Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant aHUS

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00844844
• Date of registration: 13/02/2009
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals
• Public title: Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant aHUS aHUS
• Scientific title: An Open-Label, Multi-Center Controlled Clinical Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant Atypical Hemolytic Uremic Syndrome (aHUS)
• Date of first enrolment: May 2009
• