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
- Conditions
- Generalized Myasthenia Gravis
- Interventions
- Registration Number
- NCT05070858
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
This study is researching the experimental drugs called pozelimab and cemdisiran, and cemdisiran monotherapy. The study is focused on patients with generalized myasthenia gravis (gMG). Myasthenia gravis is a disease that causes weakness and fatigue in muscles in the body because the nerves and muscles are not communicating properly. The aim of the study is to see how effective pozelimab and cemdisiran are when used in combination and when pozelimab and cemdisiran are used alone for patients with gMG.
The study is looking at several other research questions, including:
* What side effects may happen from taking the study drugs
* How the study drugs work inside the body
* How much study drugs are in the blood at different times
* Whether the body makes antibodies against pozelimab and cemdisiran (which could make the drugs less effective or could lead to side effects)
- Detailed Description
DBTP- Double blind treatment period (24 weeks) ETP - Extension treatment period (28 weeks) OLTP- Open label treatment period (68 weeks) Off-treatment follow up period (52 weeks)
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 288
- Male or female patients ≥18 years of age at screening (or ≥ legal age of adulthood based on local regulations, whichever is older)
- Patient with documented diagnosis of myasthenia gravis (MG) based on medical history and supported by previous evaluations as described in the protocol
- Documented prior history of positive serologic test or a positive result during screening of anti-acetylcholine receptor (AChR) antibodies or anti-LRP4 antibodies.
- Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II to IVa at screening
- 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 as described in the protocol
- Currently receiving an acetylcholinesterase inhibitor or documented reason for not using acetylcholinesterase inhibitor therapy per investigator
- Currently receiving an immunosuppressive therapy (IST) for MG, or documented reason why the patient is not taking an IST per investigator
- If currently receiving an IST, not anticipated to have IST dosage changed before randomization or during double-blind treatment period (DBTP).
- 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
- 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
- History of thymectomy within 12 months prior to screening or planned during the study
- 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
- Myasthenic crisis or Myasthenia Gravis Foundation of America (MGFA) Class V within 1 month of screening
- Not meeting meningococcal vaccination requirements and, at a minimum, documentation of quadrivalent meningococcal vaccination within 5 years prior to randomization and serotype B vaccine (when available) within 3 years prior to randomization as described in the protocol
- Known contraindication to meningococcal vaccines (group ACWY conjugate and group B vaccines) as described in the protocol
- 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
- 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
- History of HIV infection or a positive test at screening per local requirements
NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 2 Pozelimab + Cemdisiran Combination regimen throughout the study Group 4 Pozelimab Pozelimab monotherapy in DBTP followed by combination in ETP and OLTP Group 1 Pozelimab + Cemdisiran Placebo in DBTP; Re-randomized to Combination or Cemdisiran in ETP and OLTP Group 1 Cemdisiran Placebo in DBTP; Re-randomized to Combination or Cemdisiran in ETP and OLTP Group 3 Cemdisiran Cemdisiran throughout the study Group 1 Placebo Placebo in DBTP; Re-randomized to Combination or Cemdisiran in ETP and OLTP
- Primary Outcome Measures
Name Time Method Change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score From baseline to week 24 The total MG-ADL score ranges from 0 to 24 points, with higher scores indicating greater functional impairment and disability
- Secondary Outcome Measures
Name Time Method Change from baseline in Quantitative Myasthenia Gravis (QMG) score Week 24 QMG total scores range from 0 to 39, with higher scores representing greater impairment
Achievement of a ≥3-point reduction (improvement) in MG-ADL total score From baseline to week 24 Achievement of a ≥5-point reduction (improvement) in QMG total score From baseline to week 24 Achievement of a consistent response on the MG-ADL From baseline to week 24 A patient with a ≥2-point reduction (improvement) in MG-ADL total score on 2 or more consecutive assessments spanning 4 or more weeks during the DBTP
Achievement of minimal symptom expression (MSE) Week 24 Score of 0 to 1 on the MG-ADL
Change from baseline in the Myasthenia Gravis Composite (MGC) total score Week 24 MGC score ranges from 0 to 50, with higher score indicating higher impairment
Change from baseline in Myasthenia Gravis Quality of Life (MG QOL15r) total score Week 24 Total score ranges from 0 to 30 points; a higher score represents greater impairment
Achievement of a ≥2-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-point reduction on MG-ADL total score From baseline to week 24 Achievement of a ≥3-, 4-, 6-, 7-, 8-, 9-, or 10-point reduction on QMG From baseline to week 24 Incidence and severity of treatment-related adverse events (TEAEs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo Through week 24 Incidence and severity of serious adverse events (SAEs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo Through week 24 Incidence and severity of adverse events of special interest (AESIs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo Through week 24 Concentrations of total pozelimab in serum Through study duration, approximate 172 weeks Concentrations of total complement component 5 (C5) in plasma Through study duration, approximate 172 weeks Concentrations of cemdisiran and its metabolites in plasma Through study duration, approximate 172 weeks Incidence of treatment-emergent anti-drug antibodies (ADAs) to pozelimab over time Through study duration, approximately 172 weeks Incidence of treatment-emergent ADAs to cemdisiran over time Through study duration, approximate 172 weeks Change in total complement hemolysis activity assay (CH50) over time Through study duration, approximately 172 weeks Percent change in CH50 over time Through study duration, approximately 172 weeks
Trial Locations
- Locations (116)
HonorHealth Neurology 2018
🇺🇸Scottsdale, Arizona, United States
University of California Irvine
🇺🇸Irvine, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Colorado Springs Neurological Associates
🇺🇸Colorado Springs, Colorado, United States
SFM Clinical Research, LLC
🇺🇸Boca Raton, Florida, United States
Diverse Clinical Research
🇺🇸Miami, Florida, United States
Aqualane Clinical Research
🇺🇸Naples, Florida, United States
Neurological Services of Orlando
🇺🇸Orlando, Florida, United States
Medsol Clinical Research Center Inc
🇺🇸Port Charlotte, Florida, United States
University of South Florida Morsani Center for Advanced Healthcare
🇺🇸Tampa, Florida, United States
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