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OpenTrials
Completed

NCT Number: NCT02545868

A Study to Evaluate the Effects of Ocrelizumab on Immune Responses In Participants With Relapsing Forms of Multiple Sclerosis

This multicenter, randomized, open-label study will evaluate the immune response to vaccines (tetanus toxoid [TT]-containing adsorbed vaccine, 23-valent pneumococcal polysaccharide vaccine [23-PPV] either unboosted or boosted with 13-valent pneumococcal conjugate vaccine [13-PCV], influenza vaccine, keyhole limpet hemocyanin [KLH]) after administration of a dose of ocrelizumab (OCR) in participants with relapsing multiple sclerosis (RMS).

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Key information

Conditions

Multiple Sclerosis, Relapsing-Remitting Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Multiple Sclerosis Nervous System Diseases

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University of Calgary, Calgary, Alberta, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosis of RMS in accordance with the revised McDonald criteria
  • Received at least one previous immunization against TT or tetanus and diphtheria (DT/Td) or tetanus, diphtheria, and acellular pertussis (DTaP/Tdap)
  • Expanded Disability Status Scale (EDSS) at Screening from 0 to 5.5 points, inclusive
  • For sexually active female participants of reproductive potential, use of reliable means of contraception

Exclusion criteria

  • Contraindications for or intolerance to oral or IV corticosteroids, including IV methylprednisolone, according to the country label
  • Known presence of other neurologic disorders
  • Treatment with any investigational agent within 24 weeks of screening or 5 half-lives of the investigational drug, whichever is longer, or treatment with any experimental procedure for multiple sclerosis

Treatment and study plan

23-PPV

Biological

The 23-PPV vaccine will be given as a 0.5-milliliter (mL) intramuscular (IM) injection in the deltoid muscle on Day 112 (Group A) or Day 28 (Group B).

13-PCV Booster

Biological

The 13-PCV booster will be given as an IM injection in the deltoid muscle on Day 140 (select participants in Group A).

influenza vaccine

Biological

The influenza vaccine will be given as an IM injection in the deltoid muscle at any time between Day 85 and Day 144 (select participants in Group A) or any time between Day 1 and Day 85 (Group B).

KLH

Biological

KLH will be given as a 1-mg subcutaneous (SC) injection on Days 84, 112, and 140 (Group A) or Days 1, 28, and 56 (Group B).

OCR

Drug

OCR will be given as an intravenous (IV) infusion at a dose of 600 mg, with the first dose given as two infusions of 300mg 14 days apart, according to the specifications described in the corresponding Group A and Group B arms.

Other names: RO4964913, PRO70769, rhuMAb 2H7

TT Vaccine

Biological

The TT-containing adsorbed vaccine will be given as a 0.5-mL IM injection in the deltoid muscle on Day 85 (Group A) or Day 1 (Group B).

Primary outcomes

  1. Percentage of Participants With Positive Response to TT Vaccine Measured 8 Weeks After TT Vaccine

    Time frame: 8 weeks after TT vaccine

    For participants with pre-vaccination tetanus antibody titers < 0.1 IU/mL, a positive response was defined as an antibody titer >/= 0.2 IU/mL measured 8 weeks after vaccination. For participants with pre-vaccination tetanus antibody titers >/= 0.1 IU/mL, a positive response was defined as at least a 4-fold increase in antibody titers measured 8 weeks after vaccination compared with pre-vaccination levels.

Secondary outcomes

  1. Percentage of Participants With Positive Response to TT Vaccine Measured 4 Weeks After TT Vaccine

    Time frame: 4 weeks after TT vaccine

    For participants with pre-vaccination tetanus antibody titers < 0.1 IU/mL, a positive response was defined as an antibody titer >/= 0.2 IU/mL measured 4 weeks after vaccination. For participants with pre-vaccination tetanus antibody titers >/= 0.1 IU/mL, a positive response was defined as at least a 4-fold increase in antibody titers measured 4 weeks after vaccination compared with pre-vaccination levels.

  2. Percentage of Participants With Tetanus Antibody Titer >/=0.2 IU/mL or 2-Fold Increase in Tetanus Antibody Titers

    Time frame: 4 weeks after TT vaccine

    For participants with pre-vaccination tetanus antibody titers < 0.1 IU/mL, a positive response was defined as an antibody titer >/= 0.2 IU/mL measured 4 weeks after vaccination. For participants with pre-vaccination tetanus antibody titers >/= 0.1 IU/mL, a positive response was defined as at least a 2-fold increase in antibody titers measured 4 weeks after vaccination compared with pre-vaccination levels.

  3. Mean Levels of Anti-Tetanus Antibody

    Time frame: Immediately prior to and at 4 and 8 weeks after TT vaccine

    Anti-tetanus antibody levels were assessed by enzyme-linked immunosorbent assay (ELISA).

  4. Mean Levels of Anti-KLH Antibody: Immunoglobulin (Ig) G

    Time frame: Immediately prior to first KLH administration and 4, 8, and 12 weeks after first KLH administration

    Anti-KLH antibody levels were assessed by ELISA.

  5. Mean Levels of Anti-KLH Antibody: Ig M

    Time frame: Immediately prior to first KLH administration and 4, 8, and 12 weeks after first KLH administration

    Anti-KLH antibody levels were assessed by ELISA.

  6. Percentage of Participants With Positive Response Against Individual Pneumococcal Serotypes in 23-PPV

    Time frame: 4 weeks after 23-PPV

    Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or greater than (>) 1 microgram per milliliter (mcg/mL) rise compared with pre-vaccination levels.

