A Study to Examine the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Adult Patients With Symptomatic Generalized Myasthenia Gravis

JRCT ID: jRCT2071220059

Registered date:18/10/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Symptomatic 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)

- Placebo regimen: Pozelimab placebo subcutaneously (SC) + cemdisiran placebo SC every 4 weeks (Q4W) starting from day 1
- Combination regimen: Pozelimab SC + cemdisiran SC Q4W starting from day 1
- Cemdisiran: Cemdisiran SC Q12W starting from day 1
- Pozelimab: Pozelimab SC Q4W starting from day 1

Outcome(s)

• Primary Outcome: Change in MG-ADL total score from baseline to week 24

Secondary Outcome

1.Change from baseline in Quantitative Myasthenia Gravis (QMG) score [ Time Frame: Week 24 ]
QMG total scores range from 0 to 39, with higher scores representing greater impairment
2.Proportion of patients responding on the MG-ADL [ Time Frame: From baseline to week 24 ]
>=3-point improvement
3.Proportion of patients responding on the QMG [ Time Frame: From baseline to week 24 ]
>=5-point improvement
4.Proportion of patients with consistent response on the MG-ADL [ Time Frame: From baseline to week 24 ]
At least a 2-point MG-ADL improvement on 2 or more consecutive assessments spanning 4 or more weeks during the DBTP
5.Proportion of patients with minimal symptom expression (MSE) [ Time Frame: Week 24 ]
Score of 0 to 1 on the MG-ADL
6.Change from baseline in the Myasthenia Gravis Composite (MGC) total score [ Time Frame: Week 24 ]
MGC score ranges from 0 to 50, with higher score indicating higher impairment
7.Change from baseline in Myasthenia Gravis Quality of Life (MG QOL15r) total score [ Time Frame: Week 24 ]
Total score ranges from 0 to 30 points; a higher score represents greater impairment
8.Proportion of patients with improvement point thresholds on MG-ADL [ Time Frame: From baseline to week 24 ]
>=2, 4, 5, 6, 7, 8, 9, or 10
9.Proportion of patients with improvement point thresholds on QMG [ Time Frame: From baseline to week 24 ]
>=3, 4, 6, 7, 8, 9, or 10
10.Incidence and severity of treatment-related adverse events (TEAEs) in patients treated with pozelimab + cemdisiran or placebo [ Time Frame: Through week 24 ]
11.Incidence and severity of serious adverse events (SAEs) in patients treated with pozelimab + cemdisiran or placebo [ Time Frame: Through week 24 ]
12.Incidence and severity of adverse events of special interest (AESIs) in patients treated with pozelimab + cemdisiran or placebo [ Time Frame: Through week 24 ]
13.Concentrations of total pozelimab in serum [ Time Frame: Through study duration, approximate 172 weeks ]
14.Concentrations of cemdisiran and its metabolites in plasma [ Time Frame: Through study duration, approximate 172 weeks ]
15.Incidence of treatment-emergent anti-drug antibodies (ADAs) to pozelimab over time [ Time Frame: Through study duration, approximately 172 weeks ]
16.Incidence of treatment-emergent ADAs to cemdisiran over time [ Time Frame: Through study duration, approximate 172 weeks ]
17.Change in CH50 over time [ Time Frame: Through study duration, approximately 172 weeks ]
18.Percent change in CH50 over time [ Time Frame: Through study duration, approximately 172 weeks ]

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 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-AChR antibodies or anti-LRP4 antibodies.
4. MGFA Clinical Classification Class II to IVa at screening
5. 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 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 DBTP.
9. Other Inclusion Criteria Apply

Exclude criteria

1. Patients with antibody profile that is only positive for 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 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 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
10. Other Exclusion Criteria Apply

Related Information

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