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Clinical Trial With Riluzole in Spinocerebellar Ataxia Type 2 (ATRIL) (ATRIL)

Primary Purpose

Spinocerebellar Ataxia Type 2

Status

Completed

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

Riluzole

Placebo

About this trial

This is an interventional treatment trial for Spinocerebellar Ataxia Type 2 focused on measuring Spinocerebellar ataxia-SCA2, SARA (Scale for the Assessment and Rating of Ataxia) score, Riluzole (Rilutek)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Genetically diagnosed SCA2 (CAG triplet in ATXN2 ≥ 33)
At least 18 years of age
Signature of informed consent
Covered by social security
SARA score ≥ 5 and ≤ 26
Age at onset ≤ 50 years old

Exclusion Criteria:

Treated with riluzole prior to the study
Hepatotoxic medication
Hypersensitivity to the active substance or to any of the excipients
Serious systemic illnesses or conditions known for enhancing the side effects of riluzole
Contraindications for MRI examination
Participation in another therapeutic trial (3 months exclusion period)
Pregnancy or breastfeeding
Non abstinence or absence of effective contraception for women
Inability to understand information about the protocol
Persons deprived of their liberty by judicial or administrative decision
Adult subject under legal protection or unable to consent
Other ataxic syndromes than SCA2

Sites / Locations

Durr

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

RILUZOLE

PLACEBO

Arm Description

Riluzole PMCS 50 mg is presented as a round, biconvex, 8 mm diameter nearly white film-coated tablet. The tablets will be held under a blister of 20 tablets.

The placebo PMCS 50 mg is presented as a round, biconvex, 8 mm diameter nearly white film-coated tablet matching the appearance of the Riluzole used in this study

Outcomes

Primary Outcome Measures

Change in Ataxia symptoms (Scale for the Assessment and Rating of Ataxia (SARA))

To compare the proportion of patients with Scale for the Assessment and Rating of Ataxia (SARA) improvement (decrease) of at least one point from baseline to 12 months

Secondary Outcome Measures

Change in Ataxia symptoms (Composite Cerebellar Functional Severity (CCFS) score)

To compare the difference of the CCFS score (Composite Cerebellar Functional Severity Score) from baseline at 12 months. A decrease is expected in the intervention group.

Change in extracerebellar symptoms (Inventory of Non-Ataxia Signs (INAS))

To compare the difference of the extracerebellar symptoms (INAS, Inventory of Non-Ataxia Signs) by showing decrease in the INAS count from baseline at 12 months

12 months survival

To compare survival of the patients between the two treatment groups at 12 months

Full Information

NCT ID

NCT03347344

First Posted

September 21, 2017

Last Updated

June 18, 2021

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT03347344

Brief Title

Clinical Trial With Riluzole in Spinocerebellar Ataxia Type 2 (ATRIL)

Acronym

ATRIL

Official Title

Multicenter, Randomized, Double Blind, Placebo Controlled Clinical Trial With Riluzole in Spinocerebellar Ataxia Type 2

Study Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Completed

Study Start Date

January 17, 2018 (Actual)

Primary Completion Date

December 14, 2020 (Actual)

Study Completion Date

December 14, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

ATRIL is a multi-centric, double-blind randomized, two-arm controlled study. 42 SpinoCerebellar Ataxia type 2 (SCA2) patients, both gender, at least 18 years of age will be included. Riluzole 50 mg will be administered (per os) twice a day, versus one group with placebo for 12 months. Riluzole (Rilutek®) is a benzothiazole drug, market approved, for Amyotrophic Lateral Sclerosis (ALS). It delays the onset of ventilator-dependence or tracheostomy in selected patients and may increase survival. Scale for the Assessment and Rating of Ataxia (SARA) will be used at M0, M6 and M12. To assess primary criterion, the percentage of patients with a decrease of at least 1 point of the SARA score between the inclusion visit, and Visit 3 (Months 12) will be calculated.

