A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (PPMS)
- Conditions
- Primary Progressive Multiple Sclerosis (PPMS)
- Registration Number
- 2023-506515-18-00
- Lead Sponsor
- F. Hoffmann-La Roche AG
- Brief Summary
To demonstrate the superiority of a higher dose of ocrelizumab over the approved dose of ocrelizumab as assessed by risk reduction in composite confirmed disability progression (cCDP) sustained for at least 12 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruitment ended
- Sex
- Not specified
- Target Recruitment
- 310
-
Ages 18-55 years at time of screening
-
Diagnosis of PPMS, in accordance with the revised McDonald criteria 2017
-
Expanded disability status scale (EDSS) score at screening and baseline 3- 6.5, inclusive
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Score of ≥ 2.0 on the Functional Systems (FS) scale for the pyramidal system that was due to lower extremity findings at screening and baseline
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Documented MRI of brain with abnormalities consistent with MS
-
Patients must be neurologically stable for at least 30 days prior to randomization and baseline assessments
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History of relapsing remitting or secondary progressive MS at screening
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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
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History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
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Immunocompromised state
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Known presence of other neurologic disorders that could interfere with the diagnosis of MS or assessments of efficacy and/or safety during the study
-
History of confirmed or suspected progressive multifocal leukoencephalopathy (PML)
Study & Design
- Study Type
- Not specified
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Time to onset of cCDP sustained for at least 12 weeks. Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by EDSS, T25FWT or 9-HPT 1. Time to onset of cCDP sustained for at least 12 weeks. Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by EDSS, T25FWT or 9-HPT
- Secondary Outcome Measures
Name Time Method 1. Time to onset of 24 week cCDP (cCDP24) 1. Time to onset of 24 week cCDP (cCDP24)
2. Time to onset of cCDP12 independent of protocol-defined relapses (PDR), also termed progression independent of relapse activity (PIRA) as per Kappos et al.2020 2. Time to onset of cCDP12 independent of protocol-defined relapses (PDR), also termed progression independent of relapse activity (PIRA) as per Kappos et al.2020
3. Time to onset of 12-week CDP (CDP12) 3. Time to onset of 12-week CDP (CDP12)
4. Time to ≥ 20% increase in 12 week confirmed T25FWT 4. Time to ≥ 20% increase in 12 week confirmed T25FWT
5. Annual rate of percent change from baseline in total brain volume 5. Annual rate of percent change from baseline in total brain volume
6. Annual rate of percent change from baseline in thalamic volume 6. Annual rate of percent change from baseline in thalamic volume
7. Time to 12-week confirmed 4-point worsening in Symbol Digit Modalities Test (SDMT) 7. Time to 12-week confirmed 4-point worsening in Symbol Digit Modalities Test (SDMT)
8. Change in NfL (i.e. ratio to baseline) at Week 96 8. Change in NfL (i.e. ratio to baseline) at Week 96
9.Time to 12-week confirmed 8-point increase in 12-Item Multiple Sclerosis Walking Scale (MSWS12) 9.Time to 12-week confirmed 8-point increase in 12-Item Multiple Sclerosis Walking Scale (MSWS12)
10. Change in NfL (i.e. ratio to baseline) at Week 96 for patients in the higher dose ocrelizumab group 10. Change in NfL (i.e. ratio to baseline) at Week 96 for patients in the higher dose ocrelizumab group
11. Change in NfL (i.e. ratio to baseline) at Week 96 for patients in the approved dose ocrelizumab group 11. Change in NfL (i.e. ratio to baseline) at Week 96 for patients in the approved dose ocrelizumab group
12. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 12. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0
13. Change from baseline in clinical laboratory test results (including hematology, chemistry, and Ig levels) 13. Change from baseline in clinical laboratory test results (including hematology, chemistry, and Ig levels)
14. Change from baseline in vital signs (including systolic and diastolic blood pressure, and pulse rate) following study treatment administration 14. Change from baseline in vital signs (including systolic and diastolic blood pressure, and pulse rate) following study treatment administration
15. Serum concentration of ocrelizumab at specified timepoints 15. Serum concentration of ocrelizumab at specified timepoints
16. B-cell levels in blood (including comparing the degree of B-cell depletion between the doses) 16. B-cell levels in blood (including comparing the degree of B-cell depletion between the doses)
17. Proportion of participants achieving 5 or less B-cells per microliter of blood 17. Proportion of participants achieving 5 or less B-cells per microliter of blood
18. Proportion of participants achieving 5 or less B-cells per microliter of blood in participants with the high versus low affinity Fcgamma Receptor 3A (FcγR3A) genotype per arm 18. Proportion of participants achieving 5 or less B-cells per microliter of blood in participants with the high versus low affinity Fcgamma Receptor 3A (FcγR3A) genotype per arm
19. Change from Baseline in the anti-drug antibodies (ADAs) levels 19. Change from Baseline in the anti-drug antibodies (ADAs) levels
20. Levels of Neurofilament Light Chain (NfL) in blood 20. Levels of Neurofilament Light Chain (NfL) in blood
21. Levels of Interleukin-6 (IL-6) in blood 21. Levels of Interleukin-6 (IL-6) in blood
22. Levels of blood B-cells 22. Levels of blood B-cells
23. Levels of Lymphocytes in blood 23. Levels of Lymphocytes in blood
24. Proportion of participants with different DNA genotypes 24. Proportion of participants with different DNA genotypes
Trial Locations
- Locations (56)
Instytut Psychiatrii I Neurologii
🇵🇱Warsaw, Poland
Euromedis Sp. z o.o.
🇵🇱Szczecin, Poland
Copernicus Podmiot Leczniczy Sp. z o.o.
🇵🇱Gdansk, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Wojewodzki Szpital Specjalistyczny Nr 3 W Rybniku
🇵🇱Rybnik, Poland
Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. S.K.
🇵🇱Oswiecim, Poland
Indywidualna Praktyka Lekarska Prof. dr hab. n. med. Konrad Rejdak
🇵🇱Lublin, Poland
Szpital Specjalistyczny Im. Ludwika Rydygiera W Krakowie Sp. z o.o.
🇵🇱Cracow, Poland
Ma-Lek Clinical Sp. z o.o.
🇵🇱Katowice, Poland
Centrum Medyczne Neuroprotect
🇵🇱Warsaw, Poland
EMC Instytut Medyczny S.A.
🇵🇱Poznan, Poland
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