GV101 for Friedreich's Ataxia (FA) Treatment

Graviton Bioscience

Status and phase

Begins enrollment this month

Phase 2

Conditions

Friedreich's Ataxia

Treatments

Drug: GV101

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT07870590

GBS-GV101-FA-201

Details and patient eligibility

About

This is a dose-ranging, randomized, double-blind, placebo-controlled 12-week Phase 2a trial with an up to two week loading dose period. Eligible participants will be sequentially randomized 3:1 into three parallel groups, low-dose, mid-dose, and high-dose, to receive GV101 or placebo once daily for 12 weeks.

The low-dose group will receive 200 mg from Weeks 2-12 after a 100 mg loading dose at Week 1; the mid-dose group will receive 300 mg from Weeks 3-12 after loading doses of 100 mg and 200 mg at Weeks 1 and 2, respectively; and the high dose group will receive 400 mg from Weeks 3-12 after loading doses of 200 mg and 300 mg at Weeks 1 and 2, respectively. Target enrollment is 16 participants per dose group. The primary efficacy endpoint at 12 weeks is percent change in blood FXN-M protein in each dose group compared with placebo, the key secondary endpoints are change in hs-cTnI and mFARS score in each dose group compared with placebo. Data for exploratory, safety, PK, and PD endpoints will also be collected and analyzed.

Down-dosing will be allowed in groups dosed with > 200 mg daily. Participants who complete the 12-week trial are eligible to continue into a 52-week OLE at 200 mg until the first participant from the second dose group completes the 12-week trial, at which time all OLE participants will be asked to increase their dose (4-week window) to 300 mg per day. When the first participant from the third dose group completes the 12-week trial, all current OLE participants will be asked to increase their dose (4-week window) to 400 mg per day. Participants in the second dose group will start the OLE with a 1 week loading dose of 200 mg per day and be asked to increase to 300 mg per day after the first week. Participants in the third dose group will start the OLE with a 1 week loading dose of 200 mg per day and will be asked to increase to 300 mg per day after the first week and to 400 mg per day after the second week.

The OLE extends initially for 52 weeks from the last participant's entry; an additional OLE or expanded access is anticipated after this OLE to provide seamless treatment until program cessation or drug approval. Safety and efficacy assessment will continue throughout the dosing period. Down dosing related to tolerance is allowed during the OLE.

Enrollment

48 estimated patients

Sex

All

Ages

16 to 40 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Be male or female aged 16 - 40 years, inclusive, at the time of informed consent.
Have a genetically confirmed diagnosis of FA with homozygous GAA repeat expansions.
Have mFARS score ≥20 and ≤80. The screening and baseline mFARS values must fall within this range; these two values also must be within 4.5 points of each other.
Have an hs-c-troponin I above the laboratory defined 99th percentile at screening and at least 14 ng/L.
Be able to ambulate with or without assistance (If a participant uses an assistive device for the walk test on V1, the same or similar assistive device must be used on all subsequent walk tests throughout the trial).
Be able to sit upright.
Be willing and able to comply with all study procedures.
Heterosexually active women of child-bearing potential and males who are sexually active with female(s) of child-bearing potential must agree to highly effective contraception from screening until at least 30 days after the last dose of IMP for women and 90 days after the last dose of IMP for men. Acceptable highly effective methods include:
- Contraceptive implant.
- Intrauterine device (IUD), including hormonal or copper IUD.
- Bilateral salpingectomy or bilateral tubal occlusion (including tubal ligation).
- Vasectomized male partner(s) (6 months from vasectomy) with documented azoospermia.
Provide written informed consent.

Exclusion criteria

Be pregnant or lactating.
Have cognitive impairment that may interfere with compliance with study procedures.
Have swallowing impairment(s) that preclude IMP dosing.
Have significant cardiac disease, apart from mild/moderate cardiomyopathy associated with FA, including but not limited to severe or unstable heart failure (NYHA Class III/IV), unstable angina or recent myocardial infarction, significant arrhythmias, left-sided structural heart disease, valvular disease, pericardial constriction, or restrictive or congestive cardiomyopathy.
Have a history of significant QTcF prolongation or QTcF > 470 ms (females) or > 450 ms (males) at screening.
Have other active neurological diseases.
Have known untreated thyroid disease, or an abnormal thyroid panel at screening that is concerning for disease.
Have moderate or severe hepatic or renal impairment, including but not limited to eGFR < 60 mL/min/1.73 m² (by 2021 CKD-EPI) or creatinine clearance (CLcr- calculated by Cockcroft-Gault) >1.5 ULN or AST/ALT or total bilirubin >1.5x ULN at screening; retest allowed if abnormalities are potentially attributable to muscle injury.
Have uncontrolled diabetes, defined as HbA1c > 7.0%.
Have albumin below LLN (screening).
Have active infections or test positive for HIV, hepatitis B, or hepatitis C at screening.
Have clinically significant hematology or biochemistry abnormalities or any laboratory result or medical condition that, in the investigator's judgment, would increase patient risk.
Have a history of known or suspected drug or alcohol abuse within the last 2 years.
Participants currently receiving omaveloxolone are not eligible. Participants who have previously received omaveloxolone must complete a minimum of 4 week washout period prior to screening. Other background medications or supplements intended to treat FA must be on stable doses for ≥30 days before screening and be intended to remain unchanged throughout the 12-week trial treatment period.
Be taking medications with narrow therapeutic indices that are primarily metabolized by CYP2C8, CYP2C9, or CYP2C19 and cannot be reduced in dose; be taking medications with narrow therapeutic indices that are p-gp substrates. Be taking daily standard doses of strong inducers or inhibitors of CYP3A4 that cannot be modified.
Be taking dimethylfumerate or other medicinal products or supplements intended to raise FXN currently, within the past 45 days or within 5 half-lives of the medicinal product, whichever is longer
Have participated in any other interventional clinical trial or received any investigational drug in any other clinical trial within 30 days or 5 half-lives of the IMP, whichever is longer, prior to the Baseline visit.
Have undergone prior gene therapy for FA.
Have previously documented mitochondrial respiratory chain disease.
Have scheduled surgery for scoliosis or pes cavus during the clinical trial period.
Current or prior active suicidal ideation with intent or plan or suicidal behavior/attempt (within 6 months) at screening or between screening and baseline.