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A Study to Examine the Long-term Safety, Tolerability, and Effectiveness of Pozelimab and Cemdisiran Combination Therapy in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (ACCESS-EXT)

Primary Purpose

Paroxysmal Nocturnal Hemoglobinuria

Status
Recruiting
Phase
Phase 3
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Pozelimab
Cemdisiran
Sponsored by
Regeneron Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria focused on measuring PNH

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria: Patients Entering from the Parent Studies 1. Patients with PNH who have completed, without permanent discontinuation, study treatment in at least 1 of the parent studies (R3918-PNH-2021[NCT05133531] and/or R3918-PNH-2022 [NCT05131204]), if applicable. 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 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 Key Exclusion Criteria: Patients Entering from the Parent Studies 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 No documentation of meningococcal vaccination within 5 years prior to enrollment Positive hepatitis B surface antigen or hepatitis C virus 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 ALT or AST (unrelated to PNH or its complications) as described in the protocol Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Sites / Locations

  • Ajou University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

PNH Transition Patients

C5 Polymorphism Patients

Arm Description

Patients with PNH who completed treatment/ protocol requirements (as applicable) in the parent studies (R3918-PNH-2021 [NCT05133531] or R3918-PNH-2022 [NCT05131204])

Patients who have not been treated in either parent study but who have a documented complement component 5 (C5) polymorphism (eg, C5 variants p.Arg885His, p.Arg885R885Cys) rendering them refractory to eculizumab/ravulizumab.

Outcomes

Primary Outcome Measures

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
Severity of treatment-emergent SAEs
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
Severity of treatment emergent AESIs
Treatment emergent 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.
Percent change from baseline in lactate dehydrogenase (LDH)

Secondary Outcome Measures

Maintenance of adequate control of hemolysis (LDH ≤1.5 × ULN)
Maintenance of adequate control of hemolysis (LDH ≤1.5 × ULN)
Maintenance of adequate control of hemolysis (LDH ≤1.5 × ULN)
Maintenance of adequate control of hemolysis (LDH ≤1.5 × ULN)
Adequate control of hemolysis (LDH ≤1.5 × ULN)
Transfusion avoidance
Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values
Transfusion avoidance
Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values
Transfusion avoidance
Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values
Transfusion avoidance
Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values
Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)
Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)
Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)
Breakthrough hemolysis (defined as LDH ≥2 × ULN [subsequent to initial achievement of LDH ≤1.5 × ULN] concomitant with signs or symptoms associated with hemolysis)
Hemoglobin stabilization
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL
Hemoglobin stabilization
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL
Hemoglobin stabilization
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL
Hemoglobin stabilization
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL
Percent change in LDH
Percent change in LDH
Percent change in LDH
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Normalization of LDH
Rate of red blood cell (RBC) transfusion
Per protocol algorithm
Rate of RBC transfusion
Per protocol algorithm
Rate of RBC transfusion
Per protocol algorithm
Rate of RBC transfusion
Per protocol algorithm
Number of units of RBC transfusion
Per protocol algorithm
Number of units of RBC transfusion
Per protocol algorithm
Number of units of RBC transfusion
Per protocol algorithm
Number of units of RBC transfusion
Per protocol algorithm
Percentage of days with LDH ≤1.5x upper limit of normal (ULN)
Percentage of days with LDH ≤1.5x ULN
Percentage of days with LDH ≤1.5x ULN
Percentage of days with LDH ≤1.5x ULN
Change in hemoglobin levels
Change in hemoglobin levels
Change in hemoglobin levels
Change in hemoglobin levels
Change in total complement hemolytic activity assay (CH50)
Percent change in CH50
Concentrations of total pozelimab in serum
Concentrations of cemdisiran in plasma
Incidence of treatment-emergent anti-drug antibodies to pozelimab
Incidence of treatment-emergent anti-drug antibodies to cemdisiran
Concentration of total complement component 5 (C5) in plasma
Percent change of concentration of total C5 in plasma

Full Information

First Posted
February 6, 2023
Last Updated
April 7, 2023
Sponsor
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05744921
Brief Title
A Study to Examine the Long-term Safety, Tolerability, and Effectiveness of Pozelimab and Cemdisiran Combination Therapy in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 7, 2023 (Actual)
Primary Completion Date
March 23, 2028 (Anticipated)
Study Completion Date
March 23, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective of the study is to describe the long-term safety, tolerability, and efficacy of pozelimab and cemdisiran combination therapy in patients with PNH The secondary objectives of the study are to describe the long-term effect of the combination of pozelimab and cemdisiran on: Measures of intravascular hemolysis Transfusion parameters Hemoglobin levels Fatigue as assessed by a Patient Reported Outcome (PRO) Physical Function (PF) as assessed by a PRO Change in Global Health Status (GHS) as assessed by a PRO Complement activation Concentrations of total pozelimab in serum and cemdisiran and total complement component 5 (C5) protein in plasma Immunogenicity of pozelimab & cemdisiran

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria
Keywords
PNH

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PNH Transition Patients
Arm Type
Experimental
Arm Description
Patients with PNH who completed treatment/ protocol requirements (as applicable) in the parent studies (R3918-PNH-2021 [NCT05133531] or R3918-PNH-2022 [NCT05131204])
Arm Title
C5 Polymorphism Patients
Arm Type
Experimental
Arm Description
Patients who have not been treated in either parent study but who have a documented complement component 5 (C5) polymorphism (eg, C5 variants p.Arg885His, p.Arg885R885Cys) rendering them refractory to eculizumab/ravulizumab.
Intervention Type
Drug
Intervention Name(s)
Pozelimab
Other Intervention Name(s)
REGN3918
Intervention Description
Administered subcutaneously (SC) every 4 weeks (Q4W)
Intervention Type
Drug
Intervention Name(s)
Cemdisiran
Other Intervention Name(s)
ALN-CC5
Intervention Description
Administered SC Q4W
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent serious adverse events (SAEs)
Description
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
Title
Severity of treatment-emergent SAEs
Time Frame
Up to week 108
Title
Incidence of treatment emergent adverse events of special interest (AESIs)
Description
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
Title
Severity of treatment emergent AESIs
Time Frame
Up to week 108
Title
Treatment emergent adverse events (AEs) leading to permanent treatment discontinuation
Description
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
Title
Percent change from baseline in lactate dehydrogenase (LDH)
Time Frame
Baseline to week 36
Secondary Outcome Measure Information:
Title
Maintenance of adequate control of hemolysis (LDH ≤1.5 × ULN)
Time Frame
Post-baseline through week 36
Title
Maintenance of adequate control of hemolysis (LDH ≤1.5 × ULN)
Time Frame
Post-baseline through week 48
Title
Maintenance of adequate control of hemolysis (LDH ≤1.5 × ULN)
Time Frame
Post-baseline through week 76
Title
Maintenance of adequate control of hemolysis (LDH ≤1.5 × ULN)
Time Frame
Post-baseline through week 108
Title
Adequate control of hemolysis (LDH ≤1.5 × ULN)
Time Frame
Post-baseline through week 108
Title
Transfusion avoidance
Description
Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values
Time Frame
Post-baseline through week 36
Title
Transfusion avoidance
Description
Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values
Time Frame
Post-baseline through week 48
Title
Transfusion avoidance
Description
Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values
Time Frame
Post-baseline through week 76
Title
Transfusion avoidance
Description
Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values
Time Frame
Post-baseline through week 108
Title
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
Title
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
Title
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
Title
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
Title
Hemoglobin stabilization
Description
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL
Time Frame
Post-baseline through week 36
Title
Hemoglobin stabilization
Description
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL
Time Frame
Post-baseline through week 48
Title
Hemoglobin stabilization
Description
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL
Time Frame
Post-baseline through week 76
Title
Hemoglobin stabilization
Description
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL
Time Frame
Post-baseline through week 108
Title
Percent change in LDH
Time Frame
From baseline to week 48
Title
Percent change in LDH
Time Frame
From baseline to week 76
Title
Percent change in LDH
Time Frame
From baseline to week 108
Title
Change in fatigue
Description
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
Title
Change in fatigue
Description
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
Title
Change in fatigue
Description
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
Title
Change in fatigue
Description
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
Title
Change in physical function (PF) scores on the EORTC QLQ-C30
Description
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
Title
Change in PF scores on the EORTC QLQ-C30
Description
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 48
Title
Change in PF scores on the EORTC QLQ-C30
Description
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 76
Title
Change in PF scores on the EORTC QLQ-C30
Description
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 108
Title
Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30
Description
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
Title
Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30
Description
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 48
Title
Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30
Description
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 76
Title
Change in GHS/quality of life (QOL) scale on the EORTC QLQ-C30
Description
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 108
Title
Normalization of LDH
Time Frame
From post-baseline through week 108
Title
Rate of red blood cell (RBC) transfusion
Description
Per protocol algorithm
Time Frame
Post-baseline through week 36
Title
Rate of RBC transfusion
Description
Per protocol algorithm
Time Frame
Post-baseline through week 48
Title
Rate of RBC transfusion
Description
Per protocol algorithm
Time Frame
Post-baseline through week 76
Title
Rate of RBC transfusion
Description
Per protocol algorithm
Time Frame
Post-baseline through week 108
Title
Number of units of RBC transfusion
Description
Per protocol algorithm
Time Frame
Post-baseline through week 36
Title
Number of units of RBC transfusion
Description
Per protocol algorithm
Time Frame
Post-baseline through week 48
Title
Number of units of RBC transfusion
Description
Per protocol algorithm
Time Frame
Post-baseline through week 76
Title
Number of units of RBC transfusion
Description
Per protocol algorithm
Time Frame
Post-baseline through week 108
Title
Percentage of days with LDH ≤1.5x upper limit of normal (ULN)
Time Frame
Post-baseline through week 36
Title
Percentage of days with LDH ≤1.5x ULN
Time Frame
Post-baseline through week 48
Title
Percentage of days with LDH ≤1.5x ULN
Time Frame
Post-baseline through week 76
Title
Percentage of days with LDH ≤1.5x ULN
Time Frame
Post-baseline through week 108
Title
Change in hemoglobin levels
Time Frame
From baseline to week 36
Title
Change in hemoglobin levels
Time Frame
From baseline to week 48
Title
Change in hemoglobin levels
Time Frame
From baseline to week 76
Title
Change in hemoglobin levels
Time Frame
From baseline to week 108
Title
Change in total complement hemolytic activity assay (CH50)
Time Frame
Through week 108
Title
Percent change in CH50
Time Frame
Through week 108
Title
Concentrations of total pozelimab in serum
Time Frame
Through week 108
Title
Concentrations of cemdisiran in plasma
Time Frame
Through week 24
Title
Incidence of treatment-emergent anti-drug antibodies to pozelimab
Time Frame
Through week 108
Title
Incidence of treatment-emergent anti-drug antibodies to cemdisiran
Time Frame
Through week 108
Title
Concentration of total complement component 5 (C5) in plasma
Time Frame
Through week 108
Title
Percent change of concentration of total C5 in plasma
Time Frame
Through week 108

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Patients Entering from the Parent Studies 1. Patients with PNH who have completed, without permanent discontinuation, study treatment in at least 1 of the parent studies (R3918-PNH-2021[NCT05133531] and/or R3918-PNH-2022 [NCT05131204]), if applicable. 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 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 Key Exclusion Criteria: Patients Entering from the Parent Studies 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 No documentation of meningococcal vaccination within 5 years prior to enrollment Positive hepatitis B surface antigen or hepatitis C virus 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 ALT or AST (unrelated to PNH or its complications) as described in the protocol Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Trials Administrator
Phone
844-734-6643
Email
clinicaltrials@regeneron.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Ajou University Medical Center
City
Suwon
ZIP/Postal Code
16499
Country
Korea, Republic of
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
IPD Sharing Time Frame
When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
IPD Sharing Access Criteria
Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
IPD Sharing URL
https://vivli.org/

Learn more about this trial

A Study to Examine the Long-term Safety, Tolerability, and Effectiveness of Pozelimab and Cemdisiran Combination Therapy in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria

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