Gullain Barre SyndromePhase 2NCT02493725
JET-GBS - Japanese Eculizumab Trial for GBS
A Phase 2 study testing Eculizumab in people with Gullain Barre Syndrome, run by Chiba University at 13 sites in Japan.
Trial summary
Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy that usually follows an antecedent infection and causes acute neuromuscular paralysis. GBS is currently classified into the two major subtypes: a classical demyelinating type and axonal variant type. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Gullain Barre Syndrome
- What is being tested?
- Eculizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 13 sitesJapan
- Study dates
- Jul 2015to Oct 2016
- Phase
- Phase 2
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects ≥ 18 years of age at the time of obtaining informed consent.
- Patients with onset of muscular weakness due to GBS less than 2 weeks before the time of consent.
- Patients unable to walk unaided for ≥5 meters (progressively deteriorating FG(Functional Grade)3 or FG 4-5).
- Patients who are already on IVIg or deemed eligible for and who will start IVIg (Generally, administration of 400mg/kg over 5 days).
- Patients who can start their first dose of eculizumab within 2 weeks from onset of weakness and before the end of the IVIg treatment period.
- Female subjects of child bearing potential with a negative result in their pregnancy test. All subjects must be able to practice an effective, reliable, medically approved method of contraception during the IP(Intraperitoneal) administration period and up to 5 months after IP administration is ended.
- Patients who can be hospitalized during IP administration period.
- Patients who have signed the informed consent form.
Who cannot join
- Patients who are being considered for or are already on plasmapheresis.
- Patients who are pregnant or lactating.
- Patients showing clear clinical evidence of peripheral polyneuropathy other than GBS, e.g. diabetic (except for mild sensory disturbance) or severe vitamin B1 deficiency related.
- Patients who have received immunosuppressive treatment (e.g. azathioprine, cyclosporine, tacrolimus, or >20 mg prednisolone daily) during the 4 weeks prior to providing consent.
- Patients who are known to have severe concurrent disease (such as malignancy with uncontrolled primary tumors or metastatic lesions, severe cardiovascular disease, severe COPD(chronic obstructive pulmonary disease ), or TB).
- Patients who are unable to comply with study procedures and the treatment regimen.
Show all 15Show fewer
- Patients who have received rituximab within 24 weeks prior to providing consent.
- Patients with a history of or unresolved Neisseria meningitides.
- Patients with active infectious diseases determined to be clinically severe by the principal investigator or sub-investigator that are not being appropriately treated with antibiotics.
- Patients who that cannot be treated with antibiotic prophylaxis due to allergies.
- Patients who are allergic to eculizumab.
- Patients who are known to have or are suspected of having hereditary complement deficiencies.
- Patients who have been administered another investigational product within 12 weeks prior to providing consent or are currently participating in another trial.
- Patients with any condition that, in the opinion of the principal investigator or sub-investigator, could increase the patient's risk by participating in the study or confound the outcome of the study.
- Patients who have a history of Eculizumab treatment for GBS.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Japan13 sites
Tokyo Medical and Dental University Hospital
Bunkyo-ku, Tokyo
Tokyo University Hospital
Bunkyo-ku, Tokyo
Chiba University Hospital
Chiba
Kyushu University Hospital
Fukuoka
Kobe City Medical Center General Hospital
Kobe, Hyōgo
Dokkyo Medical University Hospital
Mibu, Tochigi
Nagoya University Hospital
Nagoya, Aichi-ken
Kindai University Hospital
Ōsaka-sayama, Osaka
Kitasato University Hospital
Sagamihara, Kanagawa
Hokkaido University Hospital
Sapporo, Hokkaido
Keio University Hospital
Shinjuku-ku, Tokyo
National Defence Medical College Hospital
Tokorozawa, Saitama
Tokushima University Hospital
Tokushima
About this study
Official title: A PROSPECTIVE, MULTI-CENTER, PHASE II STUDY TO EVALUATE THE SAFETY AND EFFICACY OF ECULIZUMAB IN SUBJECTS WITH GUILLAIN-BARRÉ SYNDROME
Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy that usually follows an antecedent infection and causes acute neuromuscular paralysis. GBS is currently classified into the two major subtypes: a classical demyelinating type and axonal variant type. Whereas in Europe and North America demyelinating GBS is the major subtype, in East Asia and Central and South America, axonal GBS is found in 30~65% of patients. Although the pathophysiology of GBS has not been fully understood, major advances have been made in understanding the pathophysiology particularly for the axonal form of GBS. It is now established that axonal GBS is caused by molecular mimicry of human gangliosides by the Campylobacter jejuni lipo-oligosaccharides. Autoantibodies bind to GM1 or GD1a at the nodes of Ranvier, activate complements, and disrupt sodium channel clusters and axo-glial junctions, resulting in the nerve conduction failure and muscle weakness. C. jejuni infection induces production of antibodies, which cross-react with gangliosides on the human nerve axolemma, and activate the complements, resulting in formation of membrane attack complex (MAC). The pathology leads to axonal degeneration.
The standard treatments for GBS are plasma exchange and intravenous immunoglobulin and the disease progression reaches its nadir within 4 weeks. However, during the acute phase, 18-28 % of the patients require artificial ventilation and 4.1-6.3 % of the patients die of complications. Recovery takes several months or years, and 16.7-19.7 % of the patients still require aid to walk one year after onset. Because of such serious disability of GBS patients, an alternative novel therapy that can prevent death during acute phase or severe sequelae is needed.
Read more
Eculizumab is a humanized monoclonal antibody of murine anti-human C5 antibody and specifically binds to the final activation complement component C5 and inhibits MAC formation by suppressing the cleavage reaction of C5 into C5a and C5b. The efficacy of eculizumab against GBS has been shown in a model of axonal GBS. At present, there are no animal models of demyelinating GBS. However, autopsy studies have shown that C3d and C5b-9 (MAC) are deposited on the Schwan cells, and therefore eculizumab can be effective also for demyelinating GBS.
This clinical trial will be conducted to investigate the efficacy and safety of eculizumab for GBS to warrant future global clinical trials. Moreover, we also study the relationship between the efficacy and clinical subtypes of GBS, such as axonal or demyelinating form. Our trial will provide insights on whether the future global developmental plan should target the whole spectrum of GBS world-wide or focusing on Asia and South America.
- Conditions
- Gullain Barre Syndrome
- Being tested
- Eculizumab, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EculizumabDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Eculizumab | Active comparator | Eculizumab, 900 mg intravenously once a week Receives: Drug: Eculizumab |
| Placebo | Placebo comparator | Matched placebo, intravenously once a week Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
[Safety] Expressed frequency and severity of incidence of AE/SAEs after treatment with investigational product.
Measured: 6 months
[Efficacy] Proportion of subjects who reach a score of FG2 or lower on the Hughes functional grading scale at week 4（Response Rate）
Measured: 4 weeks
Secondary outcomes (16)
Proportion of subjects with improvement of one or more scores on the functional grading scale at each visit
Measured: 6 months
Proportion of subjects who are able to walk unaided (FG2 or lower) at each visit
Measured: 6 months
Duration required for improvement by at least one grade on the Hughes functional grading scale
Measured: 6 months
Proportion of subjects who reach FG1 or 0 at week 24
Measured: 6 months
Change in the FG score between peak disability score and the scores at each visit
Measured: 6 months
Proportion of subjects with a clinically relevant improvement in the R-ODS score. An increase in the R-ODS score (0-48) converted to the centile metric score (0-100) by at least six points at each visit
Measured: 6 months
Proportion of subjects with a clinically relevant improvement in ONLS. (a decrease in the ONLS score from baseline by at least 1 point) at each visit
Measured: 6months
Proportion and frequency of subjects who require ventilatory support (F 5)
Measured: 4 weeks
Duration of ventilatory support
Measured: 8 weeks
Occurrence of relapse from the start of the IP(Investigational Product) administration period until the end of the post IP period
Measured: 2 years
Overall survival from the start of the IP administration period until the end of the post IP period (OS)
Measured: 6 months
Change in grip strength at each visit from baseline
Measured: 6 months
Change in results of the manual muscle test (MMT score) at each visit from baseline
Measured: 6 months
Change in the rate and results of below measures on the nerve conduction test parameter from baseline:Median and ulnar nerve 's CMAP amplitude, distal latency, F wave latency , SNAP amplitude, motor sensory nerve conduction velocity
Measured: 6 months
Change in vital capacity and % vital capacity at each visit from baseline
Measured: 6 months
Proportion of patients who undergo re-administration of IVIg
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2015 (estimated)
- Study startJul 2015
- Primary completionMay 2016
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Gullain Barre SyndromeStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiba University
- Sponsor type
- University, hospital or other
- Collaborators
- Japan Agency for Medical Research and Development
- Responsible party
- Principal investigator, Satoshi Kuwabara, Chiba University
- Investigators
- Satoshi Kuwabara, MD, Principal investigator, Chiba University Graduate School of Medicine Department of neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02493725
- Sponsor's protocol ID
- 100069
- Status last verified
- Oct 2017
- First submitted
- 7 Jul 2015
- Last updated
- 11 Oct 2017
- Results posted
- No
Publications
Misawa S, Kuwabara S, Sato Y, Yamaguchi N, Nagashima K, Katayama K, Sekiguchi Y, Iwai Y, Amino H, Suichi T, Yokota T, Nishida Y, Kanouchi T, Kohara N, Kawamoto M, Ishii J, Kuwahara M, Suzuki H, Hirata K, Kokubun N, Masuda R, Kaneko J, Yabe I, Sasaki H, Kaida KI, Takazaki H, Suzuki N, Suzuki S, Nodera H, Matsui N, Tsuji S, Koike H, Yamasaki R, Kusunoki S; Japanese Eculizumab Trial for GBS (JET-GBS) Study Group. Safety and efficacy of eculizumab in Guillain-Barre syndrome: a multicentre, double-blind, randomised phase 2 trial. Lancet Neurol. 2018 Jun;17(6):519-529. doi: 10.1016/S1474-4422(18)30114-5. Epub 2018 Apr 21.
PubMed 29685815Yamaguchi N, Misawa S, Sato Y, Nagashima K, Katayama K, Sekiguchi Y, Iwai Y, Amino H, Suichi T, Yokota T, Nishida Y, Kohara N, Hirata K, Nishiyama K, Yabe I, Kaida KI, Suzuki N, Nodera H, Tsuji S, Koike H, Kira JI, Hanaoka H, Kusunoki S, Kuwabara S; JET-GBS Group. A Prospective, Multicenter, Randomized Phase II Study to Evaluate the Efficacy and Safety of Eculizumab in Patients with Guillain-Barre Syndrome (GBS): Protocol of Japanese Eculizumab Trial for GBS (JET-GBS). JMIR Res Protoc. 2016 Nov 7;5(4):e210. doi: 10.2196/resprot.6610.
PubMed 27821382
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PROSPECTIVE, MULTI-CENTER, PHASE II STUDY TO EVALUATE THE SAFETY AND EFFICACY OF ECULIZUMAB IN SUBJECTS WITH GUILLAIN-BARRÉ SYNDROME
- ClinicalTrials.gov ID
- NCT02493725
- Acronym / sponsor ID
- 100069
- Conditions
- Gullain Barre Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Chiba UniversityUniversity, hospital or other
- Collaborators
- Japan Agency for Medical Research and Development
- Study start
- Jul 2015
- Primary completion
- May 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 9 Jul 2015 (estimated)
- 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.
Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy that usually follows an antecedent infection and causes acute neuromuscular paralysis. GBS is currently classified into the two major subtypes: a classical demyelinating type and axonal variant type. Whereas in Europe and North America demyelinating GBS is the major subtype, in East Asia and Central and South America, axonal GBS is found in 30~65% of patients. Although the pathophysiology of GBS has not been fully understood, major advances have been made in understanding the pathophysiology particularly for the axonal form of GBS. It is now established that axonal GBS is caused by molecular mimicry of human gangliosides by the Campylobacter jejuni lipo-oligosaccharides. Autoantibodies bind to GM1 or GD1a at the nodes of Ranvier, activate complements, and disrupt sodium channel clusters and axo-glial junctions, resulting in the nerve conduction failure and muscle weakness. C. jejuni infection induces production of antibodies, which cross-react with gangliosides on the human nerve axolemma, and activate the complements, resulting in formation of membrane attack complex (MAC). The pathology leads to axonal degeneration.
The standard treatments for GBS are plasma exchange and intravenous immunoglobulin and the disease progression reaches its nadir within 4 weeks. However, during the acute phase, 18-28 % of the patients require artificial ventilation and 4.1-6.3 % of the patients die of complications. Recovery takes several months or years, and 16.7-19.7 % of the patients still require aid to walk one year after onset. Because of such serious disability of GBS patients, an alternative novel therapy that can prevent death during acute phase or severe sequelae is needed.
Eculizumab is a humanized monoclonal antibody of murine anti-human C5 antibody and specifically binds to the final activation complement component C5 and inhibits MAC formation by suppressing the cleavage reaction of C5 into C5a and C5b. The efficacy of eculizumab against GBS has been shown in a model of axonal GBS. At present, there are no animal models of demyelinating GBS. However, autopsy studies have shown that C3d and C5b-9 (MAC) are deposited on the Schwan cells, and therefore eculizumab can be effective also for demyelinating GBS.
This clinical trial will be conducted to investigate the efficacy and safety of eculizumab for GBS to warrant future global clinical trials. Moreover, we also study the relationship between the efficacy and clinical subtypes of GBS, such as axonal or demyelinating form. Our trial will provide insights on whether the future global developmental plan should target the whole spectrum of GBS world-wide or focusing on Asia and South America.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Eculizumab | Active comparator | Drug: EculizumabEculizumab, 900 mg intravenously once a week |
| Placebo | Placebo comparator | Drug: PlaceboMatched placebo, intravenously once a week |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Subjects ≥ 18 years of age at the time of obtaining informed consent.
- Patients with onset of muscular weakness due to GBS less than 2 weeks before the time of consent.
- Patients unable to walk unaided for ≥5 meters (progressively deteriorating FG(Functional Grade)3 or FG 4-5).
- Patients who are already on IVIg or deemed eligible for and who will start IVIg (Generally, administration of 400mg/kg over 5 days).
- Patients who can start their first dose of eculizumab within 2 weeks from onset of weakness and before the end of the IVIg treatment period.
Key exclusion criteria (15 listed)
- Patients who are being considered for or are already on plasmapheresis.
- Patients who are pregnant or lactating.
- Patients showing clear clinical evidence of peripheral polyneuropathy other than GBS, e.g. diabetic (except for mild sensory disturbance) or severe vitamin B1 deficiency related.
- Patients who have received immunosuppressive treatment (e.g. azathioprine, cyclosporine, tacrolimus, or >20 mg prednisolone daily) during the 4 weeks prior to providing consent.
- Patients who are known to have severe concurrent disease (such as malignancy with uncontrolled primary tumors or metastatic lesions, severe cardiovascular disease, severe COPD(chronic obstructive pulmonary disease ), or TB).
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 |
|---|---|---|
| Eculizumab | Drug | Eculizumab |
| Placebo | Drug | Placebo |
Primary outcome
[Safety] Expressed frequency and severity of incidence of AE/SAEs after treatment with investigational product.
Time frame: 6 months
[Efficacy] Proportion of subjects who reach a score of FG2 or lower on the Hughes functional grading scale at week 4（Response Rate）
Time frame: 4 weeks
16 secondary outcomes
Proportion of subjects with improvement of one or more scores on the functional grading scale at each visit
Time frame: 6 months
Proportion of subjects who are able to walk unaided (FG2 or lower) at each visit
Time frame: 6 months
Duration required for improvement by at least one grade on the Hughes functional grading scale
Time frame: 6 months
Proportion of subjects who reach FG1 or 0 at week 24
Time frame: 6 months
Change in the FG score between peak disability score and the scores at each visit
Time frame: 6 months
Proportion of subjects with a clinically relevant improvement in the R-ODS score. An increase in the R-ODS score (0-48) converted to the centile metric score (0-100) by at least six points at each visit
Time frame: 6 months
Proportion of subjects with a clinically relevant improvement in ONLS. (a decrease in the ONLS score from baseline by at least 1 point) at each visit
Time frame: 6months
Proportion and frequency of subjects who require ventilatory support (F 5)
Time frame: 4 weeks
Duration of ventilatory support
Time frame: 8 weeks
Occurrence of relapse from the start of the IP(Investigational Product) administration period until the end of the post IP period
Time frame: 2 years
Overall survival from the start of the IP administration period until the end of the post IP period (OS)
Time frame: 6 months
Change in grip strength at each visit from baseline
Time frame: 6 months
Change in results of the manual muscle test (MMT score) at each visit from baseline
Time frame: 6 months
Change in the rate and results of below measures on the nerve conduction test parameter from baseline:Median and ulnar nerve 's CMAP amplitude, distal latency, F wave latency , SNAP amplitude, motor sensory nerve conduction velocity
Time frame: 6 months
Change in vital capacity and % vital capacity at each visit from baseline
Time frame: 6 months
Proportion of patients who undergo re-administration of IVIg
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2017.
- Derived from this study: PubMed 29685815Misawa S, Kuwabara S, Sato Y, Yamaguchi N, Nagashima K, Katayama K, Sekiguchi Y, Iwai Y, Amino H, Suichi T, Yokota T, Nishida Y, Kanouchi T, Kohara N, Kawamoto M, Ishii J, Kuwahara M, Suzuki H, Hirata K, Kokubun N, Masuda R, Kaneko J, Yabe I, Sasaki H, Kaida KI, Takazaki H, Suzuki N, Suzuki S, Nodera H, Matsui N, Tsuji S, Koike H, Yamasaki R, Kusunoki S; Japanese Eculizumab Trial for GBS (JET-GBS) Study Group. Safety and efficacy of eculizumab in Guillain-Barre syndrome: a multicentre, double-blind, randomised phase 2 trial. Lancet Neurol. 2018 Jun;17(6):519-529. doi: 10.1016/S1474-4422(18)30114-5. Epub 2018 Apr 21.
- Derived from this study: PubMed 27821382Yamaguchi N, Misawa S, Sato Y, Nagashima K, Katayama K, Sekiguchi Y, Iwai Y, Amino H, Suichi T, Yokota T, Nishida Y, Kohara N, Hirata K, Nishiyama K, Yabe I, Kaida KI, Suzuki N, Nodera H, Tsuji S, Koike H, Kira JI, Hanaoka H, Kusunoki S, Kuwabara S; JET-GBS Group. A Prospective, Multicenter, Randomized Phase II Study to Evaluate the Efficacy and Safety of Eculizumab in Patients with Guillain-Barre Syndrome (GBS): Protocol of Japanese Eculizumab Trial for GBS (JET-GBS). JMIR Res Protoc. 2016 Nov 7;5(4):e210. doi: 10.2196/resprot.6610.
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.
Satoshi Kuwabara, MD principal investigator
Chiba University Graduate School of Medicine Department of neurology
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eculizumab in people with Gullain Barre Syndrome, run by Chiba University at 13 sites in Japan.
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 8 inclusion and 15 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: finished, as of the sponsor's last update on 11 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
[Safety] Expressed frequency and severity of incidence of AE/SAEs after treatment with investigational product. (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02493725, which also lists 2 linked publications.
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 11 Oct 2017.