Guillain-Barré SyndromePhase 3NCT05494619
A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Participants With Guillain-Barré Syndrome (GBS)
A Phase 3 study testing Crovalimab and Intravenous immunoglobulin therapy in people with Guillain-Barré Syndrome, run by Hoffmann-La Roche.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Guillain-Barré Syndrome
- What is being tested?
- Crovalimab and Intravenous immunoglobulin therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 30 Nov 2022to 30 Sep 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
About this study
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
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.
- Conditions
- Guillain-Barré Syndrome
- Being tested
- Crovalimab, Placebo, Intravenous immunoglobulin therapy
- Medical subject headings
- Guillain-Barre Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CrovalimabDrug
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.
PlaceboDrug
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.
Intravenous immunoglobulin therapyDrug
All participants will receive background therapy of IVIg at a dose of 400 milligrams/kilograms (mg/kg) QD for 5 days.
| Study group | Role | What they receive |
|---|---|---|
| Crovalimab | Experimental | 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. Receives: Drug: Crovalimab; Drug: Intravenous immunoglobulin therapy |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo; Drug: Intravenous immunoglobulin therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Week 24
Secondary outcomes (9)
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.
Measured: Up to approximately 52 weeks
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).
Measured: Week 8
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.
Measured: Week 24
Mean Post-Recovery Time
Defined as the time from reaching FG ≤ 1 for the first time after randomization to Week 24
Measured: Randomization to Week 24
Duration of Ventilator Support
Measured: Randomization to Week 24
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
Measured: Up to approximately 52 weeks
Percentage of Participants with Treatment Emergent Adverse Events Leading to Study Drug Discontinuation
Measured: Up to approximately 52 weeks
Percentage of Participants with Anti-Drug Antibodies to Crovalimab
Measured: Up to approximately 52 weeks
Serum Concentrations of Crovalimab
Measured: From Day 1 up to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2022
- Study start30 Nov 2022 (estimated)
- Primary completion19 Mar 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
Why it stopped: This study has been withdrawn due to an internal decision. The decision was not due to any safety concerns with study drug.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Guillain-Barré SyndromeStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Chugai Pharmaceutical Co., Ltd. (Sponsor in Taiwan and Japan)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05494619
- Sponsor's protocol ID
- BN43118
- Other IDs
- 2021-002968-49
- Status last verified
- Dec 2022
- First submitted
- 8 Aug 2022
- Last updated
- 15 Dec 2022
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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)
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05494619
- Acronym / sponsor ID
- BN43118
- Conditions
- Guillain-Barré Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: This study has been withdrawn due to an internal decision. The decision was not due to any safety concerns with study drug.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Collaborators
- Chugai Pharmaceutical Co., Ltd. (Sponsor in Taiwan and Japan)
- Study start
- 30 Nov 2022 (estimated)
- Primary completion
- 19 Mar 2026 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 10 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Crovalimab | Experimental | Drug: Crovalimab, Drug: Intravenous immunoglobulin therapyParticipants 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. |
| Placebo | Placebo comparator | Drug: Placebo, Drug: Intravenous immunoglobulin therapyParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CrovalimabCrovalimab 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. | Drug | Crovalimab |
| PlaceboPlacebo 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. | Drug | Placebo |
| Intravenous immunoglobulin therapyAll participants will receive background therapy of IVIg at a dose of 400 milligrams/kilograms (mg/kg) QD for 5 days. | Drug | Crovalimab, Placebo |
Primary outcome
Percentage of Participants who Reach Hughes Functional Grade (FG) Score ≤ 1 on the Guillain-Barré Syndrome Disability Scale (GBS-DS) at Week 24
Time frame: 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).
9 secondary outcomes
Time to Recover Independent Walking Assessed Using the 10-Meter Walk Test (10-MW)
Time frame: Up to approximately 52 weeks
Functional Outcome on GBS-DS at Week 8
Time frame: Week 8
Percentage of Inflammatory Rasch-Built Overall Disability Scale (I-RODS) Responders at Week 24
Time frame: Week 24
Mean Post-Recovery Time
Time frame: Randomization to Week 24
Duration of Ventilator Support
Time frame: Randomization to Week 24
Percentage of Participants with Treatment Emergent Adverse Events
Time frame: Up to approximately 52 weeks
Percentage of Participants with Treatment Emergent Adverse Events Leading to Study Drug Discontinuation
Time frame: Up to approximately 52 weeks
Percentage of Participants with Anti-Drug Antibodies to Crovalimab
Time frame: Up to approximately 52 weeks
Serum Concentrations of Crovalimab
Time frame: From Day 1 up to Week 52
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2022.
- Individual participant dataSharing planned: Yes. 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)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Crovalimab and Intravenous immunoglobulin therapy in people with Guillain-Barré Syndrome, run by Hoffmann-La Roche.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants who Reach Hughes Functional Grade (FG) Score ≤ 1 on the Guillain-Barré Syndrome Disability Scale (GBS-DS) at Week 24 (time frame: Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2022.