Amyotrophic lateral sclerosis (bulbar-onset) MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Icerguastat
Product Code: IFB-088
Pharmaceutical Form: Tablet
INN or Proposed INN: Icerguastat
CAS Number: 469866-31-7
Current Sponsor code: IFB-088
Other descriptive name: IFB-088
Conce
Sponsors
InFlectis BioScience
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of probable or definite ALS according to the revised El Escorial criteria, 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, with score 3 or 4 for item 3 (swallowing), 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 potential who agrees to use highly effective mechanical contraception methods (condom, 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 informed consent form (ICF), 9. Patient who is willing to adhere to the study visit schedule and is capable to understand and comply with protocol requirements. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
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. Other causes of neuromuscular weakness, 4. Non progressive or very rapidly progressing ALS (ALSFRS-R decline from disease onset to randomisation = 0.1 / month or = 1.2 / month), 5. Percutaneous endoscopic gastrostomy or parenteral nutrition, 6. Non-invasive ventilation, 7. Tracheotomy, 8. Weight loss = 10% compared to weight at symptoms onset as declared by the patient or BMI 10 cigarettes per day (e-cigarettes and nicotine patches are permitted), 13. Known hypersensitivity to any of the ingredients or excipients of the investigational medicinal products (IMPs), 14. Pregnant, lactating women, 15. Patient who participated in another trial of investigational drug(s) within 30 days prior to randomisation, 16. Patient who has forfeited their freedom by administrative or legal award, or who is under guardianship or under limited judicial protection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety of IFB-088 50 mg/day in patients with bulbar-onset ALS. ;Secondary Objective: • To assess the efficacy of IFB-088 50 mg/day plus riluzole 100 mg/day versus placebo plus riluzole 100 mg/day over a 6-month period in patients with bulbar-onset ALS, • To determine pharmacokinetics (PK) parameters of IFB-088, • To investigate the effects of IFB-088 on ALS potential biomarkers, • To investigate quality of life (QoL). ;Primary end point(s): Safety endpoints include: • Incidence, grade and relationship to IFB-088 for treatment emergent AEs, SAEs, and AESIs, • AEs leading to dose interruption or premature discontinuation.;Timepoint(s) of evaluation of this end point: Safety assessments will be performed in a continuous manner during the 6 months treatment period, and at the follow-up visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: • Change in Revised ALS functional rating scale (ALSFRS-R) score from baseline to month 3 and to month 6, • Worsening according to ALS-Milano-Torino staging system (MITOS) score, i.e. progression to a higher stage at 3 and at 6 months compared to the baseline, • Change in King’s College score from baseline to month 3 and to month 6, • Assessment of respiratory function (slow vital capacity [SVC], sniff test [optional], arterial blood gases [ABG]): exploratory endpoint. PK parameters: • Plasma concentration of IFB-088 and IFB-139, • AUC of IFB-088 and IFB-139, • Maximum observed plasma concentration (Cmax), with associated Tmax, • Terminal or apparent terminal half-life (t1/2), • Apparent systemic clearance, apparent volume of distribution. Biomarkers: • Change in TDP-43 plasmatic concentration from baseline to 6 months, compared to placebo, • Change in neurofilament (NfL) light chain plasmatic concentration from baseline to 6 months, compared to placebo, • Change in plasmatic (neuro)inflammatory biomarkers from baseline to 3 months, and from baseline to 6 months, compared to placebo, • Change in plasmatic oxidative stress biomarkers from baseline to 3 months and from baseline to 6 months, compared to placebo. QoL: • Change in ALS assessment questionnaire (ALSAQ-40) from baseline to 6 months.;Timepoint(s) of evaluation of this end point: Efficacy: •Change in Revised ALS functional rating scale (ALSFRS-R) score from baseline to month 3 and to month 6, •Worsening according to ALS-Milano-Torino staging system (MITOS) score, i.e. progression to a higher stage at 3 and at 6 months compared to the baseline, •Change in King’s College score from baseline to month 3 and to month 6, •Assessment of respiratory function (slow vital capacity [SVC], sniff test [optional], arterial blood gases [ABG]). At screening, V2 and V3. PK parameters at V1. Biomarkers changes from baseline to 3 and/or 6 months compared to placebo. QoL change in ALS | — |
Countries
France, Italy
Contacts
Public ContactAnne Visbecq
InFlectis BioScience
Outcome results
None listed