Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (aHUS)

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00838513
• Date of registration: 03/02/2009
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals
• Public title: Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (aHUS) aHUS
• Scientific title: An Open-label, Multi-center Controlled Clinical Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (AHUS)
• Date of first enrolment: July 2009
• Target sample size: 15
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00838513
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

Austria, Canada, France, Germany, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States

Key inclusion & exclusion criteria

Inclusion Critera:

1. Male or female patients' =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 receive = 1 PT
treatment every two weeks and no more than 3 PT treatments/week (at an unchanged
frequency) for at least 8 weeks before first dose of IP.

3. Platelet Count Pre-PT Baseline Set-Point (collected in the hours before the Qualifying
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.

5. Lactate dehydrogenase (LDH) level at screening or at the onset of the current aHUS
episode was = ULN. If LDH is normal at screening, other markers indicative of ongoing
hemolysis such as haptoglobin, schistocytes should be evaluated and discussed with
Sponsor.

6. Creatinine level = ULN for age.

7. 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 and for up to 5 months following eculizumab treatment
discontinuation.

8. Able to give written informed consent.

9. Able and willing to comply with study procedures.

Exclusion Criteria:

1. TTP, (defined as ADAMTS-13 activity <5%) from an historical observation (prior to
initiation of plasma therapy) or as tested at the screening visit by the central
laboratory.

2. Malignancy within 5 years of screening.

3. Typical HUS (Shiga toxin +).

4. Known HIV infection.

5. Identified drug exposure-related HUS.

6. Infection-related HUS.

7. HUS related to bone marrow transplant.

8. HUS related to vitamin B12 deficiency.

9. Patients with a confirmed diagnosis of sepsis.

10. 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.

11. Pregnancy or lactation.

12. Unresolved meningococcal disease.

13. Known Systemic Lupus Erythematosus (SLE) or antiphospholipid antibody positivity or
syndrome.

14. 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.

15. Patients who have received previous treatment with eculizumab.

16. Patients receiving IVIg within 8 weeks or Rituximab therapy within 12 weeks of the
screening visit.

17. Patients receiving other immunosuppressive therapies such as steroids, mTOR inhibitors
or tacrolimus are excluded unless: [1] part of an established post-transplant
anti-rejection 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 and throughout the Observation Period or
[4] patient is experiencing an acute aHUS relapse immediately after transplant.

18. 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.

19. 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.

20. Hypersensitivity to eculizumab, to murine proteins or to one of the excipients.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Atypical Hemolytic Uremic Syndrome

Intervention(s)

Drug: eculizumab

Primary Outcome(s)

Percentage of Patients With Complete TMA Response [Time Frame: Through 26 weeks]

Percentage of Patients With TMA Event-free Status [Time Frame: Through 26 weeks]

Percentage of Patients With Hematologic Normalization [Time Frame: Through 26 weeks]

Secondary Outcome(s)

Percentage of Patients With Hematologic Normalization [Time Frame: Through End of Study, Median Exposure 156 Weeks]

Percentage of Patients With Complete TMA Response [Time Frame: Through End of Study, Median Exposure 156 Weeks]

Percentage of Patients With Platelet Count Normalization [Time Frame: Through 26 Weeks]

Percentage of Patients With Platelet Count Normalization [Time Frame: Through End of Study, Median Exposure 156 Weeks]

Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration [Time Frame: Induction Phase for 4 weeks followed by Maintenance Phase starting on Week 5 through 26 weeks or longer.]

Percentage of Patients With TMA Event-free Status [Time Frame: Through End of Study, Median Exposure 156 Weeks]

TMA Intervention Rate [Time Frame: Through 26 weeks]

TMA Intervention Rate [Time Frame: Through End of Study, Median Exposure 156 Weeks]

Platelet Count Change From Baseline to 156 Weeks [Time Frame: From Baseline to 156 Weeks]

Platelet Count Change From Baseline to 26 Weeks [Time Frame: From Baseline to 26 Weeks]

Secondary ID(s)

BB-IND 11075

C08-003A

EudraCT Number 2008-006954-17

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 26/01/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00838513