Paroxysmal Nocturnal HemoglobinuriaPhase 3ACCESS-EXTNCT05744921
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
A Phase 3 study testing Pozelimab and Cemdisiran in people with Paroxysmal Nocturnal Hemoglobinuria, run by Regeneron Pharmaceuticals at 50 sites in 21 countries.
Trial summary
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). 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
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 202 participants
- Where
- 50 sitesin 21 countries
- Study dates
- 7 Mar 2023to 10 Oct 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Patients Entering from the Parent Study
- Patients with PNH who have completed, without permanent discontinuation, study treatment in the parent study (R3918-PNH-2021[NCT05133531]), including the post-Open-label treatment period (OLTP) transition period, if applicable.
- Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol.
- Patients Entering with C5 polymorphism
- Patients with PNH who have a documented C5 polymorphism rendering them refractory to eculizumab or ravulizumab (eg, p.Arg885His, p.Arg885Cys), as described in the protocol
- Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes
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- Active disease, as defined by the presence of 1 or more PNH-related sign or symptom as described in the protocol
- LDH level ≥2 × upper limit of normal (ULN) at the screening visit
- Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol
Who cannot join
- Patients Entering from the Parent Study
- Significant protocol deviation(s) in the parent study based on the investigator's judgment and to the extent that these would (if continued) impact the study objectives and/or safety of the patient
- Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in or completing the study
- Patients Entering with C5 polymorphism
- Prior treatment with complement inhibitors within 5 half-lives of the respective agent prior to screening, except for prior eculizumab or ravulizumab which are not exclusionary
- Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
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- Not meeting meningococcal vaccination requirements and, at a minimum, documentation of quadrivalent meningococcal vaccination within 5 years prior to enrollment and serotype B vaccine within 3 years prior to enrollment as described in the protocol
- Positive hepatitis B surface antigen or hepatitis C virus Ribonucleic acid (RNA) during screening
- Patients with known HIV with history of opportunistic infections in the last 1 year as described in the protocol
- Known hereditary complement deficiency
- Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
- Documented history of liver cirrhosis or patients with liver disease with evidence of current impaired liver function or patients with elevations in Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) (unrelated to PNH or its complications) as described in the protocol
- Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Trial locations and contacts
50 sites in 21 countries. Contact the study team or a site near you to ask about taking part.
50 sites in 21 countries
South Korea8 sites, 8 recruiting
- Recruiting
Pusan National University Hospital
Busan, 49241
- Recruiting
Gachon University Gil Medical Center
Incheon, Namdong-Gu, 21565
- Recruiting
Severance Hospital Yonsei University Health System
Seoul, 03722
- Recruiting
Samsung Medical Center
Seoul, 06351
- Recruiting
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 06591
- Recruiting
Ewha Womans University Mokdong Hospital
Seoul, 07985
- Recruiting
St. Vincent Hospital
Suwon, Gyeonggi-do, 16247
- Recruiting
Ajou University Medical Center
Suwon, Gyeonggi-do, 16499
Taiwan7 sites, 7 recruiting
- Recruiting
Changhua Christian Hospital
Changhua, 500
- Recruiting
Hualien Tzu Chi Hospital
Hualien City, 97002
- Recruiting
China Medical University Hospital
Taichung, Central Taiwan, 40447
- Recruiting
Taichung Veterans General Hospital (VGHTC)
Taichung, 4070
- Recruiting
National Taiwan University Hospital
Taipei, 10002
- Recruiting
Tri-Service General Hospital
Taipei, 11490
- Recruiting
Chang Gung Memorial Hospital - Linkou Branch
Taoyuan, Hunan Province, 33305
India5 sites, 5 recruiting
- Recruiting
Postgraduate Institute of Medical Education & Research
Chandigarh, 160012
- Recruiting
Bhagwan Mahaveer Cancer Hospital and Research Centre (BMCHRC)
Jaipur, 302017
- Recruiting
Amrita Institute of Medical Sciences (AIMS) and Research Centre Aims
Kochi, Kerala, 682041
- Recruiting
K J Somaiya Super Specialty Hospital & Research Centre
Mumbai, Maharashtra, 400022
- Recruiting
Rajiv Gandhi Cancer Institute & Research Center (RGCIRC) - Rohini Campus
New Delhi, National Capital Territory of Delhi, 110085
Thailand4 sites, 4 recruiting
- Recruiting
King Chulalongkorn Memorial Hospital
Bangkok, 10330
- Recruiting
Chiang Mai University
Chiang Mai, 50200
- Recruiting
Prince Of Songkla Hospital, Prince Of Songkhla University
Hat Yai, Changwat Songkhla, 90110
- Recruiting
Faculty of Medicine Khon Kaen University
Khon Kaen, 40002
Malaysia3 sites, 3 recruiting
- Recruiting
Hospital Ampang
Ampang, Selangor, 68000
- Recruiting
Hospital Queen Elizabeth
Kota Kinabalu, Sabah, 88200
- Recruiting
Hospital Tg Ampuan Afzan
Kuantan, Pahang, 25200
Poland3 sites, 2 recruiting
- Recruiting
In-Vivo Sp. z o.o.
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-048
- Completed
Szpital Uniwersytecki Nr2 Bydgoszcz
Bydgoszcz, 85-168
- Recruiting
University Clinical Center Medical University of Gdansk
Gdansk, Pomeranian Voivodeship, 80-214
Brazil2 sites, 2 recruiting
- Recruiting
Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner
Curitiba, Jardim Santo Andre, 09090-790
- Recruiting
A Beneficencia Portuguesa de Sao Paulo, BP Mirante
São Paulo, 01321-001
Italy2 sites, 2 recruiting
- Recruiting
Aou Careggi
Florence, Firenze, 50139
- Recruiting
SC Hematology, AOU Città della Salute e della Scienza di Torino
Torino, 10126
Japan2 sites, 1 recruiting
- Withdrawn
Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
Nagoya, Aichi-ken, 466-8650
- Recruiting
University of Tsukuba Hospital
Tsukuba, Ibaraki, 305-8576
Spain2 sites, 2 recruiting
- Recruiting
Hospital Clinic de Barcelona
Barcelona, 08036
- Recruiting
Hospital Universitario Basurto
Bilbao, Vizcaya, 48013
Turkey (Türkiye)2 sites, 2 recruiting
- Recruiting
Ege University Faculty of Medicine
Bornova, İzmir, 35100
- Recruiting
Istanbul University
Istanbul, 34418
Canada1 site, 1 recruiting
- Recruiting
Toronto General Hospital
Toronto, Ontario, M5G 2C4
Colombia1 site, 1 recruiting
- Recruiting
Hospital Pablo Tobon Uribe
Medellín, Antioquia, 050034
Hungary1 site, 1 recruiting
- Recruiting
Semmelweis University/Semmelweis Egyetem
Budapest, 1083
Jordan1 site, 1 recruiting
- Recruiting
Jordan University Hospital (JUH)
Amman, 11942
Mexico1 site, 1 recruiting
- Recruiting
Servicio de Hematologia del Hospital Universitario de la UANL
Monterrey, Nuevo León, 64460
Philippines1 site, 1 recruiting
- Recruiting
St Lukes Medical Center
Quezon City, National Capital Region, 1634
Romania1 site, 1 recruiting
- Recruiting
Prof Dr Ion Chiricuta Cancer Institute
Cluj-Napoca, Cluj, 400015
Singapore1 site, 1 recruiting
- Recruiting
National University Hospital
Singapore, 119074
United Kingdom1 site, 1 recruiting
- Recruiting
Leeds Teaching Hospitals NHS Trust - St. James Institute of Oncology
Leeds, LS97TF
About this study
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
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)
- 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 per the protocol
CemdisiranDrug
Also called ALN-CC5
Administered per the protocol
| Study group | Role | What they receive |
|---|---|---|
| PNH Transition Patients | Experimental | Patients with PNH who completed treatment/ protocol requirements (as applicable) in the parent study (R3918-PNH-2021 [NCT05133531]) Receives: Drug: Pozelimab; Drug: Cemdisiran |
| C5 Polymorphism Patients | Experimental | Patients who have not been treated in either parent study but who have a documented complement component 5 (C5) variation rendering them refractory to eculizumab/ravulizumab. Note: Loading dose of pozelimab administered IV on Day 1. Receives: Drug: Pozelimab; Drug: Cemdisiran |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to week 108
Severity of treatment-emergent SAEs
Measured: 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
Measured: Up to week 108
Severity of treatment emergent AESIs
Measured: 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.
Measured: 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.
Measured: Up to week 108
Percent change from baseline in lactate dehydrogenase (LDH)
Measured: Baseline to week 36
Secondary outcomes (53)
Adequate control of hemolysis (LDH ≤1.5 × ULN)
Measured: Post-baseline through week 108
Transfusion avoidance
Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values
Measured: Post-baseline through week 36
Transfusion avoidance
Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values
Measured: Post-baseline through week 48
Transfusion avoidance
Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values
Measured: Post-baseline through week 76
Transfusion avoidance
Not requiring red blood cell (RBC) transfusion as per protocol algorithm based on hemoglobin values
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Post-baseline through week 108
Hemoglobin stabilization
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL
Measured: Post-baseline through week 36
Hemoglobin stabilization
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL
Measured: Post-baseline through week 48
Hemoglobin stabilization
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL
Measured: Post-baseline through week 76
Hemoglobin stabilization
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL
Measured: Post-baseline through week 108
Percent change in LDH
Measured: From baseline to week 48
Percent change in LDH
Measured: From baseline to week 76
Percent change in LDH
Measured: From baseline to 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From baseline to week 36
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.
Measured: From baseline to week 48
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.
Measured: From baseline to week 76
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.
Measured: 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.
Measured: From baseline to week 36
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.
Measured: From baseline to week 48
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.
Measured: From baseline to week 76
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.
Measured: From baseline to week 108
Normalization of LDH
Measured: From post-baseline through week 108
Rate of red blood cell (RBC) transfusion
Per protocol algorithm
Measured: Post-baseline through week 36
Rate of RBC transfusion
Per protocol algorithm
Measured: Post-baseline through week 48
Rate of RBC transfusion
Per protocol algorithm
Measured: Post-baseline through week 76
Rate of RBC transfusion
Per protocol algorithm
Measured: Post-baseline through week 108
Number of units of RBC transfusion
Per protocol algorithm
Measured: Post-baseline through week 36
Number of units of RBC transfusion
Per protocol algorithm
Measured: Post-baseline through week 48
Number of units of RBC transfusion
Per protocol algorithm
Measured: Post-baseline through week 76
Number of units of RBC transfusion
Per protocol algorithm
Measured: Post-baseline through week 108
Percentage of days with LDH ≤1.5x upper limit of normal (ULN)
Measured: Post-baseline through week 36
Percentage of days with LDH ≤1.5x ULN
Measured: Post-baseline through week 48
Percentage of days with LDH ≤1.5x ULN
Measured: Post-baseline through week 76
Percentage of days with LDH ≤1.5x ULN
Measured: Post-baseline through week 108
Change in hemoglobin levels
Measured: From baseline to week 36
Change in hemoglobin levels
Measured: From baseline to week 48
Change in hemoglobin levels
Measured: From baseline to week 76
Change in hemoglobin levels
Measured: From baseline to week 108
Change in total complement hemolytic activity assay (CH50)
Measured: Through week 108
Percent change in CH50
Measured: Through week 108
Concentrations of total pozelimab in serum
Measured: Through week 108
Concentrations of cemdisiran in plasma
Measured: Through week 24
Incidence of treatment-emergent anti-drug antibodies to pozelimab
Measured: Through week 108
Incidence of treatment-emergent anti-drug antibodies to cemdisiran
Measured: Through week 108
Concentration of total complement component 5 (C5) in plasma
Measured: Through week 108
Percent change of concentration of total C5 in plasma
Measured: Through week 108
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2023
- Study start7 Mar 2023
- Primary completion10 Oct 2028 (estimated)
- Study completion10 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 202 participants (estimated)
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
- NCT05744921
- Sponsor's protocol ID
- R3918-PNH-2050
- Other IDs
- 2021-004931-10, 2023-510336-36-00, 2023
- Acronym
- ACCESS-EXT
- Status last verified
- Nov 2026
- First submitted
- 6 Feb 2023
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05744921
- Acronym / sponsor ID
- ACCESS-EXT / R3918-PNH-2050
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Keywords
- PNH
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 202 participants (estimated)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 7 Mar 2023 (actual)
- Primary completion
- 10 Oct 2028 (estimated)
- Study completion
- 10 Oct 2028 (estimated)
- First posted
- 27 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PNH Transition Patients | Experimental | Drug: Pozelimab, Drug: CemdisiranPatients with PNH who completed treatment/ protocol requirements (as applicable) in the parent study (R3918-PNH-2021 [NCT05133531]) |
| C5 Polymorphism Patients | Experimental | Drug: Pozelimab, Drug: CemdisiranPatients who have not been treated in either parent study but who have a documented complement component 5 (C5) variation rendering them refractory to eculizumab/ravulizumab. Note: Loading dose of pozelimab administered IV on Day 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients Entering from the Parent Study
- Patients with PNH who have completed, without permanent discontinuation, study treatment in the parent study (R3918-PNH-2021[NCT05133531]), including the post-Open-label treatment period (OLTP) transition period, if applicable.
