Paroxysmal Hemoglobinuria, NocturnalPhase 3NCT00130000
Eculizumab to Treat Paroxysmal Nocturnal Hemoglobinuria
A Phase 3 study testing Eculizumab in people with Paroxysmal Hemoglobinuria, Nocturnal, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
This study will evaluate the safety and effectiveness of the experimental drug eculizumab for treating paroxysmal nocturnal hemoglobinuria (PNH), a disorder that can cause premature destruction of red blood cells. PNH may result in anemia requiring blood transfusions. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paroxysmal Hemoglobinuria, Nocturnal
- What is being tested?
- Eculizumab
- How many people
- 87 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Aug 2005to 25 Jun 2007
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The study population will comprise individuals who have transfusion-dependent hemolytic PNH.
- Each patient must meet the following criteria to be enrolled in this study:
- Individuals at least 18 years of age
- Patients with a diagnosis of PNH greater than 6 months
- Presence of a GPI deficient red blood cell clone (type III cells) by flow cytometry of greater than or equal to 10%
- Patients must have: at least one transfusion in the past two years for anemia or anemia-related symptoms -or personal beliefs that preclude the use of transfusion, with severe hemolytic PNH
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- Documented LDH level greater than or equal to 1.5 x upper limit of normal (ULN) within 12 weeks of Visit 1 or during the Screening Period
- Patient must be willing and able to give written informed consent.
- Patients must avoid conception during the trial using a method that is most appropriate for their physical state and culture.
- Subjects must have a Visa allowing stay in United States for the duration of the study (up to 3 years).
- Subjects must provide documentation of residence during stay in the United States.
- The subject must be willing to keep all visits and not travel outside of the country while being treated under the protocol.
- The subject must understand that the drug may not be made commercially available in their country.
- Once the protocol and extension study is complete, the subject must come off study medication and it will not be made available to them if they return to their country.
Who cannot join
- -Any patient meeting any of the following criteria will be excluded from the study:
- Platelet count of less than 30,000/mm3
- Absolute Neutrophil count less than or equal to 500/uL
- Presence or suspicion of active bacterial infection, in the opinion of the Investigator, at Visit 2 or recurrent bacterial infections
- Known or suspected hereditary complement deficiency
- History of bone marrow transplantation
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- Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days prior to screening
- Pregnant, breast-feeding, or intending to conceive during the course of the study,including the Safety Follow-up Visits
- 8 .History of meningococcal disease
- 9. Patients who are not vaccinated against N. meningitidis at least 14 days prior to Visit 2
- 10. 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 Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: SHEPHERD: Safety in Hemolytic PNH Patients Treated With Eculizumab: A Multi-Center Open-Label Research Design
This study will evaluate the safety and effectiveness of the experimental drug eculizumab for treating paroxysmal nocturnal hemoglobinuria (PNH), a disorder that can cause premature destruction of red blood cells. PNH may result in anemia requiring blood transfusions. Patients may be at high risk of life-threatening blood clots in their veins and may have urine discoloration, stomach pain, difficulty swallowing, tiredness, and poor quality of life. Men may have problems getting or maintaining an erection. Eculizumab is a monoclonal antibody that may improve the survival of red blood cells in patients with PNH.
Patients 18 years of age and older who have been diagnosed with PNH for more than 6 months, who have active disease, and who require blood transfusions may be eligible for this study. Each candidate is screened with a physical examination, electrocardiogram, blood and urine tests, and a questionnaire for information on how PNH affects the patient physically, socially, emotionally, and functionally.
Read more
Participants receive infusions of eculizumab through a needle in a vein once a week for five doses and then every two weeks for another 24 doses. All patients are vaccinated against Neisseria meningitides, a bacteria that can cause symptoms, possibly including life-threatening meningitis, in susceptible people, including people who take eculizumab.
At every treatment visit, patients update their health status, transfusion record, and medication use; review their laboratory results from the preceding visit; have vital signs measured; and provide a blood sample for laboratory tests. At selected visits, they also provide a urine sample, have a repeat electrocardiogram, and complete a questionnaire. At the final treatment visit, participants have a complete physical examination, in addition to the routine procedures.
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 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 (h5G1.1-mAb) is a humanized monoclonal antibody that like CD59 inhibits terminal complement.
This study is an open label, multi-center study of eculizumab, administered intravenously for 52 weeks to approximately 85 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
- Paroxysmal Hemoglobinuria, Nocturnal
- Being tested
- Eculizumab
- Keywords
- h5g.1, Paroxysmal Nocturnal Hemoglobinuria, SHEPHERD, 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.
EculizumabDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2005 (estimated)
- Study start9 Aug 2005
- Study completion25 Jun 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Paroxysmal Hemoglobinuria, NocturnalStudies 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
- 87 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00130000
- Sponsor's protocol ID
- 050217
- Other IDs
- 05-H-0217
- Status last verified
- 25 Jun 2007
- First submitted
- 11 Aug 2005
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Walport MJ. Complement. First of two parts. N Engl J Med. 2001 Apr 5;344(14):1058-66. doi: 10.1056/NEJM200104053441406. No abstract available.
PubMed 11287977Brodsky RA, Young NS, Antonioli E, Risitano AM, Schrezenmeier H, Schubert J, Gaya A, Coyle L, de Castro C, Fu CL, Maciejewski JP, Bessler M, Kroon HA, Rother RP, Hillmen P. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008 Feb 15;111(4):1840-7. doi: 10.1182/blood-2007-06-094136. Epub 2007 Nov 30.
PubMed 18055865
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SHEPHERD: Safety in Hemolytic PNH Patients Treated With Eculizumab: A Multi-Center Open-Label Research Design
- ClinicalTrials.gov ID
- NCT00130000
- Acronym / sponsor ID
- 050217
- Conditions
- Paroxysmal Hemoglobinuria, Nocturnal
- Keywords
- h5g.1, Paroxysmal Nocturnal Hemoglobinuria, SHEPHERD, PNH
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 9 Aug 2005
- Study completion
- 25 Jun 2007
- First posted
- 12 Aug 2005 (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 evaluate the safety and effectiveness of the experimental drug eculizumab for treating paroxysmal nocturnal hemoglobinuria (PNH), a disorder that can cause premature destruction of red blood cells. PNH may result in anemia requiring blood transfusions. Patients may be at high risk of life-threatening blood clots in their veins and may have urine discoloration, stomach pain, difficulty swallowing, tiredness, and poor quality of life. Men may have problems getting or maintaining an erection. Eculizumab is a monoclonal antibody that may improve the survival of red blood cells in patients with PNH.
Patients 18 years of age and older who have been diagnosed with PNH for more than 6 months, who have active disease, and who require blood transfusions may be eligible for this study. Each candidate is screened with a physical examination, electrocardiogram, blood and urine tests, and a questionnaire for information on how PNH affects the patient physically, socially, emotionally, and functionally.
Participants receive infusions of eculizumab through a needle in a vein once a week for five doses and then every two weeks for another 24 doses. All patients are vaccinated against Neisseria meningitides, a bacteria that can cause symptoms, possibly including life-threatening meningitis, in susceptible people, including people who take eculizumab.
At every treatment visit, patients update their health status, transfusion record, and medication use; review their laboratory results from the preceding visit; have vital signs measured; and provide a blood sample for laboratory tests. At selected visits, they also provide a urine sample, have a repeat electrocardiogram, and complete a questionnaire. At the final treatment visit, participants have a complete physical examination, in addition to the routine procedures.
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 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 (h5G1.1-mAb) is a humanized monoclonal antibody that like CD59 inhibits terminal complement.
This study is an open label, multi-center study of eculizumab, administered intravenously for 52 weeks to approximately 85 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
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- The study population will comprise individuals who have transfusion-dependent hemolytic PNH.
- Each patient must meet the following criteria to be enrolled in this study:
- Subjects must have a Visa allowing stay in United States for the duration of the study (up to 3 years).
- Subjects must provide documentation of residence during stay in the United States.
- The subject must be willing to keep all visits and not travel outside of the country while being treated under the protocol.
Key exclusion criteria (11 listed)
- Platelet count of less than 30,000/mm3
- Absolute Neutrophil count less than or equal to 500/uL
- Presence or suspicion of active bacterial infection, in the opinion of the Investigator, at Visit 2 or recurrent bacterial infections
- Known or suspected hereditary complement deficiency
- History of bone marrow transplantation
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 2 Jul 2017.
- Background: PubMed 11287977Walport MJ. Complement. First of two parts. N Engl J Med. 2001 Apr 5;344(14):1058-66. doi: 10.1056/NEJM200104053441406. No abstract available.
- Derived from this study: PubMed 18055865Brodsky RA, Young NS, Antonioli E, Risitano AM, Schrezenmeier H, Schubert J, Gaya A, Coyle L, de Castro C, Fu CL, Maciejewski JP, Bessler M, Kroon HA, Rother RP, Hillmen P. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008 Feb 15;111(4):1840-7. doi: 10.1182/blood-2007-06-094136. Epub 2007 Nov 30.
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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. 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 Paroxysmal Hemoglobinuria, Nocturnal, 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 14 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: finished, as of the sponsor's last update on 2 Jul 2017. 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 NCT00130000, which also lists 2 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 2 Jul 2017.