Amyotrophic Lateral SclerosisPhase 2NCT05508074
Treatment Combining Riluzole and IFB-088 in Bulbar Amyotrophic Lateral Sclerosis (TRIALS Protocol)
A Phase 2 study testing IFB-088 50mg/day and Riluzole 100mg/day in people with Amyotrophic Lateral Sclerosis and ALS, run by InFlectis BioScience at 9 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis, ALS
- What is being tested?
- IFB-088 50mg/day and Riluzole 100mg/day
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 2 Dec 2022to 20 Jan 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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,
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- 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.
Who cannot join
- 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,
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- 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),
- Known hypersensitivity to any of the ingredients or excipients of the IMPs,
- Pregnant, lactating women,
- 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,
- Patient who has forfeited their freedom by administrative or legal award, or who is under guardianship or under limited judicial protection.
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
France5 sites
Hôpital Neurologique Pierre Wertheimer
Bron, 69677
APHM Hôpital La Timone Adultes SCE Maladies Neuromusculaires / SLA
Marseille, 13385
CHU de Nantes - Hôpital Laennec
Nantes, 44093
CHU de Toulouse - Hôpital Pierre-Paul Riquet
Toulouse, 31059
CHU Bretonneau
Tours, 37044
Italy4 sites
Ospedale Civile Sant'Agostino Estense
Baggiovara, 41126
Centro Clinico NeMO per le Malattie Neuromuscolari
Gussago, 25064
IRCSS Istituto Neurologico Carlo Besta
Milan, 20133
Sant'Andrea Hospital Unit of Neuromuscular Disorders
Roma, 00189
About this study
Official title: A Double-blind, Placebo-controlled, Exploratory Randomised Clinical Trial to Assess the Safety and Efficacy of IFB-088 Plus Riluzole 100 mg vs Placebo Plus Riluzole 100 mg in Patients With Bulbar-onset Amyotrophic Lateral Sclerosis.
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
- Being tested
- IFB-088 50mg/day, Placebo, Riluzole 100mg/day
- Keywords
- IFB-088, Icerguastat, ALS, Amyotrophic Lateral Sclerosis, Motor Neuron Disease, Neurodegenerative Disease
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease, Neurodegenerative Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IFB-088 50mg/dayDrug
Also called IFB-088, Icerguastat
Tested product
PlaceboDrug
Placebo
Riluzole 100mg/dayDrug
Also called Riluzole
Standard of care treatment, co-administered with tested product (IFB-088 50mg/day) or placebo
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: Placebo; Drug: Riluzole 100mg/day |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised) 12 items, clinician rated including 5 choices from normal to disabled.
Maximal score: 48, minimal score: 0 (death)
Measured: Efficacy scale from baseline to V3 (3 months) and V4 (6 months).
Efficacy With Scale : ALS_MITOS (ALS Milano-Torino Staging)
ALS_MITOS (Amyotrophic Lateral Sclerosis Milano-Torino Staging) scale scores the total points of points given in 4 domains (movement, swallowing, communicating, breathing), clinician rated. The ALS8MITOS score is determined by the sum of functional score of 1 for each domain, up to 5, being death. The score may go from 0= no functionnal domain lost, up to 5=death (1 to 4 corresponding to the number of domains lost by the patient).
Measured: baseline, V3 (3 months), V4 (6 months)
Efficacy With Scale : King's College Scale (ALS Staging Form)
King's college Scale (King's ALS staging form), clinician rated, 8 items. 0=best, 5=death
Measured: Efficacy scale from baseline to 3 months and 6 months.
Efficacy Based on Assessment of Respiratory Function (Slow Vital Capacity [SVC])
Assessment of respiratory function (slow vital capacity [SVC]).
Measured: Respiratory function at screening, 3 and 6 months.
Efficacy Based on Assessment of Respiratory Function (Arterial Blood Gases [ABG]), PaCO2)
Assessment of respiratory function (Arterial Blood Gases [ABG]): description of PaCO2 (mmHg), at screening, 3 and 6 months.
Measured: Respiratory function at screening, 3 and 6 months.
Efficacy Based on Assessment of Body Composition (Exploratory)
change of body composition (% of water, muscle, bone in the body) evaluated by bioelectrical impedance
Measured: At baseline and 6 months
Pharmacokinetic Parameters (Area Under Curve [AUC])
Area Under the Curve (AUC (0-12h)) of IFB-088 and its metabolite IFB-139. As study was double blinded, the analysis was done on all the patients, either receiving IFB-088 or placebo.
Dosage of IFB-088 in patients under placebo was equal to 0 ng.h/mL.
Measured: PK parameters will be analysed after 4 weeks of treatment. Blood samples were collected at V2 (5 samples/patient: pre-IMP dose, and at one, 2, 4 and 6 hours post dose).
Pharmacokinetic Parameters (Cmax)
Maximum observed plasma concentration (Cmax) of IFB-088 and its metabolite IFB-139.
As study was double blinded, the analysis was done on all the patients, either receiving IFB-088 or placebo.
Dosage of IFB-088 in patients under placebo was equal to 0 ng/mL.