Detailed Description

Inherited cerebellar ataxias are genetically heterogeneous neurological disorders. They are characterized by ataxic gait and cerebellar dysarthria that progresses over time with loss of ambulation and speech. The mutations by expansions of CAG triplets in the genes ATXN1 (SCA1), ATXN 2 (SCA2), 3 (SCA3), CACNA1A (SCA6), ATXN 7 (SCA7), and TBP (SCA17) are responsible for 50% of hereditary forms There is no curative or preventive treatment. This phase III study is a multi-centric, double-blind randomized, two-arm controlled study (one group with 50 mg Riluzole twice a day versus one group with placebo), to measure the efficacy of treatment with riluzole in SCA2 patients during 12 months. Amelioration is defined by a 1 point decrease of the SARA score.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Spinocerebellar Ataxia Type 2

Keywords

Spinocerebellar ataxia-SCA2, SARA (Scale for the Assessment and Rating of Ataxia) score, Riluzole (Rilutek)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Multi-centric, double-blind randomized, two-arm controlled study (one group with 50 mg riluzole twice a day versus one group with placebo), during one year

Masking

ParticipantCare ProviderInvestigator

Masking Description

Treatments will be presented in numbered boxes, labeled for this study according to the Good Manufacturing Practices by the General Agency of Equipment and Health Products (AGEPS). Each numbered box will consist of 6 months of treatment: 20 blister packs of 20 active or placebo tablets

Allocation

Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

RILUZOLE

Arm Type

Experimental

Arm Description

Riluzole PMCS 50 mg is presented as a round, biconvex, 8 mm diameter nearly white film-coated tablet. The tablets will be held under a blister of 20 tablets.

Arm Title

PLACEBO

Arm Type

Placebo Comparator

Arm Description

The placebo PMCS 50 mg is presented as a round, biconvex, 8 mm diameter nearly white film-coated tablet matching the appearance of the Riluzole used in this study

Intervention Type

Drug

Intervention Name(s)

Riluzole

Intervention Description

50 mg will be administered (per os) twice a day

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

50 mg will be administered (per os) twice a day

Primary Outcome Measure Information:

Title

Change in Ataxia symptoms (Scale for the Assessment and Rating of Ataxia (SARA))

Description

To compare the proportion of patients with Scale for the Assessment and Rating of Ataxia (SARA) improvement (decrease) of at least one point from baseline to 12 months

Time Frame

at 12 months.

Secondary Outcome Measure Information:

Title

Change in Ataxia symptoms (Composite Cerebellar Functional Severity (CCFS) score)

Description

To compare the difference of the CCFS score (Composite Cerebellar Functional Severity Score) from baseline at 12 months. A decrease is expected in the intervention group.

Time Frame

at 12 months

Title

Change in extracerebellar symptoms (Inventory of Non-Ataxia Signs (INAS))

Description

To compare the difference of the extracerebellar symptoms (INAS, Inventory of Non-Ataxia Signs) by showing decrease in the INAS count from baseline at 12 months

Time Frame

at 12 months

Title

12 months survival

Description

To compare survival of the patients between the two treatment groups at 12 months

Time Frame

at 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Genetically diagnosed SCA2 (CAG triplet in ATXN2 ≥ 33) At least 18 years of age Signature of informed consent Covered by social security SARA score ≥ 5 and ≤ 26 Age at onset ≤ 50 years old Exclusion Criteria: Treated with riluzole prior to the study Hepatotoxic medication Hypersensitivity to the active substance or to any of the excipients Serious systemic illnesses or conditions known for enhancing the side effects of riluzole Contraindications for MRI examination Participation in another therapeutic trial (3 months exclusion period) Pregnancy or breastfeeding Non abstinence or absence of effective contraception for women Inability to understand information about the protocol Persons deprived of their liberty by judicial or administrative decision Adult subject under legal protection or unable to consent Other ataxic syndromes than SCA2

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

DURR Alexandra, PU-PH

Organizational Affiliation

ASSISTANCE PUBLIQUE HÖPITAUX DE PARIS

Official's Role

Principal Investigator

Facility Information:

Facility Name

Durr

City

Paris

ZIP/Postal Code

75013

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

35063116

Citation

Coarelli G, Heinzmann A, Ewenczyk C, Fischer C, Chupin M, Monin ML, Hurmic H, Calvas F, Calvas P, Goizet C, Thobois S, Anheim M, Nguyen K, Devos D, Verny C, Ricigliano VAG, Mangin JF, Brice A, Tezenas du Montcel S, Durr A. Safety and efficacy of riluzole in spinocerebellar ataxia type 2 in France (ATRIL): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2022 Mar;21(3):225-233. doi: 10.1016/S1474-4422(21)00457-9. Epub 2022 Jan 18.

Results Reference

derived

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Clinical Trial With Riluzole in Spinocerebellar Ataxia Type 2 (ATRIL)

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