AN OPEN-LABEL, MULTI-CENTER CONTROLLED CLINICAL TRIAL OF ECULIZUMAB IN ADULT PATIENTS WITH PLASMA THERAPY-RESISTANT ATYPICAL HEMOLYTIC-UREMIC SYNDROME (AHUS)
- Conditions
- Adult patients with plasma therapy-resistant Atypical Hemolytic-UremicSyndrome (aHUS)MedDRA version: 9.1Level: LLTClassification code 10018932Term: Haemolytic uraemic syndrome
- Registration Number
- EUCTR2008-006952-23-SE
- Lead Sponsor
- ALEXION PHARMACEUTICALS, INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 8
1. Male or female patients = 18 years who have been diagnosed with aHUS. Patients may
be newly diagnosed, experiencing a relapse of the disease, or having a post-transplant
recurrence of the disease.
2. Patients must exhibit a decrease in platelet count despite at least 4 PT treatments in the 1
week immediately prior to screening. At screening, platelet count must be < 150 x
109/L and at least 25% lower than the average of 3 platelet counts obtained during the
most recent TMA remission and at least 1 month apart during that remission prior to
screening (designated the average remission platelet count”).
3. If historical counts are not available, platelet count at onset of the current aHUS episode
must be = 75 x 109/L, and platelet count at screening must be = 100 x 109/L despite PT
treatment administration of at least 4 PT treatments in the 1 week immediately prior to
screening.
4. Known complement regulatory protein genetic abnormality, i.e., a mutation in
Complement Protein 3, factor H or associated factor, factor I, or membrane cofactor
protein (MCP) or known Factor B gain-of-function mutation, or known Anti-CFH
antibody (aHUS lesions”).
• Patients diagnosed with aHUS with any of these aHUS lesions are eligible and will
be assigned to one of the following parallel categories during the treatment period of
the trial:
- (Category 1) Factor H or factor I functional deficiency, abnormal factor
interaction (CFH/CFI FFP Group), or deletions of the CFHR1 and CFHR3
genes;
- (Category 2) Complement Protein 3, abnormal factor interaction (C3) or Factor
B Gain of Function;
- (Category 3) Anti-CFH Antibody (anti-CFH Group);
- (Category 4) MCP deficiency (MCP Group);
5. Patients diagnosed with aHUS without documented complement regulatory protein
genetic abnormality or known anti-CFH antibody are eligible if other etiologies of
hemolytic uremic syndrome (HUS) have been ruled out as confirmed in the Exclusion
Criteria (i.e., including Shiga-toxin negative, non-infectious, non-drug-exposure-related
[e.g., cyclosporine]), no known human immunodeficiency syndrome (HIV) positivity,
and anti-phospholipid antibody negative). Patients meeting these conditions will be
assigned to Category 5. In addition, these patients will undergo genetic testing to
determine if a mutation can be identified. If a mutation is identified, the patient will be
reassigned to the appropriate category.
6. Lactate dehydrogenase (LDH) level = upper limit of normal (ULN) unless the patient
has been receiving plasma exchange (PE) and LDH at the onset of the current aHUS
episode was at least the ULN. If LDH is normal at screening, other markers indicative
of ongoing hemolysis should be evaluated, such as haptoglobin, schistocytes, and
discussed with the Sponsor;
7. Creatinine level = ULN for age (patients requiring acute dialysis for acute renal failure
also eligible).
8. Female patients of childbearing potential must be practicing an effective, reliable and
medically approved contraceptive regimen during the entire duration of the study,
including the follow-up period. At the time of the last follow-up visit, patients will be
counseled by the principal investigator (PI) or designated study staff that they must
continue to use adequate contraception methods for up to 5 months following
discontinuation of eculizumab treatment.
9. Able and willing to comply with study procedures
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) y
1. Thrombotic Thrombocytopenic Purpura (TTP), defined as ADAMTS13 activity <5% from an historical observation (prior to initiation of Plasma Therapy) or as tested at the screening visit by the central laboratory.
2. History of malignancy within 5 years of screening.
3. Typical HUS (known Shiga toxin +).
4. Known HIVinfection.
5. Identified drug exposure-related HUS.
6. Infection-related HUS
7. HUS related to bone marrow transplant (BMT)
8. HUS related to vitamin B12 deficiency.
9. Renal function status requiring chronic dialysis (defined as dialysis on a regular basis as
renal replacement therapy).
10. Patients with a confirmed diagnosis of sepsis defined as positive blood cultures within 7
days of the screening visit and not treated with antibiotics to which the organism is
sensitive.
11. Presence or suspicion of active and untreated systemic bacterial infection that, in the
opinion of the Investigator confounds an accurate diagnosis of aHUS or impedes the
ability to manage the aHUS disease.
12. Pregnancy or lactation.
13. Unresolved meningococcal disease.
14. Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or
syndrome.
15. Any medical or psychological 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.
16. Patients who have received previous treatment with eculizumab.
17. Patients receiving intravenous immunoglobulin (IVIg) within 8 weeks or Rituximab
therapy within 12 weeks of the screening visit.
18. Patients receiving other immunosuppressive therapies such as steroids, calcineurin
inhibitors (mTOR) or tacrolimus are excluded unless: [1] part of an established posttransplant
anti-rejection regime and dose of such medications have been unchanged for
at least 4 weeks prior to the screening period, or [2] patient has confirmed anti-CFH
antibody requiring immunosuppressive therapy and dose of such medications have been
unchanged for at least 4 weeks prior to the screening period or [3] patient is
experiencing an acute aHUS relapse immediately after transplant.
19. Patients receiving Erythrocyte stimulating agents (ESAs) unless already on a stable dose
for at least 4 weeks prior to the screening period, or a washout period of at least 2 weeks from the last dose of ESA therapy.
20. Participation in any other investigational drug trial or exposure to other investigational
agent, device, or procedures beginning 4 weeks prior to screening and throughout the
entire trial.
21. Hypersensitivity to eculizumab, to murine proteins or to one of the excipients.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method