Treatment Combining Riluzole and IFB-088 in Bulbar Amyotrophic Lateral Sclerosis (TRIALS Protocol)

NCT ID: NCT05508074

Last Updated: 2025-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-02
• Study Completion Date: 2025-01-20

Brief Summary

Prospective, international, randomised, double-blind, placebo controlled, multicentre, parallel group study. Patients will be randomised in a 2:1 allocation ratio to receive either IFB-088 + riluzole 100 mg or placebo + riluzole 100 mg. This clinical trial is an exploratory study, designed to show a signal of efficacy of IFB-088 through ALSFRS-R, MITOS and King's College. Respiratory function will be followed through SVC. Biomarkers and quality of life will also be evaluated throughout the study.

Patients will be treated over a 6-month period. After a screening/consent visit, patients will undergo clinic visits at randomisation (V0), at 2 weeks (V1), and at months 1 (V2), 3 (V3) and 6 (V4). One week after V0, the patient will undergo urine analysis (dipstick)and blood sampling for measurement of creatinine

, as well as blood sampling for measurement of creatinine and calculation of eGFR at months 2, 4 and 5. At the V2 visit, in addition to other assessments, patients will undergo blood sampling for PK measurements and urine sampling for crystalluria examination. Blood and urine chemistry, as well as physical examination and vital signs assessment to assess safety will be performed at each visit for safety purpose and crystalluria examination will be repeated at the follow-up visit, performed one month ± one week after V4.

Conditions

Amyotrophic Lateral Sclerosis; ALS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

IFB-088 50 mg/day + riluzole 100 mg/day

The test product, IFB-088, will be administered orally in 50 mg/day dosage consisting of two uptakes of 25 mg each (morning and evening uptakes), as an add-on therapy to riluzole 100 mg.

Intervals for dosing should ideally be about 12 hours (± one hour). Tablets will be swallowed with a glass of water 30 minutes before the meal, in fasting condition.

Administration of riluzole 100 mg, tablet or suspension, will be at the patient's and/or investigator's choice, as per summary of product characteristics. The daily dose of 100 mg will be taken in two 50 mg doses every 12 hours, at the same time than the IMPs.

Patients will be treated for a period of 6 months (26 weeks).

Group Type: EXPERIMENTAL

IFB-088 50mg/day

Intervention Type: DRUG

Tested product

Riluzole 100mg/day

Intervention Type: DRUG

Standard of care treatment, co-administered with tested product (IFB-088 50mg/day) or placebo

placebo + riluzole 100 mg/day

The placebo will be administered orally in two uptakes (morning and evening uptakes), as an add-on therapy to riluzole 100 mg.

Intervals for dosing should ideally be about 12 hours (± one hour). Tablets will be swallowed with a glass of water 30 minutes before the meal, in fasting condition.

Administration of riluzole 100 mg, tablet or suspension, will be at the patient's and/or investigator's choice, as per summary of product characteristics. The daily dose of 100 mg will be taken in two 50 mg doses every 12 hours, at the same time than the IMPs.

Patients will be treated for a period of 6 months (26 weeks).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Riluzole 100mg/day

Intervention Type: DRUG

Standard of care treatment, co-administered with tested product (IFB-088 50mg/day) or placebo

Interventions

IFB-088 50mg/day

Tested product

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Riluzole 100mg/day

Standard of care treatment, co-administered with tested product (IFB-088 50mg/day) or placebo

Intervention Type: DRUG

Other Intervention Names

IFB-088; Icerguastat; Riluzole

Eligibility Criteria

Inclusion Criteria

1. Diagnosis of probable or definite ALS according to the revised El Escorial criteria [29], with bulbar onset of disease, familial or sporadic form,

2. Onset of symptoms ≤ 18 months prior to screening, as reported by the patient,

3. Adult males or females, aged at least 18 years old,

4. SVC > 60% of predicted value for age and sex,

5. ALSFRS-R score ≥ 36,

6. Treatment with riluzole 100 mg/day, at stable dose since at least one month and well tolerated,

7. Male or female patient of childbearing potential10 who agrees to use highly effective mechanical contraception methods (sexual abstinence, intrauterine device, bilateral tubal occlusion, vasectomised partner) throughout the study, and for 3 months after the end of the treatment,

8. Patient who read, understood and signed the ICF,

9. Patient who is willing to adhere to the study visit schedule and is capable to understand and comply with protocol requirements.

Exclusion Criteria

1. Known other significant neurological disease(s),

2. Serious illness(es) or medical condition(s) (e.g. unstable cardiac disease, cancer, hematologic disease, hepatitis or liver failure, renal failure) that is not stabilised or that could require hospitalisation and may jeopardise the participation in the study,

3. Abnormal renal function at screening defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2,

4. Abnormal liver function at screening defined as total bilirubin levels >1.5 ULN, and/or AST and/or ALT >3 ULN,

5. Neutropenia (ANC <1.5 x 109/L) at screening,

6. Other causes of neuromuscular weakness,

7. Non progressive or very rapidly progressing ALS (ALSFRS-R decline from disease onset to randomisation ≤ 0.1 / month or ≥ 1.2 / month)11,

8. Non-invasive ventilation,

9. Tracheotomy,

10. Weight loss ≥ 10% compared to weight at symptoms onset as declared by the patient or BMI <18 kg/m2 at screening,

11. Dementia or other severe active psychiatric illness, including suicidal ideation assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS),

12. Patient with a significant pulmonary disorder not attributed to ALS or who require treatments that might complicate the evaluation of the effect of ALS on respiratory function,

13. Patient treated by edaravone for ALS,

14. Patient using unauthorised concomitant treatments, namely moderate or strong inhibitors or inducers of CYP1A2, strong inhibitors or inducers of CYP2D6 or 2C19 and strong inhibitors of OCT2, as listed in Section 6.2. Combined oral contraceptives containing ethinylestradiol are forbidden concomitant medications,

15. Smoker of > 10 cigarettes per day (e-cigarettes and nicotine patches are permitted),

16. Known hypersensitivity to any of the ingredients or excipients of the IMPs,

17. Pregnant, lactating women,

18. Patient who participated in another trial of investigational drug(s) within 30 days prior to randomisation, or 5 half-lives of the previous investigational product, whichever is longer,

19. Patient who has forfeited their freedom by administrative or legal award, or who is under guardianship or under limited judicial protection.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

InFlectis BioScience

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shahram Attarian, Pr

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique Hôpitaux de Marseille (APHM) Hospital La Timone Adultes, France

Giuseppe Lauria, Pr

Role: PRINCIPAL_INVESTIGATOR

IRCCS Carlo Besta Institute of Milan, Italy

Locations

Hôpital Neurologique Pierre Wertheimer

Bron, , France

APHM Hôpital La Timone Adultes SCE Maladies Neuromusculaires / SLA

Marseille, , France

CHU de Nantes - Hôpital Laennec

Nantes, , France

CHU de Toulouse - Hôpital Pierre-Paul Riquet

Toulouse, , France

CHU Bretonneau

Tours, , France

Ospedale Civile Sant'Agostino Estense

Baggiovara, , Italy

Centro Clinico NeMO per le Malattie Neuromuscolari

Gussago, , Italy

IRCSS Istituto Neurologico Carlo Besta

Milan, , Italy

Sant'Andrea Hospital Unit of Neuromuscular Disorders

Roma, , Italy

Countries

France; Italy

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2021-003875-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P288ALS

Identifier Type: -

Identifier Source: org_study_id