- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02445794
A First in Human Study of RT001 in Patients With Friedreich's Ataxia
A Randomized, Double-blind, Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of RT001 in Patients With Friedreich's Ataxia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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-
California
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Long Beach, California, United States, 90806
- Collaborative Neuroscience Network, LLC
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Florida
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Tampa, Florida, United States, 33612
- University of South Florida
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: RT001, oral, 1.8 g/day
RT001, oral, 1.8 g QD for 28 days or matching comparator
|
RT001 is encapsulated di-deutero synthetic homologue of linoleic acid ethyl ester.
Each capsule contains 900 mg of RT001.
Other Names:
RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.
Other Names:
|
Experimental: RT001, oral, 9 g/day
RT001, oral, 4.5 g BID for 28 days or matching comparator
|
RT001 is encapsulated di-deutero synthetic homologue of linoleic acid ethyl ester.
Each capsule contains 900 mg of RT001.
Other Names:
RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of Patients With Adverse Events
Time Frame: 28 days
|
28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
24 hours
|
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
|
24 hours
|
Pharmacokinetics - Time to Reach Maximum Plasma Concentration After a Single Dose
Time Frame: 24 hours
|
TMax measured for the low and high dose cohorts
|
24 hours
|
Pharmacokinetics - Maximum Observed Plasma Concentration After Final Dose on Day 28
Time Frame: Day 28-Day 31 (3 days)
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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 |
Day 28-Day 31 (3 days)
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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 |
Day 28-Day 31 (3 days)
|
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. |
28 days
|
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
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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.
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28 days
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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.
|
28 days
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Curtis Scribner, MD, Retrotope, Inc.
- Principal Investigator: Theresa Zesiewicz, MD, USF Ataxia Research Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Genetic Diseases, Inborn
- Neurodegenerative Diseases
- Dyskinesias
- Spinal Cord Diseases
- Heredodegenerative Disorders, Nervous System
- Mitochondrial Diseases
- Cerebellar Diseases
- Spinocerebellar Degenerations
- Ataxia
- Cerebellar Ataxia
- Friedreich Ataxia
Other Study ID Numbers
- RT001-002
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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