Paroxysmal Nocturnal HemoglobinuriaPhase 3NCT07154745
A Study to Evaluate How Pozelimab + Cemdisiran Combination Therapy Works in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Whose Current Treatment is Not Working Efficiently
A Phase 3 study testing Pozelimab and Cemdisiran in people with Paroxysmal Nocturnal Hemoglobinuria, run by Regeneron Pharmaceuticals at 20 sites in 7 countries.
Trial summary
This study is researching a treatment combination with two experimental drugs called pozelimab and cemdisiran referred to as "study drugs". Researchers are looking for a better way to treat 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
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 20 sitesin 7 countries
- Study dates
- 11 Jun 2026to 4 Dec 2031
- 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
- Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
- Currently treated with marketed eculizumab, ravulizumab, or crovalimab at the labeled dose for at least 6 months
- LDH persistently > 1.5 × Upper Limit of Normal (ULN) in the previous 6 months that the Principal Investigator (PI) attributes is due to intravascular hemolysis
- At least 2 screening LDH values from different visits as described in the protocol
- Willing and able to comply with clinic/remote visits and study-related procedures, including completion of the full series of meningococcal vaccinations required per protocol and agreement to continue to remain up to date with these vaccinations during the study
Who cannot join
- Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplants
- Body weight <40 kilograms at screening visit
- Patients with a known or suspected C5 mutation that is refractory to their current C5i treatment as described in the protocol
- Any active or ongoing infection within 2 weeks of screening or during the screening period or any recent infection as described in the protocol
- Known hereditary complement deficiency
- Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Trial locations and contacts
20 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
20 sites in 7 countries
South Korea5 sites, 5 recruiting
- Recruiting
Seoul National University Hospital
Seoul, 03080
- Recruiting
Severance Hospital
Seoul, 03722
- Recruiting
Seoul St. Mary's Hospital - The Catholic University of Korea
Seoul, 065791
- Recruiting
Ewha Womans University Mokdong Hospital
Seoul, 07985
- Recruiting
Samsung Medical Center
Seoul, 6351
Spain5 sites, 5 recruiting
- Recruiting
Institut Catala d'Oncologia
Barcelona, 08908
- Recruiting
Hospital Universitario Basurto
Bilbao, Vizcaya, 48013
- Recruiting
Hospital San Pedro de Alcantara
Cáceres, 10003
- Recruiting
Hospital General JM Morales Meseguer
Murcia, 30008
- Recruiting
Hospital Universitario de Salamanca
Salamanca, 37007
Brazil3 sites, 3 recruiting
- Recruiting
Hospital das Clinicas da FMRP USP
Ribeirão Preto, São Paulo, 14051-260
- Recruiting
Faculdade de Medicina do ABC
Santo André, São Paulo, 09060 870
- Recruiting
Hospital Santa Marcelina
São Paulo, 08270-070
Italy3 sites, 3 recruiting
- Recruiting
AOU Careggi
Florence, Tuscany, 50134
- Recruiting
Universita Cattolica del Sacro Cuore - Policlinico Universitario A. Gemelli
Rome, Lazio, 00168
- Recruiting
SC Hematology, AOU Città della Salute e della Scienza di Torino
Torino, 10126
Turkey (Türkiye)2 sites, 2 recruiting
- Recruiting
Istanbul University Istanbul Faculty of Medicine
Istanbul, 34418
- Recruiting
Ege University
Izmir, 35100
Poland1 site, 1 recruiting
- Recruiting
In-Vivo Sp. z o.o.
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-048
About this study
Official title: A Single Arm Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Control of Intravascular Hemolysis on Currently Available C5 Inhibitor Therapy
This study is researching a treatment combination with two experimental drugs called pozelimab and cemdisiran referred to as "study drugs". Researchers are looking for a better way to treat Paroxysmal Nocturnal Hemoglobinuria (PNH).
The aim of the study is to see how well the pozelimab and cemdisiran combination works to lower hemolysis in participants whose PNH has been not well controlled even after taking other complement component 5 (C5) inhibitors, eculizumab/eculizumab biosimilar, ravulizumab or crovalimab.
Read more
The study is looking at several other research questions, including:
- What side effects may happen from taking the study drugs?
- How much of the study drugs are in the blood at different times?
- Whether the body makes antibodies against the study drug (which could make the study drugs not work as well or could lead to side effects)
Read the detailed description
The treatment period has two parts, a Treatment Period (TP, 28 weeks) and an Extension treatment Period (EP, 52 weeks).
- 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 |
|---|---|---|
| Pozelimab + Cemdisiran Combo | 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.
Percent change in Lactate Dehydrogenase (LDH) during TP
Measured: From baseline to week 28
Secondary outcomes (19)
Normalization of LDH
Measured: Through week 52
Adequate control of hemolysis (LDH ≤1.5 × ULN)
Measured: Through week 52
Transfusion avoidance
Not requiring a Red Blood Cell (RBC) transfusion as per protocol algorithm based on hemoglobin values
Measured: Through week 52
Hemoglobin stabilization
Participants who do not receive an RBC transfusion and have no decrease in hemoglobin level of ≥2 g/dL
Measured: Through week 52
Change in hemoglobin from baseline
Measured: Through week 52
Change in fatigue
As measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale.
