A study to determine if Vatiquinone, the study drug, is safe and effective to treat a neurological condition called Friedreich ataxia

Phase 1

• Conditions: Friedreich Ataxia (FA); Therapeutic area: Diseases [C] - Nervous System Diseases [C10]; MedDRA version: 20.0Level: PTClassification code 10017374Term: Friedreich's ataxiaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders

• Registration Number: EUCTR2020-002812-36-ES
• Lead Sponsor: PTC Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-11-19
• Last Update Posted: 7 June 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 126

Inclusion Criteria

1. mFARS =20 to =70 at baseline

2. Minimum age 7 years at the time of Screening Visit

3. Must be able to ambulate at least 10 feet in one minute with or without assistance (non-wheelchair)

4. Friedreich ataxia diagnosis (homozygous for GAA repeat expansion in intron-1 of FXN gene), confirmed by clinical testing

5. Consent to comply with study procedures. For subjects under the age of 18 (or age of consent), parent(s)/legal guardian(s) of the subject must agree to comply with the requirements of the study, including the need for frequent and prolonged follow-up; parent(s)/legal guardian(s) with custody of the subject must give their consent for subject to enroll in the study.

6. Difference in the mFARS between screening and baseline of no more than 4 points
o If the subject is taking prohibited medications (see exclusion criteria)
at Screening, this difference is to be assessed between the
post-discontinuation mFARS and the Baseline mFARS.

7. Able to abstain from anticoagulants and any aspirin (including 81 mg) for 30 days prior to the Baseline Visit and for the duration of the study

8. Ability to abstain from potent cytochrome P450 (CYP) 3A4 inducers/inhibitors (eg, ketoconazole, rifampin, St. John’s wort, grapefruit juice) for at least 4 weeks prior to enrollment

9. Ability to swallow capsules

10. Males and females of childbearing potential must be willing to use an effective method of contraception as defined in protocol Section 7.5.10 from the time consent is signed until 30 days after treatment discontinuation
Are the trial subjects under 18? yes
Number of subjects for this age range: 90
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Individuals with clinical diagnosis of FA who have point mutations or deletions or other non-GAA expansion mutations

2. Previous treatment with vatiquinone or allergy to vatiquinone, sesame oil, gelatin (bovine and/or porcine), titanium dioxide, or red iron oxide

3. Ejection fraction <50%

4. Uncontrolled diabetes (HbA1c >7.0%) at the time of screening

5. Has current suicidal ideation or suicidal behavior based on Columbia-Suicide Severity Rating Scale (C-SSRS) at screening or baseline

6. Pregnant or lactating subjects or those sexually active subjects who are unwilling to comply with proper birth control methods; females of childbearing potential must have a negative pregnancy test at Screening and during the Baseline Visit

7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =2 x ULN at time of screening

8. INR =1.5 x ULN at time of screening or clinically significant (CS) bleeding, as determined by the investigator

9. Serum creatinine =1.5 x ULN at time of screening

10. Comorbidities that may confound study results (eg, fat malabsorption syndrome, other mitochondrial disorder) in the opinion of the investigator

11. Participation in any other interventional clinical trial or received any investigational drug in any other clinical trial within 60 days prior to the Baseline Visit. Subjects may be rescreened after the exclusionary period of 60 days has passed.

12. Concomitant use of CoQ10, vitamin E, idebenone, or any other non-approved medication for FA within 30 days prior to the Screening Visit. These prohibited medications can be discontinued at the Screening Visit; if this is the case, the mFARS assessment must be repeated to confirm inclusion eligibility after a minimum of 30 days post-discontinuation and there must be no more than a 4-point difference in mFARS assessed from the Post-Discontinuation Visit to the Baseline Visit.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to evaluate the efficacy (using the modified Friedreich Ataxia Rating Scale [mFARS]) and safety of vatiquinone in subjects with FA.;Secondary Objective: • Demonstrate the effects of vatiquinone on activities of daily living as assessed by the Friedreich Ataxia Rating Scale Activities of Daily Living (FARS-ADL) scale<br>• Demonstrate the effects of vatiquinone on ambulation as assessed by the 1-minute walk test (1MWT)<br>• Demonstrate the effects of vatiquinone on falls as assessed by a fall log;Primary end point(s): The primary endpoint will be the change from baseline in the modified Friedreich Ataxia Rating Scale (mFARS) in the mITT population at Week 72.;Timepoint(s) of evaluation of this end point: A completer analysis will be performed for all subjects who took medication till the end of double-blind period as specified by the protocol and have mFARS score at Week 72 visit.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary endpoints will include change in baseline in the following assessments at Week 72.<br>• FARS-ADL scale (key secondary endpoint)<br>• 1MWT<br>• Fall log;Timepoint(s) of evaluation of this end point: Comparisons between treatment groups for change from baseline in FARS-ADL scale, one minute timed walk, MFIS score, EQ-5D-5L, and Upright Stability subscale of the mFARS to Week 72 will be analyzed using the same model as the primary efficacy variable by using its respective baseline and age as covariates. Summary statistics will be provided for total score at each visit as well as change from baseline at each visit.<br><br>A summary of the number of falls will be presented, and the number of falls over time will be compared between the two treatment groups.