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.

Paroxysmal Nocturnal Hemoglobinuria Clinical Trial

— ACCESS-EXT  

Official title:

An Open-Label Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05744921
• Other study ID #: R3918-PNH-2050
• Secondary ID: 2021-004931-1020
• Status: Recruiting
• Phase: Phase 3
• Start date: March 7, 2023
• Est. completion date: February 5, 2029

Study information

• Verified date: June 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is researching an experimental treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on patients with paroxysmal nocturnal hemoglobinuria (PNH). The aim of this study is to see how safe and effective the pozelimab + cemdisiran combination is for patients 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 202
• Est. completion date: February 5, 2029
• Est. primary completion date: February 5, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (when available) 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

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria

Intervention

Drug:
• Pozelimab
Administered subcutaneously (SC) every 4 weeks (Q4W)
• Cemdisiran
Administered SC Q4W

Locations

Country	Name	City	State
Canada	Toronto General Hospital	Toronto
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Firenze
Japan	University of Tsukuba Hospital	Tsukuba
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Korea, Republic of	Ajou University Medical Center	Suwon
Korea, Republic of	St. Vincent Hospital	Suwon
Malaysia	Hospital Ampang	Ampang
Malaysia	Hospital Queen Elizabeth	Kota Kinabalu
Malaysia	Hospital Tg Ampuan Afzan	Kuantan
Poland	Szpital Uniwersytecki Nr2 Bydgoszcz	Bydgoszcz
Romania	Prof Dr Ion Chiricuta Institute of Oncology	Cluj-Napoca
Singapore	National University Hospital	Singapore
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitario de Basurto	Bilbao
Taiwan	Hualien Tzu Chi Hospital	Hualien City
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei City
Thailand	King Chulalongkorn Memorial Hospital	Bangkok
Thailand	Chiang Mai University	Chiang Mai
Thailand	Songklanagarind Hospital	Hat Yai
Thailand	Srinagarind Hospital	Khon Kaen
Turkey	Ege Universitesi Tip Fakultesi Hastanesi	Izmir

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

Canada,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Poland,  Romania,  Singapore,  Spain,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Severity of treatment-emergent SAEs		Up to week 108
Primary	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
Primary	Severity of treatment emergent AESIs		Up to week 108
Primary	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
Primary	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
Primary	Percent change from baseline in lactate dehydrogenase (LDH)		Baseline to week 36
Secondary	Maintenance of adequate control of hemolysis (LDH =1.5 × ULN)		Post-baseline through week 36
Secondary	Maintenance of adequate control of hemolysis (LDH =1.5 × ULN)		Post-baseline through week 48
Secondary	Maintenance of adequate control of hemolysis (LDH =1.5 × ULN)		Post-baseline through week 76
Secondary	Maintenance of adequate control of hemolysis (LDH =1.5 × ULN)		Post-baseline through week 108
Secondary	Adequate control of hemolysis (LDH =1.5 × ULN)		Post-baseline through week 108
Secondary	Transfusion avoidance	Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values	Post-baseline through week 36
Secondary	Transfusion avoidance	Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values	Post-baseline through week 48
Secondary	Transfusion avoidance	Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values	Post-baseline through week 76
Secondary	Transfusion avoidance	Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values	Post-baseline through week 108
Secondary	Breakthrough hemolysis (defined as LDH =2 × ULN [subsequent to initial achievement of LDH =1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)		Post-baseline through week 36
Secondary	Breakthrough hemolysis (defined as LDH =2 × ULN [subsequent to initial achievement of LDH =1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)		Post-baseline through week 48
Secondary	Breakthrough hemolysis (defined as LDH =2 × ULN [subsequent to initial achievement of LDH =1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)		Post-baseline through week 76
Secondary	Breakthrough hemolysis (defined as LDH =2 × ULN [subsequent to initial achievement of LDH =1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)		Post-baseline through week 108
Secondary	Hemoglobin stabilization	Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of =2 g/dL	Post-baseline through week 36
Secondary	Hemoglobin stabilization	Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of =2 g/dL	Post-baseline through week 48
Secondary	Hemoglobin stabilization	Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of =2 g/dL	Post-baseline through week 76
Secondary	Hemoglobin stabilization	Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of =2 g/dL	Post-baseline through week 108
Secondary	Percent change in LDH		From baseline to week 48
Secondary	Percent change in LDH		From baseline to week 76
Secondary	Percent change in LDH		From baseline to week 108
Secondary	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.	From baseline to week 36
Secondary	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.	From baseline to week 48
Secondary	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.	From baseline to week 76
Secondary	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.	From baseline to weeks 108
Secondary	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.	From baseline to week 36
Secondary	Change in 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.	From baseline to week 48
Secondary	Change in 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.	From baseline to week 76
Secondary	Change in 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.	From baseline to week 108
Secondary	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.	From baseline to week 36
Secondary	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.	From baseline to week 48
Secondary	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.	From baseline to week 76
Secondary	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.	From baseline to week 108
Secondary	Normalization of LDH		From post-baseline through week 108
Secondary	Rate of red blood cell (RBC) transfusion	Per protocol algorithm	Post-baseline through week 36
Secondary	Rate of RBC transfusion	Per protocol algorithm	Post-baseline through week 48
Secondary	Rate of RBC transfusion	Per protocol algorithm	Post-baseline through week 76
Secondary	Rate of RBC transfusion	Per protocol algorithm	Post-baseline through week 108
Secondary	Number of units of RBC transfusion	Per protocol algorithm	Post-baseline through week 36
Secondary	Number of units of RBC transfusion	Per protocol algorithm	Post-baseline through week 48
Secondary	Number of units of RBC transfusion	Per protocol algorithm	Post-baseline through week 76
Secondary	Number of units of RBC transfusion	Per protocol algorithm	Post-baseline through week 108
Secondary	Percentage of days with LDH =1.5x upper limit of normal (ULN)		Post-baseline through week 36
Secondary	Percentage of days with LDH =1.5x ULN		Post-baseline through week 48
Secondary	Percentage of days with LDH =1.5x ULN		Post-baseline through week 76
Secondary	Percentage of days with LDH =1.5x ULN		Post-baseline through week 108
Secondary	Change in hemoglobin levels		From baseline to week 36
Secondary	Change in hemoglobin levels		From baseline to week 48
Secondary	Change in hemoglobin levels		From baseline to week 76
Secondary	Change in hemoglobin levels		From baseline to week 108
Secondary	Change in total complement hemolytic activity assay (CH50)		Through week 108
Secondary	Percent change in CH50		Through week 108
Secondary	Concentrations of total pozelimab in serum		Through week 108
Secondary	Concentrations of cemdisiran in plasma		Through week 24
Secondary	Incidence of treatment-emergent anti-drug antibodies to pozelimab		Through week 108
Secondary	Incidence of treatment-emergent anti-drug antibodies to cemdisiran		Through week 108
Secondary	Concentration of total complement component 5 (C5) in plasma		Through week 108
Secondary	Percent change of concentration of total C5 in plasma		Through week 108