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Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome

Primary Purpose

Leigh Syndrome

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Placebo

EPI-743 15 mg/kg

EPI-743 5 mg/kg

About this trial

This is an interventional treatment trial for Leigh Syndrome focused on measuring EPI743, Leigh syndrome, respiratory chain disease, mitochondrial disorders

Eligibility Criteria

6 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Clinical and MRI diagnosis of Leigh syndrome
Moderate disease severity based on NPMDS score
Age under 18 years
Documented evidence of disease progression within 12 month of enrollment
Availability of MRI that confirms necrotizing encephalopathy
Patient or guardian able to consent and comply with protocol requirements
Abstention from Coenzyme Q10, Vitamins C & E, lipoic acid and Idebenone

Exclusion Criteria:

Allergy to EPI-743, Vitamin E or sesame oil
History of bleeding abnormalities or abnormal PT/PTT
Diagnosis of concurrent inborn error of metabolism
Previous tracheostomy
Ventilator dependent or use of noninvasive ventilatory support w/in 1 month of enrollment
LFTs greater than 2 times ULN
Renal insufficiency
End stage cardiac failure
Fat malabsorption syndrome
Use of anticoagulant medications
Abstention from Botox for 6 months prior to enrollment and for duration of study

Sites / Locations

Stanford University
Akron Children's Hospital
Baylor College of Medicine
Seattle Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

EPI-743 15 mg/kg

EPI-743 5 mg/kg

Arm Description

Each patient will receive a volume of placebo based on weight

Each subjects dose will be based on their weight. 15 mg/kg with a maximum dose of 200 mg per dose, t.i.d., will be administered in this treatment arm.

Each subjects dose will be based on their weight. 5 mg/kg with a maximum dose of 100 mg per dose, t.i.d., will be administered in this treatment arm.

Outcomes

Primary Outcome Measures

Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) Sections 1-3

Change from baseline to six months will be compared between subjects in active treatment group and placebo group

Secondary Outcome Measures

Neuromuscular function

Gross Motor Function Measure; Barry Albright Dystonia Scale

Respiratory function

Need for tracheostomy

Disease morbidity

Total number of hospitalizations

Glutathione cycle biomarkers

Blood levels of glutathione will be compared between placebo and treatment group

Number of dose limiting serious adverse events

Mortality

Number of deaths

Full Information

NCT ID

NCT01721733

First Posted

November 1, 2012

Last Updated

August 24, 2020

Sponsor

PTC Therapeutics

Collaborators

Axio Research. LLC

1. Study Identification

Unique Protocol Identification Number

NCT01721733

Brief Title

Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome

Official Title

A Phase 2B Randomized, Placebo Controlled, Double Blind Clinical Trial of EPI-743 in Children With Leigh Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Completed

Study Start Date

October 31, 2012 (Actual)

Primary Completion Date

February 28, 2015 (Actual)

Study Completion Date

May 31, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

PTC Therapeutics

Collaborators

Axio Research. LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to evaluate the effects of EPI-743 in children with Leigh syndrome on disease severity, neuromuscular function, respiratory function, disease morbidity and mortality and disease associated biomarkers.

Detailed Description

The purpose of this study is to evaluate the effects of EPI-743 in patient with Leigh syndrome on disease severity, neuromuscular function, respiratory function, disease morbidity and mortality and biomarkers associated with the disease. This study is a six month prospective randomized double-blind, placebo-controlled trial with a six month extension phase of two dose levels of EPI743. The planned enrollment is for approximately 30 children with genetically confirmed Leigh syndrome. After 6 months of treatment, those children that were randomized to the placebo treatment arm will be re-randomized to one of the 2 active treatment arms.

6. Conditions and Keywords

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

Leigh Syndrome

Keywords

EPI743, Leigh syndrome, respiratory chain disease, mitochondrial disorders

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

35 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Each patient will receive a volume of placebo based on weight

Arm Title

EPI-743 15 mg/kg

Arm Type

Active Comparator

Arm Description

Each subjects dose will be based on their weight. 15 mg/kg with a maximum dose of 200 mg per dose, t.i.d., will be administered in this treatment arm.

Arm Title

EPI-743 5 mg/kg

Arm Type

Active Comparator

Arm Description

Each subjects dose will be based on their weight. 5 mg/kg with a maximum dose of 100 mg per dose, t.i.d., will be administered in this treatment arm.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Type

Drug

Intervention Name(s)

EPI-743 15 mg/kg

Intervention Type

Drug

Intervention Name(s)

EPI-743 5 mg/kg

Primary Outcome Measure Information:

Title

Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) Sections 1-3

Description

Change from baseline to six months will be compared between subjects in active treatment group and placebo group

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Neuromuscular function

Description

Gross Motor Function Measure; Barry Albright Dystonia Scale

Time Frame

6 months

Title

Respiratory function

Description

Need for tracheostomy

Time Frame

6 months

Title

Disease morbidity

Description

Total number of hospitalizations

Time Frame

6 months

Title

Glutathione cycle biomarkers

Description

Blood levels of glutathione will be compared between placebo and treatment group

Time Frame

6 months

Title

Number of dose limiting serious adverse events

Time Frame

6 months

Title

Mortality

Description

Number of deaths

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Clinical and MRI diagnosis of Leigh syndrome Moderate disease severity based on NPMDS score Age under 18 years Documented evidence of disease progression within 12 month of enrollment Availability of MRI that confirms necrotizing encephalopathy Patient or guardian able to consent and comply with protocol requirements Abstention from Coenzyme Q10, Vitamins C & E, lipoic acid and Idebenone Exclusion Criteria: Allergy to EPI-743, Vitamin E or sesame oil History of bleeding abnormalities or abnormal PT/PTT Diagnosis of concurrent inborn error of metabolism Previous tracheostomy Ventilator dependent or use of noninvasive ventilatory support w/in 1 month of enrollment LFTs greater than 2 times ULN Renal insufficiency End stage cardiac failure Fat malabsorption syndrome Use of anticoagulant medications Abstention from Botox for 6 months prior to enrollment and for duration of study

Facility Information:

Facility Name

Stanford University

City

Palo Alto

State/Province

California

ZIP/Postal Code

94304

Country

United States

Facility Name

Akron Children's Hospital

City

Akron

State/Province

Ohio

ZIP/Postal Code

44308

Country

United States

Facility Name

Baylor College of Medicine

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

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

Plan to Share IPD

Undecided

Links:

URL

http://www.edisonpharma.com

Description

Edison Pharmaceuticals Web Site

Learn more about this trial

Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome

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