Paroxysmal Nocturnal HemoglobinuriaPhase 4NCT04320602
Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab
A Phase 4 study testing Eculizumab and Ravulizumab in people with Paroxysmal Nocturnal Hemoglobinuria, run by Alexion Pharmaceuticals, Inc. at 4 sites in United Kingdom.
Trial summary
The primary purpose of this study is to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab in participants who are prescribed and are receiving a higher than approved dose of eculizumab to treat paroxysmal nocturnal hemoglobinuria (PNH). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria
- What is being tested?
- Eculizumab and Ravulizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 4 sitesUnited Kingdom
- Study dates
- 14 Apr 2021to 20 Dec 2022
- Phase
- Phase 4
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Documented diagnosis of PNH, confirmed by high-sensitivity flow cytometry evaluation of red blood cells and white blood cells, with granulocyte or monocyte clone size of ≥ 5%.
- Received 1200 mg eculizumab every 12 to 16 days (every 2 weeks) for at least 3 months prior to Screening.
- LDH ≤ 2 x upper limit of normal (ULN) according to central laboratory, at Screening.
- To reduce the risk of meningococcal infection (Neisseria meningitidis), all participants must be vaccinated against meningococcal infections within 3 years prior to initiating study drug.
- Body weight ≥ 40 kilograms.
Who cannot join
- History of major adverse vascular events within 6 months of Day 1.
- History of bone marrow transplantation.
- Lymphoma, leukemia, myelodysplastic syndrome, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
- Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to Day 1.
- Concomitant use of any of the following medications and not on a stable regimen (as judged by the Investigator) for the time period indicated prior to Screening:
- Erythropoietin or immunosuppressants for at least 8 weeks
Show all 13Show fewer
- Systemic corticosteroids for at least 4 weeks
- Vitamin K antagonists (for example, warfarin) with a stable international normalized ratio level for at least 4 weeks
- Iron supplements or folic acid for 4 weeks
- Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study.
- More than 1 LDH value > 2 × ULN within the 6 months prior to Day 1.
- Platelet count < 30,000/cubic millimeter (30 × 10^9/Liter [L]) at Screening.
- Absolute neutrophil count < 500/microliter (0.5 × 10^9/L) at Screening.
Trial locations and contacts
4 sites in 1 country.
United Kingdom4 sites
Clinical Study Site
Leeds, LS9 7TF
Research Site
Leeds, LS9 7TF
Clinical Study Site
London, SE5 9RS
Research Site
London, SE5 9RS
About this study
Official title: Phase 4, Single-Arm Study of Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab
The primary purpose of this study is to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab in participants who are prescribed and are receiving a higher than approved dose of eculizumab to treat paroxysmal nocturnal hemoglobinuria (PNH).
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Being tested
- Eculizumab, Ravulizumab
- Keywords
- Paroxysmal Nocturnal Hemoglobinuria, PNH, Ravulizumab, Ultomiris, Eculizumab, Soliris
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EculizumabBiological
Also called Soliris
Participants must have been prescribed and be receiving a stable dose of eculizumab 1200 milligrams (mg) every 2 weeks (q2w) for at least 3 months prior to the Screening Period. During the Screening Period, participants will continue to receive eculizumab 1200 mg q2w.
RavulizumabBiological
Also called ALXN1210, Ultomiris
During the Treatment Period, participants will receive a loading dose of ravulizumab on Day 1, followed by maintenance doses on Day 15 and every 8 weeks, administered by intravenous infusion. Ravulizumab loading and maintenance doses will be based on participants' body weight per approved dose regimen.
| Study group | Role | What they receive |
|---|---|---|
| Ravulizumab | Experimental | Participants will receive eculizumab during the 3-month Screening Period. Participants will then switch over to and receive weight-based doses of ravulizumab for the duration of the study Treatment Period (351 days). Receives: Biological: Eculizumab; Biological: Ravulizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Experienced Free C5-associated BTH
Free C5-associated BTH was defined as BTH concurrent with free C5 concentrations ≥0.5 micrograms (μg)/milliliter (mL). BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 grams {g}/deciliter {dL}], major adverse vascular event [MAVE], including thrombosis, dysphagia, or erectile dysfunction) in the presence of elevated lactate dehydrogenase (LDH) ≥2 * upper limit of normal (ULN).
Measured: Baseline through Day 351
Secondary outcomes (4)
Percentage of Participants Who Experienced BTH
BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 g/dL], MAVE, including thrombosis, dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 * ULN.
Measured: Baseline through Day 351
Percent Change From Baseline in LDH at Day 351
Measured: Baseline, Day 351
Percentage of Participants Who Received a Red Blood Cell (RBC) Transfusion
Measured: Baseline through Day 351
Percentage of Participants With Stabilized Hemoglobin
Stabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion from Baseline to Day 351.
Measured: Baseline through Day 351
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2020
- Study start14 Apr 2021
- Primary completion20 Dec 2022
- Study completion20 Dec 2022
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.
- Other trials for Paroxysmal Nocturnal HemoglobinuriaStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04320602
- Sponsor's protocol ID
- ALXN1210-PNH-401
- Other IDs
- 2019-003440-74, 2019
- Status last verified
- Jul 2024
- First submitted
- 23 Mar 2020
- Last updated
- 5 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 4, Single-Arm Study of Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab
- ClinicalTrials.gov ID
- NCT04320602
- Acronym / sponsor ID
- ALXN1210-PNH-401
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Keywords
- Paroxysmal Nocturnal Hemoglobinuria, PNH, Ravulizumab, Ultomiris, Eculizumab, Soliris
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 14 Apr 2021 (actual)
- Primary completion
- 20 Dec 2022 (actual)
- Study completion
- 20 Dec 2022 (actual)
- First posted
- 25 Mar 2020 (actual)
- Results
- Posted 12 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab in participants who are prescribed and are receiving a higher than approved dose of eculizumab to treat paroxysmal nocturnal hemoglobinuria (PNH).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ravulizumab | Experimental | Biological: Eculizumab, Biological: RavulizumabParticipants will receive eculizumab during the 3-month Screening Period. Participants will then switch over to and receive weight-based doses of ravulizumab for the duration of the study Treatment Period (351 days). |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Documented diagnosis of PNH, confirmed by high-sensitivity flow cytometry evaluation of red blood cells and white blood cells, with granulocyte or monocyte clone size of ≥ 5%.
- Received 1200 mg eculizumab every 12 to 16 days (every 2 weeks) for at least 3 months prior to Screening.
- LDH ≤ 2 x upper limit of normal (ULN) according to central laboratory, at Screening.
- To reduce the risk of meningococcal infection (Neisseria meningitidis), all participants must be vaccinated against meningococcal infections within 3 years prior to initiating study drug.
- Body weight ≥ 40 kilograms.
Key exclusion criteria (13 listed)
- History of major adverse vascular events within 6 months of Day 1.
- History of bone marrow transplantation.
- Lymphoma, leukemia, myelodysplastic syndrome, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
- Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to Day 1.
- Concomitant use of any of the following medications and not on a stable regimen (as judged by the Investigator) for the time period indicated prior to Screening:
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 |
|---|---|---|
| EculizumabAlso: SolirisParticipants must have been prescribed and be receiving a stable dose of eculizumab 1200 milligrams (mg) every 2 weeks (q2w) for at least 3 months prior to the Screening Period. During the Screening Period, participants will continue to receive eculizumab 1200 mg q2w. | Biological | Ravulizumab |
| RavulizumabAlso: ALXN1210, UltomirisDuring the Treatment Period, participants will receive a loading dose of ravulizumab on Day 1, followed by maintenance doses on Day 15 and every 8 weeks, administered by intravenous infusion. Ravulizumab loading and maintenance doses will be based on participants' body weight per approved dose regimen. | Biological | Ravulizumab |
Primary outcome
Percentage of Participants Who Experienced Free C5-associated BTH
Time frame: Baseline through Day 351
Free C5-associated BTH was defined as BTH concurrent with free C5 concentrations ≥0.5 micrograms (μg)/milliliter (mL). BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 grams {g}/deciliter {dL}], major adverse vascular event [MAVE], including thrombosis, dysphagia, or erectile dysfunction) in the presence of elevated lactate dehydrogenase (LDH) ≥2 * upper limit of normal (ULN).
4 secondary outcomes
Percentage of Participants Who Experienced BTH
Time frame: Baseline through Day 351
Percent Change From Baseline in LDH at Day 351
Time frame: Baseline, Day 351
Percentage of Participants Who Received a Red Blood Cell (RBC) Transfusion
Time frame: Baseline through Day 351
Percentage of Participants With Stabilized Hemoglobin
Time frame: Baseline through Day 351
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
Related trials for Paroxysmal Nocturnal Hemoglobinuria
Enrolling by invitationObservational study
An Observational Post-Authorization Safety and Effectiveness Study of Ravulizumab in Adult Patients Aged 18 and Older Diagnosed With Paroxysmal Nocturnal Hemoglobinuria Using Multicenter Electronic Medical Records in South Korea
Hemoglobinuria, Paroxysmal
RecruitingPhase 2
Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34+ Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-cells
Severe Aplastic Anemia, MDS (Myelodysplastic Syndrome)
RecruitingPhase 3
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
Paroxysmal Nocturnal Hemoglobinuria
Not yet recruitingPhase 3
A Study of Efficacy and Safety of FXS6837 in Anti-C5 Treated PNH Patients.
Paroxysmal Nocturnal Hemoglobinuria
RecruitingPhase 2
Haplo-identical Transplantation for Severe Aplastic Anemia, Hypo-plastic MDS and PNH Using Peripheral Blood Stem Cells and Post-transplant Cyclophosphamide for GVHD Prophylaxis
Severe Aplastic Anemia (SAA), Hypo-Plastic Myelodysplastic Syndrome (MDS)
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.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Eculizumab and Ravulizumab in people with Paroxysmal Nocturnal Hemoglobinuria, run by Alexion Pharmaceuticals, Inc. at 4 sites in United Kingdom.
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 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: finished, as of the sponsor's last update on 5 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United Kingdom. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 12 Aug 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?
Percentage of Participants Who Experienced Free C5-associated BTH (time frame: Baseline through Day 351). 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 Sep 2024.