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Paroxysmal Nocturnal HemoglobinuriaPhase 3ACCESS 2NCT05131204

Efficacy and Safety of the Combination of Pozelimab and Cemdisiran Versus Continued Eculizumab or Ravulizumab Treatment in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria

A Phase 3 study testing Cemdisiran, Eculizumab and Pozelimab in people with Paroxysmal Nocturnal Hemoglobinuria, run by Regeneron Pharmaceuticals at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The primary objective of the study is: To evaluate the effect of pozelimab and cemdisiran combination therapy on hemolysis, as assessed by lactate dehydrogenase (LDH), after 36 weeks of treatment, in patients with PNH who switch from eculizumab or ravulizumab therapy versus patients who continue their eculizumab or… 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?
Cemdisiran, Eculizumab and Pozelimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
6 Oct 2022to 12 Jul 2023
Phase
Phase 3
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

  • Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
  • Treated with eculizumab or ravulizumab prior to screening visit as described in the protocol Note: Biosimilars are not permitted, unless approved by the Sponsor

Who cannot join

  • Patients with a screening LDH >1.5 × ULN who have not taken their C5 inhibitor within the labeled dose interval at the dose prior to the screening LDH assessment
  • Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
  • Body weight < 40 kilograms at screening visit
  • Any use of complement inhibitor therapy other than eculizumab or ravulizumab in the 26 weeks prior to the screening visit or planned use during the study with the exception of study treatments
  • Not meeting meningococcal vaccination requirements for eculizumab or ravulizumab according to the current local prescribing information (where available) and at a minimum documentation of meningococcal vaccination within 5 years prior to screening visit.
  • Any contraindication for receiving Neisseria meningitidis vaccination.
Show all 11Show fewer
  • Positive for hepatitis B, and/ or hepatitis C as described in the protocol
  • History of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
  • Participation in another interventional clinical study (except R3918-PNH-2021) or use of any experimental therapy within 30 days before screening visit or within 5 half-lives of that investigational product, whichever is greater, with the exception of eculizumab or ravulizumab.
  • Patients with functional or anatomic asplenia
  • Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Regeneron Research Facility

    Whittier, California, 90603

Other trials in United States

About this study

Official title: A Randomized, Open-Label, Eculizumab and Ravulizumab Controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Are Currently Treated With Eculizumab or Ravulizumab

The primary objective of the study is:

To evaluate the effect of pozelimab and cemdisiran combination therapy on hemolysis, as assessed by lactate dehydrogenase (LDH), after 36 weeks of treatment, in patients with PNH who switch from eculizumab or ravulizumab therapy versus patients who continue their eculizumab or ravulizumab therapy

Read more

The secondary objectives of the study are to:

  • Evaluate the effect of pozelimab and cemdisiran combination treatment versus anti-C5 standard-of-care treatment (eculizumab or ravulizumab) on the following:
  • Transfusion requirements and transfusion parameters
  • Measures of hemolysis: LDH control, breakthrough hemolysis, and inhibition of CH50
  • Hemoglobin levels
  • Fatigue as assessed by Clinical Outcome Assessments (COAs)
  • Health-related quality of life (HRQoL) as assessed by COAs
  • Safety and tolerability
  • To assess the concentrations of total pozelimab and either total eculizumab or total ravulizumab in serum and total cemdisiran and total C5 protein in plasma
  • To assess the immunogenicity of pozelimab and cemdisiran
Being tested
Cemdisiran, Eculizumab, Pozelimab, Ravulizumab
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.

  • CemdisiranDrug

    Also called ALN-CC5

    Administered per protocol

  • EculizumabDrug

    Also called Soliris

    Administered per protocol

  • PozelimabDrug

    Also called REGN3918

    Administered per protocol

  • RavulizumabDrug

    Also called ALXN1210, Ultomiris

    Administered per protocol

Study groups in NCT05131204
Study groupRoleWhat they receive
Pozelimab and CemdisiranExperimentalRandomized 1:1
Receives: Drug: Cemdisiran; Drug: Eculizumab; Drug: Pozelimab; Drug: Ravulizumab
Anti-C5 standard-of-careExperimentalRandomized 1:1
Receives: Drug: Eculizumab; Drug: Ravulizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent Change in Lactate Dehydrogenase (LDH) From Baseline to Week 36

    Measured: From baseline to week 36

Secondary outcomes (32)

  1. Percentage of Participants With Transfusion Avoidance After Day 1 Through Week 36

    Participants who do not receive a red blood cell (RBC) transfusion as per protocol algorithm based on post baseline hemoglobin values

    Measured: Day 1 through week 36

  2. Percentage of Participants With Transfusion Avoidance From Week 4 Through Week 36

    Participants who do not receive an RBC transfusion as per protocol algorithm based on post baseline hemoglobin values

    Measured: Week 4 through week 36

  3. Percentage of Participants With Breakthrough Hemolysis After Day 1 Through Week 36

    Participants with an increase in LDH with concomitant signs or symptoms associated with hemolysis as described in the protocol

    Measured: Day 1 through week 36

  4. Percentage of Participants With Breakthrough Hemolysis From Week 4 Through Week 36

    Participants with an increase in LDH with concomitant signs or symptoms associated with hemolysis as described in the protocol

    Measured: Week 4 (day 29) through week 36

  5. Percentage of Participants With Hemoglobin Stabilization After Day 1 Through Week 36

    Participants who do not receive an RBC transfusion and have no decrease in hemoglobin level as defined in the protocol