  7. Percentage of Participants With Positive Response Against >/=2 Pneumococcal Serotypes

    Time frame: 4 weeks after 23-PPV

    Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or > 1 mcg/mL rise compared with pre-vaccination levels.

  8. Percentage of Participants With Positive Response Against >/=12 Pneumococcal Serotypes

    Time frame: 4 weeks after 23-PPV

    Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or > 1 mcg/mL rise compared with pre-vaccination levels.

  9. Mean Levels of Anti-Pneumococcal Antibody

    Time frame: Immediately prior to and 4 weeks after 23-PPV

    Serotype-specific antibody levels (IgG) were assessed by bead-based multi-analyte immunodetection (MAID).

  10. Percentage of Participants With Positive Response Against Individual Pneumococcal Serotypes in 13-PCV

    Time frame: 8 weeks after 23-PPV, which was 4 weeks after Group A1 participants received 13-PCV

    Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or > 1 mcg/mL rise compared with pre-vaccination levels.

  11. Mean Level of Anti-Pneumococcal Antibody

    Time frame: Immediately prior to 23-PPV and 4 and 8 weeks after 23-PPV

    Serotype-specific antibody levels (IgG) were assessed by bead-based multi-analyte immunodetection (MAID).

  12. Percentage of Participants With Seroprotection

    Time frame: 4 weeks after seasonal influenza vaccine administration

    Seroprotection was defined as specific hemagglutination inhibition (HI) titers >40 at 4 weeks after vaccination.

  13. Percentage of Participants With 2-Fold Increase in Strain-Specific HI Titers

    Time frame: 4 weeks after seasonal influenza vaccine administration

    2-fold increase from prevaccination HI titer.

  14. Percentage of Participants With 4-Fold Increase in Strain-Specific HI Titers

    Time frame: 4 weeks after seasonal influenza vaccine administration

    4-fold increase from prevaccination HI titer.

  15. Percentage of Participants With Seroconversion

    Time frame: 4 weeks after influenza immunization

    Seroconversion at 4 weeks after vaccination defined, as per protocol, as a prevaccination HI titer <10 and an HI titer >40 at 4 weeks after vaccination. Seroconversion at 4 weeks after vaccination, defined per FDA guidance, as either a) a pre-vaccination HI titer <10 and HI titer >/= 40 at 4 weeks after vaccination, or b) a pre-vaccination HI titer >/= 10 and at least 4-fold increase in HI antibody titer at 4 weeks after vaccination.

  16. Strain-Specific Geometric Mean Titer Levels

    Time frame: Baseline and Week 4

    Geometric mean titers (GMTs) in participants in Groups A2 and B were measured 4 weeks after vaccination.

  17. Ratio of Strain-Specific Geometric Mean Titer Levels Postvaccination to Prevaccination

    Time frame: Immediately prior to and 4 weeks after influenza vaccine

    Strain-specific GMT ratios were calculated as post-vaccination : pre-vaccination.

  18. Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions

    Time frame: Baseline

    MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.

  19. MRI Parameters: Number of T2 Lesions

    Time frame: Baseline

    MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.

  20. MRI Parameters: Categorical Number of T2 Lesions

    Time frame: Baseline

    MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.

  21. MRI Parameters: Number of Gadolinium (Gd)-Enhancing T1 Lesions

    Time frame: Baseline

    MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.

  22. MRI Parameters: Categorical Number of Gd-enhancing T1 Lesions

    Time frame: Baseline

    MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.

  23. MRI Parameters: Normalized Brain Volume

    Time frame: Baseline

    MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.

  24. MRI Parameters: Volume of T2 Lesions: White Matter Volume

    Time frame: Baseline

    MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.

  25. MRI Parameters: Cortical Grey Matter Volume

    Time frame: Baseline

    MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.

  26. MRI Parameters: T1 Unenhancing Lesion Volume

    Time frame: Baseline

    MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.

  27. MRI Parameters: Total Number of Lesions

    Time frame: Baseline

    MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.

  28. Cellular Immune Response Assessed by Flow Cytometry

    Time frame: Days 1, 15, 85, 112, 140 and 169

    Flow cytometry is a laser-based technology commonly used for cell counting and sorting. In this study, this outcome measure is focusing on a single variable, CD19 count (total B cells). LLN = 80 cells/ul.

    Repleted is defined as CD19 >= LLN or baseline, whichever is lower.

  29. Total Immunoglobulin

    Time frame: Days 1, 85, and 169

  30. Percentage of Participants With Anti-Drug Antibody Formation

    Time frame: Up to 24 Weeks (ISP)

    Anti-Drug Antibodies (ADA) may induce unwanted side effects, especially in biotechnology-derived pharmaceuticals, such as therapeutic antibodies and growth factors.

  31. Percentage of Participants With Adverse Events (AEs), Serious AEs, or AEs Leading to Study Discontinuation

    Time frame: During ISP (24 weeks for Group A and 12 weeks for Group B)

    An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious AE is any AE that is fatal, life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug, or is a significant medical event in the investigator's judgment.

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

A Phase IIIB, Multicenter, Randomized, Parallel-Group, Open-Label Study to Evaluate the Effects of Ocrelizumab on Immune Responses in Patients With Relapsing Forms of Multiple Sclerosis

Important dates

Study start
2015
Primary completion
2017
Study completion
2021
First posted
Sep 10, 2015
Registry last updated
Mar 26, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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