A Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Friedreich’s Ataxia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Reata Pharmaceuticals Inc., Reata Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

21 Jul 2016 → 19 Dec 2025

Decision date (initial)

2024-11-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen

External identifiers

EU CT number

2024-517436-22-00

EudraCT number

2015-002762-23

ClinicalTrials.gov

NCT02255435

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy, Pharmacodynamic, Dose response, Pharmacokinetic

Part 1
• To evaluate the change in peak work during maximal exercise testing
• To evaluate the safety and tolerability of RTA 408

Part 2
• To evaluate the change in the modified Friedreich's ataxia rating scale
(mFARS) score at Week 48
• To evaluate the safety and tolerability of RTA 408

Secondary objectives 4

1. Part 1: To evaluate the change in the modified Friedreich's ataxia rating scale (FARS) score
2. Part 2: To evaluate the change in peak work during maximal exercise testing at Week 48
3. Part 2: To evaluate the Patient Global Impression of Change at Week 48
4. Part 2: To evaluate the Clinical Global Impression of Change at Week 48

Conditions and MedDRA coding

Friedreich's ataxia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. Part 1 and Part 2: Patients must have genetically confirmed Friedreich’s ataxia
2. Part 1 and Part 2: Patients must have an mFARS score ≥ 20 and ≤ 80. The average of the two mFARS values collected at Screening and Day 1 visits must fall within the allowable range, and they must be within 4.5 points of each other
3. Part 1 and Part 2: Patients must be male or female and ≥ 16 years of age and ≤ 40 years of age
4. Part 1 and Part 2: Patients must have no changes to their exercise regimen within 30 days prior to Study Day 1 and be willing to remain on the same exercise regimen during the study period
5. Part 1 and Part 2: Patients must have the ability to complete maximal exercise testing
6. Part 1 and Part 2: Patients must have adequate kidney function defined as an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m^2 using the Modification of Diet in Renal Disease (MDRD) 4-variable formula
7. Part 1 and Part 2: Patients must have a left ventricular ejection fraction ≥ 40% (based on echocardiogram performed at Screening Visit or within 90 days prior to Screening Visit)
8. Part 1 and Part 2: Patients must be able to swallow capsules
9. Part 1 and Part 2: Patients must be willing and able to cooperate with all aspects of the protocol
10. Part 1 and Part 2: Patients must be willing to practice medically acceptable methods of birth control
11. Part 1 and Part 2: Patients must provide written informed consent for study participation, approved by the appropriate Institutional Review Board
12. Extension eligibility: Patients must complete 12 weeks of treatment in Part 1 or 24 weeks of treatment in Part 2, have no major protocol deviations, and meet inclusion criteria as follows
13. Extension eligibility: Patients must have adequate kidney function defined as an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m^2 using the Modification of Diet in Renal Disease (MDRD) 4-variable formula
14. Extension eligibility: Patients must have a left ventricular ejection fraction ≥ 40% (based on echocardiogram performed at Screening Visit or within 90 days prior to Screening Visit)
15. Extension eligibility: Patients must be able to swallow capsules
16. Extension eligibility: Patients must be willing and able to cooperate with all aspects of the extension
17. Extension eligibility: Patients must be willing to practice medically acceptable methods of birth control
18. Extension eligibility: Patients must provide written informed consent for study participation, approved by the appropriate Institutional Review Board
19. Extension eligibility: Patients must have been enrolled in Part 1 or Part 2 and completed assessments through the follow-up visit with no major protocol deviations

