A global Phase III study to investigate the safety and efficacy of a higher dose of the approved multiple sclerosis medication Ocrelizumab (Ocrevus®) in adult patients with relapsing multiple sclerosis.

Identifiant de l'essai ICTRP
EUCTR2020-000893-69 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
PROTOCOL BN42082: A PHASE IIIB MULTICENTER, RANDOMIZED, DOUBLE-BLIND, CONTROLLED STUDY TO EVALUATE THE EFFICACY, SAFETY AND PHARMACOKINETICS OF A HIGHER DOSE OF OCRELIZUMAB IN ADULTS WITH RELAPSING MULTIPLE SCLEROSIS (BASEC)

Titre académique
A PHASE IIIB MULTICENTER, RANDOMIZED, DOUBLE-BLIND, CONTROLLED STUDY TO EVALUATE THE EFFICACY, SAFETY AND PHARMACOKINETICS OF A HIGHER DOSE OF OCRELIZUMAB IN ADULTS WITH RELAPSING MULTIPLE SCLEROSIS (ICTRP)

Titre public
A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults with Relapsing Multiple Sclerosis (ICTRP)

Maladie en cours d'investigation
Relapsing Multiple Sclerosis (MS)
MedDRA version: 20.1Level: PTClassification code 10028245Term: Multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 21.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0Level: PTClassification code 10048393Term: Multiple sclerosis relapseSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.1Level: LLTClassification code 10039720Term: Sclerosis multipleSystem Organ Class: 10029205 - Nervous system disorders;Therapeutic area: Diseases [C] - Nervous System Diseases [C10] (ICTRP)

Intervention étudiée

Trade Name: Ocrevus
Product Name: Ocrelizumab
Product Code: RO4964913/F07-01
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Ocrelizumab
CAS Number: 637334-45-3
Current Sponsor code: RO4964913
Other descriptive name: OCRELIZUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

(ICTRP)

Type d'essai
Interventional clinical trial of medicinal product (ICTRP)

Plan de l'étude
Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Ocrelizumab approved dose compared to higher dose Number of treatment arms in the trial: 2 (ICTRP)

Critères d'inclusion/exclusion
Gender:
Female: yes
Male: yes

Inclusion criteria:
? Ages 18-55 years at time of screening
? Ability to comply with the study protocol
? Diagnosis of RMS (i.e., RRMS or aSPMS where patients still experience relapses)in accordance with the revised McDonald Criteria 2017
? At least two documented clinical relapses within the last 2 years prior to screening, or one clinical relapse in the year prior to screening (with no relapse 30 days prior to screening and at baseline)
? Patients must be neurologically stable for at least 30 days prior to randomization and baseline assessments
? Expanded disability status scale (EDSS) score, at screening and baseline, from 0 to 5.5 inclusive
- Average T25FWT score over two trials at screening and over two trials at baseline respectively, up to 150 (inclusive) seconds
? Average 9HPT score over four trials at screening and over four trials at baseline respectively, up to 250 (inclusive) seconds
? Documented MRI of brain with abnormalities consistent with MS at screening
- Participants requiring symptomatic treatment for MS and/or physiotherapy must be treated at a stable dose. No initiation of symptomatic treatment for MS or physiotherapy within 4 weeks of randomization
- For females of childbearing potential, agreement to remain abstinent or use adequate contraceptive method.
? For female patients without reproductive potential: Females may be enrolled if post menopausal unless the patient is receiving a hormonal therapy for her menopause or if surgically sterile.

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 786
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
(ICTRP)

Exclusion criteria:
? History of primary progressive MS at screening
? 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
? History of confirmed or suspected progressive multifocal leukoencephalopathy (PML)
? History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
? Immunocompromised state
? Receipt of a live or live attenuated vaccine within 6 weeks prior to randomization
? Inability to complete an MRI or contraindication to gadolinium administration
? Contraindications to mandatory pre medications for IRRs, including uncontrolled psychosis for corticosteroids or closed angle glaucoma for antihistamines
? Known presence of other neurologic disorders that could interfere with the diagnosis of MS or assessments of efficacy and/or safety during the
study
? Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
? Significant, uncontrolled disease that may preclude patient from participating in the study
? History of or currently active primary or secondary (non-drug related) immunodeficiency
? Pregnant or breastfeeding or intending to become pregnant during the study
? Lack of peripheral venous access
? History of alcohol or other drug abuse within 12 months prior to screening
? Treatment with any investigational agent within 24 weeks prior to screening or treatment with any experimental procedure for MS
? Previous use of anti-CD20s (including ocrelizumab) if in the last 2 years before screening, or if B-cell count is normal, or if the stop of the treatment was not motivated by safety reasons or lack of efficacy
? Any previous treatment with mitoxantrone, cladribine, atacicept, and alemtuzumab
- Previous treatment with fingolimod, siponimod, or ozanimod within 6 weeks of baseline
? Previous treatment with natalizumab within 4.5 months of baseline
? Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2 weeks of baseline
? Previous treatment with any other immunomodulatory or immunosuppressive medication not already listed above without appropriate washout as described in the applicable local label (washout to be completed prior to baseline). If the washout requirements are not described in the applicable local label, then the wash out period must be five times the half-life of the medication. The PD effects of the previous medication must also be considered when determining the required time for washout.
? Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
? Any of previous history transplantation or anti-rejection therapy
? Treatment with IV Ig or plasmapheresis within 12 weeks prior to randomization
? Systemic corticosteroid therapy within 4 weeks prior to screening
? Positive screening tests for active, latent, or inadequately treated hepatitis B
? Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab
? Any additional exclusionary criterion as per ocrelizumab (Ocrevus) local label, if more stringent than the above



