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Trial record 11 of 14 for:    vatiquinone

EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment

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ClinicalTrials.gov Identifier: NCT01793090
Recruitment Status : Completed
First Posted : February 15, 2013
Last Update Posted : April 25, 2017
Sponsor:
Collaborator:
Catholic University of the Sacred Heart
Information provided by (Responsible Party):
Giancarlo Iarossi, Bambino Gesù Hospital and Research Institute

Tracking Information
First Submitted Date  ICMJE February 8, 2013
First Posted Date  ICMJE February 15, 2013
Last Update Posted Date April 25, 2017
Actual Study Start Date  ICMJE January 2013
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2013)
Change in Visual Function [ Time Frame: Baseline, six months, twelve months ]
Visual acuity: - Patients age 0-2: Durand acuity cards procedure: Improvement from baseline or nadir by greater than 2 lines when converted to EDTRS values.-Patients age 2-4: LEA Symbols for crowding binocular acuity: Improvement from baseline or nadir by greater than 2 lines when converted to EDTRS values; -Patients age > 4 years: Cambridge acuity cards: Improved from baseline or nadir by greater than 2 lines on the EDTRS acuity testing chart at 4 meters. Eye-hand coordination: -Patients age 0-2: Improvement over baseline of 20% on Griffiths Mental Development Scale subscales D,E; - Patients age > 2: Improvement over baseline of 20% on Movement Assessment Battery for Children
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01793090 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2013)
  • Change in steady-state luminance Visual Evoked Potentials [ Time Frame: Baseline, six months, twelve months ]
    Steady-state luminance VEPs to sinusoidal flicker at the optimal frequency of 8 Hz.
  • Evaluation of neurological function [ Time Frame: Baseline, six months, twelve months ]
    Evaluation of neurological function with Gross motor function measure, movement ABC
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 13, 2013)
Biomarkers of redox state [ Time Frame: Baseline, six months, twelve months ]
Glutathione species in blood cells, Antioxidant enzymes expression, redox proteomic studies
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
Official Title  ICMJE Phase 2, Double-Blind, Placebo Controlled Clinical Trial of EPI-743 in Subjects With Cobalamin C Defect
Brief Summary The aim of the research is to investigate the safety and efficacy of EPI-743 treatment in patients with Cbl-C defect and related visual and neurological impairment. Primary Endpoints will be the improvement in visual function as assessed by visual acuity and eye-hand coordination and manual dexterity. Secondary Endpoints will be the improvement in neurologic function, evaluated by a battery of age-appropriated psychophysical tests, and/or in objective electrophysiological tests such as Visual Evoked potentials (VEP) and Electroretinogram (ERG) and/or the change in serum markers of redox state.
Detailed Description

Cobalamin C (Cbl-C) defect is the most common inborn error of cobalamin metabolism causing methylmalonic aciduria and homocystinuria. Cbl-Cdefect is due to impaired activity of MMACHC, a cobalamin trafficking protein, involved in the decyanation of cyanocobalamin as well as in the dealkylation of alkylcobalamins through a glutathione transferase activity. Despite pharmacological treatment with hydroxycobalamin, betaine, folic acid, (and carnitine), long-term outcome in early-onset patients is in most cases unsatisfactory with progression of visual and neurological impairment, mainly expressed in the form of retinal degeneration and/or maculopathy. Moreover, despite some hypotheses have been proposed, the pathophysiological mechanism causing progressive eye and brain damage still remains unclear. Recently, the contribution of oxidative stress has been hypothesized based on in vitro studies showing in Cbl-C fibroblasts a significant increase of reactive oxygen species (ROS) and in vivo studies documenting severe alteration of glutathione species, the main cellular redox buffer.

EPI-743 is a small molecule therapeutic that has demonstrated beneficial effects in diseases characterized by oxidative stress and alterations in glutathione redox balance including Leigh syndrome and other inherited respiratory chain diseases.

Based on the principle that Cbl-C defect causes both in vivo and in vitro perturbations of redox state, the aim of our study is to verify the potential beneficial effects of EPI-743 in preventing/reducing progression of neurological and visual signs, as well as in ameliorating redox abnormalities in Cbl-C patients, in combination with standard therapy.

Primary Endpoints will include the improvement in visual function as assessed by visual acuity and eye-hand coordination and manual dexterity. Secondary Endpoints will be improvement in neurologic function, evaluated by a battery of age-appropriated psychophysical tests, and/or in objective electrophysiological tests such as VEP and ERG, and/or the change in serum markers of redox state. Patient's and parental Quality of life will be regularly assessed prior of treatment start and periodically while on EPI-743.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Methylmalonic Aciduria and Homocystinuria,Cblc Type
  • Genetic Disease
  • Retinopathy
Intervention  ICMJE
  • Drug: Epi-743
    EPI- 743 in capsule or formulation comprised of USP/NF Sesame Oil at a potency of 100 mg EPI-743/ 1 mL total volume. Mode of Administration: Oral with meal or G-Tube infusion with food.
  • Other: Placebo supplementation
    Placebo will be administered in the same formulation as the active comparator
Study Arms  ICMJE
  • Active Comparator: EPI-743

    EPI- 743 in capsule or formulation comprised of USP/NF (United States Pharmacopeia and The National Formulary)Sesame Oil at a potency of 100 mg EPI-743/ 1 mL total volume. Mode of Administration: Oral with meal or G-Tube infusion with food.

    Dose: 100mg or 200 mg tid for 12 months, to be continued if clinically effective

    Intervention: Drug: Epi-743
  • Placebo Comparator: Placebo supplementation
    placebo in the same formulation as the active comparator will be administered to patients, assigned to this arm in a randomized design
    Intervention: Other: Placebo supplementation
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 13, 2013)
30
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 2017
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • genetically confirmed Cbl-C defect;
  • abstention from antioxidant medications (i.e. coenzyme Q10, idebenone, vitamin E) prior to trial initiation and throughout conduct of trial.

Exclusion Criteria:

  • allergy to EPI-743 or sesame oil (a screening test will be performed);
  • abnormal coagulation;
  • hepatic insufficiency with Liver Function Tests greater than 2-times normal values;
  • renal insufficiency requiring dialysis;
  • fat malabsorption precluding drug absorption.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 20 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01793090
Other Study ID Numbers  ICMJE R-12-92
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Giancarlo Iarossi, Bambino Gesù Hospital and Research Institute
Study Sponsor  ICMJE Bambino Gesù Hospital and Research Institute
Collaborators  ICMJE Catholic University of the Sacred Heart
Investigators  ICMJE
Study Chair: Carlo Dionisi-Vici, MD Bambino Gesù Hospital and Research Institute
Principal Investigator: Giancarlo Iarossi, MD Bambino Gesù Hospital and Research Institute
Principal Investigator: Daniela Ricci, MD,PhD Catholic University of the Sacred Heart
Principal Investigator: Diego Martinelli, MD, PhD Bambino Gesù Hospital and Research Institute
PRS Account Bambino Gesù Hospital and Research Institute
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP