Hemoglobinuria, ParoxysmalPhase 3NCT00098280
Eculizumab to Treat Paroxysmal Nocturnal Hemoglobinuria
A Phase 3 study testing Eculizumab in people with Hemoglobinuria, Paroxysmal, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
This study will examine the safety and effectiveness of the experimental drug eculizumab in treating patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare disorder of red blood cells that leads to premature destruction of the cells and resulting anemia. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Hemoglobinuria, Paroxysmal
- What is being tested?
- Eculizumab
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2004to Feb 2006
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Individuals at least 18 years of age;
- Patients must have required at least 4 episodes of transfusions in the 12 months prior to Visit 1 for anemia or anemia-related symptoms;
- Presence of a GPI deficient red blood cell clone (type II cells) by flow cytometry of greater than or equal to 10%;
- Patients taking erythropoietin must be on a stable dose for 26 weeks prior to visit 1 and the dose must be expected to remain stable during the Observation Period and the Treatment Phase;
- Patients taking immunosuppressants must be on a stable dose for at least 26 weeks prior to Visit 1 and the dose must be expected to remain stable during the Observation period and the Treatment Phase;
- Patients taking corticosteroids must be on a stable dose for at least 4 weeks prior to Visit 1. The dose level may be decreased during the study as clinically appropriate. If the corticosteroids need to be increased, they may not be increased above the dose reported at Visit 1;
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- Patients are allowed to take coumadin, but must be at a stable international normalized ratio (INR) level for 4 weeks prior to Visit 1 and are expected to maintain a stable INR level during the Observation Period and the Treatment Phase;
- Patients taking iron supplements or folic acid must be on a stable dose for 4 weeks prior to Visit 3 and be expected to remain stable during Observation Period and the Treatment Phase;
- Patients are allowed to take low molecular weight heparin, but must be on a stable dose for 4 weeks prior to Visit 1 and the dose must be expected to remain stable during Observation period and the Treatment Phase;
- Patient must be willing and able to give written informed consent;
- Patients must be vaccinated against N. meningitidis at Visit 1 or at least 14 days prior to Visit 3;
- Patient must avoid conception during the trial using a method that is most appropriate for their physical state and culture.
- Documented LDH level greater than or equal to 1.5 x upper limit of normal (ULN) either at Visit 1 or during the Observation Period;
- Patients who have received one PRBC transfusion during the Observation Period at a hemoglobin value of less than or equal to 9 gm/dL with symptoms or at a hemoglobin value of less than or equal to 7 gm/dL without symptoms, and also within 1.5 gm/dL of the mean hemoglobin pre-transfusion value for the previous 12 months. This transfusion should be in accordance with that patient's individual transfusion hemoglobin algorithm, and occur within 48 hours of the hemoglobin sample that precipitated the transfusion;
- Platelet count greater than or equal to 100,000/mm(3) either at Visit 1 or during the Observation Period.
Who cannot join
- Patients whose mean hemoglobin levels prior to transfusion over the previous 12 months is greater than 10.5 gm/dL;
- Absolute Neutrophil count less than or equal to 500/microL;
- Presence or suspicion of active bacterial infection, in the opinion of the Investigator, at Visit 3 or recurrent bacterial infections;
- Known or suspected hereditary complement deficiency;
- Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days prior to Visit 1;
- Pregnant, breast-feeding, or intending to conceive during the course of the study, including the Post-treatment Phase;
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- History of meningococcal disease;
- History of bone marrow transplantation;
- Any condition that, in the opinion of the Investigator, could increase the patient's risk by participating in the study or confound the outcome of the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, 20892
About this study
Official title: A Hemoglobin Stabilization and Transfusion Reduction Efficacy and Safety Clinical Investigation, Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Using Eculizumab in Paroxysmal Nocturnal Hemoglobinuria Patients
This study will examine the safety and effectiveness of the experimental drug eculizumab in treating patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare disorder of red blood cells that leads to premature destruction of the cells and resulting anemia. Patients may be at high risk of blood clots and may develop bone marrow failure or aplastic anemia, with low white blood cell and platelet counts. Eculizumab is a monoclonal antibody that may help improve the survival of red blood cells.
Patients 18 years of age and older with PNH who require blood transfusions for anemia and have received at least four transfusions in the 12 months preceding evaluation for this study may be eligible to enroll. Candidates are screened with a medical history, physical examination, and check of vital signs.
