Friedreich's Ataxia
Conditions
Brief summary
This 24-week study will test the safety and effectiveness of synthetically produced (+) Epicatechin in treating patients who have Friedreich's Ataxia, a neurological disorder.
Interventions
DRUG(+)-Epicatechin
25mg (+)-Epicatechin capsules. Starting dose 75mg total daily dose (one 25mg cap taken three times per day). Dose escalation at 12 weeks for non-responders to 150mg total daily dose (two 25mg caps taken three times per day)
Sponsors
Cardero Therapeutics, Inc.
Ralitza Gavrilova
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of Friedreich's Ataxia (FA) by Frataxin genetic testing and/or Frataxin enzyme analysis * Between age 10 and 50 years of age, inclusive * Body weight of 25 kilograms or higher * Minimum of one affected organ (cardiac or neurological) system, as evidenced by clinical signs/symptoms * Disease duration ≤7 years, based on onset date of FA symptoms * Has no known contraindication to gadolinium contrast such as severe allergy or Glomerular Filtration Rate \<30 ml/min/m\^2. * Has no known contraindication to non-contrast Magnetic Resonance Imaging (MRI) evaluation such as pacemaker or magnetically active metal fragments. * Women of childbearing age must: * Have a negative pregnancy human chorionic gonadotropin test prior to receiving study drug. * Agree to use contraception for the duration of the study drug dosing, plus 1 month after completion of the study.
Exclusion criteria
* Advanced cardiac failure, New York Heart Association (NYHA) Classification Scale-Class IV (advanced stage heart failure) * Clinically significant comorbidities that may also lead to cardiomyopathy, for example long standing hypertension, familial cardiomyopathy. * Clinically significant comorbidities that would, in the opinion of the investigators, compromise the interpretation of test results. * Pregnant, breast-feeding or planning to become pregnant during study timeframe. * Patients with contraindications to regadenoson, i. e. second- or third-degree atrioventricular (AV) block or sinus node dysfunction. Has received an investigational drug within thirty (30) days of baseline visit. * Thrombocytopenia (\<125 x 10\^9/Liter) or prolonged Prothrombin Time/Partial Thromboplastin Time (PT/PTT) at baseline. * Clinically significant hypotension (systolic blood pressure \<90) due to heart failure or other conditions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Friedreich Ataxia Rating Scale (FARS) Composite Score | Baseline, 24 weeks | The Friedreich Ataxia Rating Scale (FARS) is made up of a measure of ataxia, an activities of daily living subscale and a neurological subscale. This scale also includes the 8m walk at maximum speed (8MW), the 9-hole peg test (9HPT), PATA rate (assesses speech speed by repetitions of pronouncing PaTa ) and low-contrast letter acuity. FARS is made up of a measure of ataxia, an activities of daily living subscale and a neurological subscale. This scale also includes the 8m walk at maximum speed (8MW), the 9-hole peg test (9HPT), PATA rate and low-contrast letter acuity. The scores from the three subscales are added to generate a total score ranging from 0 to 159, with a higher score indicating a greater level of disability. |
| Change in Ventricular Hypertrophy as Shown on Cardiac MRI | Baseline, 24 weeks | Left ventricular mass and left ventricular (LV) mass indexed to body surface area estimated by Left Ventricle (LV)cavity dimension and wall thickness at end-diastole. Normal values of LV mass indexed to body surface area are found to be 49-115 gL/m2 in men and 43-95 g/m2 in women. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| (+)-Epicatechin Total daily dose 75mg (+)-Epicatechin; 25mg cap three times per day by mouth for 24 weeks
(+)-Epicatechin: 25mg (+)-Epicatechin capsules. Starting dose 75mg total daily dose (one 25mg cap taken three times per day). Dose escalation at 12 weeks for non-responders to 150mg total daily dose (two 25mg caps taken three times per day) | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | (+)-Epicatechin | — |
|---|---|---|
| Age, Continuous | 14.5 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 10 participants | — |
| Sex: Female, Male Female | 4 Participants | — |
| Sex: Female, Male Male | 6 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 3 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Change From Baseline in Friedreich Ataxia Rating Scale (FARS) Composite Score
The Friedreich Ataxia Rating Scale (FARS) is made up of a measure of ataxia, an activities of daily living subscale and a neurological subscale. This scale also includes the 8m walk at maximum speed (8MW), the 9-hole peg test (9HPT), PATA rate (assesses speech speed by repetitions of pronouncing PaTa ) and low-contrast letter acuity. FARS is made up of a measure of ataxia, an activities of daily living subscale and a neurological subscale. This scale also includes the 8m walk at maximum speed (8MW), the 9-hole peg test (9HPT), PATA rate and low-contrast letter acuity. The scores from the three subscales are added to generate a total score ranging from 0 to 159, with a higher score indicating a greater level of disability.
Time frame: Baseline, 24 weeks
Population: One subject did not complete week 24 questionnaire
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (+)-Epicatechin | Change From Baseline in Friedreich Ataxia Rating Scale (FARS) Composite Score | 55.0 score on a scale | Standard Deviation 18.72 |
p-value: 0.336Wilcoxon (Mann-Whitney)
Primary
Change in Ventricular Hypertrophy as Shown on Cardiac MRI
Left ventricular mass and left ventricular (LV) mass indexed to body surface area estimated by Left Ventricle (LV)cavity dimension and wall thickness at end-diastole. Normal values of LV mass indexed to body surface area are found to be 49-115 gL/m2 in men and 43-95 g/m2 in women.
Time frame: Baseline, 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| (+)-Epicatechin | Change in Ventricular Hypertrophy as Shown on Cardiac MRI | 55.9 mL/m2 | Standard Deviation 9.49 |