AN OPEN-LABEL, MULTI-CENTER CONTROLLED CLINICAL TRIAL OF ECULIZUMAB IN ADOLESCENT PATIENTS WITH PLASMA THERAPY-SENSITIVE ATYPICAL HEMOLYTIC UREMIC SYNDROME (AHUS)
- Conditions
- atypical hemolytic uremic syndrome10018911
- Registration Number
- NL-OMON33085
- Lead Sponsor
- Alexion Pharmaceuticals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 2
1. Male or female patients from 12 and up to 18 years of age who have been diagnosed with Atypical Hemolytic-Uremic Syndrome (aHUS).
2. Patients must be receiving PT for aHUS and must be observed to (i) receive *1 PT treatment every two weeks and no more than 3 PT treatments/week (at an unchanged frequency) for at least 8 weeks immediately prior to first dose of Investigational Product and (ii) receive the same volume of PP or PE and units of FFP for at least 8 weeks immediately prior to first dose of Investigational Product.
3. Platelet Count Pre-PT Baseline Set-Point (collected immediately prior to the ualifying PT Episode) is within 75% of the average of the pre-PT platelet counts collected at Screening and during the Observation Period.
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 1 (MCP-1) or known Factor B gainof-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) Complement Protein 3 or factor H or factor I functional deficiency or abnormal factor interaction (C3/CFH/CFI FFP Group);
* (Category 2) Factor B Gain of Function;
* (Category 3) Anti-CFH Antibody (Anti-CFH Group);
* (Category 4) MCP-1 deficiency (MCP-1 Group);
5. Patients diagnosed with HUS of the atypical type without documented complement regulatory protein genetic abnormality or known anti-CFH antibody are eligible if other etiologies of HUS have been ruled out as confirmed in the Exclusion Criteria (i.e., including Shiga-toxin negative, non-infectious, nondrug-exposure-related [e.g., cyclosporine]), no known HIV positivity, and anti-phospholipid antibody
negative). Thrombotic thrombocytopenic purpura also must be ruled out (i.e., ADAMTS-13 activity must be > 5%; see Exclusion Criteria). 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 * ULN.
7. Creatinine level * ULN for age.
8. Female patients of childbearing potential must be practicing an effective, reliable and medically acceptable contraceptive regimen during the entire duration of the study, including the follow-up period.
9. Patient*s parents/legal guardian must be willing and able to give written informed consent and patients must be willing to give written informed assent (if applicable as determined by the IRB/IEC).
10. Able and willing to comply with study procedures.
1. ADAMTS-13 inhibitor or deficiency (i.e., ADAMTS-13 activity <5%) as measured
at the screening visit.
2. Malignancy.
3. Typical HUS (Shiga toxin +).
4. Known HIV infection.
5. Identified drug exposure-related HUS.
6. Infection-related HUS.
7. 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.
8. 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.
9. Pregnancy or lactation.
10. Unresolved meningococcal disease.
11. Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody
positivity or syndrome.
12. 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.
13. Patients receiving IVIg or Rituximab therapy.
14. Patients receiving other immunosuppressive therapies such as steroids, mTOR
inhibitors or FK506 inhibitors are excluded unless: [1] part of a post-transplant antirejection
regime, [2] patient has confirmed anti-CFH antibody requiring
immunosuppressive therapy and [3] dose of such medications have been unchanged
for at least 4 weeks prior to the screening period.
15. Patients receiving Erythrocyte Stimulating Agents (ESAs) unless already on a stable
dose for at least 4 weeks prior to the screening period.
16. 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint:<br /><br>* The primary efficacy endpoint for this protocol is TMA-Event Free status<br /><br>defined as the absence of [1] decrease in platelet count of >25% from the<br /><br>Platelet Count Pre-PT Baseline Set-Point; [2] PT while the patient is receiving<br /><br>eculizumab, and<br /><br>[3] new dialysis for at least 12 weeks in adolescent patients with plasma<br /><br>therapysensitive Atypical Hemolytic-Uremic Syndrome (aHUS). Dialysis events<br /><br>occurring within the 14 days after the first dose of Investigational Product<br /><br>will<br /><br>not be considered as a new Treatment Period dialysis event. In addition,<br /><br>dialysis events that commence within the 14 days before the first dose of<br /><br>Investigational Product and continue up to 14 days after the first dose of<br /><br>Investigational Product<br /><br>will not be considered a new Treatment Period dialysis event;</p><br>
- Secondary Outcome Measures
Name Time Method