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

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ClinicalTrials.gov Identifier: NCT02445794
Recruitment Status : Completed
First Posted : May 15, 2015
Results First Posted : November 27, 2020
Last Update Posted : November 27, 2020
Sponsor:
Information provided by (Responsible Party):
Retrotope, Inc.

Tracking Information
First Submitted Date  ICMJE May 6, 2015
First Posted Date  ICMJE May 15, 2015
Results First Submitted Date  ICMJE August 19, 2020
Results First Posted Date  ICMJE November 27, 2020
Last Update Posted Date November 27, 2020
Study Start Date  ICMJE August 2015
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 12, 2015)
Number of Patients With Adverse Events [ Time Frame: 28 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 24, 2020)
  • 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
  • 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
  • Pharmacokinetics - Time to Reach Maximum Plasma Concentration After a Single Dose [ Time Frame: 24 hours ]
    TMax measured for the low and high dose cohorts
  • 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
  • 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
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2015)
  • Pharmacokinetics - Area Under the Concentration-time Curve After a Single Dose [ Time Frame: 24 hours ]
  • Pharmacokinetics - Maximum Observed Plasma Concentration After a Single Dose [ Time Frame: 24 hours ]
  • Pharmacokinetics - Time to Reach Maximum Plasma Concentration After a Single Dose [ Time Frame: 24 hours ]
  • Pharmacokinetics - Area under the concentration-time curve during a dosing interval at steady state [ Time Frame: 72 hours ]
  • Pharmacokinetics - Maximum observed plasma concentration at steady state [ Time Frame: 72 hours ]
  • Pharmacokinetics - Time to reach maximum plasma concentration at steady state [ Time Frame: 72 hours ]
  • Pharmacokinetics - Time to reach minimum plasma concentration at steady state [ Time Frame: 72 hours ]
  • Pharmacokinetics - Minimum observed plasma concentration at steady state [ Time Frame: 72 hours ]
  • Pharmacokinetics - Area under the concentration-time curve from time 0 to infinity [ Time Frame: 72 hours ]
  • Pharmacokinetics - Area under the concentration-time curve from time 0 to the last measurable time point [ Time Frame: 72 hours ]
  • Pharmacokinetics - Apparent total plasma clearance after oral administration [ Time Frame: 72 hours ]
  • Pharmacokinetics - Elimination rate constant [ Time Frame: 72 hours ]
  • Pharmacokinetics - Terminal half-life estimation [ Time Frame: 72 hours ]
  • Pharmacokinetics - Apparent volume of distribuation after oral dosing at steady state [ Time Frame: 72 hours ]
  • Change from baseline 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.
  • Change from baseline in the Friedreich Ataxia Rating Scale (FARS) - Neurological Score [ Time Frame: 28 days ]
    The FARS is neurological rating scale specifically developed and validated for Friedreich's Ataxia.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A First in Human Study of RT001 in Patients With Friedreich's Ataxia
Official Title  ICMJE A Randomized, Double-blind, Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of RT001 in Patients With Friedreich's Ataxia
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Friedreich's Ataxia
Intervention  ICMJE
  • Drug: Low dose cohort
    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)
  • Drug: High dose cohort
    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)
Study Arms  ICMJE
  • Experimental: RT001, oral, 1.8 g/day
    RT001, oral, 1.8 g QD for 28 days or matching comparator
    Interventions:
    • Drug: Low dose cohort
    • Drug: High dose cohort
  • Experimental: RT001, oral, 9 g/day
    RT001, oral, 4.5 g BID for 28 days or matching comparator
    Interventions:
    • Drug: Low dose cohort
    • Drug: High dose cohort
Publications * Not Provided

*   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: May 20, 2016)
19
Original Estimated Enrollment  ICMJE
 (submitted: May 12, 2015)
18
Actual Study Completion Date  ICMJE July 2016
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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

Exclusion Criteria:

  1. Received treatment with other experimental therapies within the last 30 days prior to the first dose
  2. Known point mutation in the FXN gene
  3. History of malignancies (other than basal cell carcinomas)
  4. Impaired renal function at screening
  5. Alanine transaminase (ALT) or aspartate transaminase (AST) laboratory values > 2 x upper limit of normal (ULN) at screening
  6. 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
  7. Female who is breastfeeding or has a positive pregnancy test
  8. 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
  9. Unwilling or unable to comply with the requirements of the protocol
  10. Clinically significant cardiac abnormalities at screening that, in the opinion of the Investigator, would make the patient unsuitable for enrollment
  11. Diabetes mellitus (Type 1 or 2)
  12. Suicidal ideation as determined by the Columbia-Suicide Severity Rating Scale
  13. History, within the last 2 years, of alcohol abuse, significant mental illness, or physical opioid dependence
  14. Cannot adhere to the dietary guidance required to be followed by the protocol
  15. Cannot take the medication due to impairment in swallowing capsules
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02445794
Other Study ID Numbers  ICMJE RT001-002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Retrotope, Inc.
Study Sponsor  ICMJE Retrotope, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Curtis Scribner, MD Retrotope, Inc.
Principal Investigator: Theresa Zesiewicz, MD USF Ataxia Research Center
PRS Account Retrotope, Inc.
Verification Date September 2020

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