- Willing and able to comply with clinic visits and study-related procedures, including meningococcal vaccinations required per protocol.
- Patients Entering with C5 polymorphism
- Patients with PNH who have a documented C5 polymorphism rendering them refractory to eculizumab or ravulizumab (eg, p.Arg885His, p.Arg885Cys), as described in the protocol
Key exclusion criteria (13 listed)
- Patients Entering from the Parent Study
- Significant protocol deviation(s) in the parent study based on the investigator's judgment and to the extent that these would (if continued) impact the study objectives and/or safety of the patient
- Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in or completing the study
- Patients Entering with C5 polymorphism
- Prior treatment with complement inhibitors within 5 half-lives of the respective agent prior to screening, except for prior eculizumab or ravulizumab which are not exclusionary
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 per the protocol | Drug | C5 Polymorphism Patients, PNH Transition Patients |
| CemdisiranAlso: ALN-CC5Administered per the protocol | Drug | C5 Polymorphism Patients, PNH Transition Patients |
Primary outcome
Incidence of treatment-emergent serious adverse events (SAEs)
Time frame: Up to week 108
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
Time frame: Up to week 108
Incidence of treatment emergent adverse events of special interest (AESIs)
Time frame: Up to week 108
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
Time frame: Up to week 108
Incidence of adverse events (AEs) leading to permanent treatment discontinuation
Time frame: Up to week 108
Any untoward medical occurrence in a patient administered a study drug which may or may not have a causal relationship with the study drug.
Severity of adverse events (AEs) leading to permanent treatment discontinuation
Time frame: Up to week 108
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)
Time frame: Baseline to week 36
53 secondary outcomes
Adequate control of hemolysis (LDH ≤1.5 × ULN)
Time frame: Post-baseline through week 108
Transfusion avoidance
Time frame: Post-baseline through week 36
Transfusion avoidance
Time frame: Post-baseline through week 48
Transfusion avoidance
Time frame: Post-baseline through week 76
Transfusion avoidance
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
Hemoglobin stabilization
Time frame: Post-baseline through week 36
Hemoglobin stabilization
Time frame: Post-baseline through week 48
Hemoglobin stabilization
Time frame: Post-baseline through week 76
Hemoglobin stabilization
Time frame: Post-baseline through week 108
Percent change in LDH
Time frame: From baseline to week 48
Percent change in LDH
Time frame: From baseline to week 76
Percent change in LDH
Time frame: From baseline to week 108
Change in fatigue
Time frame: From baseline to week 36
Change in fatigue
Time frame: From baseline to week 48
Change in fatigue
Time frame: From baseline to week 76
Change in fatigue
Time frame: From baseline to weeks 108
Change in physical function (PF) scores on the EORTC QLQ-C30
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
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
Normalization of LDH
Time frame: From post-baseline through week 108
Rate of red blood cell (RBC) transfusion
Time frame: Post-baseline through week 36
Rate of RBC transfusion
Time frame: Post-baseline through week 48
Rate of RBC transfusion
Time frame: Post-baseline through week 76
Rate of RBC transfusion
Time frame: Post-baseline through week 108
Number of units of RBC transfusion
Time frame: Post-baseline through week 36
Number of units of RBC transfusion
Time frame: Post-baseline through week 48
Number of units of RBC transfusion
Time frame: Post-baseline through week 76
Number of units of RBC transfusion
Time frame: Post-baseline through week 108
Percentage of days with LDH ≤1.5x upper limit of normal (ULN)
Time frame: Post-baseline through week 36
Percentage of days with LDH ≤1.5x ULN
Time frame: Post-baseline through week 48
Percentage of days with LDH ≤1.5x ULN
Time frame: Post-baseline through week 76
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- 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.
Clinical Trial Management study director
Regeneron Pharmaceuticals
50 sites in 21 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pozelimab and Cemdisiran in people with Paroxysmal Nocturnal Hemoglobinuria, run by Regeneron Pharmaceuticals at 50 sites in 21 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 9 inclusion and 13 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: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in South Korea, Taiwan, India, Thailand, Malaysia and 16 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Trials Administrator (844-734-6643, clinicaltrials@regeneron.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-emergent serious adverse events (SAEs) (time frame: Up to week 108). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Nov 2026.