A First in Human Study of RT001 in Patients With Friedreich's Ataxia

Phase 1

Completed

Conditions: Friedreich's Ataxia

Interventions: Drug: Low dose cohort
Drug: High dose cohort

Registration Number: NCT02445794

Lead Sponsor: Retrotope, Inc.

Brief Summary: The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of RT001 in patients with Friedreich's ataxia.

Detailed Description: Study RT001-002 is a randomized, double-blind, controlled, ascending dose study to evaluate the safety, tolerability, pharmacokinetic, disease state, and exploratory endpoints in patients with Friedreich's ataxia after oral administration. The study includes 2 dose levels of RT001.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

Inclusion Criteria

Male or female 18 to 50 years of age
Medical history consistent with the symptoms of FRDA at ≤ 25 years of age
Homozygous for GAA repeat expansions in the Frataxin gene in the affected range for FRDA
FARS-Neurological score of 20-90 points
Ambulatory (with or without assistive device) and capable of performing assessments/evaluations
Body Mass Index ≤ 29.9 kg/m2
Agrees to dietary restrictions and agrees to receive calls from a dietary coach
Signed the informed consent form prior to entry into the study
Agrees to spend the required number of overnight clinic days
Able to provide the necessary repeated blood samples

Exclusion Criteria

Received treatment with other experimental therapies within the last 30 days prior to the first dose
Known point mutation in the FXN gene
History of malignancies (other than basal cell carcinomas)
Impaired renal function at screening
Alanine transaminase (ALT) or aspartate transaminase (AST) laboratory values > 2 x upper limit of normal (ULN) at screening
Known hepatitis B surface antigen (HBsAg)-positive, or known or suspected active hepatitis C infection, or is known to be human immunodeficiency virus (HIV) positive
Female who is breastfeeding or has a positive pregnancy test
Male participant or female participant of child bearing potential, who is sexually active and unwilling/unable to use a medically acceptable and effective double barrier birth control method throughout the study
Unwilling or unable to comply with the requirements of the protocol
Clinically significant cardiac abnormalities at screening that, in the opinion of the Investigator, would make the patient unsuitable for enrollment
Diabetes mellitus (Type 1 or 2)
Suicidal ideation as determined by the Columbia-Suicide Severity Rating Scale
History, within the last 2 years, of alcohol abuse, significant mental illness, or physical opioid dependence
Cannot adhere to the dietary guidance required to be followed by the protocol
Cannot take the medication due to impairment in swallowing capsules

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RT001, oral, 1.8 g/day	Low dose cohort	RT001, oral, 1.8 g QD for 28 days or matching comparator
RT001, oral, 1.8 g/day	High dose cohort	RT001, oral, 1.8 g QD for 28 days or matching comparator
RT001, oral, 9 g/day	Low dose cohort	RT001, oral, 4.5 g BID for 28 days or matching comparator
RT001, oral, 9 g/day	High dose cohort	RT001, oral, 4.5 g BID for 28 days or matching comparator

Primary Outcome Measures

Name	Time	Method
Number of Patients With Adverse Events	28 days

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics - Area Under the Concentration-time Curve After a Single Dose	24 hours	AUC 0-24 hours post-dose (Hours -1.0 to -0.5 (pre-breakfast, pre-dose), 0.5 (± 5 min), 1 (± 5 min), 1.5 (± 5 min), 2 (± 10 min), 4 (± 10 min) (pre-lunch), 6 (± 10 min), 8 (± 10 min), 12 (± 10 min), and 16 (± 30 min) Day 2: 24 hours following dosing on Day 1 (± 30 min; pre-breakfast, pre-dose) was measured for the low and high dose cohorts after a single dose of RT001
Pharmacokinetics - Maximum Observed Plasma Concentration After a Single Dose	24 hours	Plasma levels were measured for the following time points: Day 1: Hours -1.0 to -0.5 (pre-breakfast, pre-dose), 0.5 (± 5 min), 1 (± 5 min), 1.5 (± 5 min), 2 (± 10 min), 4 (± 10 min) (pre-lunch), 6 (± 10 min), 8 (± 10 min), 12 (± 10 min), and 16 (± 30 min) Day 2: 24 hours following dosing on Day 1 (± 30 min; pre-breakfast, pre-dose) PK curves were constructed from these data and CMax measured on the curves for the low and high dose cohorts
Pharmacokinetics - Time to Reach Maximum Plasma Concentration After a Single Dose	24 hours	TMax measured for the low and high dose cohorts
Pharmacokinetics - Maximum Observed Plasma Concentration After Final Dose on Day 28	Day 28-Day 31 (3 days)	After 28 days of dosing, the final dose of RT001 was administered, and PK samples were obtained at the following timepoints (all timepoints refer to final dose on Day 28): Day 28: Hours -1.0 to -0.5 (pre-breakfast, pre-dose on Day 28), 0.5 (± 5 min), 1 (± 5 min), 1.5 (± 5 min), 2 (± 10 min), 4 (± 10 min) (pre-lunch), 6 (± 10 min), 8 (± 10 min), 12 (± 10 min), and 16 (± 30 min) Day 29: Hours 24 (± 30 min; pre-breakfast) and 32 (± 30 min) hours following final dose on Day 28 Day 30: 48 hours following final dose on Day 28 (± 30 min; pre-breakfast) Day 31: 72 hours following final dose on Day 28 (± 30 min; pre-breakfast) PK curves were constructed, and CMax at 28 days was determined from these curves
Pharmacokinetics - Terminal Half-life Estimation After Final Dose on Day 28	Day 28-Day 31 (3 days)	After 28 days of dosing, the final dose of RT001 was administered, and PK samples were obtained at the following timepoints (all timepoints refer to final dose on Day 28): Day 28: Hours -1.0 to -0.5 (pre-breakfast, pre-dose on Day 28), 0.5 (± 5 min), 1 (± 5 min), 1.5 (± 5 min), 2 (± 10 min), 4 (± 10 min) (pre-lunch), 6 (± 10 min), 8 (± 10 min), 12 (± 10 min), and 16 (± 30 min) Day 29: Hours 24 (± 30 min; pre-breakfast) and 32 (± 30 min) hours following final dose on Day 28 Day 30: 48 hours following final dose on Day 28 (± 30 min; pre-breakfast) Day 31: 72 hours following final dose on Day 28 (± 30 min; pre-breakfast) PK curves were constructed, and T1/2 at 28 days was determined from these curves
Change From Baseline at 28 Days in the Timed 25 Foot Walk (T25FW)	28 days	The T25FW is a quantitative mobility and leg function performance test based on a timed 25-foot walk. T25FW was measured at baseline and at 28 days. These data were compared.
Change From Baseline at 28 Days in the Friedreich Ataxia Rating Scale (FARS) - Neurological Score (Minimum Score 0, Maximum Score 125, Lower is Better)	28 days	The FARS-neurological rating scale specifically developed and validated for Friedreich's Ataxia. The FARS-Neurological included evaluations of the neurological signs that specifically reflect neural substrates affected in patients with FA. Based on a neurological examination bulbar (11 points), upper limb coordination (36 points), lower limb coordination (16 points), peripheral nervous system (26 points), and upright stability (36 points) functions were assessed for individual sub-scores (11, 36, 16, 26, and 36) with a maximum score of 125 (Friedreich's Ataxia Study Group, Subramony et al., 2005, Lynch et al., 2006). FARS-Neurologic examinations were conducted by a qualified physician or health professional trained in the use of the FARS format. A lower score is better. The minimum score is 0, the maximum score is 125.
Change From Baseline at 28 Days in Peak Workload for the Treated Population vs. the Comparator Population	28 days	Peak workload was measured using cardiopulmonary exercise testing at baseline and after 28 days of treatment. The results of treatment were compared to baseline examination.

Trial Locations

Locations (2): Collaborative Neuroscience Network, LLC
🇺🇸
Long Beach, California, United States
University of South Florida
🇺🇸
Tampa, Florida, United States