EPI-743 for Mitochondrial Respiratory Chain Diseases

• ClinicalTrials.gov Identifier: NCT01370447
• Recruitment Status: Active, not recruiting
• First Posted: June 10, 2011
• Last Update Posted: March 1, 2023
• Sponsor: PTC Therapeutics
• Information provided by (Responsible Party): PTC Therapeutics

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.

Condition or disease	Intervention/treatment	Phase
Mitochondrial Diseases	Drug: EPI-743	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 94 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 28, 2010
• Estimated Primary Completion Date: May 31, 2023
• Estimated Study Completion Date: May 31, 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: EPI-743; 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.

Drug: EPI-743; 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.; Other Name: Vincerinone, Vatiquinone

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Experiencing Adverse Events [ Time Frame: Baseline up to Week 13 ]

Secondary Outcome Measures :

1. Change From Baseline in Neurological Function, as Determined by Standard Neurological Examination at Week 13 [ Time Frame: Baseline, 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
2. Change From Baseline in Newcastle Pediatric Mitochondrial Disease Score (NPMDS) at Week 13 [ Time Frame: Baseline, 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.

Eligibility Criteria

• Ages Eligible for Study: 1 Year and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

UCLA

Los Angeles, California, United States, 90095

CHOC Children's Clinic

Orange, California, United States, 92868

Lucille Packard Children's Hospital

Palo Alto, California, United States, 94304

UCSD

San Diego, California, United States, 92123

Stanford Children's Health

Stanford, California, United States, 94304

United States, Georgia

Emory University

Decatur, Georgia, United States, 30033

United States, New York

CUMC (Columbia University)

New York, New York, United States, 10032

United States, North Carolina

Carolinas Medical Center

Charlotte, North Carolina, United States, 28203

United States, Ohio

Akron Children's Hospital

Akron, Ohio, United States, 44308

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

United States, South Carolina

MUSC

North Charleston, South Carolina, United States, 29406

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

UTH

Houston, Texas, United States, 77030

United States, Washington

Naval Hospital, Bremerton

Bremerton, Washington, United States, 98312

Seattle Children's Hospital

Seattle, Washington, United States, 98105

Sponsors and Collaborators

PTC Therapeutics

Investigators

• Principal Investigator: Gregory Enns, MB, ChB; Stanford University

More Information

• Responsible Party: PTC Therapeutics
• ClinicalTrials.gov Identifier: NCT01370447
• Other Study ID Numbers: EPI-2009-1
• First Posted: June 10, 2011
• Last Update Posted: March 1, 2023
• Last Verified: February 2023

Keywords provided by PTC Therapeutics:

Leigh syndrome; MELAS; Kearns-Sayre; Alper's; Inherited mitochondrial disease; Friedreich's ataxia; POLG1 deficiency

Additional relevant MeSH terms:

Mitochondrial Diseases; Metabolic Diseases