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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05232825




Registration number
NCT05232825
Ethics application status
Date submitted
27/01/2022
Date registered
10/02/2022
Date last updated
10/06/2024

Titles & IDs
Public title
A Phase III, Non-Inferiority, Randomized, Open-Label, Parallel Group, Multicenter Study To Investigate The Pharmacokinetics, Pharmacodynamics, Safety And Radiological And Clinical Effects Of Subcutaneous Ocrelizumab Versus Intravenous Ocrelizumab In Patients With Multiple Sclerosis
Scientific title
A Study To Investigate The Pharmacokinetics, Pharmacodynamics, Safety And Radiological And Clinical Effects Of Subcutaneous Ocrelizumab Versus Intravenous Ocrelizumab In Patients With Multiple Sclerosis
Secondary ID [1] 0 0
CN42097
Universal Trial Number (UTN)
Trial acronym
Ocarina II
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ocrelizumab IV
Treatment: Drugs - Ocrelizumab SC
Treatment: Drugs - Methylprednisolone IV
Treatment: Drugs - Diphenhydramine IV
Treatment: Drugs - Dexamethasone given orally
Treatment: Drugs - Desloratadine given orally

Active Comparator: Ocrelizumab: Intravenous (IV) formulation - Participants will receive the first dose of ocrelizumab IV as two IV infusions given 14 days apart. The subsequent doses of study drug will be administered as SC injections. A minimum of 22 weeks should be kept between SC doses. Participants will undergo 96 weeks of study treatment.

Experimental: Ocrelizumab: Subcutaneous (SC) formulation - Participants will receive the first dose of ocrelizumab SC as one SC injection at a dose which is expected to result in non-inferior exposure to ocrelizumab IV. The subsequent doses of study drug will be administered as SC injections. A minimum of 22 weeks should be kept between the first and second SC doses, and between subsequent SC doses. Participants will undergo 96 weeks of study treatment.


Treatment: Drugs: Ocrelizumab IV
IV Injection

Treatment: Drugs: Ocrelizumab SC
SC Injection

Treatment: Drugs: Methylprednisolone IV
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab infusion

Treatment: Drugs: Diphenhydramine IV
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab infusion

Treatment: Drugs: Dexamethasone given orally
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab injection

Treatment: Drugs: Desloratadine given orally
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab injection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Serum ocrelizumab area under the concentration-time curve (AUCW1-12)
Timepoint [1] 0 0
Day 1 to Week 12
Secondary outcome [1] 0 0
Maximum serum concentration (Cmax) of ocrelizumab SC in patients with MS
Timepoint [1] 0 0
Day 1 to Week 12
Secondary outcome [2] 0 0
Total number of T1Gd+ lesions as detected by brain MRI
Timepoint [2] 0 0
Weeks 8 and 24
Secondary outcome [3] 0 0
Total number of new or enlarging T2 lesions as detected by brain MRI
Timepoint [3] 0 0
Weeks 12 and 24
Secondary outcome [4] 0 0
Percentage of participants with Adverse Events
Timepoint [4] 0 0
Day 1 to Week 48
Secondary outcome [5] 0 0
Incidence of treatment-emergent antidrug antibodies to ocrelizumab after SC or IV administration
Timepoint [5] 0 0
Day 1 to Week 48
Secondary outcome [6] 0 0
Incidence of treatment-emergent antibodies to rHuPH20
Timepoint [6] 0 0
Day 1 to Week 48
Secondary outcome [7] 0 0
Proportion of participants achieving CD19+ B cell level =5 cells/uL
Timepoint [7] 0 0
Day 1 to Week 48

Eligibility
Key inclusion criteria
- Diagnosis of PPMS or RMS according to the revised McDonald 2017 criteria (Thompson et
al. 2018)

- EDSS score, 0-6.5, inclusive, at screening

- Neurological stability for =30 days prior to both screening and baseline

- Disease duration from onset of MS symptoms of less than 15 years for patients with
EDSS score <2.0 at screening

- For females participants, without reproductive potential may be enrolled if
post-menopausal, unless receiving a hormonal therapy for menopause or if surgically
sterile

- For females of childbearing potential, agreement to remain abstinent or use adequate
contraceptive methods
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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 anti microbials within 8 weeks prior to and during screening or treatment with
oral anti microbials within 2 weeks prior to and during screening

- History of confirmed or suspected progressive multifocal leukoencephalopathy (PML)

- History of cancer, including hematologic malignancy and solid tumors, within 10 years
of screening

