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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

Phase 3
Recruiting
Conditions
Generalised myasthenia gravis
Registration Number
2023-508842-17-00
Lead Sponsor
Regeneron Pharmaceuticals Inc.
Brief Summary

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

(gMG)

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing, recruiting
Sex
Not specified
Target Recruitment
118
Inclusion Criteria

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

Exclusion Criteria

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)

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

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 clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score

Change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score

Secondary Outcome Measures
NameTimeMethod
Change from baseline in Quantitative Myasthenia Gravis (QMG) score

Change from baseline in Quantitative Myasthenia Gravis (QMG) score

Achievement of a ≥3-point reduction (improvement) in MG-ADL total score

Achievement of a ≥3-point reduction (improvement) in MG-ADL total score

Achievement of a ≥5-point reduction (improvement) in QMG total score

Achievement of a ≥5-point reduction (improvement) in QMG total score

Achievement of a consistent response on the MG-ADL

Achievement of a consistent response on the MG-ADL

Achievement of minimal symptom expression (MSE)

Achievement of minimal symptom expression (MSE)

Change from baseline in the Myasthenia Gravis Composite (MGC) total score

Change from baseline in the Myasthenia Gravis Composite (MGC) total score

Change from baseline in Myasthenia Gravis Quality of Life (MG QOL15r) total score

Change from baseline in Myasthenia Gravis Quality of Life (MG QOL15r) total score

Achievement of a ≥2-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-point reduction on MG-ADL total score

Achievement of a ≥2-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-point reduction on MG-ADL total score

Achievement of a ≥3-, 4-, 6-, 7-, 8-, 9-, or 10-point reduction on QMG

Achievement of a ≥3-, 4-, 6-, 7-, 8-, 9-, or 10-point reduction on QMG

Incidence and severity of treatment-related adverse events (TEAEs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo

Incidence and severity of treatment-related adverse events (TEAEs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo

Incidence and severity of serious adverse events (SAEs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo

Incidence and severity of serious adverse events (SAEs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo

Incidence and severity of adverse events of special interest (AESIs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo

Incidence and severity of adverse events of special interest (AESIs) in patients treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo

Concentrations of total pozelimab in serum

Concentrations of total pozelimab in serum

Concentrations of total complement component 5 (C5) in plasma

Concentrations of total complement component 5 (C5) in plasma

Concentrations of cemdisiran and its metabolites in plasma

Concentrations of cemdisiran and its metabolites in plasma

Incidence of treatment-emergent anti-drug antibodies (ADAs) to pozelimab over time

Incidence of treatment-emergent anti-drug antibodies (ADAs) to pozelimab over time

Incidence of treatment-emergent ADAs to cemdisiran over time

Incidence of treatment-emergent ADAs to cemdisiran over time

Change in total complement hemolysis activity assay (CH50) over time

Change in total complement hemolysis activity assay (CH50) over time

Percent change in CH50 over time

Percent change in CH50 over time

Trial Locations

Locations (30)

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Hospital Universitario Y Politecnico La Fe

🇪🇸

Valencia, Spain

Hospital De La Santa Creu I Sant Pau

🇪🇸

Barcelona, Spain

Odense University Hospital

🇩🇰

Odense C, Denmark

Rigshospitalet

🇩🇰

Copenhagen Oe, Denmark

Aalborg University Hospital

🇩🇰

Aalborg, Denmark

Aarhus Universitetshospital

🇩🇰

Aarhus N, Denmark

Hopitaux Universitaires Pitie Salpetriere

🇫🇷

Paris, France

CHRU De Nancy

🇫🇷

Nancy, France

Centre Hospitalier Universitaire De Nice

🇫🇷

Nice, France

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Hospital Universitario La Paz
🇪🇸Madrid, Spain
Francisco Javier Rodriguez de Rivera
Site contact
+34917277444
frriveragarrido@salud.madrid.org

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