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
Assistance Publique - Hôpitaux de Paris
70 participants
Oct 21, 2025
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria6
- 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 Criteria17
- 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
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Interventions
Patients randomized in the experimental arm will take 1 tablet twice a day, 12 hours apart, on an empty stomach, for 12 weeks.
Patients randomized in the control arm will take 1 tablet twice a day, 12 hours apart, on an empty stomach, for 12 weeks.
Locations(9)
View Full Details on ClinicalTrials.gov
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NCT07185347