- Immunocompromised state

- Receipt of a live-attenuated vaccine within 6 weeks prior to randomization Influenza
vaccination is permitted if the inactivated vaccine formulation is administered

- Inability to complete an MRI or contraindication to gadolinium administration

- Contraindications to mandatory premedications for IRRs, including closed-angle
glaucoma for antihistamines

- Known presence of other neurologic disorders

- Any concomitant disease that may require chronic treatment with systemic
corticosteroids or immunosuppressants during the course of the study

- 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

- History of or currently active primary or secondary (non-drug-related)
immunodeficiency

- Pregnant or breastfeeding, or intending to become pregnant during the study and 6 or
12 months

- Lack of peripheral venous access

- History of alcohol or other drug abuse within 12 months prior to screening

- Treatment with any investigational agent within 24 weeks prior to screening or 5
half-lives of the investigational drug (whichever is longer), or treatment with any
experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous
insufficiency)

- Participants who have previously received anti-CD20s if the last treatment was less
than 2 years before screening, and/or if B-cell count is below lower limit of normal,
and/or the discontinuation of the treatment was due to safety reasons or lack of
efficacy

- Previous treatment with cladribine, atacicept, and alemtuzumab

- Previous treatment with fingolimod, siponimod, ponesimod, or ozanimod within 6 weeks
of baseline

- Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2
weeks of baseline

- Previous treatment with natalizumab within 4.5 months of baseline

- Treatment with mitoxantrone within 2 years prior to baseline visit or evidence of
cardiotoxicity following mitoxantrone use or a cumulative lifetime dose of more than
60 mg/m2

- Previous treatment with any other immunomodulatory or immunosuppressive medication not
already listed above without appropriate washout as described in the applicable local
label.

- If the washout requirements are not described in the applicable local label, then the
wash out period must be 5 times the half-life of the medication. The PD effects of the
previous medication must also be considered when determining the required time for
washout.

- 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 screening tests for active, latent, or inadequately treated hepatitis B

- Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab

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

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/05/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2025
Actual
Sample size
Target
Accrual to date
Final
236
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
South Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
Brazil
State/province [8] 0 0
BA
Country [9] 0 0
Brazil
State/province [9] 0 0
ES
Country [10] 0 0
Czechia
State/province [10] 0 0
Brno
Country [11] 0 0
Czechia
State/province [11] 0 0
Hradec Králové
Country [12] 0 0
Czechia
State/province [12] 0 0
Jihlava
Country [13] 0 0
Czechia
State/province [13] 0 0
Ostrava-Poruba
Country [14] 0 0
Czechia
State/province [14] 0 0
Pardubice
Country [15] 0 0
Czechia
State/province [15] 0 0
Praha 2
Country [16] 0 0
Czechia
State/province [16] 0 0
Praha
Country [17] 0 0
Czechia
State/province [17] 0 0
Teplice
Country [18] 0 0
Italy
State/province [18] 0 0
Lazio
Country [19] 0 0
Italy
State/province [19] 0 0
Lombardia
Country [20] 0 0
Italy
State/province [20] 0 0
Molise
Country [21] 0 0
New Zealand
State/province [21] 0 0
Auckland
Country [22] 0 0
New Zealand
State/province [22] 0 0
Hastings
Country [23] 0 0
Poland
State/province [23] 0 0
Bydgoszcz
Country [24] 0 0
Poland
State/province [24] 0 0
Katowice
Country [25] 0 0
Poland
State/province [25] 0 0
Lodz
Country [26] 0 0
Poland
State/province [26] 0 0
Wroc?aw
Country [27] 0 0
Spain
State/province [27] 0 0
Madrid
Country [28] 0 0
Spain
State/province [28] 0 0
Sevilla
Country [29] 0 0
Spain
State/province [29] 0 0
Tenerife
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
Country [31] 0 0
Spain
State/province [31] 0 0
Cordoba
Country [32] 0 0
Turkey
State/province [32] 0 0
Istanbul
Country [33] 0 0
Turkey
State/province [33] 0 0
Izmir
Country [34] 0 0
Turkey
State/province [34] 0 0
Kocaeli
Country [35] 0 0
Turkey
State/province [35] 0 0
Süleymanpa?a

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

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the pharmacokinetics, pharmacodynamics, safety, immunogenicity, and
radiological and clinical effects of subcutaneous (SC) administration of ocrelizumab compared
with the intravenous (IV) infusion of ocrelizumab in patients with either relapsing multiple
sclerosis (RMS) or primary progressive multiple sclerosis (PPMS).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05232825
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries