| CTRI Number |
CTRI/2025/03/082143 [Registered on: 11/03/2025] Trial Registered Prospectively |
| Last Modified On: |
10/06/2026 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
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Type of Study
|
Biological |
| Study Design |
Single Arm Study |
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Public Title of Study
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To Assess The Safety And Effectiveness Of Ocrelizumab In Multiple Sclerosis (RMS And PPMS) Patients In India |
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Scientific Title of Study
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A multi-centre, open label, single arm phase IV study to assess the safety and effectiveness of Ocrelizumab in multiple sclerosis (RMS And PPMS) patients in India (Overture) |
| Trial Acronym |
Overture |
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Secondary IDs if Any
|
| Secondary ID |
Identifier |
| ML45008_Version 2 dated 24 Jun 2024 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
Modification(s)
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| Name |
Dr Jyotii Poddaar |
| Designation |
Lead- Clinical Operations |
| Affiliation |
Roche Products India Private Limited |
| Address |
Roche Products (India) Pvt. Ltd. 146-B, 166 A, Unit No. 7, 8, 9 8th Floor, R City Office, R City Mall, Mumbai.
Mumbai
MAHARASHTRA
400086
India |
| Phone |
9136064373 |
| Fax |
|
| Email |
jyotii.poddaar@roche.com |
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Details of Contact Person
Public Query
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| Name |
Mr Rashmin Shukla |
| Designation |
Clinical Operations Manager |
| Affiliation |
Roche Products India Private Limited |
| Address |
Roche Products (India) Pvt. Ltd. 146-B, 166 A, Unit No. 7, 8, 9 8th Floor, R City Office, R City Mall, Ghatkopar, Mumbai.
Mumbai
MAHARASHTRA
400086
India |
| Phone |
9819930460 |
| Fax |
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| Email |
rashmin.shukla@roche.com |
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Source of Monetary or Material Support
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| Roche Products India Pvt Ltd |
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Primary Sponsor
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| Name |
Roche Products India Pvt Ltd |
| Address |
146-B, 166 A, Unit No. 7, 8, 9 8th Floor, R City Office, R City Mall Lal Bahadur Shastri Marg Ghatkopar, Mumbai, 400086 |
| Type of Sponsor |
Pharmaceutical industry-Indian |
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Details of Secondary Sponsor
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Countries of Recruitment
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India |
Sites of Study
Modification(s)
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| No of Sites = 8 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Sumit Singh |
Artemis Hospital |
Sector 51, Gurugram, Haryana 122001
Gurgaon
HARYANA |
9810052615
sumit.singh@artemishospitals.com |
| Dr Biman Kanti Ray |
Bangur Institute of Medical Science, Kolkata |
Department of neuromedicine, Bangur Institute of neurology, IPGME & R, Kolkata, 700020
Kolkata
WEST BENGAL |
9433185327
biman.kanti@rediffmail.com |
| Dr Saranya Gomathy |
Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) |
Department of Neurology, JIPMER Campus Rd, JIPMER Campus, Dhanvantari Nagar, Puducherry- 605006, India
Pondicherry
PONDICHERRY |
91 8129606651
saranyabgomathy@gmail.com |
| Dr Rahul Kulkarni |
Lata Mangeshkar Medical Foundations, Deenanath Mangeshkar Hospital and Research Centre |
Off Karve Road, Erandawane, Pune, 411004, Maharashtra, India
Pune
MAHARASHTRA |
9822012588
rahulneuro@gmail.com |
| Dr Mukesh Kumar |
Max Super Speciality Hospital, Saket, (West Block), (A Unit of Max Healthcare Institute Ltd.) |
1, Press Enclave Road, Saket, New Delhi- 110017, India
New Delhi
DELHI |
9716946264
mukeshkumar@maxhealthcare.com |
| Dr Dheeraj Khurana |
Postgraduate Institute of Medical Education and Research (PGIMER) Nehru Hospital |
Department of Neurology,
Ground Floor, Block A,
Sector 12, Chandigarh, 160012
Chandigarh
CHANDIGARH |
7087009695
dherajk@yahoo.com |
| Dr Rajesh Iyer |
Sparsh Super Specialty Hospital |
No. 146 Infantry Road, Opposite to police commissioners office Bangalore 560001
Bangalore
KARNATAKA |
807100450
sparshclinical@gmail.com |
| Dr Sruthi S Nair |
Sree Chitra Tirunal Institute for Medical Sciences and Technology |
Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Medical College PO, Tiruvananthapuram- 695011, Kerala
Thiruvananthapuram
KERALA |
9895045032
sruthisn@sctimst.ac.in |
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Details of Ethics Committee
Modification(s)
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| No of Ethics Committees= 8 |
| Name of Committee |
Approval Status |
| Artemis Health Sciences IEC |
Approved |
| Institutional Ethics committee Deenanath Mangeshkar Hospital And Research Centre |
Submittted/Under Review |
| Institutional Ethics Committee Human studies for Intervention studies JIPMER |
Approved |
| Institutional Ethics Committee Post Graduate Institute of Medical Education and Research |
Approved |
| Institutional Ethics committee Sparsh Hospital |
Approved |
| Institutional Ethics Committee, SCTIMST |
Approved |
| IPGME&R Research Oversight Committee |
Approved |
| Max Healthcare Ethics Committee |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: G35||Multiple sclerosis, |
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Intervention / Comparator Agent
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| Type |
Name |
Details |
| Comparator Agent |
Nil |
Nil |
| Intervention |
OCRELIZUMAB |
The initial 600 mg dose is administered as two separate intravenous infusions; first as a 300 mg infusion, followed 2 weeks later by a second 300 mg infusion. Subsequent doses of ocrelizumab thereafter are administered as a single 600 mg intravenous infusion every 6 months. |
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Inclusion Criteria
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| Age From |
18.00 Year(s) |
| Age To |
55.00 Year(s) |
| Gender |
Both |
| Details |
1. Age 18 to 55 years
2. For RMS: A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria (Thompson et al. 2018) and one of the following:
At least two documented clinical relapses within the last 1.5 years or one documented clinical relapse within 12 months of screening (but not within the 30 days prior to screening)
Documented evidence of the presence of at least one T1Gd+ lesion on MRI in the 12 months prior to screening
RMS may include active secondary progressive multiple sclerosis (aSPMS) as defined by Lublin et al. 2014.
For PPMS-Progressive disease from the onset
One year of disability progression (retrospectively or prospectively determined) independent of clinical relapse
Plus two of the following criteria:
Documented evidence of one or more T2-hyperintense MRI lesions characteristic of MS in one or more of the following brain regions: periventricular, cortical or juxtacortical, or infratentorial
Documented evidence of two or more T2-hyperintense MRI lesions in the spinal cord
Documented evidence of the presence of cerebrospinal fluid-specific oligoclonal bands (established by a historical lumbar puncture)
This will be confirmed centrally by an independent neurologist.
3. No prior exposure to long-term immunomodulatory medication, however, appropriate washout period may be allowed for few immunomodulatory medications
4. Ability to provide informed consent
5. For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate non-hormonal contraception during the treatment period and for 6 months’ time needed to eliminate drug after the final dose of ocrelizumab
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| ExclusionCriteria |
| Details |
1. Any known or suspected active infection at screening or baseline, 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
2. History of confirmed or suspected progressive multifocal leukoencephalopathy (PML)
3. Patients with a previous history of a serious infusion-related reactions (IRR) (Common Terminology Criteria for Adverse Events [CTCAE] Grade more than or equal to 4) and/or any hypersensitivity reaction to ocrelizumab
4. History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
Basal or squamous cell carcinoma of the skin that has been excised and is considered cured is not exclusionary. In situ carcinoma of the cervix treated with apparent success by curative therapy > 1 year prior to screening is not exclusionary.
5. Immunocompromised state, defined as one or more of the following: CD4 count less than 250/mL or absolute neutrophil count 1.5x10 raise-to 3 /mL or serum IgG less than 500 mg/dL
6. Known presence of other significant neurological disorders
7. Evidence of clinically significant systemic/organ disorders that, in the investigators opinion, would preclude patient participation
8. Screening 12 lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect patient safety or interpretation of study results including QT interval corrected through use of Fridericias formula (QTcF) more than 440 ms demonstrated by at least two ECGs more than 30 minutes apart
9. Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
10. Pregnant or breastfeeding, or intending to become pregnant during the study or 6 or 12 months (as applicable from the local label for ocrelizumab) after final dose of study drug
11. All women of childbearing potential will have a serum pregnancy test at screening.
12. Positive screening tests for active, latent, or inadequately treated hepatitis B (as evidenced by either of the following): Positive hepatitis B surface antigen
Positive hepatitis B core antibody [total HBcAb] and detectable Hep B virus DNA
13. Positive screening tests for hepatitis C (positive hepatitis C antibodies)
14. Evidence of active or latent or inadequately treated infection with tuberculosis (TB) as defined by the following: A positive QuantiFERON TB Gold (QFT) test at screening or within the 3 months prior to screening is required (see Section 8.2.5 for test requirements).
An indeterminate QFT test should be repeated. A positive QFT test or two successive indeterminate QFT results should be considered a positive diagnostic TB test. An indeterminate QFT test followed by a negative QFT test should be considered a negative diagnostic TB test.
15. History of or currently active primary or secondary (non-drug related) immunodeficiency, including known history of HIV infection or IgG less than 500 mg/dL
16. Contraindications to mandatory pre-medications (i.e., corticosteroids and antihistamines) for IRRs, including:
Uncontrolled psychosis for corticosteroids
Closed angle glaucoma for antihistamines
17. Inability to complete an MRI scan (contraindications for MRI scan, including but not restricted to, pacemaker, cochlear implants, intracranial vascular clips, surgery within 6 weeks of entry in the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI scan) or contraindication to gadolinium administration
18. Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants
19. Receipt of a live or live attenuated vaccine within 6 weeks prior to dosing. Influenza vaccination is permitted if the inactivated vaccine formulation is administered.
20. 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
21. Any abnormal laboratory findings that can interfere with ocrelizumab dosing as judged by the investigator to be clinically significant
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Method of Generating Random Sequence
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Not Applicable |
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Method of Concealment
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Not Applicable |
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Blinding/Masking
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Open Label |
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Primary Outcome
|
| Outcome |
TimePoints |
1.To describe the safety of ocrelizumab in RMS and PPMS patients (separate and pooled analysis) over a period of approximately 96 weeks
2. To describe the time to treatment discontinuation with ocrelizumab and reasons for treatment discontinuation
3. To describe the effectiveness of ocrelizumab treatment on relapse in RMS patients.
4. To describe the effectiveness of ocrelizumab treatment on progression of disability in RMS and PPMS patients |
1. Incidence & time and reason of ocrelizumab discontinuation from Day 1 to Week 96
2. Number of relapses in RMS patients from Day 1 to
Week 96.
3. Annualized relapse rate, defined as number of
relapses per patient-year
4. Time to first relapse
5. The change in T25FWT from Day 1 to Week 96
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Secondary Outcome
|
| Outcome |
TimePoints |
To describe the effectiveness of
ocrelizumab on subclinical
disease activity through imaging
endpoint in RMS & PPMS
(separate & pooled analysis) |
- Total number of T1Gd plus lesions from the baseline as detected by brain MRI scan at Weeks 24, 48, 72 & 96
- Total number of new/enlarging T2-weighted lesions as detected by MRI scan at Weeks 24, 48, 72 & 96 |
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Target Sample Size
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Total Sample Size="32"
Sample Size from India="32"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
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Phase 4 |
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Date of First Enrollment (India)
|
15/04/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
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Estimated Duration of Trial
|
Years="3"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
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Publication Details
|
N/A |
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Individual Participant Data (IPD) Sharing Statement
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Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
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Study ML45008 is a Phase IV study to evaluate the safety and effectiveness of ocrelizumab in adult patients with RMS and PPMS. All eligible patients will receive 600 mg intravenously ocrelizumab. Approximately 32 patients will be enrolled (in which minimum 10% patients with PPMS will be enrolled) by approximately 10 Indian sites. Patients who discontinue study medication early or discontinue from the study will not be replaced.
This study will follow study patients for up to 24 weeks after the last dose to determine safety and effectiveness of ocrelizumab therapy. The effectiveness of ocrelizumab therapy will be based on clinical assessments as well as various MS-related clinical and radiological outcomes.
All patients will be treated with ocrelizumab. Patient’s participation in the study will consists of three periods: screening period of 28 days, treatment period of 72 weeks, and post-treatment follow-up period of 24 weeks. The eligibility of the patients will be assessed within 28 days of the screening period. The estimated duration of patient enrollment is approximately 12 months.
During the study treatment period, RMS and PPMS patients will receive ocrelizumab as per the label. The initial 600 mg dose is administered as two separate intravenous (IV) infusions; first as a 300 mg infusion, followed 2 weeks later by a second 300 mg infusion. Subsequent doses of ocrelizumab thereafter are administered as a single 600 mg IV infusion every 6 months. Pre-medication is administered as per the local prescribing information and according to the physician’s judgment.
Patients will be assessed for effectiveness of ocrelizumab treatment on relapse in RMS patients via number of relapses; annualized relapse rate, and time to first relapse. Patients will be assessed for effectiveness of ocrelizumab treatment on progression of disability in RMS and PPMS patients by assessing the change in T25FWT.
In addition, subclinical disease activity will be assessed through imaging endpoints in RMS and PPMS, separate and pooled analysis by assessing total number of T1 gadolinium enhancing (T1Gd+) lesions from the baseline and new/enlarging T2-weighted lesions as detected by magnetic resonance imaging (MRI) scan. |