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A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis

PHASE3RECRUITING

This study will evaluate the efficacy and safety of ocrelizumab ( Ocrevus®) compared with placebo in participants with primary progressive multiple sclerosis (PPMS), including participants later in their disease course. This study focuses on upper limit disability progression. This study will consist of the following phases: screening, double-blind treatment, follow-up 1 (FU1), an optional open-label extension (OLE), follow-up 2 (FU2), and B-cell monitoring (BCM).

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Study details:

The screening phase will last up to 24 weeks. In the double-blind treatment phase, participants will undergo at least 120 weeks of study treatment. Study drug (ocrelizumab or placebo) will be administered every 24 weeks.

In the FU1 phase, all participants who discontinue prematurely from the double-blind treatment phase will enter the FU1 phase, including participants who receive post-double progression ocrelizumab (PDP OCR) treatment, other immunomodulatory or immunosuppressive treatment(s) for MS, commercial ocrelizumab, or no treatment. The FU1 phase will run in parallel with the double-blind treatment phase until the primary analysis is performed. If the primary analysis is positive, an optional OLE phase is planned for eligible participants who either have remained in the double-blind treatment phase or are on PDP OCR treatment at the time of the primary analysis and, in the opinion of the investigator, could benefit from ocrelizumab treatment.

The follow-up 2 (FU2) phase will begin after the primary analysis is performed. The following participants will move into the FU2 phase: participants who are ongoing in the FU1 and not on PDP OCR treatment at the time of primary analysis; participants who are ongoing in the double-blind treatment phase or receiving PDP OCR at the time of the primary analysis and do not enter the OLE phase; participants who complete or withdraw from the OLE phase. At the end of the FU2, all participants will move into B-cell monitoring (BCM) phase until the end of the study.

This study will end when all participants who are not being treated with an alternative B-cell depleting therapy have repleted his or her B-cells.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

EDSS score at screening and baseline >= 3.0 to 8.0, inclusive

Disease duration from the onset of MS symptoms relative to randomization date: Less than 20 years in patients with an EDSS score at screening 7.0 - 8.0; Less than 15 years in patients with an EDSS at screening 5.5 - 6.5; Less than 10 years in patients with an EDSS at screening <= 5.0

Documented history or presence at screening of at least one of the following laboratory findings in a cerebrospinal fluid specimen: Elevated IgG index or one or more IgG oligoclonal bands detected by isoelectric focusing

Screening and baseline 9-HPT completed in > 25 seconds (average of the two hands)

Neurological stability for ≥ 30 days prior to baseline

Ability to complete the 9-HPT within 240 seconds with each hand at screening and baseline

Neurological stability for >= 30 days prior to baseline

Patients previously treated with immunosuppressants, immunomodulators, or other immunomodulatory therapies must undergo an appropriate washout period according to the local label of the immunosuppressant/immunomodulatory drug used

For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraceptive methods during the treatment period and for 6 or 12 months after the final dose of ocrelizumab. Adherence to local requirements, if more stringent, is required.

For female patients without reproductive potential: Women may be enrolled if surgically sterile (i.e hysterectomy, complete bilateral oophorectomy) or post-menopausal unless the patient is receiving a hormonal therapy for her menopause or if surgically sterile

Exclusion criteria

History of relapsing-remitting or secondary progressive MS at screening

Confirmed serious opportunistic infection including: active bacterial, viral, fungal, mycobacterial infection or other infection, including tuberculosis or atypical mycobacterial disease

Patients who have or have had confirmed or a high degree of suspicion of progressive multifocal leukoencephalopathy (PML)

Known active malignancy or are being actively monitored for recurrence of malignancy

Immunocompromised state

Receipt of a live-attenuated vaccine within 6 weeks prior to randomization

Inability to complete an MRI or contraindication to Gd administration.

Patients requiring symptomatic treatment of MS and/or physiotherapy who are not on a stable regimen. Patients must not initiate symptomatic treatment of MS or physiotherapy within 4 weeks of randomization.