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 a higher quality of life
Measured: Through week 52
Occurrence of all Adverse Events (AEs)
Measured: Through week 52
Severity of all AEs
Measured: Through week 52
Occurrence of all Treatment-Emergent Adverse Events (TEAEs)
Measured: Through week 52
Severity of all TEAEs
Measured: Through week 52
Change from baseline in Total Complement Hemolytic Activity Assay (CH50)
Measured: Through week 52
Concentrations of total pozelimab
Measured: Through week 52
Concentrations of cemdisiran
Measured: Through week 52
Concentrations of total C5
Measured: Through week 52
Incidence of Anti-Drug Antibody (ADA) to pozelimab
Measured: Through week 52
Magnitude of ADA to pozelimab
Measured: Through week 52
Incidence of ADA to cemdisiran
Measured: Through week 52
Magnitude of ADA to cemdisiran
Measured: Through week 52
Percent change in LDH during EP
Measured: From baseline to week 24 and week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2025
- Study start11 Jun 2026
- Primary completion18 Jan 2030 (estimated)
- Study completion4 Dec 2031 (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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 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
- NCT07154745
- Sponsor's protocol ID
- R3918-PNH-2483
- Other IDs
- 2024-519709-37-00
- Status last verified
- Jul 2026
- First submitted
- 13 Aug 2025
- Last updated
- 5 Aug 2026
- Results posted
- No
- 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
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria With Inadequate Control of Intravascular Hemolysis on Currently Available C5 Inhibitor Therapy
- ClinicalTrials.gov ID
- NCT07154745
- Acronym / sponsor ID
- R3918-PNH-2483
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Keywords
- PNH
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 11 Jun 2026 (actual)
- Primary completion
- 18 Jan 2030 (estimated)
- Study completion
- 4 Dec 2031 (estimated)
- First posted
- 4 Sep 2025 (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 a treatment combination with two experimental drugs called pozelimab and cemdisiran referred to as "study drugs". Researchers are looking for a better way to treat Paroxysmal Nocturnal Hemoglobinuria (PNH).
The aim of the study is to see how well the pozelimab and cemdisiran combination works to lower hemolysis in participants whose PNH has been not well controlled even after taking other complement component 5 (C5) inhibitors, eculizumab/eculizumab biosimilar, ravulizumab or crovalimab.
The study is looking at several other research questions, including:
- What side effects may happen from taking the study drugs?
- How much of the study drugs are in the blood at different times?
- Whether the body makes antibodies against the study drug (which could make the study drugs not work as well or could lead to side effects)
Detailed description
The treatment period has two parts, a Treatment Period (TP, 28 weeks) and an Extension treatment Period (EP, 52 weeks).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pozelimab + Cemdisiran Combo | 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 (5 listed)
- Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
- Currently treated with marketed eculizumab, ravulizumab, or crovalimab at the labeled dose for at least 6 months
- LDH persistently > 1.5 × Upper Limit of Normal (ULN) in the previous 6 months that the Principal Investigator (PI) attributes is due to intravascular hemolysis
- At least 2 screening LDH values from different visits as described in the protocol
- Willing and able to comply with clinic/remote visits and study-related procedures, including completion of the full series of meningococcal vaccinations required per protocol and agreement to continue to remain up to date with these vaccinations during the study
Key exclusion criteria (6 listed)
- Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplants
- Body weight <40 kilograms at screening visit
- Patients with a known or suspected C5 mutation that is refractory to their current C5i treatment as described in the protocol
- Any active or ongoing infection within 2 weeks of screening or during the screening period or any recent infection as described in the protocol
- Known hereditary complement deficiency
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 | Pozelimab + Cemdisiran Combo |
| CemdisiranAlso: ALN-CC5Administered per the protocol | Drug | Pozelimab + Cemdisiran Combo |
Primary outcome
Percent change in Lactate Dehydrogenase (LDH) during TP
Time frame: From baseline to week 28
19 secondary outcomes
Normalization of LDH
Time frame: Through week 52
Adequate control of hemolysis (LDH ≤1.5 × ULN)
Time frame: Through week 52
Transfusion avoidance
Time frame: Through week 52
Hemoglobin stabilization
Time frame: Through week 52
Change in hemoglobin from baseline
Time frame: Through week 52
Change in fatigue
Time frame: Through week 52
Occurrence of all Adverse Events (AEs)
Time frame: Through week 52
Severity of all AEs
Time frame: Through week 52
Occurrence of all Treatment-Emergent Adverse Events (TEAEs)
Time frame: Through week 52
Severity of all TEAEs
Time frame: Through week 52
Change from baseline in Total Complement Hemolytic Activity Assay (CH50)
Time frame: Through week 52
Concentrations of total pozelimab
Time frame: Through week 52
Concentrations of cemdisiran
Time frame: Through week 52
Concentrations of total C5
Time frame: Through week 52
Incidence of Anti-Drug Antibody (ADA) to pozelimab
Time frame: Through week 52
Magnitude of ADA to pozelimab
Time frame: Through week 52
Incidence of ADA to cemdisiran
Time frame: Through week 52
Magnitude of ADA to cemdisiran
Time frame: Through week 52
Percent change in LDH during EP
Time frame: From baseline to week 24 and week 52
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 Aug 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
20 sites in 7 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 20 sites in 7 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 5 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: looking for participants now, as of the sponsor's last update on 5 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in South Korea, Spain, Brazil, Italy, Turkey (Türkiye) and 2 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?
Percent change in Lactate Dehydrogenase (LDH) during TP (time frame: From baseline to week 28). 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 Aug 2026.