Critères d'évaluation principaux et secondaires
Main Objective: ? To demonstrate the superiority of a higher dose of ocrelizumab over the approved dose of ocrelizumab as assessed by risk reduction in composite confirmed disability progression (cCDP) sustained for at least 12 weeks;Secondary Objective: ? To demonstrate superiority of a higher dose of ocrelizumab over the approved dose of ocrelizumab on the basis of time to onset of 24 week cCDP (cCDP24), CDP12, CDP24, time to >= 20% increase in 12 and 24 week confirmed timed 25 foot walk test (T25FWT), annual rate of change from baseline in the Multiple Sclerosis Impact Scale (MSIS 29), annual rate of percent change from baseline in total brain volume, time to 12 week confirmed 4 point worsening in Symbol Digit Modality test (SDMT)
? To evaluate the safety profile of a higher dose of ocrelizumab compared with the approved dose of ocrelizumab as well as the overall safety profile and safety profile by treatment arm over time
? To assess the exposure to ocrelizumab in serum in all patients in both study arms
? To characterize the ocrelizumab PD profile
? To evaluate the immune response to ocrelizumab
? To identify biomarkers that are predictive of response to a higher dose of ocrelizumab
;Primary end point(s): 1. Reduction in cCDP sustained for at least 12 weeks measured by time to onset of cCDP sustained for at least 12 weeks. Time to onset of cCDP
is defined as the first occurrence of a predefined confirmed progression even measured by EDSS, T25FWT or 9-HPT;Timepoint(s) of evaluation of this end point: 1.From Baseline up to 4.3 years (Double blind treatment [DBT]) (ICTRP)

Secondary end point(s): 1. Time to onset of 24 week cCDP (cCDP24)
2. Time to onset of 12-week CDP (CDP12)
3. Time to onset of 24-week CDP (CDP24)
4. Time to >= 20% increase in 12 week confirmed T25FWT
5. Time to >= 20% increase in 24 week confirmed T25FWT
6. Annual rate of change from baseline in the Multiple Sclerosis Impact Scale (MSIS 29) physical scale at Week 120
7. Annual rate of percent change in total brain volume from Week 24 to Week 120
8. Time to 12 week confirmed 4 point worsening in Symbol Digit Modality test (SDMT)
9. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute?s Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
10. Change from baseline in clinical laboratory test results (including hematology, chemistry, Ig levels)
11. Change from baseline in vital signs (including systolic and diastolic blood pressure, pulse rate) following study treatment administration
12. Serum concentration of ocrelizumab at specified timepoints
13. B cell levels in blood (including comparing the degree of B-cell depletion between the doses)
14. Proportion of patients achieving 5 or less B-cells per microliter of blood
15. Proportion of patients achieving 5 or less B-cells per microliter of blood in patients with the high versus low affinity Fcgamma Receptor 3A (FcgR3A) genotype per arm
16. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study
17. Levels of soluble biomarkers
18. Levels of blood B-cells based on a highly sensitive assay that can accurately measure below 5 B-cells per microliter in blood
19. Levels of B or T cell subsets in blood
20. DNA genotype of patients
;Timepoint(s) of evaluation of this end point: 1-5. Up to Week 120 (DBT)
6-7. Baseline to Week 120
8. Up to Week 120 (DBT)
9. Up to Week 120 (DBT)
10-11. Baseline to Week 120 (DBT)
12-15. Week 0, 2, 12, 24, 36, 48, 60, 72, 84, 96, 120
16. Week 0, 24, 48, 72, 96, 120
17-20. DBT: Week 0, 2, 12, 24, 48, 72, 96, 120 (ICTRP)

Date d'enregistrement
09.07.2020 (ICTRP)

Inclusion du premier participant
28.10.2020 (ICTRP)

Sponsors secondaires
non disponible

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

ID secondaires
BN42082 (ICTRP)

Résultats-Données individuelles des participants
non disponible

Informations complémentaires sur l'essai
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-000893-69 (ICTRP)