CEMDISIRAN for Paroxysmal nocturnal haemoglobinuria

Inclusion criteria

• {"criterion_text":"- Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes as described in the protocol\n- Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms as described in the protocol\n- LDH level ≥2 × ULN at the screening visit\n- Willing and able to comply with clinic/remote visits and study-related procedures, including completion of the full series of meningococcal vaccinations required per protocol Note: Other protocol-defined Inclusion Criteria apply"}

Exclusion criteria

• {"criterion_text":"- Prior treatment with eculizumab within 3 months prior to screening, ravulizumab within 6 months prior to screening, or other complement inhibitors within 5 half-lives of the respective agent prior to screening\n- Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant\n- Body weight <40 kilograms at screening visit\n- Planned use of any complement inhibitor therapy other than study drugs during the treatment period\n- 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.\n- Any contraindication for receiving Neisseria meningitidis vaccinations (serotypes ACWY and B)\n- Unable to take antibiotics for meningococcal prophylaxis (if required by local ravulizumab [Cohort A] or eculizumab [Cohort B] prescribing information, where available, or national guidelines/local practice, or if necessary when administration of the first dose of the quadrivalent meningococcal vaccine [serotype ACWY] or the second dose of the serotype B meningococcal vaccine [when available] is less than 2 weeks prior to study treatment initiation) as described in the protocol.\n- Any active, ongoing infection or a recent infection requiring ongoing systemic treatment with antibiotics, antivirals, or antifungals within 2 weeks of screening or during the screening period\n- Documented history of active, uncontrolled, ongoing systemic autoimmune diseases Note: Other protocol-defined Exclusion Criteria apply"}

Primary endpoints

• {"endpoint_text":"- Cohort A: Percent change in lactate dehydrogenase (LDH)","definition_or_measurement_approach":"Percent change in lactate dehydrogenase (LDH)"}
• {"endpoint_text":"- Cohort B: Adequate control of hemolysis (defined as LDH ≤1.5 × ULN) at each visit","definition_or_measurement_approach":"Adequate control of hemolysis defined as LDH ≤1.5 × ULN at each visit"}
• {"endpoint_text":"- Cohort B: Transfusion avoidance (not requiring a red blood cell (RBC) transfusion per the protocol)","definition_or_measurement_approach":"Transfusion avoidance defined as not requiring an RBC transfusion per the protocol"}

Secondary endpoints

• {"endpoint_text":"- Maintenance of adequate control of hemolysis (defined as LDH ≤1.5 × ULN) (Cohort A and B)","definition_or_measurement_approach":"Defined as LDH ≤1.5 × ULN"}
• {"endpoint_text":"- Breakthrough hemolysis (defined as LDH ≥2 × ULN per the protocol) (Cohort A and B)","definition_or_measurement_approach":"Defined as LDH ≥2 × ULN per the protocol"}
• {"endpoint_text":"- Adequate control of hemolysis (defined as LDH ≤1.5 × ULN) (Cohort A)","definition_or_measurement_approach":"Defined as LDH ≤1.5 × ULN"}
• {"endpoint_text":"- Hemoglobin stabilization (defined as patients who do not receive an RBC transfusion and have no decrease in hemoglobin level per the protocol) (Cohort A and B)","definition_or_measurement_approach":"Defined as patients who do not receive an RBC transfusion and have no decrease in hemoglobin level per the protocol"}
• {"endpoint_text":"- Normalization of LDH (defined as LDH ≤1.0 × ULN per the protocol) (Cohort A and B)","definition_or_measurement_approach":"Defined as LDH ≤1.0 × ULN per the protocol"}
• {"endpoint_text":"- Transfusion Avoidance (defined as Not requiring an RBC transfusion as per protocol algorithm based on post-baseline hemoglobin values) (Cohort A)","definition_or_measurement_approach":"Defined as not requiring an RBC transfusion as per protocol algorithm based on post‑baseline hemoglobin values"}
• {"endpoint_text":"- Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT)-Fatigue Scale (Cohort A and B)","definition_or_measurement_approach":"Measured by change in FACIT-Fatigue Scale scores"}
• {"endpoint_text":"- Change in physical function (PF) scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) (Cohort A and B)","definition_or_measurement_approach":"Measured by change in EORTC-QLQ-C30 physical function scores"}
• {"endpoint_text":"- Change in global health status (GHS)/QoL scale score on the EORTC-QLC- C30 (Cohort A and B)","definition_or_measurement_approach":"Measured by change in EORTC-QLQ-C30 global health status/QoL score"}
• {"endpoint_text":"- Percent change in LDH (Cohort B)","definition_or_measurement_approach":"Percent change in LDH"}
• {"endpoint_text":"- Rate of RBC transfused per protocol algorithm (Cohort A and B)","definition_or_measurement_approach":"Rate of RBC units transfused per the protocol algorithm"}
• {"endpoint_text":"- Number of units of RBC transfused per protocol algorithm (Cohort A and B)","definition_or_measurement_approach":"Number of RBC units transfused per the protocol algorithm"}
• {"endpoint_text":"- Time to first LDH ≤1.5 × ULN (Cohort A and B)","definition_or_measurement_approach":"Time from baseline to first occurrence of LDH ≤1.5 × ULN"}
• {"endpoint_text":"- Time to first LDH ≤1.0 × ULN (Cohort A and B)","definition_or_measurement_approach":"Time from baseline to first occurrence of LDH ≤1.0 × ULN"}
• {"endpoint_text":"- Percentage of days with LDH ≤1.5 × ULN (Cohort A and B)","definition_or_measurement_approach":"Percentage of days during observation with LDH ≤1.5 × ULN"}
• {"endpoint_text":"- Change in hemoglobin levels (Cohort A and B)","definition_or_measurement_approach":"Change from baseline in hemoglobin levels"}
• {"endpoint_text":"- Incidence and severity of treatment emergent serious adverse events (SAEs) (Cohort A and B)","definition_or_measurement_approach":"Incidence and severity reporting of treatment-emergent SAEs"}
• {"endpoint_text":"- Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest (Cohort A and B)","definition_or_measurement_approach":"Incidence and severity reporting of TEAEs of special interest"}
• {"endpoint_text":"- Incidence and severity of TEAEs leading to treatment discontinuation (Cohort A and B)","definition_or_measurement_approach":"Incidence and severity of TEAEs that lead to treatment discontinuation"}
• {"endpoint_text":"- Change in total CH50 (Cohort A and B)","definition_or_measurement_approach":"Change from baseline in total CH50"}
• {"endpoint_text":"- Percent change in total CH50 (Cohort A and B)","definition_or_measurement_approach":"Percent change in total CH50"}
• {"endpoint_text":"- Concentration of total C5 in plasma (Cohort A and B)","definition_or_measurement_approach":"Measured concentration of total C5 in plasma"}
• {"endpoint_text":"- Concentrations of total pozelimab in serum (Cohort A and B)","definition_or_measurement_approach":"Measured serum concentrations of total pozelimab"}
• {"endpoint_text":"- Concentrations of cemdisiran in plasma (Cohort A and B)","definition_or_measurement_approach":"Measured plasma concentrations of cemdisiran"}
• {"endpoint_text":"- Concentrations of total ravulizumab (Cohort A) and total eculizumab (Cohort B) in serum","definition_or_measurement_approach":"Measured serum concentrations of total ravulizumab (Cohort A) and total eculizumab (Cohort B)"}
• {"endpoint_text":"- Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab (Cohort A and B)","definition_or_measurement_approach":"Incidence of treatment-emergent ADAs to pozelimab"}
• {"endpoint_text":"- Incidence of treatment emergent ADAs to cemdisiran (Cohort A and B)","definition_or_measurement_approach":"Incidence of treatment-emergent ADAs to cemdisiran"}

Greece

Earliest CTIS Part Ii Submission Date

24-08-2022

Latest Decision Or Authorization Date

03-10-2025

Processing Time Days

1136

Number Of Sites

1

Number Of Participants

1

Hungary

Earliest CTIS Part Ii Submission Date

07-11-2024

Latest Decision Or Authorization Date

10-11-2025

Processing Time Days

368

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

02-05-2023

Latest Decision Or Authorization Date

02-10-2025

Processing Time Days

884

Number Of Sites

3

Number Of Participants

5

Romania

Earliest CTIS Part Ii Submission Date

21-05-2024

Latest Decision Or Authorization Date

03-11-2025

Processing Time Days

531

Number Of Sites

3

Number Of Participants

2

Spain

Earliest CTIS Part Ii Submission Date

05-05-2023

Latest Decision Or Authorization Date

03-10-2025

Processing Time Days

882

Number Of Sites

4

Number Of Participants

4

Poland

Earliest CTIS Part Ii Submission Date

23-11-2023

Latest Decision Or Authorization Date

06-10-2025

Processing Time Days

683

Number Of Sites

3

Number Of Participants

4

Primary sponsor

Full Name

Regeneron Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Global Ltd.

Responsibilities

[{"id":903776,"code":"15","value":"CRO"}]

Third parties

• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"[{\"id\":903774,\"code\":\"3\"}]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Iqvia Holdings Inc.","duties_or_roles":"[{\"id\":903783,\"code\":\"6\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"[{\"id\":903784,\"code\":\"4\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"[{\"id\":903777,\"code\":\"15\",\"value\":\"eCOA vendor\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"PPD Global Ltd.","duties_or_roles":"[{\"id\":903776,\"code\":\"15\",\"value\":\"CRO\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yourway Transport Inc.","duties_or_roles":"[{\"id\":903782,\"code\":\"15\",\"value\":\"IP distribution, return/destruction\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"[{\"id\":903778,\"code\":\"1\"},{\"id\":903779,\"code\":\"12\"},{\"id\":903780,\"code\":\"2\"},{\"id\":903781,\"code\":\"8\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Charles River Laboratories Inc.","duties_or_roles":"[{\"id\":903773,\"code\":\"4\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"[{\"id\":903772,\"code\":\"15\",\"value\":\"Data Monitoring Committee\"}]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"[{\"id\":903775,\"code\":\"4\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"[{\"id\":903785,\"code\":\"15\",\"value\":\"IP Packaging\"}]","organisation_type":"Pharmaceutical company"}