A Study to Investigate the Pharmacokinetics, Pharmacodynamics, Safety and Radiological and Clinical Effects of Subcutaneous (SC) Ocrelizumab versus Intravenous (IV) Ocrelizumab in Patients with Multiple Sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Nervous System Diseases [C10]

Trial duration

28 Mar 2022 → 7 Jun 2025

Decision date (initial)

2024-06-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-505975-54-00

EudraCT number

2020-005448-48

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Others, Pharmacokinetic

To demonstrate pharmacokinetics (PK) non-inferiority of the SC formulation of ocrelizumab in patients with MS

Secondary objectives 6

1. To determine the maximum serum concentration (Cmax) of ocrelizumab SC in patients with MS
2. To evaluate the radiological effects of ocrelizumab SC compared with ocrelizumab IV in patients with MS
3. To evaluate and compare the safety profile after administration of ocrelizumab SC versus ocrelizumab IV and to assess the safety of ocrelizumab SC at the selected dose in patients with MS
4. To evaluate the immune response to ocrelizumab SC and IV, and rHuPH0
5. To evaluate the effect of ocrelizumab SC compared with IV ocrelizumab on the pharmacodynamics (PD) marker for the mechanism of action of ocrelizumab (i.e. B cell depletion)
6. To evaluate biomarkers that are predictive of response to ocrelizumab (i.e., predictive biomarkers), are early surrogates of efficacy, are associated with progression to a more severe disease state (i.e., prognostic biomarkers), can provide evidence of ocrelizumab activity (i.e., PD biomarkers), or can increase the knowledge and understanding of disease biology

Conditions and MedDRA coding

Multiple Sclerosis (MS)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Diagnosis of primary progressive MS (PPMS) or relapsing forms of MS (RMS) according to the revised McDonald 2017 criteria
2. Age 18-65 years, inclusive, at time of signing Informed Consent Form
3. Expanded disability status scale (EDSS) score, 0-6.5, inclusive, at screening
4. Neurological stability for ≥30 days prior to both screening and baseline
5. Disease duration from onset of MS symptoms of less than 15 years for patients with EDSS score <2.0 at screening
6. Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for 6 months or 12 months (as applicable by the ocrelizumab IV [Ocrevus] local label) after the final dose of ocrelizumab

Exclusion criteria 6

1. Any known or suspected active infection at screening or baseline (except nailbed infections), or any major episode of infection requiring hospitalization or treatment with IV antimicrobials within 8 weeks prior to and during screening or treatment with oral anti microbials within 2 weeks prior to and during screening
2. History of confirmed or suspected progressive multifocal leukoencephalopathy (PML)
3. History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
4. Immunocompromised state
5. Receipt of a live attenuated vaccine within 6 weeks prior to randomization
6. Inability to complete an MRI or contraindication to gadolinium administration

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Serum ocrelizumab area under the concentration-time curve (AUC[w1-12]) after SC administration compared to IV infusion from Day 1 to Week 12

Secondary endpoints 12

1. 1. Maximum serum concentration (Cmax) of ocrelizumab SC in patients with MS
2. 2. Total number of T1Gd+ lesions as detected by brain magnetic resonance imaging (MRI) at Weeks 8 and 24
3. 3. Total number of new or enlarging T2 lesions as detected by brain MRI at Weeks 12 and 24 relative to the previous scan
4. 4. Incidence and severity of adverse events, with severity determined according to the national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 5.0
5. 5. Change from baseline in targeted vital signs
6. 6. Change from baseline in targeted clinical laboratory test results
7. 7. Incidence of treatment-emergent antidrug antibodies (ADAs) to ocrelizumab after SC or IV administration relative to the presence of ADAs at baseline
8. 8. Relationship between ADA status to ocrelizumab and pharmacokinetics, pharmacodynamics, and safety
9. 9. Incidence of treatment-emergent antibodies to rHuPH20 after SC administration relative to the presence at baseline
10. 10. Relationships between antibodies to rHuPH20 and safety
11. 11. Percentage of patients achieving CD19+ B cell level <5 cells/microliter at Weeks 12, 24, 48, and/or 96
12. 12. Levels of biomarkers including but not limited to neurofilament light (NfL) in serum compared between dosing arms at Weeks 12, 24, 48 and/or 96 compared to baseline

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 8

Locations

4 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Documents 25 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications