A Study in Adult Patients With Paroxysmal Nocturnal Hemog... | NCT05744921

NCT05744921

ID	Type	Description	Link
2021-004931-10	EudraCT Number
2023-510336-36-00	EU Trial (CTIS) Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
PNH Transition Patients	Experimental	Patients with PNH who completed treatment/ protocol requirements (as applicable) in the parent study (R3918-PNH-2021 [NCT05133531])	Drug: Pozelimab Drug: Cemdisiran
C5 Polymorphism Patients	Experimental	Patients who have not been treated in either parent study but who have a documented complement component 5 (C5) variation rendering them refractory to eculizumab/ravulizumab. Note: Loading dose of pozelimab administered IV on Day 1.	Drug: Pozelimab Drug: Cemdisiran

Name	Type	Description	Arm Group Labels	Other Names
Pozelimab	Drug	Administered per the protocol	C5 Polymorphism Patients PNH Transition Patients

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Incidence of treatment-emergent serious adverse events (SAEs)	An SAE is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires in-patient hospitalization or prolongation of existing hospitalization. Results in persistent or significant disability/incapacity Is a congenital anomaly/birth defect. Is an important medical event	Up to week 108
Severity of treatment-emergent SAEs		Up to week 108
Incidence of treatment emergent adverse events of special interest (AESIs)	An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the sponsor can be appropriate. Such an event might warrant further investigation in order to characterize and understand it	Up to week 108
Severity of treatment emergent AESIs		Up to week 108
Incidence of adverse events (AEs) leading to permanent treatment discontinuation	Any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug.	Up to week 108
Severity of adverse events (AEs) leading to permanent treatment discontinuation	Any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug.	Up to week 108
Percent change from baseline in lactate dehydrogenase (LDH)

Secondary Outcomes

Measure	Description	Time Frame
Adequate control of hemolysis (LDH ≤1.5 × ULN)		Post-baseline through week 108
Transfusion avoidance	Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Patients Entering from the Parent Study

Patients with PNH who have completed, without permanent discontinuation, study treatment in the parent study (R3918-PNH-2021[NCT05133531]), including the post-Open-label treatment period (OLTP) transition period, if applicable.
Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol.

Patients Entering with C5 polymorphism

Patients with PNH who have a documented C5 polymorphism rendering them refractory to eculizumab or ravulizumab (eg, p.Arg885His, p.Arg885Cys), as described in the protocol
Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes
Active disease, as defined by the presence of 1 or more PNH-related sign or symptom as described in the protocol
LDH level ≥2 × upper limit of normal (ULN) at the screening visit
Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol

Key Exclusion Criteria:

Patients Entering from the Parent Study

Significant protocol deviation(s) in the parent study based on the investigator's judgment and to the extent that these would (if continued) impact the study objectives and/or safety of the patient
Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in or completing the study

Patients Entering with C5 polymorphism

Prior treatment with complement inhibitors within 5 half-lives of the respective agent prior to screening, except for prior eculizumab or ravulizumab which are not exclusionary
Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
Not meeting meningococcal vaccination requirements and, at a minimum, documentation of quadrivalent meningococcal vaccination within 5 years prior to enrollment and serotype B vaccine within 3 years prior to enrollment as described in the protocol
Positive hepatitis B surface antigen or hepatitis C virus Ribonucleic acid (RNA) during screening
Patients with known HIV with history of opportunistic infections in the last 1 year as described in the protocol
Known hereditary complement deficiency
Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
Documented history of liver cirrhosis or patients with liver disease with evidence of current impaired liver function or patients with elevations in Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) (unrelated to PNH or its complications) as described in the protocol

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Name	Role	Phone	Extension	Email
Clinical Trials Administrator	Contact	844-734-6643		clinicaltrials@regeneron.com

Name	Affiliation	Role
Clinical Trial Management	Regeneron Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Toronto General Hospital	Recruiting	Toronto	Ontario	M5G 2C4	Canada
Hospital Pablo Tobon Uribe

IPD Sharing Statement Module

ID	Term
D000743	Anemia, Hemolytic
D000740	Anemia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D009190	Myelodysplastic Syndromes
D001855	Bone Marrow Diseases