Paroxysmal Nocturnal HemoglobinuriaPhase 2NCT04811716
Pozelimab and Cemdisiran Combination Treatment in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Who Have Received Pozelimab Monotherapy
A Phase 2 study testing Pozelimab and Cemdisiran in people with Paroxysmal Nocturnal Hemoglobinuria, run by Regeneron Pharmaceuticals at 13 sites in 6 countries.
Trial summary
The primary objective of the study is to evaluate the safety and tolerability of 2 dosing regimens of pozelimab and cemdisiran combination therapy during the open-label treatment period (OLTP) The secondary objectives of the study are: To evaluate the effect of the combination treatment on the following parameters of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria
- What is being tested?
- Pozelimab and Cemdisiran
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 13 sitesin 6 countries
- Study dates
- 29 Jul 2021to 18 Oct 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Participants with PNH who are receiving treatment with pozelimab monotherapy in the R3918- PNH-1868 study (NCT04162470)
Who cannot join
- Documented, positive polymerase chain reaction (PCR) or equivalent test based on regional recommendations for COVID-19 or suspected SARS-CoV-2 infection as defined in the protocol
- Participants with documented history of liver cirrhosis or participants with liver disease with evidence of currently impaired liver function; or participants with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) as described in the protocol
- Significant protocol deviation(s) in the parent study based on the investigator's judgment as described in the protocol
- Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the participant unsuitable for enrollment or would jeopardize the safety of the participant
- Known hypersensitivity to cemdisiran or any component of cemdisiran formulation
- NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply
Trial locations and contacts
13 sites in 6 countries.
13 sites in 6 countries
South Korea5 sites
Pusan National University Hospital
Busan, 49241
Samsung Medical Center
Seoul, Seoul Teugbyeolsi, 06351
Seoul National University Hospital
Seoul, 03080
Yonsei University College of Medicine, Severance Hospital
Seoul, 3722
Ewha Womans University Medical Centre
Seoul, 7985
Malaysia3 sites
Hospital Sultanah Nur Zahirah
Kuala Terengganu, Terengganu, 20400
Hospital Miri
Miri, Sarawak, 98000
Hospital Sibu
Sibu, Sarawak, 96000
Taiwan2 sites
National Taiwan University Hospital
Taipei, 10002
Chang Gung Memorial Hospital
Taoyuan City, 333
Hungary1 site
D l Pesti Centrumk rh z Orsz gos Hematol giai s Infektol giai Int zet
Budapest, Nagyvárad Tér 1, 1907
United Kingdom1 site
St. James's University Hospital
Leeds, West Yorkshire, LS97TF
About this study
Official title: A Randomized, Open-label, Two-arm Study to Evaluate the Safety, Efficacy, and Pharmacodynamic Effects of Pozelimab and Cemdisiran Combination Treatment in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Have Received Pozelimab Monotherapy
The primary objective of the study is to evaluate the safety and tolerability of 2 dosing regimens of pozelimab and cemdisiran combination therapy during the open-label treatment period (OLTP)
The secondary objectives of the study are:
- To evaluate the effect of the combination treatment on the following parameters of intravascular hemolysis: lactate dehydrogenase (LDH) control, breakthrough hemolysis, and inhibition of total complement hemolysis activity (CH50)
- To evaluate the effect of the combination treatment on hemoglobin levels
- To evaluate the effect of the combination treatment on red blood cell (RBC) transfusion requirements
- To evaluate the effect of the combination treatment on clinical outcome assessments (COAs) measuring fatigue and health related quality of life
- To assess the concentrations of total pozelimab in serum and total complement component (C) 5 and cemdisiran in plasma
- To assess immunogenicity to pozelimab and cemdisiran
- To evaluate the long-term safety and efficacy of pozelimab and cemdisiran in an optional open-label extension period (OLEP)
- To assess safety after treatment intensification with pozelimab and cemdisiran
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Being tested
- Pozelimab, Cemdisiran
- Keywords
- PNH
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PozelimabDrug
Also called REGN3918
Administered Sub-cutaneous (SC) per protocol
CemdisiranDrug
Also called ALN-CC5
Administered SC per protocol
| Study group | Role | What they receive |
|---|---|---|
| Pozelimab Q4W + Cemdisiran | Experimental | Not described Receives: Drug: Pozelimab; Drug: Cemdisiran |
| Pozelimab Q2W + Cemdisiran | Experimental | Not described Receives: Drug: Pozelimab; Drug: Cemdisiran |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
Open Label Treatment Period (OLTP)
Measured: Through Week 28
Secondary outcomes (57)
Percent Change of Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period
OLTP Pre-treatment (mean of LDH values prior to combination dosing); End-of-treatment (mean of LDH value at week 24- through week 28); percentage of change in Upper Limit of Normal (xULN).
Measured: End of treatment period, approximately 28 Weeks
Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1) Through Week 28
OLTP Adequate control of hemolysis is defined as LDH values ≤1.5 × Upper limit of normal (ULN) from baseline (day 1) to week 28
Measured: Baseline (Day 1) through Week 28
Percentage of Participants Maintaining Adequate Control of Hemolysis From Week 4 Through Week 28
OLTP
Measured: Week 4 through Week 28
Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28
OLTP; Adequate control at a visit is defined as having LDH <=1.5 x ULN at that visit
Measured: Day 1 through Week 28
Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28
OLTP; Normalization of LDH was defined as LDH ≤1.0 × ULN at each visit
Measured: Baseline (Day 1) through Week 28
Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Baseline (Day 1) Through Week 28
OLTP
Measured: Baseline (Day 1) through Week 28
Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Week 4 Through Week 28
OLTP
Measured: Week 4 through Week 28
Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1) Through Week 28
OLTP
Breakthrough hemolysis is defined as an increase in LDH with concomitant signs or symptoms associated with hemolysis:
- An increase in LDH occurs when:
- LDH ≥2 × ULN if pre-treatment LDH is ≤1.5 × ULN or
- LDH ≥2 × ULN after initial achievement of LDH ≤1.5 × ULN if pre-treatment LDH is >1.5 × ULN Signs or symptoms should correspond to those known to be associated with intravascular hemolysis due to Paroxysmal nocturnal hemoglobinuria (PNH) limited to the following: new onset or worsening fatigue, headache, dyspnea, hemoglobinuria, abdominal pain, scleral icterus, erectile dysfunction, chest pain, confusion, dysphagia, anemia including hemoglobin value significantly lower (ie, ≥2g/dL decrease) compared to patient's known baseline hemoglobin values, and thrombotic event.
Measured: Baseline (Day 1) through Week 28
Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1) Through Week 28
OLTP Hemoglobin stabilization was defined as participants who did not receive an RBC transfusion and had no decrease in hemoglobin level of ≥2 grams per deciLiter (g/dL).
Measured: Baseline (Day 1) through Week 28
Change in Hemoglobin Levels From Baseline (Day 1) Through Week 28
OLTP
Measured: Baseline (Day 1) to Week 28
Percentage of Participants With Transfusion Avoidance From Baseline (Day 1) Through Week 28
OLTP Not requiring a red blood cell (RBC) transfusion as per protocol algorithm
Measured: Baseline (Day 1) to Week 28
Rate of Red Blood Cells (RBCs) Transfused From Baseline (Day 1) to Week 28
OLTP Rate of RBCs transfused is defined as number of events per person-years of treatment. For each participant, the participant-years are the time from first dose date to week 28 (or early terminations visit if subject discontinued the study early) in the OLTP.
Measured: Baseline (Day 1) to Week 28
Number of Per-Protocol RBC Units Transfused From Baseline (Day 1) Through Week 28
OLTP
Measured: Baseline (Day 1) to Week 28
Change in Total Complement Hemolysis Activity Assay (CH50) From Baseline (Day 1) Through Week 28
OLTP
Measured: Baseline (Day 1) to Week 28
Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1) Through Week 28
OLTP FACIT fatigue is a 13-item scale and for each item 4 is not at all fatigued to 0 very much fatigued. Higher FACIT-Fatigue scores indicate less fatigue (scores range from 0-52). A 5-point change is considered clinically meaningful.
Measured: Baseline (Day 1) to Week 28
Change in Global Health Status/Quality of Life Scale (GHS/QoL) on the European Organization for Research and Treatment of Cancer: Quality-of-Life Questionnaire Core 30 Items (EORTC QLQ-C30) From Baseline (Day 1) Through Week 28
OLTP EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement.
Measured: Baseline (Day 1) to Week 28
Change in Physical Function (PF) Scores on the EORTC QLQ-C30 From Baseline (Day 1) Through Week 28
OLTP; EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement.
Measured: Baseline (Day 1) to Week 28
Concentrations of Total Pozelimab in Serum on Week 28
OLTP
Measured: On Week 28
Concentrations of Cemdisiran in Plasma on Week 28
OLTP
Measured: On Week 28
Concentrations of Total C5 on Week 28
OLTP
Measured: On Week 28
Number of Participants With Pozelimab Anti-Drug Antibody (ADA) Responses Over Time
OLTP and OLEP
Measured: Up to Week 52 (OLTP [ Week 0 - Week 28] + OLEP [Week 28 - Week 52])
Number of Participants With Cemdisiran Anti-Drug Antibody (ADA) Responses Over Time
OLTP and OLEP
Measured: Up to Week 52 (OLTP [ Week 0 - Week 28] + OLEP [Week 28 - Week 52])
Percentage of Participants With TEAEs for Participants Who Received Treatment Intensification
OLTP No participants received dose intensification during the study; Therefore, assessment of the safety of pozelimab + cemdisiran combination therapy in participants requiring dose intensification was not conducted.
Measured: Through Week 28
Change of LDH From Baseline (Day 1e) to Week 24e
Optional Open-Label Extension Period (OLEP)
Measured: Baseline (Day 1e) to Week 24e
Percent Change of LDH From OLEP Baseline (Day 1e) to Week 24e
OLEP; Percentage of change for units per liter (U/L)
Measured: Baseline (Day 1e) to Week 24e
Change of LDH From Baseline (Day 1e) to Week 52e
OLEP
Measured: Baseline (Day 1e) to Week 52e
Percent Change of LDH From Baseline (Day 1e) to Week 52e
OLEP
Measured: Baseline (Day 1e) to Week 52e
Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 24e
OLEP
Measured: Baseline (Day 1e) through Week 24e
Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 52e
OLEP
Measured: Baseline (Day 1e) through Week 52e
Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e
OLEP Adequate control at a visit is defined as having LDH <=1.5 x ULN at that visit
Measured: Baseline (Day 1e) through Week 52e
Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e
OLEP
Measured: Baseline (Day 1e) through week 52e
Average LDH (U/L) Based on Area Under the Curve (AUC) From OLEP Baseline (Day 1e) Through Week 52e
OLEP
Measured: Baseline (Day 1e) through Week 52e
Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 24e
OLEP
Measured: Baseline (Day 1e) through Week 24e
Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 52e
OLEP
Measured: Baseline (Day 1e) through Week 52e
Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 24e
OLEP Participants who did not receive RBC transfusion and had no decrease in hemoglobin levels
Measured: Baseline (Day 1e) through Week 24e
Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 52e
OLEP Participants who did not receive RBC transfusion and had no decrease in hemoglobin levels
Measured: Baseline (Day 1e) through Week 52e
Change in Hemoglobin Levels From Baseline (Day 1e) to Week 24e
OLEP
Measured: Baseline (Day 1e) to Week 24e
Change in Hemoglobin Levels From Baseline (Day 1e) to Week 52e
OLEP
Measured: Baseline (Day 1e) to Week 52e
Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 24e
OLEP Not requiring a RBC transfusion as per protocol algorithm
Measured: Baseline (Day 1e) through Week 24e
Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 52e
OLEP Not requiring a RBC transfusion as per protocol algorithm
Measured: Baseline (Day 1e) to Week 52e
Rate of RBCs Transfused From Baseline (Day 1e) to Week 24e
OLEP
Measured: Baseline (Day 1e) to Week 24e
Rate of RBCs Transfused From Baseline (Day 1e) to Week 52e
OLEP
Measured: Baseline (Day 1e) to Week 52e
Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 24e
OLEP
Measured: Baseline (Day 1e) to Week 24e
Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 52e
OLEP
Measured: Baseline (Day 1e) to Week 52e
Change in CH50 From Baseline (Day 1e) to Week 16e
OLEP
Measured: Baseline (Day 1e) to Week 16e
Change in CH50 From Baseline (Day 1e) to Week 24e
OLEP
Measured: Baseline (Day 1e) to Week 24e
Change in CH50 From Baseline (Day 1e) to Week 52e
OLEP
Measured: Baseline (Day 1e) to Week 52e
Percent Change in CH50 From Baseline (Day 1e) to Week 16e
OLEP
Measured: Baseline (Day 1e) to Week 16e
Percent Change in CH50 From Baseline (Day 1e) to Week 24e
OLEP
Measured: Baseline (Day 1e) to Week 24e
Percent Change in CH50 From Baseline (Day 1e) to Week 52e
OLEP
Measured: Baseline (Day 1e) to Week 52e
Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1e) to Week 52e
OLEP; The FACIT-Fatigue is a 13-item, self-administered assessment of 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 participants with cancer and other chronic illnesses. The FACIT-Fatigue items are measured with 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 less fatigue. A 5-point change is considered clinically meaningful.
Measured: Baseline (Day 1e) to Week 52e
Change in GHS/QoL on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e
OLEP; EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement.
Measured: Baseline (Day 1e) to Week 52e
Change in PF Scores on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e
OLEP; EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement.
Measured: Baseline (Day 1e) to Week 52e
Percentage of Participants With TEAEs Up to Week 52
OLEP
Measured: Up to Week 52
Concentrations of Total Pozelimab in Serum on Week 52
OLEP
Measured: On Week 52
Concentrations of Total C5 on Week 52
OLEP
Measured: On Week 52
Concentrations of Cemdisiran in Plasma on Week 52
OLEP
Measured: On Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2021
- Study start29 Jul 2021
- Primary completion25 Oct 2022
- Study completion18 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Paroxysmal Nocturnal HemoglobinuriaStudies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04811716
- Sponsor's protocol ID
- R3918-PNH-2092
- Other IDs
- 2020-005005-17
- Status last verified
- Apr 2025
- First submitted
- 19 Mar 2021
- Last updated
- 8 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Publications
Jang JH, Wong RSM, Hartford C, Pavani R, Aurand L, Nguyen Q, Mohan K, Meagher K, Sherman S, Rofail D, Perlee L, Souttou A, Kelly RJ. Safety, Efficacy, and Patient-Reported Outcomes From a Phase 2 Randomized Trial of Pozelimab and Cemdisiran Combination in Patients With Paroxysmal Nocturnal Hemoglobinuria. EJHaem. 2025 Jul 24;6(4):e70095. doi: 10.1002/jha2.70095. eCollection 2025 Aug.
