Arm Description

Participants will receive EPI-743 at a dose of 50 milligrams (mg) at Day 1, 50 mg twice daily for 13 days, 100 mg on Day 15, and 100 mg twice daily until Day 28; either by mouth with a meal or via their G-tube with feeds. In the absence of clinical or laboratory indications of any safety concerns, participants will receive 100 mg EPI-743 three times daily until end of study.

Outcomes

Primary Outcome Measures

Number of Participants Experiencing Adverse Events

Secondary Outcome Measures

Change From Baseline in Neurological Function, as Determined by Standard Neurological Examination at Week 13
Neurological exams to determine neuro-muscular function, which is typically compromised in participants with inherited mitochondrial diseases. Standard clinical neurological/neuromuscular assessment scales will be used
Change From Baseline in Newcastle Pediatric Mitochondrial Disease Score (NPMDS) at Week 13
NPMDS is a validated scale to assess the clinical severity of mitochondrial disease. The NPMDS will be scored at baseline and at Week 13, and the difference will be assessed as improved, stable or deteriorated.

Full Information

First Posted
June 7, 2011
Last Updated
October 10, 2023
Sponsor
PTC Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT01370447
Brief Title
EPI-743 for Mitochondrial Respiratory Chain Diseases
Official Title
Emergency Use Protocol for EPI-743 in Acutely Ill Patients With Inherited Mitochondrial Respiratory Chain Disease Within 90 Days of End-of-Life Care
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
February 28, 2010 (Actual)
Primary Completion Date
September 28, 2023 (Actual)
Study Completion Date
September 28, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PTC Therapeutics

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will evaluate the safety and efficacy of EPI-743 in participants with severe mitochondrial respiratory chain diseases who are considered to be within 90 days of end-of-life care.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mitochondrial Diseases
Keywords
Leigh syndrome, MELAS, Kearns-Sayre, Alper's, Inherited mitochondrial disease, Friedreich's ataxia, POLG1 deficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
94 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EPI-743
Arm Type
Experimental
Arm Description
Participants will receive EPI-743 at a dose of 50 milligrams (mg) at Day 1, 50 mg twice daily for 13 days, 100 mg on Day 15, and 100 mg twice daily until Day 28; either by mouth with a meal or via their G-tube with feeds. In the absence of clinical or laboratory indications of any safety concerns, participants will receive 100 mg EPI-743 three times daily until end of study.
Intervention Type
Drug
Intervention Name(s)
EPI-743
Other Intervention Name(s)
Vincerinone, Vatiquinone
Intervention Description
EPI-743 (oral solution [100 mg/mL] or liquid-filled capsules [100 mg or 200 mg]) will be administered per dose and schedule specified in the arm.
Primary Outcome Measure Information:
Title
Number of Participants Experiencing Adverse Events
Time Frame
Baseline up to Week 13
Secondary Outcome Measure Information:
Title
Change From Baseline in Neurological Function, as Determined by Standard Neurological Examination at Week 13
Description
Neurological exams to determine neuro-muscular function, which is typically compromised in participants with inherited mitochondrial diseases. Standard clinical neurological/neuromuscular assessment scales will be used
Time Frame
Baseline, Week 13
Title
Change From Baseline in Newcastle Pediatric Mitochondrial Disease Score (NPMDS) at Week 13
Description
NPMDS is a validated scale to assess the clinical severity of mitochondrial disease. The NPMDS will be scored at baseline and at Week 13, and the difference will be assessed as improved, stable or deteriorated.
Time Frame
Baseline, Week 13

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Participants with genetic diagnosis: Genetically confirmed diagnosis of Inherited mitochondrial respiratory chain disease Participants with clinical diagnosis: Diagnosis of inherited mitochondrial disease absent genetic confirmation; Specifically, participants must meet the diagnostic criteria of "definite" or "probable" mitochondrial disease as defined by Bernier et al., 2002 Deemed by principal investigator to be within 90 days of end-of-life hospice/terminal care Male or female age > one year Hematocrit within normal range for age group Agreement to use contraception if within reproductive years Participant or participant's guardian able to consent and comply with protocol requirements Presence of caregiver to ensure study compliance Abstention from use of all pill-form dietary supplements and non-prescribed medications (except as allowed by the investigator) Abstention from foods or beverages or bars fortified with Coenzyme Q10, vitamin E, super-fortified "functional" foods or beverages Abstention from use of idebenone Clinically staged with a Mitochondrial Disease Scale such as the Newcastle Score Exclusion criteria: Allergy to EPI-743, vitamin E or sesame oil Clinical history of bleeding or abnormal prothrombin time (PT)/partial thromboplastin time (PTT) (excluding anticoagulation Rx) Hepatic insufficiency with liver function tests (LFTs) greater than two times normal Renal insufficiency requiring dialysis Fat malabsorption syndromes precluding drug absorption Any other concurrent inborn errors of metabolism Severe end-organ hypo-perfusion syndrome secondary to cardiac failure resulting in lactic acidosis Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory Enns, MB, ChB
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
CHOC Children's Clinic
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Lucille Packard Children's Hospital
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
UCSD
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Stanford Children's Health
City
Stanford
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Emory University
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
CUMC (Columbia University)
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Akron Children's Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
MUSC
City
North Charleston
State/Province
South Carolina
ZIP/Postal Code
29406
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
UTH
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Naval Hospital, Bremerton
City
Bremerton
State/Province
Washington
ZIP/Postal Code
98312
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

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EPI-743 for Mitochondrial Respiratory Chain Diseases

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