Guillain-Barré syndrome (GBS) MedDRA version: 22.1 Level: PT Classification code 10018767 Term: Guillain-Barre syndrome System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: LLT Classification code 10018766 Term: Guillain Barre syndrome System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: LLT Classification code 10042812 Term: Syndrome Guillain-Barre System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Crovalimab
Product Code: RO7112689
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: CROVALIMAB
Current Sponsor code: RO7112689
Concentration unit
Sponsors
Roche Farma S. A. U. que realiza el ensayo en España y que actúa como representante F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age >= 18 at the time of signing Informed Consent Form • 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 (=65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
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: • Only applicable for participants receiving sucrose/glucose/maltose-containing IVIg products • Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 24 weeks after the final dose of crovalimab
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of crovalimab compared with placebo as an add-on therapy to IVIg based on proportion of participants who reach Hughes functional grade (FG) <=1 on Guillain-Barré Syndrome Disability Scale (GBS-DS);Secondary Objective: • To evaluate the efficacy of crovalimab compared with placebo as an add-on therapy to IVIg based on time to recover independent walking, functional outcome on GBS-DS, proportion of inflammatory Rasch-built Overall Disability Scale (I-RODS) responders, average post recovery time and duration of ventilator support • To evaluate the safety of crovalimab compared with placebo as an add-on therapy to IVIg • To evaluate the immune response to crovalimab as an add-on therapy to IVIg • To characterize crovalimab PK profile as an add-on therapy to IVIg;Primary end point(s): 1. Proportion of participants who reach FG <=1 on GBS-DS at Week 24;Timepoint(s) of evaluation of this end point: 1. Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Time to recover independent walking, defined as time from randomization to the first time point at which the participant is able to walk independently, as assessed using 10-MWT 2. Functional outcome on GBS-DS at Week 8 3. Proportion of 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) 4. Average postrecovery time, defined as the time from reaching FG <= 1 for the first time after randomization to Week 24 5. Duration of ventilator support during the 24 weeks following randomization 6. Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0 grading 7. Change from baseline in targeted vital signs and clinical laboratory test results 8. Incidence and severity of injection site reactions, infusion-related reactions, and hypersensitivity 9. Incidence and severity of infections (including meningococcal meningitis) 10. Incidence of adverse events leading to study drug discontinuation 11. Prevalence of ADAs at baseline and incidence of ADAs during the study 12. Descriptive summary of crovalimab serum concentrations per time point;Timepoint(s) of evaluation of this end point: 1. Day 1, Day 2, Week 1-4, Week 8, 12, 20, 24, 28, 36, 52 2. Week 8 3. Week 24 4-5. Randomization to Week 24 6-10. Up to 52 weeks 11. Day 1, Day 2, Week 1-4, Week 8, 12, 20, 24, 28, 36, 52 12. Day 1, Week 1-4, Week 8, 12, 20, 24, 28, 36, 52 | — |
Countries
Australia, Canada, India, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Peru, Spain, Turkey, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed