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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05070858




Registration number
NCT05070858
Ethics application status
Date submitted
27/09/2021
Date registered
7/10/2021
Date last updated
3/06/2024

Titles & IDs
Public title
A Study to Examine the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Adult Patients With Symptomatic Generalized Myasthenia Gravis
Scientific title
Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy 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 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 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 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 cemdisiran and its metabolites in plasma
Timepoint [14] 0 0
Through study duration, approximate 172 weeks
Secondary outcome [15] 0 0
Incidence of treatment-emergent anti-drug antibodies (ADAs) to pozelimab over time
Timepoint [15] 0 0
Through study duration, approximately 172 weeks
Secondary outcome [16] 0 0
Incidence of treatment-emergent ADAs to cemdisiran over time
Timepoint [16] 0 0
Through study duration, approximate 172 weeks
Secondary outcome [17] 0 0
Change in CH50 over time
Timepoint [17] 0 0
Through study duration, approximately 172 weeks
Secondary outcome [18] 0 0
Percent change in CH50 over time
Timepoint [18] 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).

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. No documented meningococcal vaccination within 5 years prior to screening visit unless
vaccination will be administered during the screening period and prior to initiation
of study treatment

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
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United States of America
State/province [2] 0 0
California
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United States of America
State/province [3] 0 0
Colorado
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United States of America
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Florida
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United States of America
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Illinois
Country [6] 0 0
United States of America
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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
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Pennsylvania
Country [11] 0 0
United States of America
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Texas
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Belgium
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Antwerp
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Belgium
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Hainaut
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Belgium
State/province [14] 0 0
Oost-Vlaanderen
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
Czechia
State/province [19] 0 0
Jihomoravsky Kraj
Country [20] 0 0
Czechia
State/province [20] 0 0
Moravskoslezsky Kraj
Country [21] 0 0
Denmark
State/province [21] 0 0
Nordjylland
Country [22] 0 0
Denmark
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Aarhus N
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Denmark
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Copenhagen
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Denmark
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Odense
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France
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Alpes-Maritimes
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France
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Le Kremlin-Bicetre
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France
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Nancy
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France
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Paris
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Georgia
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Tbilisi
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Germany
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Bayern
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Germany
State/province [31] 0 0
Nordrhein-Westfalen
Country [32] 0 0
Germany
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NRW
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Germany
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Sachsen
Country [34] 0 0
Germany
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Berlin
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Germany
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Jena
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India
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Andhra Pradesh
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India
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Delhi
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India
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Gujarat
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India
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Hyderabad
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India
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Karnataka
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India
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Kerala
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India
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Maharashtra
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India
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Mumbai
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India
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Punjab
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India
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Rajasthan
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India
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Telangana
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India
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Uttar Pradesh
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India
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Bangalore
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India
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Chandigarh
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Italy
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Lazio
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Italy
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Lombardia
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Italy
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Napoli
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Italy
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Toscana
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Italy
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Bergamo
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Italy
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Roma
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Japan
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Hyogo
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Koti
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Okinawa
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Saitama
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Japan
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Tokoyo
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Japan
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Tokyo
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Japan
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Yamaguchi
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Japan
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Chiba
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Japan
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Hiroshima
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Japan
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Osaka
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Korea, Republic of
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North Gyeongsang
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Korea, Republic of
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Seoul Teugbyeolsi
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Poland
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Malopolskie
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Mazovian
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Mazowieckie
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Pomorskie
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Poland
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Wielkopolskie
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Serbia
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Belgrade
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Serbia
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Nis
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Valencia
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Taiwan
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Kaohsiung City
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Taichung
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Taiwan
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Tainan City
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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Turkey
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Van
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Izmir
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Turkey
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Samsun
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Turkey
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Trabzon
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United Kingdom
State/province [87] 0 0
South Yorkshire
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Birmingham

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective is:

To evaluate the effect of pozelimab + cemdisiran on daily functioning that is impacted by
signs and symptoms in patients with symptomatic generalized myasthenia gravis (gMG)

The secondary objectives of the study are:

- To evaluate the effect of pozelimab + cemdisiran (ie, combination) and cemdisiran
monotherapy on:

- Clinician-assessed signs of myasthenia gravis (MG) and muscle strength

- Daily functioning that is impacted by signs and symptoms in patients with
symptomatic gMG (cemdisiran monotherapy only).

- Proportion of patients with improvements in daily function that is impacted by
signs and symptoms of MG

- Proportion of patients that have improvements in clinician-assessed signs of MG and
muscle strength

- Health related quality of life

- Proportion of patients with minimal MG symptoms

- Patient- and clinician-reported signs and symptoms of MG

- To evaluate the safety and tolerability of pozelimab + cemdisiran and cemdisiran
monotherapy

- To assess the concentration of total pozelimab in serum

- To assess the concentrations of cemdisiran and its metabolites in plasma

- To assess the immunogenicity of pozelimab

- To assess the concentration of total C5 in plasma

- To assess the immunogenicity of cemdisiran

- To study the effect of pozelimab + cemdisiran and cemdisiran monotherapy on complement
activation
Trial website
https://clinicaltrials.gov/ct2/show/NCT05070858
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
clinicaltrials@regeneron.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05070858