    Measured: Day 1 through week 36

  6. Percentage of Participants With Hemoglobin Stabilization From Week 4 Through Week 36

    Participants who do not receive an RBC transfusion and have no decrease in hemoglobin level as defined in the protocol

    Measured: Week 4 (day 29) through week 36

  7. Percentage of Participants With Adequate Control of LDH From Week 8 Through Week 36

    Percentage of participants with adequate control of LDH as defined in the protocol

    Measured: Week 8 (day 57) through week 36

  8. Percentage of Participants With Adequate Control of LDH After Day 1 Though Week 36

    Percentage of participants with adequate control of LDH as defined in the protocol

    Measured: Day 1 through week 36

  9. Percentage of Participants Who Maintained Adequate Control of Hemolysis From Week 8 Through Week 36

    Percentage of participants with adequate control of LDH as defined in the protocol

    Measured: Week 8 through week 36

  10. Percentage of Participants Who Maintained Adequate Control of Hemolysis After Day 1 Through Week 36

    Percentage of participants with adequate control of LDH as defined in the protocol

    Measured: Day 1 through week 36

  11. Percentage of Participants With Normalization of LDH From Week 8 Through Week 36

    Percentage of participants with normalization of LDH as defined in the protocol

    Measured: Week 8 (day 57) through week 36

  12. Percentage of Participants With Normalization of LDH After Day 1 Through Week 36

    Percentage of participants with normalization of LDH as defined in the protocol

    Measured: Day 1 through week 36

  13. Change in Fatigue as Measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline to Week 36

    The FACIT-Fatigue is a 13 item, self-administered clinical outcome assessment (COA) 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 quality of life (QoL) in patients with cancer and other chronic illnesses. The FACIT-Fatigue assesses the level of fatigue using a 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

  14. Change in Physical Function (PF) Score on the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 Items (EORTC-QLQ-C30) From Baseline to Week 36

    EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."

    Measured: From baseline to week 36

  15. Change in Global Health Status (GHS)/QoL Scale Score on the EORTC-QLQ-C30 From Baseline to Week 36

    EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 7 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, sleep and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."

    Measured: From baseline to week 36

  16. Rate of RBCs Transfused Per Protocol Algorithm After Day 1 Through Week 36

    Per protocol algorithm

    Measured: Day 1 through week 36

  17. Rate of RBCs Transfused Per Protocol Algorithm From Week 4 Through Week 36

    Per protocol algorithm

    Measured: Week 4 through week 36

  18. Number of Units of RBCs Transfused Per Protocol Algorithm After Day 1 Through Week 36

    Per protocol algorithm

    Measured: Day 1 through week 36

  19. Number of Units of RBCs Transfused Per Protocol Algorithm From Week 4 Through Week 36

    Per protocol algorithm

    Measured: Week 4 through week 36

  20. Change in Hemoglobin Levels From Baseline to Week 36

    Per protocol algorithm

    Measured: From baseline to week 36

  21. Incidence of Treatment Emergent Serious Adverse Events (SAEs)

    Treatment period and safety follow up period

    Measured: Up to week 29

  22. Incidence of Treatment-emergent Adverse Events (TEAEs) of Special Interest

    Treatment period and safety follow up period

    Measured: Up to week 29

  23. Incidence of TEAEs Leading to Treatment Discontinuation

    Treatment period and safety follow up period

    Measured: Up to week 29

  24. Change in Total CH50 From Baseline to Week 36

    Measured: From baseline to week 36

  25. Percent Change in Total CH50 From Baseline to Week 36

    Measured: From baseline to week 36

  26. Concentration of Total C5 in Plasma Through Week 62

    Treatment period and safety follow up period

    Measured: Through week 62

  27. Concentrations of Total Pozelimab in Serum Through Week 62

    Treatment period and safety follow up period

    Measured: Through week 62

  28. Concentrations of Total Cemdisiran in Plasma Through Week 32

    Treatment period

    Measured: Through week 32

  29. Concentrations of Total Eculizumab in Serum Through Week 40

    Treatment period

    Measured: Through week 40

  30. Concentrations of Total Ravulizumab in Plasma Through Week 44

    Treatment period

    Measured: Through week 44

  31. Incidence of Treatment Emergent Anti-drug Antibodies (ADAs) to Pozelimab Through Week 62

    Treatment period and safety follow up period

    Measured: Through week 62

  32. Incidence of Treatment Emergent ADAs to Cemdisiran Through Week 62

    Treatment period and safety follow up period

    Measured: Through week 62

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Nov 2021
  2. Study start6 Oct 2022
  3. Primary completion12 Jul 2023
  4. Study completion12 Jul 2023

Why it stopped: Sponsor decision not related to efficacy or safety.

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05131204
Sponsor's protocol ID
R3918-PNH-2022
Other IDs
2020-002761-33
Acronym
ACCESS 2
Status last verified
Apr 2025
First submitted
12 Nov 2021
Last updated
8 Apr 2025
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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cemdisiran, Eculizumab and Pozelimab in people with Paroxysmal Nocturnal Hemoglobinuria, run by Regeneron Pharmaceuticals at 1 site in United States.

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 2 inclusion and 11 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: stopped early, 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 1 site in United States. 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?

Yes. Results are posted in the registry (first posted 19 Sep 2024). 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?

Percent Change in Lactate Dehydrogenase (LDH) From Baseline to Week 36 (time frame: From baseline to week 36). 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 NCT05131204.

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.

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