PubMed 40708708
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label, Two-arm Study to Evaluate the Safety, Efficacy, and Pharmacodynamic Effects of Pozelimab and Cemdisiran Combination Treatment in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Have Received Pozelimab Monotherapy
- ClinicalTrials.gov ID
- NCT04811716
- Acronym / sponsor ID
- R3918-PNH-2092
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Keywords
- PNH
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 29 Jul 2021 (actual)
- Primary completion
- 25 Oct 2022 (actual)
- Study completion
- 18 Oct 2023 (actual)
- First posted
- 23 Mar 2021 (actual)
- Results
- Posted 16 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the study is to evaluate the safety and tolerability of 2 dosing regimens of pozelimab and cemdisiran combination therapy during the open-label treatment period (OLTP)
The secondary objectives of the study are:
- To evaluate the effect of the combination treatment on the following parameters of intravascular hemolysis: lactate dehydrogenase (LDH) control, breakthrough hemolysis, and inhibition of total complement hemolysis activity (CH50)
- To evaluate the effect of the combination treatment on hemoglobin levels
- To evaluate the effect of the combination treatment on red blood cell (RBC) transfusion requirements
- To evaluate the effect of the combination treatment on clinical outcome assessments (COAs) measuring fatigue and health related quality of life
- To assess the concentrations of total pozelimab in serum and total complement component (C) 5 and cemdisiran in plasma
- To assess immunogenicity to pozelimab and cemdisiran
- To evaluate the long-term safety and efficacy of pozelimab and cemdisiran in an optional open-label extension period (OLEP)
- To assess safety after treatment intensification with pozelimab and cemdisiran
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pozelimab Q4W + Cemdisiran | Experimental | Drug: Pozelimab, Drug: Cemdisiran |
| Pozelimab Q2W + Cemdisiran | Experimental | Drug: Pozelimab, Drug: Cemdisiran |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 1. Participants with PNH who are receiving treatment with pozelimab monotherapy in the R3918- PNH-1868 study (NCT04162470)
Key exclusion criteria (6 listed)
- Documented, positive polymerase chain reaction (PCR) or equivalent test based on regional recommendations for COVID-19 or suspected SARS-CoV-2 infection as defined in the protocol
- Participants with documented history of liver cirrhosis or participants with liver disease with evidence of currently impaired liver function; or participants with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) as described in the protocol
- Significant protocol deviation(s) in the parent study based on the investigator's judgment as described in the protocol
- Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the participant unsuitable for enrollment or would jeopardize the safety of the participant
- Known hypersensitivity to cemdisiran or any component of cemdisiran formulation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PozelimabAlso: REGN3918Administered Sub-cutaneous (SC) per protocol | Drug | Pozelimab Q2W + Cemdisiran, Pozelimab Q4W + Cemdisiran |
| CemdisiranAlso: ALN-CC5Administered SC per protocol | Drug | Pozelimab Q2W + Cemdisiran, Pozelimab Q4W + Cemdisiran |
Primary outcome
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: Through Week 28
Open Label Treatment Period (OLTP)
57 secondary outcomes
Percent Change of Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period
Time frame: End of treatment period, approximately 28 Weeks
Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1) Through Week 28
Time frame: Baseline (Day 1) through Week 28
Percentage of Participants Maintaining Adequate Control of Hemolysis From Week 4 Through Week 28
Time frame: Week 4 through Week 28
Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28
Time frame: Day 1 through Week 28
Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28
Time frame: Baseline (Day 1) through Week 28
Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Baseline (Day 1) Through Week 28
Time frame: Baseline (Day 1) through Week 28
Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Week 4 Through Week 28
Time frame: Week 4 through Week 28
Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1) Through Week 28
Time frame: Baseline (Day 1) through Week 28
Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1) Through Week 28
Time frame: Baseline (Day 1) through Week 28
Change in Hemoglobin Levels From Baseline (Day 1) Through Week 28
Time frame: Baseline (Day 1) to Week 28
Percentage of Participants With Transfusion Avoidance From Baseline (Day 1) Through Week 28
Time frame: Baseline (Day 1) to Week 28
Rate of Red Blood Cells (RBCs) Transfused From Baseline (Day 1) to Week 28
Time frame: Baseline (Day 1) to Week 28
Number of Per-Protocol RBC Units Transfused From Baseline (Day 1) Through Week 28
Time frame: Baseline (Day 1) to Week 28
Change in Total Complement Hemolysis Activity Assay (CH50) From Baseline (Day 1) Through Week 28
Time frame: Baseline (Day 1) to Week 28
Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1) Through Week 28
Time frame: Baseline (Day 1) to Week 28
Change in Global Health Status/Quality of Life Scale (GHS/QoL) on the European Organization for Research and Treatment of Cancer: Quality-of-Life Questionnaire Core 30 Items (EORTC QLQ-C30) From Baseline (Day 1) Through Week 28
Time frame: Baseline (Day 1) to Week 28
Change in Physical Function (PF) Scores on the EORTC QLQ-C30 From Baseline (Day 1) Through Week 28
Time frame: Baseline (Day 1) to Week 28
Concentrations of Total Pozelimab in Serum on Week 28
Time frame: On Week 28
Concentrations of Cemdisiran in Plasma on Week 28
Time frame: On Week 28
Concentrations of Total C5 on Week 28
Time frame: On Week 28
Number of Participants With Pozelimab Anti-Drug Antibody (ADA) Responses Over Time
Time frame: Up to Week 52 (OLTP [ Week 0 - Week 28] + OLEP [Week 28 - Week 52])
Number of Participants With Cemdisiran Anti-Drug Antibody (ADA) Responses Over Time
Time frame: Up to Week 52 (OLTP [ Week 0 - Week 28] + OLEP [Week 28 - Week 52])
Percentage of Participants With TEAEs for Participants Who Received Treatment Intensification
Time frame: Through Week 28
Change of LDH From Baseline (Day 1e) to Week 24e
Time frame: Baseline (Day 1e) to Week 24e
Percent Change of LDH From OLEP Baseline (Day 1e) to Week 24e
Time frame: Baseline (Day 1e) to Week 24e
Change of LDH From Baseline (Day 1e) to Week 52e
Time frame: Baseline (Day 1e) to Week 52e
Percent Change of LDH From Baseline (Day 1e) to Week 52e
Time frame: Baseline (Day 1e) to Week 52e
Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 24e
Time frame: Baseline (Day 1e) through Week 24e
Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 52e
Time frame: Baseline (Day 1e) through Week 52e
Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e
Time frame: Baseline (Day 1e) through Week 52e
Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e
Time frame: Baseline (Day 1e) through week 52e
Average LDH (U/L) Based on Area Under the Curve (AUC) From OLEP Baseline (Day 1e) Through Week 52e
Time frame: Baseline (Day 1e) through Week 52e
Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 24e
Time frame: Baseline (Day 1e) through Week 24e
Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 52e
Time frame: Baseline (Day 1e) through Week 52e
Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 24e
Time frame: Baseline (Day 1e) through Week 24e
Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 52e
Time frame: Baseline (Day 1e) through Week 52e
Change in Hemoglobin Levels From Baseline (Day 1e) to Week 24e
Time frame: Baseline (Day 1e) to Week 24e
Change in Hemoglobin Levels From Baseline (Day 1e) to Week 52e
Time frame: Baseline (Day 1e) to Week 52e
Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 24e
Time frame: Baseline (Day 1e) through Week 24e
Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 52e
Time frame: Baseline (Day 1e) to Week 52e
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40708708Jang JH, Wong RSM, Hartford C, Pavani R, Aurand L, Nguyen Q, Mohan K, Meagher K, Sherman S, Rofail D, Perlee L, Souttou A, Kelly RJ. Safety, Efficacy, and Patient-Reported Outcomes From a Phase 2 Randomized Trial of Pozelimab and Cemdisiran Combination in Patients With Paroxysmal Nocturnal Hemoglobinuria. EJHaem. 2025 Jul 24;6(4):e70095. doi: 10.1002/jha2.70095. eCollection 2025 Aug.
- A Plain Language Summary is available on TrialSummaries.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trial Management study director
Regeneron Pharmaceuticals
13 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pozelimab and Cemdisiran in people with Paroxysmal Nocturnal Hemoglobinuria, run by Regeneron Pharmaceuticals at 13 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in South Korea, Malaysia, Taiwan, Hong Kong, Hungary and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) (time frame: Through Week 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04811716, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2025.