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

JRCT ID: jRCT2071220059

Registered date:18/10/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Generalized Myasthenia Gravis
• Date of first enrollment: 21/12/2022
• Target sample size: 17
• Countries of recruitment: United States,Japan,Canada,Japan,Belgium,Japan,Denmark,Japan,France,Japan,Germany,Japan,Italy,Japan,Poland,Japan,Spain,Japan,UK,Japan,Turkey,Japan,Australia,Japan,South Korea,Japan,Taiwan,Japan,India,Japan,China,Japan,Serbia,Japan,Georgia,Japan
• Study type: Interventional

Intervention(s)

Group 1 (Placebo in DBTP; Re-randomized to Combination or Cemdisiran in ETP and OLTP):
-Drug: Pozelimab + Cemdisiran
Subcutaneous (SC) administration as described in the protocol
-Drug: Cemdisiran
SC administration as described in the protocol
Other Names: ALN-CC5
-Other: Placebo
SC administration as described in the protocol

Group 2 (Combination regimen throughout the study):
-Drug: Pozelimab + Cemdisiran
Subcutaneous (SC) administration as described in the protocol

Group 3 (Cemdisiran throughout the study):
-Drug: Cemdisiran
SC administration as described in the protocol
Other Names: ALN-CC5

Group 4 (Pozelimab monotherapy in DBTP followed by combination in ETP and OLTP):
-Drug: Pozelimab
SC administration as described in the protocol
Other Names: REGN3918

Outcome(s)

• Primary Outcome: Change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score

Secondary Outcome

1. Change from baseline in Quantitative Myasthenia Gravis (QMG) score
2. Proportion of patients responding on the MG-ADL
3. Proportion of patients responding on the QMG
4. Proportion of patients with consistent response on the MG-ADL
5. Proportion of patients with minimal symptom expression (MSE)
6. Change from baseline in the Myas-thenia Gravis Composite (MGC) total score
7. Change from baseline in Myasthenia Gravis Quality of Life (MG QOL15r) total score
8. Proportion of patients with improvement point thresholds on MG-ADL
9. Proportion of patients with improvement point thresholds on QMG
10. Incidence and severity of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy, or placebo
11. Concentrations of total pozelimab in serum
12. Concentrations of total complement component 5 (C5) in plasma
13. Concentrations of cemdisiran and its metabolites in plasma
14. Incidence of treatment-emergent anti-drug antibodies (ADAs) to pozelimab over time
15. Incidence of treatment-emergent ADAs to cemdisiran over time
16. Change and percent change in CH50 over time

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

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
Other protocol-defined Inclusion Criteria apply.

Exclude 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
Other protocol-defined Exclusion Criteria apply.

Related Information

• Primary Sponsor: Pavani Rodrigo
• Secondary ID(s): NCT05070858,2020-003272-41,2023-508842-17-00