Exclusion criteria 31

1. Part 1 and Part 2: Patients must not have uncontrolled diabetes (HbA1c > 11.0%)
2. Part 1 and Part 2: Patients must not have BNP level > 200 pg/mL
3. Part 1 and Part 2: Patients must not have a history of clinically significant left-sided heart disease and/or clinically significant cardiac disease, with the exception of mild to moderate cardiomyopathy associated with Friedreich’s ataxia, including but not limited to any of the following: a. Clinically significant congenital or acquired valvular disease; b. Pericardial constriction (based on echocardiogram performed at Screening Visit or within 90 days prior to Screening Visit); c. Restrictive or congestive cardiomyopathy (based on echocardiogram performed at Screening Visit or within 90 days prior to Screening Visit); d. Symptomatic coronary disease (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or angina); e. History of hospitalization for heart failure in the last five years; f. Cardiac insufficiency, defined as New York Heart Association Class > 2; g. History of atrial fibrillation; h. History of unstable arrhythmias
4. Part 1 and Part 2: Patients must not have known active fungal, bacterial, and/or viral infection, including human immunodeficiency virus (HIV) or hepatitis virus (B or C)
5. Part 1 and Part 2: Patients must not have known or suspected active drug or alcohol abuse, as per investigator judgment
6. Part 1 and Part 2: Patients must not have clinically significant abnormalities of clinical hematology or biochemistry, including but not limited to elevations greater than 1.5 times the upper limit of normal (ULN) of AST or ALT. Levels above this threshold are allowable if attributable to muscle injury
7. Part 1 and Part 2: Patients must not have any abnormal laboratory test value or clinically significant pre-existing medical condition that, in the opinion of the investigator, would put the patient at risk by study enrollment
8. Part 1 and Part 2: Patients must not have taken any of the following drugs within 7 days prior to Study Day 1 or plan to take any of these drugs during the time of study participation: a. Sensitive substrates for cytochrome P450 2C8 or 3A4 (e.g., repaglinide, midazolam, sildenafil); b. Moderate or strong inhibitors or inducers of cytochrome P450 3A4 (e.g., carbamazepine, phenytoin, ciprofloxacin, grapefruit juice); c. Substrates for p-glycoprotein transporter (e.g., ambrisentan, digoxin)
9. Part 1 and Part 2: Patients must not have a history of clinically significant liver disease (e.g., fibrosis, cirrhosis, hepatitis), or has, at screening, clinically relevant deviations in laboratory tests including any one of the following: a. ALT and/or AST > 1.5-fold ULN; b. bilirubin > 1.2-fold ULN; c. ALP > 2-fold ULN; d. albumin < lower limit of normal (LLN)
10. Part 1 and Part 2: Patients must not have participated in any other interventional clinical study within 30 days prior to Study Day 1
11. Part 1 and Part 2: Patients must not have a cognitive impairment that may preclude ability to comply with study procedures
12. Part 1 and Part 2: Patients must not be unable to comply with the requirements of the study protocol or be unsuitable for the study for any reason, in the opinion of the investigator
13. Part 1 and Part 2: Patients must not have used antioxidant supplements, including but not limited to idebenone, coenzyme Q10, nicotinamide, and vitamin E above the recommended daily allowance, within 14 days prior to Study Day 1, or plan to take any of these supplements during the time of study participation
14. Part 1 and Part 2: Patients must not have previously documented mitochondrial respiratory chain disease
15. Part 1 and Part 2: Patients must not have a history of thromboembolic events within the past 5 years
16. Part 1 and Part 2: Patients must not have taken anticoagulant therapy within 30 days prior to Study Day 1
17. Part 1 and Part 2: Patients must not have scheduled surgical treatment for scoliosis or foot deformity during the study
18. Part 1 and Part 2: Patients must not have had significant suicidal ideation within 1 month prior to Screening Visit as per investigator judgment or any history of suicide attempts
19. Part 1 and Part 2: Patients must not be pregnant or breastfeeding
20. Part 1 and Part 2: Prior participation in a trial with RTA 408
21. Extension eligibility: Patients must not have uncontrolled diabetes (HbA1c > 11.0%)
22. Extension eligibility: Patients must not have B-type natriuretic peptide (BNP) level > 200 pg/mL
23. Extension eligibility: Patients must not have a history of clinically significant left-sided heart disease and/or clinically significant cardiac disease, with the exception of mild to moderate cardiomyopathy associated with Friedreich's ataxia
24. Extension eligibility: Patients must not have a history of clinically significant liver disease or has, at screening, clinically relevant deviations in laboratory tests
25. Extension eligibility: Patients must not have a cognitive impairment that may preclude ability to comply with study procedures
26. Extension eligibility: Patients must not be unable to comply with the requirements of the study protocol or be unsuitable for the study for any reason, in the opinion of the investigator
27. Extension eligibility: Patients must not have a history of thromboembolic events within the past 5 years
28. Extension eligibility: Patients must not have taken anticoagulant therapy within 30 days prior to Extension Day 1
29. Extension eligibility: Patients must not be pregnant or breastfeeding
30. Extension eligibility: Patients must not have an ongoing SAE from a clinical study that is assessed by the investigator as related to RTA 408
31. Extension eligibility: Patients must not have discontinued treatment early in Part 1 or Part 2

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part 1: To evaluate the change in peak work during maximal exercise testing
2. Part 1: To evaluate the safety and tolerability of RTA 408
3. Part 2: To evaluate the change in the mFARS score at Week 48
4. Part 2: To evaluate the safety and tolerability of RTA 408

Secondary endpoints 4

1. Part 1: To evaluate the change in the modified Friedreich’s ataxia rating scale (mFARS) score
2. Part 2: To evaluate the change in peak work during maximal exercise testing at Week 48
3. Part 2: To evaluate the Patient Global Impression of Change at Week 48
4. Part 2: To evaluate the Clinical Global Impression of Change at Week 48

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Reata Pharmaceuticals Inc.

Sponsor organisation

Reata Pharmaceuticals Inc.

Address

225 Binney Street

City

Cambridge

Postcode

02142-1031

Country

United States

Scientific contact point

Organisation

Reata Pharmaceuticals Inc.

Contact name

CTA Lead Dept

Public contact point

Organisation

Reata Pharmaceuticals Inc.

Contact name

CTA Lead Dept

Third parties 10

Reata Pharmaceuticals Inc.

Sponsor organisation

Reata Pharmaceuticals Inc.

Address

225 Binney Street

City

Cambridge

Postcode

02142-1031

Country

United States

Third parties 10

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications