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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04035005




Registration number
NCT04035005
Ethics application status
Date submitted
17/07/2019
Date registered
29/07/2019

Titles & IDs
Public title
A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis
Scientific title
A Phase IIIb Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis
Secondary ID [1] 0 0
WA40404
Universal Trial Number (UTN)
Trial acronym
O'HAND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis, Primary Progressive 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ocrelizumab
Treatment: Drugs - Placebo

Experimental: Ocrelizumab - Participants will receive ocrelizumab by IV infusion every 24 weeks.

Placebo comparator: Placebo - Participants will receive placebo matched to ocrelizumab by IV infusion every 24 weeks.


Treatment: Drugs: 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.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to Upper Limb Disability Progression Confirmed For at Least 12 Weeks
Timepoint [1] 0 0
Baseline up to approximately 5.5 years
Secondary outcome [1] 0 0
Time to Upper Limb Disability Progression Confirmed For at Least 24 Weeks
Timepoint [1] 0 0
Baseline up to approximately 5.5 years
Secondary outcome [2] 0 0
Time to Disability Progression Confirmed For at Least 12 Weeks
Timepoint [2] 0 0
Baseline up to approximately 5.5 years
Secondary outcome [3] 0 0
Time to Disability Progression Confirmed For at Least 24 Weeks
Timepoint [3] 0 0
Baseline up to approximately 5.5 years
Secondary outcome [4] 0 0
Percent Change in Total Volume of T2 Lesions on MRI
Timepoint [4] 0 0
Baseline up to week 120
Secondary outcome [5] 0 0
Percent Change in Total Brain Volume on MRI Scans
Timepoint [5] 0 0
Week 24 to Week 120
Secondary outcome [6] 0 0
Percentage of Participants with Adverse Events
Timepoint [6] 0 0
Baseline up to 8.5 years
Secondary outcome [7] 0 0
Percentage of Participants With Serious Adverse Events
Timepoint [7] 0 0
Baseline up to 8.5 years
Secondary outcome [8] 0 0
Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
Evaluation of Ocrelizumab Pharmacodynamics, as measured by B-Cell Levels in Blood
Timepoint [9] 0 0
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

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 ß-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

Eligibility Criteria for Open-Label Extension Phase:

* Completed the double-blind treatment phase of the trial or have received PDP OCR in the FU1 phase, and who, in the opinion of the investigator, may benefit from treatment with Ocrelizumab. Patients who withdrew from study treatment and received another disease-modifying therapy (DMT) or commercial ocrelizumab will not be allowed to enter in the OLE phase.
* Meet the re-treatment criteria for ocrelizumab
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/08/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
19/01/2028
Actual
Sample size
Target
1000
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Brain and Mind Research Institute - Camperdown
Recruitment hospital [2] 0 0
John Hunter Hospital - New Lambton
Recruitment hospital [3] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2305 - New Lambton
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
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United States of America
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Arizona
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California
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Linz
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Bruxelles
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Edegem
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La Louvière
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Overpelt
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Pleven
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KIEV Governorate
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Podolia Governorate
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Polissya Okruha
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Tavria Okruha
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Volhynian Governorate
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Kyiv
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Lutsk
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United Kingdom
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Cardiff
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Glasgow
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Inverness
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Liverpool
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London
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Nottingham
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Plymouth
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Salford
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Sheffield
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Swansea

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: WA40404 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04035005