A Study to Assess Efficacy, Long Term Safety and Tolerability of RT001 in Subjects With Friedreich's Ataxia

• ClinicalTrials.gov Identifier: NCT04102501
• Recruitment Status: Active, not recruiting
• First Posted: September 25, 2019
• Last Update Posted: March 9, 2021
• Sponsor: Retrotope, Inc.
• Information provided by (Responsible Party): Retrotope, Inc.

Study Description

Brief Summary:

The purpose of this study is to assess the Efficacy, Long Term Safety and Tolerability of RT001 in subjects with Friedreich's Ataxia

Condition or disease	Intervention/treatment	Phase
Friedreich's Ataxia	Drug: RT001; Drug: Placebo	Phase 3

Detailed Description:

This is a randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, tolerability, in subjects with FRDA following the oral administration of study drug (active or placebo capsules). Sixty eligible patients will undergo various assessments at different time points during the the study. The study duration is 13 months which includes screening, treatment and safety follow up phone call.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Controlled, Phase 2/3 Study to Assess Efficacy, Long Term Safety and Tolerability of RT001 in Subjects With Friedreich's Ataxia
• Actual Study Start Date: October 30, 2019
• Estimated Primary Completion Date: November 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: RT001; 9 capsules daily (8.64 g total dose) given as 3 capsules three times a day (TID) with meals for the first month of treatment.; Six capsules daily (5.76 g total dose) given as 3 capsules (BID) with breakfast, and 3 capsules with dinner after the first month of treatment	Drug: RT001; RT001 is encapsulated 9-cis, 12-cis-11,11-D2-linoleic acid ethyl ester, which is a site specific (C11) di-deutero synthetic homologue of LA ethyl ester. Each capsule contains 960 mg of RT001.
Placebo Comparator: Placebo; 9 capsules daily (8.64 g total dose) given as 3 capsules three times a day (TID) with meals for the first month of treatment.; Six capsules daily (5.76 g total dose) given as 3 capsules (BID) with breakfast, and 3 capsules with dinner after the first month of treatment	Drug: Placebo; The placebo product is composed of encapsulated USP safflower oil. The placebo capsules are identical in appearance and size to RT001.

Outcome Measures

Primary Outcome Measures :

1. Peak workload change from baseline to 11 months using cardiopulmonary exercise testing (CPET) [ Time Frame: 11 months ]
   To measure the percentage change in peak workload from baseline to Month 11 using CPET

Secondary Outcome Measures :

1. Effect of RT001 on modified Friedreich Ataxia Rating Scale (mFARS) [ Time Frame: 11 months ]
   The modified FARS is derived from the FARS Neuro Scale. The FARS Neuro Scale is based on the neurological examination of the Bulbar System, Upper Limb Coordination, Lower Limb Coordination, Peripheral Nervous System and Upright Stability Function. The mFARS will not include sub-scores from Peripheral Nervous System.
2. Distance walked during a 1-minute walk (T1MW) [ Time Frame: 11 months ]
   The T1MW is a quantitative measure of lower extremity function. The distance walked over 1 minute is measured
3. Effects of RT001 on a Fatigue scale [ Time Frame: 11 months ]
   To measure the change in score from baseline to Month 11 on a fatigue scale. This scale rates your fatigue over the last 7 days and is rated on a 5 point scale with a range of responses from not at all, a little bit, some what, quite a bit and very much.
4. Effects of RT001 on Clinical Global Impression [CGI] [ Time Frame: 11 months ]
   The CGI is a 3-item observer rated scale that measures illness severity, global improvement and therapeutic response.The illness severity is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through 7 (amongst the most severely ill patients). The global improvement scores range from 1 (very much improved) through to 7 (very much worse). Treatment response ratings should take account of both therapeutic efficacy and treatment-related adverse events and range from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score.

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 50 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

1. Male or female 12 to 50 years of age
2. Medical history consistent with the symptoms of FRDA at ≤ 25 years of age
3. Detection of biallelic pathogenic variants in frataxin gene (FXN)
4. Ambulatory (with or without assistive device) and capable of performing other assessments/evaluations.
5. Must be able to walk 25 feet during the timed 1-minute walk

Key Exclusion Criteria:

1. Received treatment with other experimental therapies within the last 30 days prior to the first dose
2. Previously participated in the RT001 trial
3. Refusal to discontinue fish oils or other oil-based supplements for the duration of the study (Screening till last study procedure completed)
4. History of malignancies (other than basal cell carcinomas)
5. Inability to complete CPET protocol
6. Female who is breastfeeding or has a positive pregnancy test
7. History of uncontrolled diabetes mellitus (Type 1 or 2)

Contacts and Locations

Locations

United States, California

Collaborative Neuroscience Network, LLC

Long Beach, California, United States, 90806

UCLA

Los Angeles, California, United States, 90095

United States, Florida

University of Florida

Gainesville, Florida, United States, 32608

USF Ataxia Research Center

Tampa, Florida, United States, 33612

United States, Iowa

University of Iowa Stead Family Children's Hospital

Iowa City, Iowa, United States, 52242

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Retrotope, Inc.

Investigators

• Study Director: Peter Milner, MD; Chief Medical Officer

More Information

• Responsible Party: Retrotope, Inc.
• ClinicalTrials.gov Identifier: NCT04102501
• Other Study ID Numbers: RT001-006
• First Posted: September 25, 2019
• Last Update Posted: March 9, 2021
• Last Verified: December 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Mitochondrial Diseases; Metabolic Diseases