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

• Fampridine 10 mg prolonged-release tablet (per os) (Drug): Patients randomized in the experimental arm will take 1 tablet twice a day, 12 hours apart, on an empty stomach, for 12 weeks.
• Placebo (tablets per os) (Drug): Patients randomized in the control arm will take 1 tablet twice a day, 12 hours apart, on an empty stomach, for 12 weeks.

Primary outcomes

• Proportion of patients showing an improvement of at least 0.5 point on the Friedreich's Ataxia Rating Scale (FARS) -Functional Staging at week 12 [At week 12]

Secondary outcomes

• Improvement of at least 0.5 point on the Friedreich's Ataxia Rating Scale (FARS) -Functional Staging at week 2 [At week 2]
• Variation in cerebellar syndrome assessed by the Scale for the assessment and rating of ataxia (SARA) at week 2 and week 12 [At week 2 and week 12]
• Variation in cerebellar syndrome assessed by the modified Friedreich Ataxia Rating Scale (mFARS) at week 2 and week 12 [At week 2 and week 12]
• Variation in cerebellar syndrome assessed by the Composite Cerebellar Functional Severity Score (CCFS score) at week 2 and week 12 [At week 2 and week 12]
• Variation in extracerebellar signs assessed by the Inventory of Non-Ataxia Signs (INAS) at week 12 [At week 12]
• Variation on Timed 25-foot walk (T25FW) at week 2 and week 12 [At week 2 and week 12]
• Variation in oculomotor signs assessed by the Scale for Ocular motor Disorders in Ataxia (SODA) at week 2 and week 12 [At week 2 and week 12]
• Variation in oculomotor signs assessed by oculomotor recording (OMR) at week 2 and week 12 [At week 2 and week 12]
• Variation in daily frequency of diplopia assessed on a Numerical Diplopia Rating Scale (NDRS) at week 2 and week 12 [At week 2 and week 12]
• Variation in daily living activities evaluated by the FARS -Activities of Daily Living scale (FARS-ADL) at week 12 [At week 12]
• Quality of life evaluated by the Patient Reported Outcome Measure of Ataxia (PROM-ATAXIA) questionnaire at week 12 [At week 12]
• Quality of life evaluated by the 36-Item Short Form Health Survey (SF-36) questionnaire at week 12 [At week 12]
• Patient's impression evaluated by the Patient Global Impression of change (PGI-C) at week 2 and week 12 [At week 2 and week 12]
• Clinician's impression evaluated by the Clinician Global Impression of Change (CGI-C) at week 2 and week 12 [At week 2 and week 12]
• Tolerance to the investigational drug [At week 2 and week 12]: Tolerance will be evaluated through clinical examination, blood analysis, and electrocardiogram (ECG) performed at Week 2 and Week 12. In addition, adverse events will be systematically recorded throughout the study period.
• Clinical assessments at week 16, i.e. 4 weeks after treatment interruption [At week 16]
• Variation in cerebellar syndrome assessed by the FARS-Functional Staging at week 16, i.e. 4 weeks after treatment interruption [At week 16]
• Variation in cerebellar syndrome assessed by the SARA scale at week 16, i.e. 4 weeks after treatment interruption [At week 16]
• Variation in cerebellar syndrome assessed by the mFARS scale at week 16, i.e. 4 weeks after treatment interruption [At week 16]
• Variation in cerebellar syndrome assessed by the CCFS score at week 16, i.e. 4 weeks after treatment interruption [At week 16]
• Variation in extracerebellar signs assessed by the Inventory of Non-Ataxia Signs (INAS) at week 16, i.e. 4 weeks after treatment interruption [At week 16]
• Variation on Timed 25-foot walk (T25FW) at week 16, i.e. 4 weeks after treatment interruption [At week 16]
• Variation in oculomotor signs assessed by the Scale for Ocular motor Disorders in Ataxia (SODA) at week 16, i.e. 4 weeks after treatment interruption [At week 16]
• Variation in oculomotor signs assessed by oculomotor recording (OMR) at week 16, i.e. 4 weeks after treatment interruption [At week 16]
• Variation in daily frequency of diplopia assessed on a Numerical Diplopia Rating Scale (NDRS) at week 16, i.e. 4 weeks after treatment interruption [At week 16]
• Variation in daily living activities evaluated by the FARS -Activities of Daily Living scale at week 16, i.e. 4 weeks after treatment interruption [At week 16]
• Quality of life evaluated by the PROM-ATAXIA questionnaire at week 16, i.e. 4 weeks after treatment interruption [At week 16]
• Quality of life evaluated by the 36-Item Short Form Health Survey (SF-36) questionnaire at week 16, i.e. 4 weeks after treatment interruption [At week 16]
• Patient's impression evaluated by the Patient Global Impression of change (PGI-C) at week 16, i.e. 4 weeks after treatment interruption [At week 16]
• Clinician's impression evaluated by the Clinician Global Impression of Change (CGI-C) at week 16, i.e. 4 weeks after treatment interruption [At week 16]

Sex: All, ages: 18 Years to any

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

• Giulia COARELLI, Principal investigator, Assistance Publique - Hôpitaux de Paris (AP-HP)