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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05070858




Registration number
NCT05070858
Ethics application status
Date submitted
27/09/2021
Date registered
7/10/2021

Titles & IDs
Public title
A Study to Test How Safe Pozelimab and Cemdisiran Combination Therapy and Cemdisiran Alone Are and How Well They Work in Adult Patients With Generalized Myasthenia Gravis
Scientific title
Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy and Cemdisiran Monotherapy in Patients With Symptomatic Generalized Myasthenia Gravis
Secondary ID [1] 0 0
2020-003272-41
Secondary ID [2] 0 0
R3918-MG-2018
Universal Trial Number (UTN)
Trial acronym
NIMBLE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Generalized Myasthenia Gravis 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Neurological 0 0 0 0
Other neurological disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pozelimab + Cemdisiran
Treatment: Drugs - Cemdisiran
Other interventions - Placebo
Treatment: Drugs - Pozelimab

Experimental: Group 1 - Placebo in DBTP; Re-randomized to Combination or Cemdisiran in ETP and OLTP

Experimental: Group 2 - Combination regimen throughout the study

Experimental: Group 3 - Cemdisiran throughout the study

Experimental: Group 4 - Pozelimab monotherapy in DBTP followed by combination in ETP and OLTP


Treatment: Drugs: Pozelimab + Cemdisiran
Subcutaneous administration as described in the protocol

Treatment: Drugs: Cemdisiran
SC administration as described in the protocol

Other interventions: Placebo
SC administration as described in the protocol

Treatment: Drugs: Pozelimab
SC administration as described in the protocol
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score
Timepoint [1] 0 0
From baseline to week 24
Secondary outcome [1] 0 0
Change from baseline in Quantitative Myasthenia Gravis (QMG) score
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Proportion of patients responding on the MG-ADL
Timepoint [2] 0 0
From baseline to week 24
Secondary outcome [3] 0 0
Proportion of patients responding on the QMG
Timepoint [3] 0 0
From baseline to week 24
Secondary outcome [4] 0 0
Proportion of patients with consistent response on the MG-ADL
Timepoint [4] 0 0
From baseline to week 24
Secondary outcome [5] 0 0
Proportion of patients with minimal symptom expression (MSE)
Timepoint [5] 0 0
Week 24
Secondary outcome [6] 0 0
Change from baseline in the Myasthenia Gravis Composite (MGC) total score
Timepoint [6] 0 0
Week 24
Secondary outcome [7] 0 0
Change from baseline in Myasthenia Gravis Quality of Life (MG QOL15r) total score
Timepoint [7] 0 0
Week 24
Secondary outcome [8] 0 0
Proportion of patients with improvement point thresholds on MG-ADL
Timepoint [8] 0 0
From baseline to week 24
Secondary outcome [9] 0 0
Proportion of patients with improvement point thresholds on QMG
Timepoint [9] 0 0
From baseline to week 24
Secondary outcome [10] 0 0
Incidence and severity of treatment-related adverse events (TEAEs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo
Timepoint [10] 0 0
Through week 24
Secondary outcome [11] 0 0
Incidence and severity of serious adverse events (SAEs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo
Timepoint [11] 0 0
Through week 24
Secondary outcome [12] 0 0
Incidence and severity of adverse events of special interest (AESIs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo
Timepoint [12] 0 0
Through week 24
Secondary outcome [13] 0 0
Concentrations of total pozelimab in serum
Timepoint [13] 0 0
Through study duration, approximate 172 weeks
Secondary outcome [14] 0 0
Concentrations of total complement component 5 (C5) in plasma
Timepoint [14] 0 0
Through study duration, approximate 172 weeks
Secondary outcome [15] 0 0
Concentrations of cemdisiran and its metabolites in plasma
Timepoint [15] 0 0
Through study duration, approximate 172 weeks
Secondary outcome [16] 0 0
Incidence of treatment-emergent anti-drug antibodies (ADAs) to pozelimab over time
Timepoint [16] 0 0
Through study duration, approximately 172 weeks
Secondary outcome [17] 0 0
Incidence of treatment-emergent ADAs to cemdisiran over time
Timepoint [17] 0 0
Through study duration, approximate 172 weeks
Secondary outcome [18] 0 0
Change in total complement hemolysis activity assay (CH50) over time
Timepoint [18] 0 0
Through study duration, approximately 172 weeks
Secondary outcome [19] 0 0
Percent change in CH50 over time
Timepoint [19] 0 0
Through study duration, approximately 172 weeks

Eligibility
Key inclusion criteria
Key

1. Male or female patients =18 years of age at screening (or = legal age of adulthood based on local regulations, whichever is older)
2. Patient with documented diagnosis of myasthenia gravis (MG) based on medical history and supported by previous evaluations as described in the protocol
3. Documented prior history of positive serologic test or a positive result during screening of anti-acetylcholine receptor (AChR) antibodies or anti-LRP4 antibodies.
4. Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II to IVa at screening
5. Myasthenia Gravis-Activities of Daily Living (MG-ADL) score =6 at screening. Ocular items should not contribute more than 50% of MG-ADL total score
6. Currently receiving an acetylcholinesterase inhibitor or documented reason for not using acetylcholinesterase inhibitor therapy per investigator 7. Currently receiving an immunosuppressive therapy (IST) for MG, or documented reason why the patient is not taking an IST per investigator

8. If currently receiving an IST, not anticipated to have IST dosage changed before randomization or during double-blind treatment period (DBTP).

9. Willing and able to comply with clinic visits and study-related procedures, including completion of the primary series of the meningococcal vaccinations required per protocol

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with antibody profile that is only positive for muscle specific tyrosine kinase (MuSK) (MuSK positivity is based on a documented prior history of positive serologic test for antibodies to MuSK or a positive result during screening
2. History of thymectomy within 12 months prior to screening or planned during the study
3. History of malignant thymoma (patients with stage 1 may be enrolled), or history of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
4. Myasthenic crisis or Myasthenia Gravis Foundation of America (MGFA) Class V within 1 month of screening
5. Not meeting meningococcal vaccination requirements and, at a minimum, documentation of quadrivalent meningococcal vaccination within 5 years prior to the screening visit and serotype B vaccine within 3 years prior to the screening visit as described in the protocol
6. Known contraindication to meningococcal vaccines (group ACWY conjugate and group B vaccines) as described in the protocol
7. Patients who require antibiotics for meningococcal prophylaxis and have a contraindication, warning, or precaution precluding the use of penicillin class and penicillin-alternative antibiotics planned to be used for prophylaxis, or a history of intolerance leading to the discontinuation of these antibiotics
8. Positive hepatitis B surface antigen or hepatitis C virus ribonucleic acid (RNA) during screening. NOTE: Cases with unclear interpretation should be discussed with the medical monitor
9. History of HIV infection or a positive test at screening per local requirements

NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
23/03/2028
Actual
Sample size
Target
235
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Southern Neurology - Sydney
Recruitment hospital [2] 0 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [3] 0 0
St. Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [4] 0 0
Perron Institute for Neurological and Translational Science - Nedlands
Recruitment postcode(s) [1] 0 0
2217 - Sydney
Recruitment postcode(s) [2] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
Belgium
State/province [12] 0 0
Antwerp
Country [13] 0 0
Belgium
State/province [13] 0 0
Hainaut
Country [14] 0 0
Belgium
State/province [14] 0 0
Oost-Vlaanderen
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles
Country [16] 0 0
Brazil
State/province [16] 0 0
Rio Grande Do Sul
Country [17] 0 0
Brazil
State/province [17] 0 0
Sao Paulo
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
China
State/province [21] 0 0
Guangdong
Country [22] 0 0
China
State/province [22] 0 0
Hubei
Country [23] 0 0
China
State/province [23] 0 0
Jilin
Country [24] 0 0
China
State/province [24] 0 0
Shanghai
Country [25] 0 0
China
State/province [25] 0 0
Shanxi
Country [26] 0 0
China
State/province [26] 0 0
Sichuan
Country [27] 0 0
Czechia
State/province [27] 0 0
Jihomoravsky Kraj
Country [28] 0 0
Czechia
State/province [28] 0 0
Moravskoslezsky Kraj
Country [29] 0 0
Denmark
State/province [29] 0 0
Nordjylland
Country [30] 0 0
Denmark
State/province [30] 0 0
Aarhus N
Country [31] 0 0
Denmark
State/province [31] 0 0
Copenhagen
Country [32] 0 0
Denmark
State/province [32] 0 0
Odense
Country [33] 0 0
France
State/province [33] 0 0
Alpes-Maritimes
Country [34] 0 0
France
State/province [34] 0 0
Le Kremlin-Bicetre
Country [35] 0 0
France
State/province [35] 0 0
Nancy
Country [36] 0 0
France
State/province [36] 0 0
Paris
Country [37] 0 0
Georgia
State/province [37] 0 0
Tbilisi
Country [38] 0 0
Germany
State/province [38] 0 0
Bayern
Country [39] 0 0
Germany
State/province [39] 0 0
Nordrhein-Westfalen
Country [40] 0 0
Germany
State/province [40] 0 0
NRW
Country [41] 0 0
Germany
State/province [41] 0 0
Sachsen
Country [42] 0 0
Germany
State/province [42] 0 0
Berlin
Country [43] 0 0
Germany
State/province [43] 0 0
Jena
Country [44] 0 0
India
State/province [44] 0 0
Andhra Pradesh
Country [45] 0 0
India
State/province [45] 0 0
Delhi
Country [46] 0 0
India
State/province [46] 0 0
Gujarat
Country [47] 0 0
India
State/province [47] 0 0
Hyderabad
Country [48] 0 0
India
State/province [48] 0 0
Karnataka
Country [49] 0 0
India
State/province [49] 0 0
Kerala
Country [50] 0 0
India
State/province [50] 0 0
Maharashtra
Country [51] 0 0
India
State/province [51] 0 0
Mumbai
Country [52] 0 0
India
State/province [52] 0 0
Punjab
Country [53] 0 0
India
State/province [53] 0 0
Rajasthan
Country [54] 0 0
India
State/province [54] 0 0
Telangana
Country [55] 0 0
India
State/province [55] 0 0
Uttar Pradesh
Country [56] 0 0
India
State/province [56] 0 0
Bangalore
Country [57] 0 0
India
State/province [57] 0 0
Chandigarh
Country [58] 0 0
Italy
State/province [58] 0 0
Lazio
Country [59] 0 0
Italy
State/province [59] 0 0
Lombardia
Country [60] 0 0
Italy
State/province [60] 0 0
Napoli
Country [61] 0 0
Italy
State/province [61] 0 0
Toscana
Country [62] 0 0
Italy
State/province [62] 0 0
Bergamo
Country [63] 0 0
Italy
State/province [63] 0 0
Roma
Country [64] 0 0
Japan
State/province [64] 0 0
Hyogo
Country [65] 0 0
Japan
State/province [65] 0 0
Koti
Country [66] 0 0
Japan
State/province [66] 0 0
Okinawa
Country [67] 0 0
Japan
State/province [67] 0 0
Saitama
Country [68] 0 0
Japan
State/province [68] 0 0
Tokoyo
Country [69] 0 0
Japan
State/province [69] 0 0
Tokyo
Country [70] 0 0
Japan
State/province [70] 0 0
Yamaguchi
Country [71] 0 0
Japan
State/province [71] 0 0
Chiba
Country [72] 0 0
Japan
State/province [72] 0 0
Hiroshima
Country [73] 0 0
Japan
State/province [73] 0 0
Osaka
Country [74] 0 0
Korea, Republic of
State/province [74] 0 0
North Gyeongsang
Country [75] 0 0
Korea, Republic of
State/province [75] 0 0
Seoul Teugbyeolsi
Country [76] 0 0
Poland
State/province [76] 0 0
Malopolskie
Country [77] 0 0
Poland
State/province [77] 0 0
Mazovian
Country [78] 0 0
Poland
State/province [78] 0 0
Mazowieckie
Country [79] 0 0
Poland
State/province [79] 0 0
Pomorskie
Country [80] 0 0
Poland
State/province [80] 0 0
Wielkopolskie
Country [81] 0 0
Serbia
State/province [81] 0 0
Belgrade
Country [82] 0 0
Serbia
State/province [82] 0 0
Nis
Country [83] 0 0
Spain
State/province [83] 0 0
Barcelona
Country [84] 0 0
Spain
State/province [84] 0 0
Madrid
Country [85] 0 0
Spain
State/province [85] 0 0
Valencia
Country [86] 0 0
Taiwan
State/province [86] 0 0
Kaohsiung City
Country [87] 0 0
Taiwan
State/province [87] 0 0
Taichung
Country [88] 0 0
Taiwan
State/province [88] 0 0
Tainan City
Country [89] 0 0
Taiwan
State/province [89] 0 0
Taipei
Country [90] 0 0
Taiwan
State/province [90] 0 0
Taoyuan
Country [91] 0 0
Turkey
State/province [91] 0 0
Van
Country [92] 0 0
Turkey
State/province [92] 0 0
Izmir
Country [93] 0 0
Turkey
State/province [93] 0 0
Samsun
Country [94] 0 0
Turkey
State/province [94] 0 0
Trabzon
Country [95] 0 0
United Kingdom
State/province [95] 0 0
South Yorkshire
Country [96] 0 0
United Kingdom
State/province [96] 0 0
Birmingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Regeneron Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial Management
Address 0 0
Regeneron Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical Trials Administrator
Address 0 0
Country 0 0
Phone 0 0
844-734-6643
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR), Analytic code
When will data be available (start and end dates)?
When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
Available to whom?
Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05070858