Read more
Participants have an electrocardiogram (EKG) and blood and urine tests, and are vaccinated against Neisseria meningitides, a common bacteria that can cause a disabling or fatal type of meningitis. They then enter an observation phase of the study, with monthly visits during which they complete a questionnaire; update their health status, transfusion record, and medication use; have their vital signs checked and PNH symptoms evaluated; have blood and urine tests; and receive a transfusion, if necessary. These visits continue for up to 3 months until patients receive a "qualifying" transfusion; that is, a transfusion given as a consequence of a certain hemoglobin level with symptoms or a different level without symptoms.
Patients are then randomly assigned to receive either eculizumab or a placebo (salt solution with no active ingredient). Both study medications are given intravenously (through a vein) over 30 minutes once a week for five doses and then once every 2 weeks for another 11 doses. At each treatment visit (study weeks 0-24), patients update their health status, transfusion records, and medication use; have their vital signs checked; and provide a blood sample. At various visits, they also complete a questionnaire, provide a urine sample and have an EKG. At the last treatment visit (week 26 or the final visit for patients who end their participation before visit 18) patients have a complete physical examination in addition to the procedures listed above.
Read the detailed description
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder of the hematopoietic stem cell characterized by intravascular hemolysis, hemoglobinuria, anemia, and thrombosis. The clinical features of PNH result from the lack of one or more of the GPI-linked proteins that serve to protect cells from autologous complement mediated attack. Two such proteins, CD55 (decay accelerating factor) and CD59 (reactive lysis inhibitor) have been shown to be absent from PNH erythrocytes and platelets as well as other cell types.
Evidence strongly suggests that lack of the terminal complement inhibitor CD59 is responsible for the sensitivity of PNH erythrocytes and platelets to the effects of autologous complement. Since the pathogenesis of PNH is due to the inability of PNH red cells and platelets to inhibit the activation of terminal complement, it is logical to hypothesize that a terminal complement inhibitor could effectively stop the intravascular hemolysis, obviate or lessen the need for transfusions, and possibly decrease the propensity of life threatening thrombosis. Eculizumab is a humanized monoclonal antibody that like CD59 inhibits terminal complement.
This study is a randomized, double-blind, placebo controlled, multi-center study of eculizumab or placebo administered intravenously to approximately 75 PNH patients. The study is designed to evaluate the safety of eculizumab in transfusion dependent patients with paroxysmal nocturnal hemoglobinuria (PNH) and to determine if the administration of this terminal complement inhibitor could provide a safe and effective substitute for CD59 function.
- Conditions
- Hemoglobinuria, Paroxysmal
- Being tested
- Eculizumab
- Keywords
- H5g1, PNH, TRIUMPH, Paroxysmal Nocturnal Hemoglobinuria
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EculizumabDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2004 (estimated)
- Study startDec 2004
- Study completionFeb 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hemoglobinuria, ParoxysmalStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)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 3
- Primary purpose
- Treatment
- Enrolment
- 75 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00098280
- Sponsor's protocol ID
- 050048
- Other IDs
- 05-H-0048
- Status last verified
- Feb 2006
- First submitted
- 3 Dec 2004
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995 Nov 9;333(19):1253-8. doi: 10.1056/NEJM199511093331904.
PubMed 7566002Tabbara IA. Hemolytic anemias. Diagnosis and management. Med Clin North Am. 1992 May;76(3):649-68. doi: 10.1016/s0025-7125(16)30345-5.
PubMed 1578962Rosse WF. Phosphatidylinositol-linked proteins and paroxysmal nocturnal hemoglobinuria. Blood. 1990 Apr 15;75(8):1595-601. No abstract available.
PubMed 2183885
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Hemoglobin Stabilization and Transfusion Reduction Efficacy and Safety Clinical Investigation, Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Using Eculizumab in Paroxysmal Nocturnal Hemoglobinuria Patients
- ClinicalTrials.gov ID
- NCT00098280
- Acronym / sponsor ID
- 050048
- Conditions
- Hemoglobinuria, Paroxysmal
- Keywords
- H5g1, PNH, TRIUMPH, Paroxysmal Nocturnal Hemoglobinuria
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Dec 2004
- Study completion
- Feb 2006
- First posted
- 6 Dec 2004 (estimated)
- 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 will examine the safety and effectiveness of the experimental drug eculizumab in treating patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare disorder of red blood cells that leads to premature destruction of the cells and resulting anemia. Patients may be at high risk of blood clots and may develop bone marrow failure or aplastic anemia, with low white blood cell and platelet counts. Eculizumab is a monoclonal antibody that may help improve the survival of red blood cells.
Patients 18 years of age and older with PNH who require blood transfusions for anemia and have received at least four transfusions in the 12 months preceding evaluation for this study may be eligible to enroll. Candidates are screened with a medical history, physical examination, and check of vital signs.
Participants have an electrocardiogram (EKG) and blood and urine tests, and are vaccinated against Neisseria meningitides, a common bacteria that can cause a disabling or fatal type of meningitis. They then enter an observation phase of the study, with monthly visits during which they complete a questionnaire; update their health status, transfusion record, and medication use; have their vital signs checked and PNH symptoms evaluated; have blood and urine tests; and receive a transfusion, if necessary. These visits continue for up to 3 months until patients receive a "qualifying" transfusion; that is, a transfusion given as a consequence of a certain hemoglobin level with symptoms or a different level without symptoms.
Patients are then randomly assigned to receive either eculizumab or a placebo (salt solution with no active ingredient). Both study medications are given intravenously (through a vein) over 30 minutes once a week for five doses and then once every 2 weeks for another 11 doses. At each treatment visit (study weeks 0-24), patients update their health status, transfusion records, and medication use; have their vital signs checked; and provide a blood sample. At various visits, they also complete a questionnaire, provide a urine sample and have an EKG. At the last treatment visit (week 26 or the final visit for patients who end their participation before visit 18) patients have a complete physical examination in addition to the procedures listed above.
Detailed description
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder of the hematopoietic stem cell characterized by intravascular hemolysis, hemoglobinuria, anemia, and thrombosis. The clinical features of PNH result from the lack of one or more of the GPI-linked proteins that serve to protect cells from autologous complement mediated attack. Two such proteins, CD55 (decay accelerating factor) and CD59 (reactive lysis inhibitor) have been shown to be absent from PNH erythrocytes and platelets as well as other cell types.
Evidence strongly suggests that lack of the terminal complement inhibitor CD59 is responsible for the sensitivity of PNH erythrocytes and platelets to the effects of autologous complement. Since the pathogenesis of PNH is due to the inability of PNH red cells and platelets to inhibit the activation of terminal complement, it is logical to hypothesize that a terminal complement inhibitor could effectively stop the intravascular hemolysis, obviate or lessen the need for transfusions, and possibly decrease the propensity of life threatening thrombosis. Eculizumab is a humanized monoclonal antibody that like CD59 inhibits terminal complement.
This study is a randomized, double-blind, placebo controlled, multi-center study of eculizumab or placebo administered intravenously to approximately 75 PNH patients. The study is designed to evaluate the safety of eculizumab in transfusion dependent patients with paroxysmal nocturnal hemoglobinuria (PNH) and to determine if the administration of this terminal complement inhibitor could provide a safe and effective substitute for CD59 function.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- Individuals at least 18 years of age;
- Patients must have required at least 4 episodes of transfusions in the 12 months prior to Visit 1 for anemia or anemia-related symptoms;
- Presence of a GPI deficient red blood cell clone (type II cells) by flow cytometry of greater than or equal to 10%;
- Patients taking erythropoietin must be on a stable dose for 26 weeks prior to visit 1 and the dose must be expected to remain stable during the Observation Period and the Treatment Phase;
- Patients taking immunosuppressants must be on a stable dose for at least 26 weeks prior to Visit 1 and the dose must be expected to remain stable during the Observation period and the Treatment Phase;
Key exclusion criteria (9 listed)
- Patients whose mean hemoglobin levels prior to transfusion over the previous 12 months is greater than 10.5 gm/dL;
- Absolute Neutrophil count less than or equal to 500/microL;
- Presence or suspicion of active bacterial infection, in the opinion of the Investigator, at Visit 3 or recurrent bacterial infections;
- Known or suspected hereditary complement deficiency;
- Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days prior to Visit 1;
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 |
|---|---|---|
| Eculizumab | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 7566002Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995 Nov 9;333(19):1253-8. doi: 10.1056/NEJM199511093331904.
- Background: PubMed 1578962Tabbara IA. Hemolytic anemias. Diagnosis and management. Med Clin North Am. 1992 May;76(3):649-68. doi: 10.1016/s0025-7125(16)30345-5.
- Background: PubMed 2183885Rosse WF. Phosphatidylinositol-linked proteins and paroxysmal nocturnal hemoglobinuria. Blood. 1990 Apr 15;75(8):1595-601. No abstract available.
Related trials for Hemoglobinuria, Paroxysmal
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eculizumab in people with Hemoglobinuria, Paroxysmal, run by National Heart, Lung, and Blood Institute (NHLBI) 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 15 inclusion and 9 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 4 Mar 2008. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00098280, which also lists 3 linked publications.
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 4 Mar 2008.