Clinical trial NCT05168774: FRDA Investigator Initiated Study (IIS) With Elamipretide
Official title: A Pilot Investigator Initiated Study to Evaluate the Safety, Tolerability and Efficacy of Elamipretide in the Treatment of Advanced Symptoms of Friedreich Ataxia (FRDA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Friedreich Ataxia
Keywords: Friedreich Ataxia
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: Friedreich's Ataxia Research Alliance
name: Stealth BioTherapeutics Inc.
First posted: 2021-12-23
Enrollment: 20
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the safety, tolerability, and activity of Elamipretide in treating vision loss in Friedreich Ataxia (FRDA).

Detailed description: To evaluate the effect of high dose (40-60mg) versus low dose (20-30mg) Elamipretide on high contrast visual acuity in FRDA compared to baseline at 52 weeks with the option to extend for an additional 52 weeks if there are objective signs of clinical improvement on primary or secondary endpoints. The interim analysis will be based on data from a 36-week visit. For subjects worse than 20/800 at study start, they will be followed using low vision alternatives only.

Eligibility criteria: Inclusion Criteria:

1. Genetically confirmed FRDA (point mutations allowed).
2. Age \>16 years.
3. Disease onset before 18 years of age.
4. If female, the subject is not pregnant or lactating or intending to become pregnant before, during, or within 30 days after the last dose of study drug. Female subjects of child-bearing potential must have a negative serum pregnancy test result at Screening, a negative urine pregnancy test result at Baseline.
5. All subjects must agree to use a reliable method of contraception throughout the study and for 30 days after the last dose of study drug. Male subjects should not father a baby during the study or for at least 30 days after the last dose of study drug.
6. All concomitant medications (including over-the-counter medications), vitamins, and supplements must be at stable doses for 30 days prior to study entry and kept stable throughout the study to the best of their ability.
7. Visual acuity (VA) worse than 20/40 (binocular) on the basis of FRDA. Must not be correctable by refraction, or subjects must have sufficient physical exam findings of optic neuropathy (funduscopic, visual fields, or retinal ganglion cell loss) to justify the primary diagnosis of FRDA related optic neuropathy

   Or
8. Ejection Fraction (EF) less than 50% at last evaluation (within 1 year before screening), with a history consistent with cardiomyopathy from FRDA, and VA 20/25- 20/40.

Exclusion Criteria:

1. Any unstable illness that in the investigator's opinion precludes participation in the study.
2. Use of any investigational product within 30 days prior to Screening.
3. A history of substance abuse.
4. Diagnosis of active HIV or Hepatitis B or C infection.
5. Presence of severe renal disease (eGFR \<30 mL/min) or hepatic disease \[aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2x the upper limit of normal\] as evidenced by laboratory results at Screening.
6. Clinically significant abnormal white blood cell count (ANC \<1500), hemoglobin (\< 9.0 gm/dL), or platelet count (100 K or \>500 K) as evidenced by laboratory test results at Screening.
7. Any other active cause of optic neuropathy (Vitamin B12 deficiency, Vitamin E deficiency, etc.) or cardiac disease
8. EF less than 35% at last echocardiographic evaluation
9. Uncontrolled arrhythmia
10. Current use of any systemic chronic immunosuppressive drugs
11. Current use of Metformin

Primary outcomes:
measure: Change in High Contrast Visual Acuity
timeFrame: Baseline to 52 weeks
Secondary outcomes:
measure: Change in Low Contrast Visual Acuity
timeFrame: Baseline to 52 weeks
measure: Change in Low Luminescence Visual Activity
timeFrame: Baseline to 52 weeks
measure: Change in retinal nerve fiber layer by Optical Coherence Tomography (OCT)
timeFrame: Baseline to 52 weeks
measure: Change in visual quality of life by Visual Functioning Questionnaire (VFQ)
timeFrame: Baseline to 52 weeks
measure: Change in Cardiac Strain
timeFrame: Baseline to 36 weeks
measure: Change in Cardiac Fibrosis
timeFrame: Baseline to 36 weeks
measure: Change Cardiac Stroke Volume
timeFrame: Baseline to 36 weeks
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia - Neurology
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: David Lynch, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: