A Study in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) to Evaluate How Safe Long-term Treatment With Pozelimab + Cemdisiran Combination Therapy is and How Well it Works

Phase 3RecruitingNCT05744921

Regeneron Pharmaceuticals202 enrolled

Overview

This study is researching an experimental treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on people with paroxysmal nocturnal hemoglobinuria (PNH). The aim of this study is to see how safe and effective the pozelimab + cemdisiran combination is for people with PNH in the long term. The pozelimab + cemdisiran combination may be referred to as "study drugs" in this section. This study is looking at several other research questions, including: * How effective is the pozelimab + cemdisiran combination? * What side effects may happen from taking the study drugs? * How much of each study drug is in the blood at different times? * Whether the body makes antibodies against the study drugs (which could make the drugs less effective or could lead to side effects)

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

202

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: Patients Entering from the Parent Study 1. 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. 2. Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol. Patients Entering with C5 polymorphism 1. 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 2. Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes 3. Active disease, as defined by the presence of 1 or more PNH-related sign or symptom as described in the protocol 4. LDH level ≥2 × upper limit of normal (ULN) at the screening visit 5. 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 1. 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 2. 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 1. 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 2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant 3. 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 4. Positive hepatitis B surface antigen or hepatitis C virus Ribonucleic acid (RNA) during screening 5. Patients with known HIV with history of opportunistic infections in the last 1 year as described in the protocol 6. Known hereditary complement deficiency 7. Documented history of active, uncontrolled, ongoing systemic autoimmune diseases 8. 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

Locations (47)

Toronto General Hospital

Toronto, Ontario, Canada

RECRUITING

Hospital Pablo Tobon Uribe

Medellín, Antioquia, Colombia

RECRUITING

Semmelweis University/Semmelweis Egyetem

Budapest, Hungary

RECRUITING

Amrita Institute of Medical Sciences (AIMS) and Research Centre Aims

Kochi, Kerala, India

Outcomes

Primary Outcomes

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

Time frame: Up to week 108

Severity of treatment-emergent SAEs

Time frame: 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

Time frame: Up to week 108

Severity of treatment emergent AESIs

Time frame: 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.

Time frame: 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.

Time frame: Up to week 108

Percent change from baseline in lactate dehydrogenase (LDH)

Time frame: Baseline to week 36

Secondary Outcomes

Adequate control of hemolysis (LDH ≤1.5 × ULN)

Time frame: Post-baseline through week 108

Transfusion avoidance

Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values

Time frame: Post-baseline through week 36

Transfusion avoidance

Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values

Time frame: Post-baseline through week 48

Transfusion avoidance

Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values

Time frame: Post-baseline through week 76

Transfusion avoidance

Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values

Time frame: Post-baseline through week 108

Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)

Time frame: Post-baseline through week 36

Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)

Time frame: Post-baseline through week 48

Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)

Time frame: Post-baseline through week 76

Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)

Time frame: Post-baseline through week 108

Change in fatigue

Measured by the FACIT-Fatigue scale The FACIT-F is a 13-item, self-reported PRO measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.

Time frame: From baseline to week 36

Change in fatigue

Measured by the FACIT-Fatigue scale The FACIT-F is a 13-item, self-reported PRO measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a 4-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.

Time frame: From baseline to week 48

Change in fatigue

Measured by the FACIT-Fatigue scale The FACIT-F is a 13-item, self-reported PRO measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a 4-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.

Time frame: From baseline to week 76

Change in fatigue

Measured by the FACIT-Fatigue scale The FACIT-F is a 13-item, self-reported PRO measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a 4-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.

Time frame: From baseline to weeks 108

Change in physical function (PF) scores on the EORTC QLQ-C30

EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire) EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

Time frame: From baseline to week 36

Change in PF scores on the EORTC QLQ-C30

Time frame: From baseline to week 48

Change in PF scores on the EORTC QLQ-C30

Time frame: From baseline to week 76

Change in PF scores on the EORTC QLQ-C30

Time frame: From baseline to week 108

Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30

GHS/QoL (Global Health Status/ Quality of Life) Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

Time frame: From baseline to week 36

Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30

Time frame: From baseline to week 48

Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30

Time frame: From baseline to week 76

Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30

Time frame: From baseline to week 108

A Study in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) to Evaluate How Safe Long-term Treatment With Pozelimab + Cemdisiran Combination Therapy is and How Well it Works

Overview

Conditions

Interventions

Eligibility

Locations (47)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts