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This study will evaluate the pharmacokinetics, safety and tolerability, and immunogenicity of ocrelizumab administered subcutaneously to participants with multiple sclerosis (MS).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A: Cohorts A1-A4 | Experimental | Participants (participants pretreated with ocrelizumab) will receive a single injection of subcutaneous (SC) ocrelizumab co-mixed with rHuPH20 in the abdomen. For every new dose level, recruitment will be staggered by enrolling 1 participant in each cohort followed by a 48-hour waiting period to review safety and tolerability data by the Safety Monitoring Committee (SMC) prior to enrolling subsequent participants in the same cohort. Currently, the planned dose escalation steps for patients who enroll in Group A are as follows:
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| Group A: Cohort A5 | Experimental | In the non-randomized subphase, participants will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen. |
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| Group A: Cohort AA | Experimental | Participants will receive a single 600-mg dose ocrelizumab by intravenous (IV) infusion |
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| Group B: Cohorts B1-B4 | Experimental | Ocrelizumab treatment- naive participants will receive a minimum of 3 patients in Cohort B will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ocrelizumab | Drug | Administered by subcutaneous Injection |
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| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following subcutaneous (SC) administration | At predefined intervals from baseline through end of study (approximately 5 years) | |
| Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following single IV (intravenous Infusion)administration | At predefined intervals from baseline through end of study (approximately 5 years) | |
| Percentage of participants with adverse events | Baseline to end of study (approximately 5 years) | |
| Percentage of participants with change from baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters | Baseline to end of study (approximately 5 years) | |
| Incidence of local pain at site of injection assessed using Visual Analog Scale (VAS | Baseline to end of study (approximately 5 years) | |
| Incidence of local-injection reaction (ISR) assessed using Local Injection-Site Symptom Assessment (LISSA) | Baseline to end of study (approximately 5 years) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants with Anti-Drug Antibodies (ADAs) to ocrelizumab | Baseline to end of study (approximately 5 years) | |
| Percentage of Participants with Anti-Drug Antibodies (ADAs) to rHuPH20 | Baseline to end of study (approximately 5 years) |
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Inclusion Criteria:
treatment with IV ocrelizumab for at least 1 year prior to screening (i.e., at least two 600-mg doses of ocrelizumab separated by 24 weeks)
Women may be enrolled if post-menopausal unless the participant is receiving a hormonal therapy for her menopause or if surgically sterile (i.e., hysterectomy, complete bilateral oophorectomy).
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado | Aurora | Colorado | 80045 | United States | ||
| Georgetown University Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39460719 | Derived | Newsome SD, Goldstick L, Robertson DS, Bowen JD, Naismith RT, Townsend B, Figueiredo C, Kletzl H, Giraudon M, Bortolami O, Zecevic D, Giacobino C, Clinch S, Shen YA, Deol-Bhullar G, Bermel RA. Subcutaneous ocrelizumab in multiple sclerosis: Results of the Phase 1b OCARINA I study. Ann Clin Transl Neurol. 2024 Dec;11(12):3215-3226. doi: 10.1002/acn3.52229. Epub 2024 Oct 26. |
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| Ocrelizumab | Drug | Administered by Intravenous (IV) Injection |
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| rHuPH20 | Drug | Administered in a 2-mL glass vial as a sterile, single-use, injectable liquid to be manually mixed with SC ocrelizumab |
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| Washington D.C. |
| District of Columbia |
| 20007 |
| United States |
| The NeuroMedical Clinic of Central Louisiana | Alexandria | Louisiana | 71301 | United States |
| Ochsner Clinic Foundation | New Orleans | Louisiana | 70121 | United States |
| John Hopkins University School of Medicine | Baltimore | Maryland | 21287 | United States |
| University of Massachusetts Medical School | Worcester | Massachusetts | 01655 | United States |
| Wayne State University | Detroit | Michigan | 48201 | United States |
| Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis | Owosso | Michigan | 48867 | United States |
| Washington Univ School of Med | St Louis | Missouri | 63110 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| Cleveland Clinic Mellen Center | Cleveland | Ohio | 44195 | United States |
| UC Health Neurology | Dayton | Ohio | 45417 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| University of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
| Neurology Clinic PC | Cordova | Tennessee | 38018 | United States |
| University of Texas at Houston | Houston | Texas | 77030 | United States |
| Swedish Neuroscience Institute | Seattle | Washington | 98122 | United States |
| MultiCare Health System Institute for Research and Innovation | Tacoma | Washington | 98405 | United States |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C533411 | ocrelizumab |
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