Measured: PK parameters will be analysed after 4 weeks of treatment. Blood samples were collected at V2 (5 samples/patient: pre-IMP dose, and at one, 2, 4 and 6 hours post dose).
Pharmacokinetic Parameters (Tmax)
Time at which maximum plasma concentration (Cmax) of IFB-088 and its metabolite IFB-139 is measured As study was double blinded, the analysis was done on all the patients, either receiving IFB-088 or placebo.
Dosage of IFB-088 in patients under placebo was equal to 0 h
Measured: PK parameters will be analysed after 4 weeks of treatment. Blood samples were collected at V2 (5 samples/patient: pre-IMP dose, and at one, 2, 4 and 6 hours post dose).
Pharmacokinetic Parameters (t1/2)
Terminal or apparent terminal half-life (t1/2) of IFB-088 and its metabolite IFB-139.
As study was double blinded, the analysis was done on all the patients, either receiving IFB-088 or placebo.
Dosage of IFB-088 in patients under placebo was equal to 0 h.
Measured: PK parameters will be analysed after 4 weeks of treatment. Blood samples were collected at V2 (5 samples/patient: pre-IMP dose, and at one, 2, 4 and 6 hours post dose).
Pharmacokinetic Parameters (Clearance)
IFB-088 Apparent systemic clearance calculation (CL/F) As study was double blinded, the analysis was done on all the patients, either receiving IFB-088 or placebo.
Dosage of IFB-088 in patients under placebo was equal to 0 L/h.
Measured: PK parameters will be analysed after 4 weeks of treatment. Blood samples were collected at V2 (5 samples/patient: pre-IMP dose, and at one, 2, 4 and 6 hours post dose).
Pharmacokinetic Parameters (Vd)
IFB-088 Apparent volume of distribution (Vd). As study was double blinded, the analysis was done on all the patients, either receiving IFB-088 or placebo.
Dosage of IFB-088 in patients under placebo was equal to 0 L.
Measured: PK parameters will be analysed after 4 weeks of treatment.
Biomarkers (TDP-43)
Change in TDP-43 plasmatic concentration from baseline to 6 months, compared to placebo (concentration in pg/mL, technology Simoa®).
Measured: At baseline and 6 months.
Biomarkers (Neurofilament Light Chain)
Change in neurofilament (NfL) light chain plasmatic concentration from baseline to 6 months, compared to placebo (concentration in pg/mL, technology Simoa®).
Measured: At baseline and 6 months.
Biomarkers (Inflammation Biomarkers)
Inflammation biomarkers (interleukin [IL]-6, tumour necrosis factor-α [TNFα], interferon γ [IFNγ], IL-1β, IL-8, IL-10, monocyte chemoattractant protein-1 [MCP-1], nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor [VEGF]): (concentration of each biomarker in ng/mL, technology Luminex®)).
Measured: All assessed at baseline and V4 visit (6 months). Only GDF15, MCP1, BDNF, and TGFb1 also assessed at V3 visit (3 months)
Biomarkers (3-Nitrotyrosine)
3-Nitrotyrosine (Oxidative stress biomarker): at baseline, 3 and 6 months (concentration in ng/mL, ELISA method).
Measured: At baseline, 3 months, and 6 months.
Quality of Life With ALSAQ-40 (ALS Assessment Questionnaire)
Change in ALS assessment questionnaire (ALSAQ-40). ALSAQ-40 (Amyotrophic Lateral Sclerosis Assessment Questionnaire) Quality of Life questionnaire 40 items, patient rated including 5 choices from never to always.
best=0, worse=100
Measured: QoL will be assessed from baseline to 6 months
Efficacy Based on Assessment of Respiratory Function (Arterial Blood Gases [ABG]), PO2 (mmHg)
Assessment of respiratory function (Arterial Blood Gases [ABG]): description of PO2 (mmHg) at screening, 3 and 6 months.
Measured: Respiratory function at screening, 3 and 6 months.
Efficacy Based on Assessment of Respiratory Function (Arterial Blood Gases [ABG]), HCO3 (mEq/L)
Assessment of respiratory function (Arterial Blood Gases [ABG]): description of HCO3 (mEq/L) at screening, 3 and 6 months.
Measured: Respiratory function at screening, 3 and 6 months.
Efficacy Based on Assessment of Respiratory Function (Arterial Blood Gases [ABG]), Oxygen Saturation (%)
Assessment of respiratory function (Arterial Blood Gases [ABG]): description of Oxygen saturation (%) at screening, 3 and 6 months.
Measured: Respiratory function at screening, 3 and 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2022
- Study start2 Dec 2022
- Primary completion14 Nov 2024
- Study completion20 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomised in a 2:1 allocation ratio to receive either IFB-088 + riluzole 100 mg or placebo + riluzole 100 mg.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- InFlectis BioScience
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shahram Attarian, Pr, Principal investigator, Assistance Publique Hôpitaux de Marseille (APHM) Hospital La Timone Adultes, FranceGiuseppe Lauria, Pr, Principal investigator, IRCCS Carlo Besta Institute of Milan, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05508074
- Sponsor's protocol ID
- P288ALS
- Other IDs
- 2021-003875-32
- Status last verified
- Jul 2025
- First submitted
- 27 Jul 2022
- Last updated
- 10 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No