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A clinical trial to compare the safety and effectiveness of ocrelizumab with placebo in people with primary progressive multiple sclerosis (PPMS)
A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis
- Autoimmune Disorder
- Multiple Sclerosis (MS)
- Primary Progressive Multiple Sclerosis (PPMS)
Please note that the recruitment status of the trial at your site may differ from the overall study status because some study sites may recruit earlier than others.
Trial Status:
Recruiting
This trial runs in
Countries
- Canada
- Colombia
- Italy
- Lebanon
- Mexico
- Morocco
- New Zealand
- Poland
- Portugal
- Romania
- Russia
- Spain
- Ukraine
- United Kingdom
- United States
Trial Identifier:
NCT04035005 2018-001511-73 WA40404
Trial Summary
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).
Hoffmann-La Roche
Sponsor
Phase 3
Phase
NCT04035005,WA40404,2018-001511-73
Trial Identifier
All
Gender
≥18 Years & ≤ 65 Years
Age
No
Healthy Volunteers
1. Why is the O’HAND clinical trial needed?
Multiple sclerosis (MS) is a condition where the immune system attacks myelin, the protective layer around nerve fibres. This makes it difficult for the brain to send signals to the rest of the body. In people with MS symptoms include unsteadiness, tiredness, weakness, blurred vision and tingling sensations. Primary progressive multiple sclerosis (PPMS) is a form of MS that is slow to start and symptoms steadily worsen.
At this time, there is no cure for MS. Ocrelizumab is approved for the treatment of PPMS and studies show it may help people with PPMS to keep their ability to use their hands, arms and shoulders (known as ‘upper limb function’) for longer – but more information is needed.
This clinical trial aims to look at how safe and how well ocrelizumab works to keep upper limb function versus a drug that contains no active ingredients (placebo) in people with PPMS.
2. How does the O’HAND clinical trial work?
This clinical trial is recruiting people diagnosed with PPMS. The trial has two treatment phases.
In the first phase, people who take part in this clinical trial (participants) will be given the clinical trial treatments, either ocrelizumab or placebo, 6 times over about 2 and half years. The clinical trial doctor will see them twice during the first month of treatment then every 3 months in this phase.
In the second phase, participants who completed phase 1 treatment and can still benefit from ocrelizumab treatment can choose to be given treatment with ocrelizumab for at least 2 years (at least 4 doses). If a participant`s MS progresses during the first phase, they may begin ocrelizumab treatment in the second phase sooner. The clinical trial doctor will see them twice during the first month of treatment in the second phase then every 6 months. Hospital visits will include checks to see how the participant responds to the treatment and any side effects they may have. After the last dose of clinical trial treatment, participants may be seen every 3 or 6 months until the end of the study, depending on how long they were given treatment, to check their health.
The total time of participation in the clinical trial will be about 9 and half years depending on when they join the trial and if they take part in the second phase. Participants can stop trial treatment and leave the clinical trial at any time.
3. What are the main endpoints of the O’HAND clinical trial?
The main clinical trial endpoint (the main result measured in the trial to see if the drug has worked) is the amount of time before upper limb function worsens by 20% measured using the 9-Hole Peg Test (9-HPT).
The other clinical trial endpoints include:
- The amount of time before physical ability worsens measured by an Expanded Disability Status Scale (EDSS) score
- Changes detected by brain scans (magnetic resonance imaging; MRI)
- Number and seriousness of side effects
- How the body breaks down and gets rid of ocrelizumab
- How treatment affects the immune system
4. Who can take part in this clinical trial?
People can take part in this trial if they are aged 18–65 years old, have an EDSS score between 3.0 (mild – moderate disability with no problem walking) and 8.0 (restricted to a bed or chair with some use of arms) and can complete the 9-HPT in more than 25 seconds but within 4 minutes, with each hand.
People may not be able to take part in this trial if they have or had certain treatments before, including ocrelizumab. Certain medical conditions such as active infections, another disease of the brain or spinal cord, heart, liver or lung problems, cancer, or are pregnant or breastfeeding will prevent participation too. People cannot take part if they are not able to have an MRI scan.
5. What treatment will participants be given in this clinical trial?
In the first phase, everyone who joins this clinical trial will join 1 of 2 groups randomly (like flipping a coin) and be given either:
- Ocrelizumab, given as an infusion (into the vein) every 6 months for about 2 and half years
- OR placebo, given as an infusion (into the vein) every 6 months for about 2 and half years
Participants will have an equal chance of being placed in either group. The first phase will take about 2 and a half years for each participant. The first phase is double-blinded, which means neither the participant nor the clinical trial doctor can choose or know the group the participant is in, until the phase is over for all the participants. This helps to prevent bias and expectations about what will happen. However, the participant’s clinical trial doctor can find out which group the participant is in, if their safety is at risk.
After this phase, participants who meet criteria and agree to continue treatment will join the second phase and will be given:
- Ocrelizumab, as an infusion (into the vein) every 6 months for at least 2 years.
The second phase is ‘open-label’, which means everyone involved, including the participant and the clinical trial doctor, will know the participant has been given ocrelizumab.
6. Are there any risks or benefits in taking part in this clinical trial?
The safety or effectiveness of the experimental treatment or use may not be fully known at the time of the trial. Most trials involve some risks to the participant. However, it may not be greater than the risks related to routine medical care or the natural progression of the health condition. People who would like to participate will be told about any risks and benefits of taking part in the clinical trial, as well as any additional procedures, tests, or assessments they will be asked to undergo. All of these will be described in an informed consent document (a document that provides people with the information they need to decide to volunteer for the clinical trial).
Risks associated with the clinical trial drug
Participants may have side effects (an unwanted effect of a drug or medical treatment) from the drug used in this clinical trial. Side effects can be mild to severe, even life-threatening, and vary from person to person. Participants will be closely monitored during the clinical trial; safety assessments will be performed regularly.
Participants will be told about the known side effects of ocrelizumab, and possible side effects based on human and laboratory studies or knowledge of similar drugs. Participants will be told about any known side effects of infusions into a vein (intravenous infusions).
Potential benefits associated with the clinical trial
Participants' health may or may not improve from participation in the clinical trial. Still, the information collected may help other people with similar medical conditions in the future.
Trial Summary
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).
Hoffmann-La Roche
Sponsor
Phase 3
Phase
NCT04035005,WA40404,2018-001511-73
Trial Identifier
Ocrelizumab, Placebo
Treatments
Multiple Sclerosis, Primary Progressive
Condition
Official 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
Eligibility Criteria
All
Gender
≥18 Years & ≤ 65 Years
Age
No
Healthy Volunteers
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
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
For the latest version of this information please go to www.forpatients.roche.com