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Completed

NCT Number: NCT02445794

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

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

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Key information

Conditions

Friedreich's Ataxia Brain Diseases Central Nervous System Diseases Cerebellar Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Friedreich Ataxia Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Metabolic Diseases Mitochondrial Diseases Nervous System Diseases Neurodegenerative Diseases Nutritional and Metabolic Diseases Spinal Cord Diseases Spinocerebellar Degenerations

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Collaborative Neuroscience Network, LLC, Long Beach, California, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Low dose cohort

Drug

RT001 is encapsulated di-deutero synthetic homologue of linoleic acid ethyl ester. Each capsule contains 900 mg of RT001.

Other names: RT001 1.8 g/d (2 capsule per day), RT001 comparator 1.8 g/d (2 capsule per day)

High dose cohort

Drug

RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.

Other names: RT001 9.0 g/d (9 capsule per day), RT001 comparator 9.0 g/d (9 capsule per day)

Primary outcomes

  1. Number of Patients With Adverse Events

    Time frame: 28 days

Secondary outcomes

  1. Pharmacokinetics - Area Under the Concentration-time Curve After a Single Dose

    Time frame: 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

  2. Pharmacokinetics - Maximum Observed Plasma Concentration After a Single Dose

    Time frame: 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

  3. Pharmacokinetics - Time to Reach Maximum Plasma Concentration After a Single Dose

    Time frame: 24 hours

    TMax measured for the low and high dose cohorts

  4. Pharmacokinetics - Maximum Observed Plasma Concentration After Final Dose on Day 28

    Time frame: 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

  5. Pharmacokinetics - Terminal Half-life Estimation After Final Dose on Day 28

    Time frame: 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

  6. Change From Baseline at 28 Days in the Timed 25 Foot Walk (T25FW)

    Time frame: 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.

  7. Change From Baseline at 28 Days in the Friedreich Ataxia Rating Scale (FARS) - Neurological Score (Minimum Score 0, Maximum Score 125, Lower is Better)

    Time frame: 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.

  8. Change From Baseline at 28 Days in Peak Workload for the Treated Population vs. the Comparator Population

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Biojiva LLC

Industry

Registry information

Official study title

A Randomized, Double-blind, Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of RT001 in Patients With Friedreich's Ataxia

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
May 15, 2015
Registry last updated
Nov 27, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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