Back to resultsA First in Human Study of RT001 in Patients With Friedreich's Ataxia
Primary Purpose
Friedreich's Ataxia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Low dose cohort
High dose cohort
Sponsored by
About this trial
This is an interventional treatment trial for Friedreich's Ataxia
Eligibility Criteria
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
Sites / Locations
- Collaborative Neuroscience Network, LLC
- University of South Florida
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
RT001, oral, 1.8 g/day
RT001, oral, 9 g/day
Arm Description
RT001, oral, 1.8 g QD for 28 days or matching comparator
RT001, oral, 4.5 g BID for 28 days or matching comparator
Outcomes
Primary Outcome Measures
Number of Patients With Adverse Events
Secondary Outcome Measures
Pharmacokinetics - Area Under the Concentration-time Curve After a Single Dose
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
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
TMax measured for the low and high dose cohorts
Pharmacokinetics - Maximum Observed Plasma Concentration After Final Dose on Day 28
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
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)
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)
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02445794
Brief Title
A First in Human Study of RT001 in Patients With Friedreich's Ataxia
Official Title
A Randomized, Double-blind, Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of RT001 in Patients With Friedreich's Ataxia
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
August 2015 (undefined)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
July 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Retrotope, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Friedreich's Ataxia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RT001, oral, 1.8 g/day
Arm Type
Experimental
Arm Description
RT001, oral, 1.8 g QD for 28 days or matching comparator
Arm Title
RT001, oral, 9 g/day
Arm Type
Experimental
Arm Description
RT001, oral, 4.5 g BID for 28 days or matching comparator
Intervention Type
Drug
Intervention Name(s)
Low dose cohort
Other Intervention Name(s)
RT001 1.8 g/d (2 capsule per day), RT001 comparator 1.8 g/d (2 capsule per day)
Intervention Description
RT001 is encapsulated di-deutero synthetic homologue of linoleic acid ethyl ester. Each capsule contains 900 mg of RT001.
Intervention Type
Drug
Intervention Name(s)
High dose cohort
Other Intervention Name(s)
RT001 9.0 g/d (9 capsule per day), RT001 comparator 9.0 g/d (9 capsule per day)
Intervention Description
RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.
Primary Outcome Measure Information:
Title
Number of Patients With Adverse Events
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Pharmacokinetics - Area Under the Concentration-time Curve After a Single Dose
Description
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
Time Frame
24 hours
Title
Pharmacokinetics - Maximum Observed Plasma Concentration After a Single Dose
Description
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
Time Frame
24 hours
Title
Pharmacokinetics - Time to Reach Maximum Plasma Concentration After a Single Dose
Description
TMax measured for the low and high dose cohorts
Time Frame
24 hours
Title
Pharmacokinetics - Maximum Observed Plasma Concentration After Final Dose on Day 28
Description
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
Time Frame
Day 28-Day 31 (3 days)
Title
Pharmacokinetics - Terminal Half-life Estimation After Final Dose on Day 28
Description
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
Time Frame
Day 28-Day 31 (3 days)
Title
Change From Baseline at 28 Days in the Timed 25 Foot Walk (T25FW)
Description
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.
Time Frame
28 days
Title
Change From Baseline at 28 Days in the Friedreich Ataxia Rating Scale (FARS) - Neurological Score (Minimum Score 0, Maximum Score 125, Lower is Better)
Description
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.
Time Frame
28 days
Title
Change From Baseline at 28 Days in Peak Workload for the Treated Population vs. the Comparator Population
Description
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.
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Curtis Scribner, MD
Organizational Affiliation
Retrotope, Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Theresa Zesiewicz, MD
Organizational Affiliation
USF Ataxia Research Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Collaborative Neuroscience Network, LLC
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A First in Human Study of RT001 in Patients With Friedreich's Ataxia
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