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A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Participants With Guillain-Barré Syndrome (GBS)

Primary Purpose

Guillain-Barré Syndrome

Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Crovalimab
Placebo
Intravenous immunoglobulin therapy
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Guillain-Barré Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Body weight >= 40 kg at screening
  • Confirmed diagnosis of GBS according to National Institute of Neurological Disorders and Stroke (NINDS) classification system
  • Onset of weakness due to GBS within 2 weeks before randomization
  • Able to start the first dose of blinded study drug within 2 weeks of onset of weakness
  • Able to climb a flight of stairs prior to GBS
  • Unable to walk independently for >=10 meters (FG >=3) with deteriorating weakness as per investigator judgment, or FG 4 or FG 5 on the GBS-DS. These criteria must be satisfied during screening.
  • Undergoing or starting IVIg treatment (400 mg/kg QD for 5 days) prior to first blinded study drug administration. Participants must be able to receive the first dose of blinded study drug before the final dose of IVIg during the 5-day period of IVIg treatment.
  • A record of vaccination (<=3 years) against Neisseria meningitidis, Haemophilus influenzae type B, and Streptococcus pneumonia prior to initiation of blinded study drug, in accordance with most current local guidelines as applicable for patients with complement deficiency.
  • Adequate hepatic and renal function
  • For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for up to 11 months after the final dose of study treatment.

Exclusion Criteria:

  • Clear clinical and historical evidence of significant or disabling acute or chronic peripheral neuropathy of alternative etiology, chronic inflammatory demyelinating polyneuropathy, severe vitamin deficiency, porphyria, or diagnosis of Charcot Marie Tooth disease or other genetic neuropathy
  • History of requiring a permanent aid to walk prior to GBS
  • Treatment with plasmapheresis or PLEX after GBS diagnosis, or a plan to receive this treatment
  • Receipt of systemic immunosuppressive treatment within 4 weeks prior to randomization
  • Known or suspected hereditary complement deficiency
  • Known or suspected immune deficiency
  • Recent use (up to five half-lives) of treatment with complement inhibitors (e.g., 10 weeks for eculizumab, 41 weeks for ravulizumab)
  • History of Neisseria meningitidis infection within 12 months prior to screening and up to first blinded study drug administration (Day 1)
  • Contraindication that would prevent use of any class of antibiotics as Neisseria meningitides prophylaxis
  • Immunization with a live attenuated vaccine within 1 month before first blinded study drug administration (Day 1)
  • Participants who have been partially or fully vaccinated against SARS-CoV-2 with a locally approved vaccine are eligible to be enrolled in the study, 3 days or longer after inoculation.
  • Recent SARS-CoV-2 infection (defined by a positive PCR test within the 2-week period prior to screening), or ongoing symptoms of active COVID-19
  • Any systemic bacterial, viral, or fungal infection ongoing at screening and up to the first blinded study drug administration (Day 1) which, in the investigators' judgment, is active and could potentially be worsened by immunosuppression
  • Current hepatitis B, hepatitis C, or HIV infection
  • History of malignancy within 5 years prior to screening and up to the first blinded study drug administration (Day 1)
  • History of hypersensitivity, allergic, or anaphylactic reactions to crovalimab or IVIg, including hypersensitivity to human, humanized, or murine monoclonal antibodies, or known hypersensitivity to any constituent of the products
  • For participants with prior exposure to anti-CD20 agents, most recent anti-CD20 treatment within 6 months prior to screening
  • Substance abuse within 12 months prior to screening, in the investigator's judgment
  • Active suicidal ideation within 6 months prior to screening or history of suicide attempt within 3 years prior to screening
  • Concurrent disease, treatment, procedure or surgery, or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose any additional risk for the patient, or would, in the opinion of the investigator, preclude the patient's safe participation in and completion of the study
  • Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within 28 days of screening or within five half-lives of that investigational product, whichever is longer
  • Splenectomy <= 6 months prior to screening
  • Selective IgA deficiency with development of antibodies to IgA
  • Only applicable for participants receiving proline-containing IVIg products: History or ongoing hyperprolinaemia type I or II at screening
  • Only applicable for participants receiving sucrose/glucose/maltose-containing IVIg products: History of or ongoing diabetes mellitus or use of concomitant nephrotoxic medications
  • Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 11 months after the final dose of crovalimab.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Crovalimab

    Placebo

    Arm Description

    Participants will receive a single intravenous (IV) infusion of crovalimab on Day 1 based on body weight, followed by crovalimab subcutaneous (SC) injection on Days 2, 8, 15, and 22 for a total of 4 weeks. Additionally, intravenous immunoglobulin (IVIg) background therapy will be administered once a day (QD) for 5 days.

    Participants will receive a single IV infusion of placebo on Day 1 based on body weight, followed by placebo SC injections on Days 2, 8, 15, and 22 for a total of 4 weeks. Additionally, IVIg background therapy will be administered QD for 5 days.

    Outcomes

    Primary Outcome Measures

    Percentage of Participants who Reach Hughes Functional Grade (FG) Score ≤ 1 on the Guillain-Barré Syndrome Disability Scale (GBS-DS) at Week 24
    The Guillain-Barré Syndrome disability score (GBS DS) is used to assess the degree of functional disability of study participants. The scale consists of seven grades of functional disability ranging from 0 (healthy with no symptoms attributable to GBS) to 6 (death).

    Secondary Outcome Measures

    Time to Recover Independent Walking Assessed Using the 10-Meter Walk Test (10-MW)
    Defined as time from randomization to the first time point at which the participant is able to walk independently, assessed using the 10-MWT.
    Functional Outcome on GBS-DS at Week 8
    The Guillain-Barré Syndrome disability score (GBS DS) is used to assess the degree of functional disability of study participants. The scale consists of seven grades of functional disability ranging from 0 (healthy with no symptoms attributable to GBS) to 6 (death).
    Percentage of Inflammatory Rasch-Built Overall Disability Scale (I-RODS) Responders at Week 24
    Defined as a participant who is able to perform all activities assessed by the I-RODS with or without some difficulties (graded 1 or 2). I-RODs is a 24-item scale to rate a participant's general ability to function and complete activities of daily living. The items range in difficulty from very easy ("reading a newspaper/book" and "eating") to very difficult ("standing for hours" and "running"). The participant assigns a score between 0 and 3 (0: not possible, 1: possible with difficulty, 2: possible without any difficulty, 3: unable to perform before GBS [option 3 only available at the baseline visit]) to each item.
    Mean Post-Recovery Time
    Defined as the time from reaching FG ≤ 1 for the first time after randomization to Week 24
    Duration of Ventilator Support
    Percentage of Participants with Treatment Emergent Adverse Events
    Adverse events severity was determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) grading
    Percentage of Participants with Treatment Emergent Adverse Events Leading to Study Drug Discontinuation
    Percentage of Participants with Anti-Drug Antibodies to Crovalimab
    Serum Concentrations of Crovalimab

    Full Information

    First Posted
    August 8, 2022
    Last Updated
    December 14, 2022
    Sponsor
    Hoffmann-La Roche
    Collaborators
    Chugai Pharmaceutical Co., Ltd. (Sponsor in Taiwan and Japan)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05494619
    Brief Title
    A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Participants With Guillain-Barré Syndrome (GBS)
    Official Title
    A Phase III Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Patients With Guillain-Barré Syndrome
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2022
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    This study has been withdrawn due to an internal decision. The decision was not due to any safety concerns with study drug.
    Study Start Date
    November 30, 2022 (Anticipated)
    Primary Completion Date
    March 19, 2026 (Anticipated)
    Study Completion Date
    September 30, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Hoffmann-La Roche
    Collaborators
    Chugai Pharmaceutical Co., Ltd. (Sponsor in Taiwan and Japan)

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of crovalimab compared with placebo as an add-on therapy to intravenous immunoglobulin (IVIg) in participants with severe GBS.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Guillain-Barré Syndrome

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Crovalimab
    Arm Type
    Experimental
    Arm Description
    Participants will receive a single intravenous (IV) infusion of crovalimab on Day 1 based on body weight, followed by crovalimab subcutaneous (SC) injection on Days 2, 8, 15, and 22 for a total of 4 weeks. Additionally, intravenous immunoglobulin (IVIg) background therapy will be administered once a day (QD) for 5 days.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Participants will receive a single IV infusion of placebo on Day 1 based on body weight, followed by placebo SC injections on Days 2, 8, 15, and 22 for a total of 4 weeks. Additionally, IVIg background therapy will be administered QD for 5 days.
    Intervention Type
    Drug
    Intervention Name(s)
    Crovalimab
    Intervention Description
    Crovalimab will be administered at a dose of 1000 milligrams (mg) IV (for participants with body weight ≥ 40 kilograms (kg) and <100 kg) or 1500 mg IV (for participants with body weight ≥ 100 kg) on Day 1, followed by crovalimab 340 mg SC injections on Days 2, 8, 15 and 22 in all participants.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo will be administered IV on Day 1 at a dose of 1000 mg for participants with body weight ≥ 40 kg to < 100 kg, or 1500 mg for participants with body weight ≥ 100 kg. It will be administered SC on Days 2, 8, 15, and 22 at a dose 340 mg in all participants.
    Intervention Type
    Drug
    Intervention Name(s)
    Intravenous immunoglobulin therapy
    Intervention Description
    All participants will receive background therapy of IVIg at a dose of 400 milligrams/kilograms (mg/kg) QD for 5 days.
    Primary Outcome Measure Information:
    Title
    Percentage of Participants who Reach Hughes Functional Grade (FG) Score ≤ 1 on the Guillain-Barré Syndrome Disability Scale (GBS-DS) at Week 24
    Description
    The Guillain-Barré Syndrome disability score (GBS DS) is used to assess the degree of functional disability of study participants. The scale consists of seven grades of functional disability ranging from 0 (healthy with no symptoms attributable to GBS) to 6 (death).
    Time Frame
    Week 24
    Secondary Outcome Measure Information:
    Title
    Time to Recover Independent Walking Assessed Using the 10-Meter Walk Test (10-MW)
    Description
    Defined as time from randomization to the first time point at which the participant is able to walk independently, assessed using the 10-MWT.
    Time Frame
    Up to approximately 52 weeks
    Title
    Functional Outcome on GBS-DS at Week 8
    Description
    The Guillain-Barré Syndrome disability score (GBS DS) is used to assess the degree of functional disability of study participants. The scale consists of seven grades of functional disability ranging from 0 (healthy with no symptoms attributable to GBS) to 6 (death).
    Time Frame
    Week 8
    Title
    Percentage of Inflammatory Rasch-Built Overall Disability Scale (I-RODS) Responders at Week 24
    Description
    Defined as a participant who is able to perform all activities assessed by the I-RODS with or without some difficulties (graded 1 or 2). I-RODs is a 24-item scale to rate a participant's general ability to function and complete activities of daily living. The items range in difficulty from very easy ("reading a newspaper/book" and "eating") to very difficult ("standing for hours" and "running"). The participant assigns a score between 0 and 3 (0: not possible, 1: possible with difficulty, 2: possible without any difficulty, 3: unable to perform before GBS [option 3 only available at the baseline visit]) to each item.
    Time Frame
    Week 24
    Title
    Mean Post-Recovery Time
    Description
    Defined as the time from reaching FG ≤ 1 for the first time after randomization to Week 24
    Time Frame
    Randomization to Week 24
    Title
    Duration of Ventilator Support
    Time Frame
    Randomization to Week 24
    Title
    Percentage of Participants with Treatment Emergent Adverse Events
    Description
    Adverse events severity was determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) grading
    Time Frame
    Up to approximately 52 weeks
    Title
    Percentage of Participants with Treatment Emergent Adverse Events Leading to Study Drug Discontinuation
    Time Frame
    Up to approximately 52 weeks
    Title
    Percentage of Participants with Anti-Drug Antibodies to Crovalimab
    Time Frame
    Up to approximately 52 weeks
    Title
    Serum Concentrations of Crovalimab
    Time Frame
    From Day 1 up to Week 52