Contraindications to mandatory premedications for infusion-related reactions, including: uncontrolled psychosis for corticosteroids and closed-angle glaucoma for antihistamines

Known presence of other neurologic disorders

Pregnant or breastfeeding, or intending to become pregnant during the study and for 6 or 12 months after last infusion of the study drug

Lack of peripheral venous access

Significant, uncontrolled disease, such as cardiovascular, pulmonary, renal, hepatic, endocrine or gastrointestinal, or any other significant disease that may preclude patient from participating in the study

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

History of primary or secondary immunodeficiency

Treatment with any investigational agent within 24 weeks prior to screening (Visit 1) or 5 half-lives of the investigational drug (whichever is longer), or treatment with any experimental procedure for MS

Previous treatment with B-cell targeting therapies

Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation

Any previous history of 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 serum hCG measured at screening or positive urine β-hCG at baseline

Positive screening tests for hepatitis B

Any additional exclusionary criterion as per ocrelizumab (Ocrevus®) local label, if more stringent than the above

Lack of MRI activity at screening/baseline if more than 650 patients without MRI activity have already been enrolled, as defined by T1 Gd+ lesion(s) and/or new and/or enlarged T2 lesion(s) in the screening, to ensure that at least 350 patients with MRI activity will be randomized

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2019-08-12

Primary completion: 2025-01-15

Study completion finish: 2028-01-19

Study type

TREATMENT

Phase

PHASE3

Trial ID

NCT04035005

Intervention or treatment

DRUG: Ocrelizumab

DRUG: Placebo

Conditions

• Multiple Sclerosis, Primary Progressive

Image related to Multiple Sclerosis, Primary Progressive

Condition: Multiple Sclerosis, Primary Progressive
DRUG: Ocrelizumab and other drugs
New Lambton, New South Wales, Australia and more
Sponsor: Hoffmann-La Roche

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

John Hunter Hospital

Research sites nearby

Select from list below to view details:

John Hunter Hospital
New Lambton, New South Wales, Australia
Austin Hospital
Heidelberg, Victoria, Australia
Royal Melbourne Hospital
Parkville, Victoria, Australia
Brain and Mind Research Institute
Camperdown, New South Wales, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Ocrelizumab Participants will receive ocrelizumab by IV infusion every 24 weeks.	DRUG: Ocrelizumab The first dose of ocrelizumab will be administered as two 300 mg IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg infusion every 24 weeks. A minimum interval of 20 or 22 weeks, depending if the previous dose was administered in one or two infusion, should be maintained between each infusion.
PLACEBO_COMPARATOR: Placebo Participants will receive placebo matched to ocrelizumab by IV infusion every 24 weeks.	DRUG: Placebo The first dose of placebo will be administered as two 300 mg IV infusions given 14 days apart. For the subsequent doses, placebo will be administered as a single 600 mg infusion every 24 weeks, with a minimum interval of 20 or 22 weeks, depending if the previous dose was administered in one or two infusion, should be maintained between each infusion.

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Time to Upper Limb Disability Progression Confirmed For at Least 12 Weeks	20% increase from baseline in Nine-Hole Peg Test (9-HPT) confirmed for at least 12 weeks.	Baseline up to approximately 5.5 years

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Time to Upper Limb Disability Progression Confirmed For at Least 24 Weeks	20% increases from baseline in 9-HPT confirmed for at least 24 weeks.	Baseline up to approximately 5.5 years
Time to Disability Progression Confirmed For at Least 12 Weeks	Increase in EDSS Score is defined as an increase of \>= 1.0 point from baseline EDSS score in participants with a baseline EDSS score \<= 5.5 or an increase of \>= 0.5 point in participants with a baseline EDSS score of \> 5.5.	Baseline up to approximately 5.5 years
Time to Disability Progression Confirmed For at Least 24 Weeks	Increase in EDSS Score is defined as an increase of \>= 1.0 point from baseline EDSS score in participants with a baseline EDSS score \<= 5.5 or an increase of \>= 0.5 point in participants with a baseline EDSS score of \> 5.5.	Baseline up to approximately 5.5 years
Percent Change in Total Volume of T2 Lesions on MRI	Not Specified	Baseline up to week 120
Percent Change in Total Brain Volume on MRI Scans	Not Specified	Week 24 to Week 120
Percentage of Participants with Adverse Events	Not Specified	Baseline up to 8.5 years
Percentage of Participants With Serious Adverse Events	Not Specified	Baseline up to 8.5 years
Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab	Not Specified	Baseline, Weeks 2, 12, 24, 48, 60, 72, and every 12 weeks till the end of the double-blind period and Weeks 0 and 48 of the OLE period
Evaluation of Ocrelizumab Pharmacodynamics, as measured by B-Cell Levels in Blood	Not Specified	Baseline, Weeks 2, 24, 48, 72 and every 12 weeks till the end of the double-blind period and Weeks 0, 22, 46, 70 and 96 of the OLE period

Frequently Asked Questions

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References

Clinical Trials Gov: A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis