A Randomized, Parallel-arm, Double Blind, Placebo-controlled Study to Assess the Efficacy of Fampridine for Patients With Spinocerebellar Ataxia SCA27B Caused by a GAA Expansion in the FGF14 Gene (TREAT-FGF14)

Assistance Publique - Hôpitaux de Paris

Status and phase

Enrolling

Phase 3

Conditions

Spinocerebellar Ataxia 27B (SCA27B)

Treatments

Drug: Placebo (tablets per os)

Drug: Fampridine 10 mg prolonged-release tablet (per os)

Study type

Interventional

Funder types

Other

Identifiers

NCT07185347

APHP240921

2024-520413-53-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

Spinocerebellar ataxias 27B (SCA27B) is caused by an expansion of ≥ 250 GAA triplets in the FGF14 gene and accounts for 15% of cerebellar ataxias (around 500 patients in France). It is a late-onset form often presenting paroxysmal episodes of ataxia and/or diplopia. The disease progresses slowly, with an average increase of 0.10 points/year on the Friedreich's Ataxia Rating Scale (FARS) - Functional Staging and by 0.23 points/year on the Scale for the Assessment and Rating of Ataxia (SARA). To date, no treatment has been proven to be effective in these patients. Three open-label studies using 4-aminopyridine, have shown improvements in visual symptoms and gait in a total of 36 out of 44 patients, although these improvements were evaluated through diverse methodologies. In a subgroup of patients (n=7), administration of 4-aminopyridine resulted in a reduction in FARS - Functional Staging, ranging from 0.5 to 2 points. Notably, this beneficial effect rapidly disappearing in all patients stopping the drug. 4-aminopyridine, a potassium channel blocker, may involve restoration of cerebellar Purkinje cell rhythmic firing property, impaired with the loss of FGF14 function. Although these results appear very promising, the positive effect of 4-aminopyridine is reported only in restricted sample sizes and open-label experiences. Therefore, a robust clinical trial is necessary to provide the level of evidence required for a definitive conclusion on the benefit-risk of fampridine and before introducing the treatment into the regular patient clinical management.

Hence, to confirm the beneficial effect of 4-aminopyridine treatment, this study will compare fampridine 10 mg bid (sustained-release form) to placebo during a 3-month treatment in a randomized, double-blind, multicenter, placebo-controlled study, on functional handicap in SCA27B cerebellar ataxia patients.

Enrollment

70 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Genetic diagnosis of spinocerebellar ataxia SCA27B caused by an expansion ≥ 250 GAA repeats in the FGF14 gene
At least 18 years of age
SARA total score > 3 and score ≥ 1 on the "gait" item of the SARA scale.
Physically able and expected to complete the trial as designed and having the ability to take oral medication
Signature of informed consent
Covered by social security

Exclusion criteria

Hypersensitivity to fampridine
Hypersensitivity to any excipients present in fampridine
Serious systemic illnesses or conditions known for enhancing the side-effects of fampridine (i.e., creatinine clearance < 50 ml/min, hepatic insufficiency, medically significant heart conduction disorders such as occurrence of torsades de pointes or another severe ventricular arrhythmia, high-degree atrioventricular block (Mobitz II or complete), Brugada pattern, QTcF time of >480 msec in 3 consecutive ECG recordings taken at least 5 minutes apart, uncompensated cardiovascular disorder, epilepsy)
Unstable, clinically significant neurologic (other than the disease being studied; eg, recurrent strokes), psychiatric, cardiovascular (eg, pulmonary arterial hypertension, cardiac valvulopathy, orthostatic hypotension/tachycardia), pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, hematopoietic, or endocrine disease or other abnormality which may impact the ability of the participant to participate or potentially confound the study results.
Patients with known recurrent, active, or chronic infections.
Patients with prior history of seizure.
Concurrent treatment with other medicinal products containing fampridine (4-aminopyridine).
Concomitant use of Fampyra with medicinal products that are inhibitors or substrates of Organic Cation Transporter 2 (OCT2) for example, cimetidine.
Participation in another clinical trial with an investigational drug or receipt of an investigational product within 12 weeks or 5 times the half-life of the product (whichever is longer) prior to Baseline visit
Previous treatment with fampridine
Patients considered at risk of suicidal behavior based on the Columbia-Suicide Severity Rating Scale (C-SSRS), defined as reporting suicidal ideation with intent to act (C-SSRS items 4 or 5) within the 6 months prior to randomization, or any suicidal behavior (including actual, aborted, or interrupted attempts) within the past 12 months.
Pregnancy and breastfeeding (women in childbearing potential will have a urine pregnancy test at each visit)
Sexual non abstinence or absence of effective contraception (for child-bearing aged women, contraception using highly effective methods (see section 6.2 of the protocol) for the duration of treatment and up to 7 days after the last dose of treatment)
Inability to understand information about the protocol
Legally incapacitated adults (e.g., individuals under legal protection such as guardianship or curatorship)
Persons deprived of their liberty by judicial decision
Other ataxic syndromes than SCA27B