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.

Study Purpose:

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. 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.

Study Status:

Not yet recruiting

Disease:

Amyotrophic Lateral Sclerosis , ALS

Study Type:

Interventional

Type of Intervention:

Drug

Intervention Name:

IFB-088 50mg/day, Placebo, Riluzole 100mg/day

Placebo:

Yes

Phase:

Phase 2

Study Chair(s)/Principal Investigator(s):

Shahram Attarian, Pr, Assistance Publique Hôpitaux de Marseille (APHM) Hospital La Timone Adultes, France, Giuseppe Lauria, Pr, IRCCS Carlo Besta Institute of Milan, Italy

Clinicaltrials.gov ID:

NCT05508074

Neals Affiliated?

No

Coordinating Center Contact Information

Anne VISBECQ, MD / email hidden; JavaScript is required / 33 6 30 63 20 20

Study Sponsor:

InFlectis BioScience

Estimated Enrollment:

50

Estimated Study Start Date:

09 / 01 / 2022

Estimated Study Completion Date:

01 / 01 / 2025

Posting Last Modified Date:

08 / 19 / 2022

Date Study Added to neals.org:

08 / 19 / 2022

Minimum Age:

18 Years

Maximum Age:

N/A

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, 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 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.

CHU d'Angers

Julien CASSEREAU, Dr / 33 2 41 35 38 31 / email hidden; JavaScript is required

Angers 49100
France

CHU de Nantes - Hôpital Laennec

Claire BOUTOLEAU BRETONNIERE, Dr / 33 2 40 16 52 81 / email hidden; JavaScript is required

Nantes 44093
France

CHU Bretonneau

Philippe CORCIA, Pr / 33 2 47 47 37 24 / email hidden; JavaScript is required

Tours Cedex 1 37044
France

CHU de Toulouse - Hôpital Pierre-Paul Riquet

Pascal CINTAS, Dr / 33 5 61 77 94 40 / email hidden; JavaScript is required

Toulouse Cedex 9 31059
France

CHRU Hôpital de la Cavale Blanche

Steeve GENESTET, Dr / 33 2 98 34 73 09 / email hidden; JavaScript is required

Brest 29200
France

CHU de Nice Pasteur 2-zone C

Marie-Hélène SORIANI, Dr / 33 4 92 03 55 04 / email hidden; JavaScript is required

NICE Cedex 1 06001
France

Hôpital Pitié-Salpêtrière

François SALACHAS, Dr / 33 1 42 16 24 72 / email hidden; JavaScript is required

Paris 75013
France

Hôpital Central

Sophie PITTION- VOUYOVITCH, Dr / 33 3 83 85 16 88 / email hidden; JavaScript is required

NANCY Cedex 54035
France

APHM Hôpital La Timone Adultes SCE Maladies Neuromusculaires / SLA

Shahram ATTARIAN, Pr / 33 4 91 38 65 79 / email hidden; JavaScript is required

Marseille Cedex 05 13385
France

CHU Dupuytren

Philippe COURATIER, Pr / 33 5 55 05 65 59 / email hidden; JavaScript is required

Limoges 87042
France

Hôpital Roger Salengro - Centre SLA

Veronique DANEL-BRUNAUD, Dr / 33 3 20 44 67 52 / email hidden; JavaScript is required

LILLE cedex 59037
France

CHU de Clermont-Ferrand, Hôpital Gabriel Montpied

Nathalie GUY, Dr / 33 4 73 75 20 43 / email hidden; JavaScript is required

Clermont-Ferrand 63003
France

Hôpital Neurologique Pierre Wertheimer

Emilien BERNARD, Dr / 33 4 72 35 72 18 / email hidden; JavaScript is required

Bron 69677
France

Ospedale Civile Sant'Agostino Estense

Jessica Mandrioli, Dr / email hidden; JavaScript is required

Baggiovara 41126
Italy

Clinica Neurologica Amaducci (tertiary motor neuron Centre)

Isabella Simone, Dr / email hidden; JavaScript is required

Bari 70124
Italy

Centro Clinico NeMO per le Malattie Neuromuscolari

Massimiliano Filosto, Pr / email hidden; JavaScript is required

Gussago 25064
Italy

IRCSS Istituto Neurologico Carlo Besta

Giuseppe Lauria, Pr / email hidden; JavaScript is required

Milano 20133
Italy

AOU Università degli Studi della Campania "Luigi Vanvitelli"

Francesca Trojsi, Dr / email hidden; JavaScript is required

Napoli 80138
Italy

Sant'Andrea Hospital Unit of Neuromuscular Disorders

Giovanni Antonini, Pr / email hidden; JavaScript is required

Roma 00189
Italy

Centro Regionale Esperto per la Sclerosi Laterale Amiotrofica (C.R.E.S.L.A.)

Adriano Chiò, Pr / email hidden; JavaScript is required

Torino 10126
Italy