An international research study to assess the safety and efficacy of a new multiple sclerosis medication called Fenebrutinib compared to the standard medication Teriflunomide (Aubagio®) in adult patients with relapsing multiple sclerosis.

Algeria, Argentina, China, Dominican Republic, Egypt, Finland, France, Georgia, Germany, Hong Kong, Hungary, Italy, Kenya, Mexico, Morocco, Netherlands, North Macedonia, Peru, Poland, Portugal, Russian Federation, Serbia, Spain, Switzerland, Taiwan, Tunisia, Ukraine, United States (ICTRP)

ID di studio ICTRP
EUCTR2019-004857-10 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
A PHASE III MULTICENTER, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PARALLEL-GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF FENEBRUTINIB COMPARED WITH TERIFLUNOMIDE IN ADULT PATIENTS WITH RELAPSING MULTIPLE SCLEROSIS (BASEC)

Titolo accademico
A PHASE III MULTICENTER, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PARALLEL-GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF FENEBRUTINIB COMPARED WITH TERIFLUNOMIDE IN ADULT PATIENTS WITH RELAPSING MULTIPLE SCLEROSIS (ICTRP)

Titolo pubblico
To Evaluate the Efficacy and Safety of Fenebrutinib Compared with Teriflunomide in Adult Patients with Relapsing Multiple Sclerosis (ICTRP)

Malattie studiate
Relapsing multiple sclerosis (RMS)
MedDRA version: 20.0Level: PTClassification code 10048393Term: Multiple sclerosis relapseSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 27.0Level: PTClassification code 10080700Term: Relapsing multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders;Therapeutic area: Diseases [C] - Immune System Diseases [C20] (ICTRP)

Intervento studiato

Product Name: fenebrutinib
Product Code: RO7010939
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: FENEBRUTINIB
Current Sponsor code: RO7010939
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Aubagio
Product Name: Teriflunomide
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: TERIFLUNOMIDE
CAS Number: 108605-62-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 14-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

(ICTRP)

Tipo di studio
Interventional clinical trial of medicinal product (ICTRP)

Disegno dello studio
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Double-Dummy If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: Aubagio Number of treatment arms in the trial: 2 (ICTRP)

Criteri di inclusione/esclusione
Gender:
Female: yes
Male: yes

Inclusion criteria:
? Age 18-55 years
? Expanded Disability Status Scale score (EDSS) of 0.0-5.5 at screening
? A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria
? Neurologically stable for at least 30 days prior to randomization and baseline assessments
? Ability to complete the 9-HPT for each hand in < 240 seconds
? Ability to perform the timed 25-Foot Walk Test in <150 seconds
? For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs, women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period, for 8 weeks after the final dose of study medication, and until the teriflunomide elimination protocol is completed
? For men: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm, with a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment phase, for 8 weeks after the final dose of study drug, and until completion of the teriflunomide elimination protocol. Men must also refrain from donating sperm during this same period
OLE Inclusion Criteria:
? Completed the Double-Blind Treatment (DBT) phase of the study (remaining on study treatment; no other Disease-Modifying Therapy (DMT) administered) and who, in the opinion of the investigator, may benefit from treatment with fenebrutinib.
? Patients randomized to the teriflunomide treatment arm during the DBT phase must undergo the ATEP prior to the first administration of open-label fenebrutinib
? For female participants of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs, women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period, the OLE treatment phase and for 28 days after the final dose of open-label fenebrutinib. Women must also refrain from donating eggs during this same period
? For male participants: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm, with a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment phase, OLE treatment phase and for 28 days after the final dose of open-label fenebrutinib to avoid exposing the embryo. Men must also refrain from donating sperm during this same period
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 736
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
(ICTRP)

Exclusion criteria:
? A diagnosis of PPMS or non-active SPMS
? Disease duration of > 10 years from the onset of symptoms and an EDSS score at screening < 2.0
? Any known or suspected active infection at screening or baseline, or any major episode of infection requiring hospitalization or treatment with IV anti-microbials within 8 weeks prior to and during screening or treatment with oral anti-microbials within 2 weeks prior to and during screening. Onychomycosis is not exclusionary unless it is being treated with systemic therapy
? History of cancer including hematologic malignancy and solid tumors within 10 years of screening.
? Known presence of other neurological disorders that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study, clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal disease
? Any concomitant disease that may require chronic treatment with systemic corticosteroids, or immunosuppressants during the course of the study
? History of alcohol or other drug abuse within 12 months prior to screening
? Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period
? Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization
? Female participants who are pregnant or breastfeeding or intending to become pregnant during the study or 8 weeks (with ATEP) after final dose of study drug
? Male participants intending to father a child during the study or 8 weeks (with ATEP) after final dose of study drug
? Presence of cirrhosis (Child-Pugh Class A, B, or C) or Gilbert's Syndrome


Endpoint primari e secondari
Main Objective: ? To evaluate the efficacy of fenebrutinib compared with teriflunomide on the basis of annualized relapse rate (ARR);Secondary Objective: ? To evaluate the efficacy of fenebrutinib treatment compared with teriflunomide on the basis of time to onset of composite 24-week confirmed composite disability progression (cCDP24), time to onset of composite 12-week confirmed disability progression (cCDP12), time to onset of 12-week confirmed disability progression (CDP12), time to onset of 24-week CDP (CDP24), total number of T1Gd+ lesions as detected by MRI, total number of new and/or enlarging T2-weighted lesions as detected by MRI, rate of percent change in total brain volume from Week 24 as assessed by MRI, change in patient-reported physical impacts of MS, time to onset of 12-week confirmed 4-point worsening in Symbol Digit Modalities Test (SDMT) score, change from baseline to Week 48 in the concentration of serum neurofilament light chain (NfL)
? To evaluate the safety of fenebrutinib compared with teriflunomide
? To characterize the fenebrutinib pharmacokinetics profile;Primary end point(s): 1. Annualized relapse rate
;Timepoint(s) of evaluation of this end point: 1. 96 Weeks (ICTRP)

Secondary end point(s): 1. Time to onset of cCDP12
2. Time to onset of CDP12
3. Time to onset of cCDP24
4. Time to onset of CDP24
5. Total number of gadolinium-enhancing lesions on T1-weighted MRI lesions as detected by MRI
6. Total number of new and/or enlarging T2-weighted lesions as detected by MRI
7. Rate of percent change in total brain volume from Week 24 as assessed by MRI
8. Rate of change from baseline in patient-reported physical impacts of MS, as measured by the Multiple Sclerosis Impact Scale (29-Item), Version 2 (MSIS-29 v2) physical scale)
9. Time to onset of 12-week confirmed 4-point worsening in SDMT score
10. Change from baseline to Week 48 in the concentration of serum neurofilament light chain (NfL)
11. The nature, frequency, timing, and severity of adverse events; serious adverse events; and adverse events leading to study treatment discontinuation or dose interruptions
12. Change from baseline in targeted vital signs
13. Change from baseline in targeted ECG parameters
14. Change from baseline in clinical laboratory results
15. Proportion of patients with suicidal ideation or behavior
16. Plasma concentration of fenebrutinib at specified timepoints;Timepoint(s) of evaluation of this end point: 1-2. Time from baseline to the first occurrence of a progression event and must be confirmed at least 12 weeks after the initial disability progression
3-4. Time from baseline to first occurrence of a progression event and must be confirmed at least 24 weeks after initial disability progression
5-6. Timepoints up to primary analysis
7. Week 24 to Week 96
8. At baseline, Week 12, 24, 36, 48, 60, 72, 84, 96
9. Time from baseline to first occurrence of 4-point worsening in SDMT event and must be confirmed at least 12 weeks after the initial event
10. Baseline to Week 48
11. Baseline to primary analysis
12-15. From baseline to primary analysis
16. Week 4, 12, 24, 48, 72, 96 and at treatment discontinuation, unscheduled visit (ICTRP)

Data di registrazione
11.12.2020 (ICTRP)

Inclusione del primo partecipante
29.03.2021 (ICTRP)

Sponsor secondari
non disponibile

Contatti aggiuntivi
Trial Information Support Line-TISL, global.rochegenentechtrials@roche.com, F. Hoffmann-La Roche Ltd (ICTRP)

ID secondari
GN41851, NCT04586010, 2019-004857-10-FI (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-004857-10 (ICTRP)