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Body weight >= 40 kg at screening Confirmed diagnosis of GBS according to National Institute of Neurological Disorders and Stroke (NINDS) classification system Onset of weakness due to GBS within 2 weeks before randomization Able to start the first dose of blinded study drug within 2 weeks of onset of weakness Able to climb a flight of stairs prior to GBS Unable to walk independently for >=10 meters (FG >=3) with deteriorating weakness as per investigator judgment, or FG 4 or FG 5 on the GBS-DS. These criteria must be satisfied during screening. Undergoing or starting IVIg treatment (400 mg/kg QD for 5 days) prior to first blinded study drug administration. Participants must be able to receive the first dose of blinded study drug before the final dose of IVIg during the 5-day period of IVIg treatment. A record of vaccination (<=3 years) against Neisseria meningitidis, Haemophilus influenzae type B, and Streptococcus pneumonia prior to initiation of blinded study drug, in accordance with most current local guidelines as applicable for patients with complement deficiency. Adequate hepatic and renal function For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for up to 11 months after the final dose of study treatment. Exclusion Criteria: Clear clinical and historical evidence of significant or disabling acute or chronic peripheral neuropathy of alternative etiology, chronic inflammatory demyelinating polyneuropathy, severe vitamin deficiency, porphyria, or diagnosis of Charcot Marie Tooth disease or other genetic neuropathy History of requiring a permanent aid to walk prior to GBS Treatment with plasmapheresis or PLEX after GBS diagnosis, or a plan to receive this treatment Receipt of systemic immunosuppressive treatment within 4 weeks prior to randomization Known or suspected hereditary complement deficiency Known or suspected immune deficiency Recent use (up to five half-lives) of treatment with complement inhibitors (e.g., 10 weeks for eculizumab, 41 weeks for ravulizumab) History of Neisseria meningitidis infection within 12 months prior to screening and up to first blinded study drug administration (Day 1) Contraindication that would prevent use of any class of antibiotics as Neisseria meningitides prophylaxis Immunization with a live attenuated vaccine within 1 month before first blinded study drug administration (Day 1) Participants who have been partially or fully vaccinated against SARS-CoV-2 with a locally approved vaccine are eligible to be enrolled in the study, 3 days or longer after inoculation. Recent SARS-CoV-2 infection (defined by a positive PCR test within the 2-week period prior to screening), or ongoing symptoms of active COVID-19 Any systemic bacterial, viral, or fungal infection ongoing at screening and up to the first blinded study drug administration (Day 1) which, in the investigators' judgment, is active and could potentially be worsened by immunosuppression Current hepatitis B, hepatitis C, or HIV infection History of malignancy within 5 years prior to screening and up to the first blinded study drug administration (Day 1) History of hypersensitivity, allergic, or anaphylactic reactions to crovalimab or IVIg, including hypersensitivity to human, humanized, or murine monoclonal antibodies, or known hypersensitivity to any constituent of the products For participants with prior exposure to anti-CD20 agents, most recent anti-CD20 treatment within 6 months prior to screening Substance abuse within 12 months prior to screening, in the investigator's judgment Active suicidal ideation within 6 months prior to screening or history of suicide attempt within 3 years prior to screening Concurrent disease, treatment, procedure or surgery, or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose any additional risk for the patient, or would, in the opinion of the investigator, preclude the patient's safe participation in and completion of the study Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within 28 days of screening or within five half-lives of that investigational product, whichever is longer Splenectomy <= 6 months prior to screening Selective IgA deficiency with development of antibodies to IgA Only applicable for participants receiving proline-containing IVIg products: History or ongoing hyperprolinaemia type I or II at screening Only applicable for participants receiving sucrose/glucose/maltose-containing IVIg products: History of or ongoing diabetes mellitus or use of concomitant nephrotoxic medications Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 11 months after the final dose of crovalimab.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Clinical Trials
    Organizational Affiliation
    Hoffmann-La Roche
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm)

    Learn more about this trial

    A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Participants With Guillain-Barré Syndrome (GBS)

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