A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults with Primary Progressive 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] - Nervous System Diseases [C10], Diseases [C] - Immune System Diseases [C20]

Trial duration

19 Sep 2019 → ongoing

Decision date (initial)

2024-02-05

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

2023-505980-36-00

EudraCT number

2018-001511-73

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Pharmacodynamic, Others

To evaluate the efficacy of ocrelizumab compared with placebo-in all randomized patients
and in patients with MRI activity (MRI activity is defined as presence of T1 Gd+ lesion[s] and/or new and/or enlarging T2 lesion[s] as detected by MRI scans during the screening phase) on the basis of the following endpoint:Time to onset of composite 12-week CDP defined as the time from randomization to the first occurrence of at least one of the following progression events:
 12-week CDP in 9-HPT, defined as a 20% worsening from baseline in 9-HPT confirmed for at least 12 weeks
 12-week CDP in EDSS score, defined as an increase of ≥ 1.0 point from baseline EDSS score in patients with a baseline EDSS score ≤ 5.5 or an increase of ≥0.5 point in patients with a baseline EDSS score of > 5.5 that is confirmed for at least 12 weeks

Secondary objectives 4

1. To evaluate the efficacy of ocrelizumab compared with placebo for all randomized patients on the basis of the endpoints below • Time to 12-week CDP in 9-HPT • Time to 12-week CDP in EDSS • Time to 24-week CDP in 9-HPT • Time to 24-week CDP in EDSS • Annual rate of percent change from baseline in total volume of T2 lesions Annual rate of percent change from Week 24 in total brain volume
2. To evaluate the safety of ocrelizumab compared with placebo and over time for all patients by the proportion of patients with adverse events, laboratory abnormalities
3. To assess the immunogenicity, by the presence of anti-drug antibody to ocrelizumab during the study relative to baseline and the relationship to pharmacokinetics (PK), pharmacodynamics, efficacy and safety
4. To characterize the PK profile of the ocrelizumab and its PD, measured by blood B-cell levels

Conditions and MedDRA coding

Primary progressive multiple sclerosis (PPMS)

Study design 7 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Diagnosis of PPMS in accordance with the McDonald criteria (Thompson et al. 2017)
2. 2. EDSS score at screening and baseline ≥ 3.0 to 8.0, inclusive
3. 3. Disease duration from the onset of multiple sclerosis (MS) symptoms relative to randomization date: o Less than 20 years in patients with an EDSS score at screening 7.0-8.0 o Less than 15 years in patients with an EDSS at screening 5.5-6.5 o Less than 10 years in patients with an EDSS at screening ≤ 5.0
4. 4. Documented history or presence at screening of at least one of the following laboratory findings in a cerebrospinal fluid specimen o Elevated IgG index o One or more IgG oligoclonal bands detected by isoelectric focusing
5. 5. Screening and baseline 9-HPT completed in > 25 seconds (average of the two hands)
6. 6. Neurological stability for ≥ 30 days prior to baseline

Exclusion criteria 6

1. 1. History of relapsing-remitting or secondary progressive MS at screening
2. 2. Confirmed serious opportunistic infection
3. 3. Patients who have or have had confirmed or a high degree of suspicion of progressive multifocal leukoencephalopathy
4. 4. Known active malignancy or are being actively monitored for recurrence of malignancy
5. 5. Immunocompromised state defined as one or more of the following: CD4 count < 250/μL, absolute neutrophil count <1.5 x 103/μL, Serum IgG < 4.6 g/L
6. 6. Receipt of a live-attenuated vaccine within 6 weeks prior to randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Time to onset of composite 12-week CDP defined as the time from randomization to the first occurrence of either 12-week CDP in 9-HPT, or 12-week CDP in EDSS

Secondary endpoints 11

1. 1. Time to 12-week CDP in EDSS, as a pre-defined increase in EDSS score confirmed for at least 12 weeks
2. 2. Time to 24-week CDP in 9-HPT
3. 3. Time to 24-week CDP in EDSS, as a pre-defined increase in EDSS score confirmed for at least 24 weeks
4. 4. Annual rate of percent change from baseline in total volume of T2 lesions
5. 5. Annual rate of percent change from Week 24 in total brain volume
6. 6. Incidence and nature of adverse events, serious adverse events, adverse events leading to study treatment withdrawal
7. 7. Change from baseline in laboratory test results for hematology and chemistry association of decrease in certain laboratory parameters, and serious infections
8. 8. Presence of ADA during the study relative to baseline
9. 9. Total plasma clearances (CL) of ocrelizumab
10. 10. Volumes of distribution(Vd) of ocrelizumab
11. 11. Area under the concentration-time curve (AUC) of ocrelizumab

Investigational products

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

Test 2

Placebo 1

Auxiliary 7

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

9 EU/EEA countries · 64 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

Documents 276 files

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

Application history

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