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

NCT05508074 | Completed Phase 2 Results DMC

• 2 other identifiers: P288ALS2021-003875-32
• Study Type: interventional
• Target: 51
• Locations: 2 countries
• Sites: 9

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

Keywords

IFB-088; Icerguastat; ALS; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neurodegenerative Disease

Outcome Measures

Primary Outcomes (1)

• Safety Assessment of IFB-088 50 mg/Day in Patients With Bulbar-onset ALS. Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]

  * Incidence, grade and relationship to IFB-088 for treatment emergent AEs (TEAEs), SAEs, and AESIs, * AEs leading to dose interruption or premature discontinuation.

  from beginning of IMP intake up to 30 days after stopping the intake, an average of 7 months

Secondary Outcomes (20)

• Efficacy With Scale : ALSFRS-R (ALS Functional Rating Scale Revised)

  Efficacy scale from baseline to V3 (3 months) and V4 (6 months).

• Efficacy With Scale : ALS_MITOS (ALS Milano-Torino Staging)

  baseline, V3 (3 months), V4 (6 months)

• Efficacy With Scale : King's College Scale (ALS Staging Form)

  Efficacy scale from baseline to 3 months and 6 months.

• Efficacy Based on Assessment of Respiratory Function (Slow Vital Capacity [SVC])

  Respiratory function at screening, 3 and 6 months.

• Efficacy Based on Assessment of Respiratory Function (Arterial Blood Gases [ABG]), PaCO2)

  Respiratory function at screening, 3 and 6 months.

Study Arms (2)

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

EXPERIMENTAL

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).

Drug: IFB-088 50mg/day; Drug: Riluzole 100mg/day

placebo + riluzole 100 mg/day

PLACEBO COMPARATOR

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).

Drug: Placebo; Drug: Riluzole 100mg/day

Interventions

IFB-088 50mg/day DRUG

Tested product

Also known as: IFB-088, Icerguastat

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

Placebo DRUG

Placebo

placebo + riluzole 100 mg/day

Riluzole 100mg/day DRUG

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

Also known as: Riluzole

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of probable or definite ALS according to the revised El Escorial criteria \[29\], with bulbar onset of disease, familial or sporadic form,
• Onset of symptoms ≤ 18 months prior to screening, as reported by the patient,
• Adult males or females, aged at least 18 years old,
• SVC \> 60% of predicted value for age and sex,
• ALSFRS-R score ≥ 36,
• Treatment with riluzole 100 mg/day, at stable dose since at least one month and well tolerated,
• 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,
• Patient who read, understood and signed the ICF,
• Patient who is willing to adhere to the study visit schedule and is capable to understand and comply with protocol requirements.

You may not qualify if:

• Known other significant neurological disease(s),
• 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,
• Abnormal renal function at screening defined as estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m2,
• Abnormal liver function at screening defined as total bilirubin levels \>1.5 ULN, and/or AST and/or ALT \>3 ULN,
• Neutropenia (ANC \<1.5 x 109/L) at screening,
• Other causes of neuromuscular weakness,
• Non progressive or very rapidly progressing ALS (ALSFRS-R decline from disease onset to randomisation ≤ 0.1 / month or ≥ 1.2 / month)11,
• Non-invasive ventilation,
• Tracheotomy,
• Weight loss ≥ 10% compared to weight at symptoms onset as declared by the patient or BMI \<18 kg/m2 at screening,
• Dementia or other severe active psychiatric illness, including suicidal ideation assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS),
• 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,
• Patient treated by edaravone for ALS,
• 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,
• Smoker of \> 10 cigarettes per day (e-cigarettes and nicotine patches are permitted),

Sponsors & Collaborators

• InFlectis BioScience: lead

Study Sites (9)

Hôpital Neurologique Pierre Wertheimer

Bron, 69677, France

Location

APHM Hôpital La Timone Adultes SCE Maladies Neuromusculaires / SLA

Marseille, 13385, France

Location

CHU de Nantes - Hôpital Laennec

Nantes, 44093, France

Location

CHU de Toulouse - Hôpital Pierre-Paul Riquet

Toulouse, 31059, France

Location

CHU Bretonneau

Tours, 37044, France

Location

Ospedale Civile Sant'Agostino Estense

Baggiovara, 41126, Italy

Location

Centro Clinico NeMO per le Malattie Neuromuscolari

Gussago, 25064, Italy

Location

IRCSS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

Sant'Andrea Hospital Unit of Neuromuscular Disorders

Roma, 00189, Italy

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neurodegenerative Diseases

Interventions

Riluzole

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Assessment of Body Composition (Exploratory) could not be assessed properly due to late availability of the devices. Biomarkers analysis performed by the primary laboratory plant lead to important BLQ data, important CV deviations, requiring cautious interpretation of the results. Additional biomarker analysis were performed in another lab, and were used for post hoc analysis.

Results Point of Contact

• Title: Beatrice Lejeune
• Organization: InFlectis Bioscience

beatricelejeune@inflectisbioscience.com

+33 668919060

Study Officials

• Shahram Attarian, Pr

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

  PRINCIPAL INVESTIGATOR

• Giuseppe Lauria, Pr

  IRCCS Carlo Besta Institute of Milan, Italy

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Study double-blind.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will be randomised in a 2:1 allocation ratio to receive either IFB-088 + riluzole 100 mg or placebo + riluzole 100 mg.

Study Record Dates

• First Submitted: July 27, 2022
• First Posted: August 19, 2022
• Study Start: December 2, 2022
• Primary Completion: November 14, 2024
• Study Completion: January 20, 2025
• Last Updated: October 10, 2025
• Results First Posted: October 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5); IT (4)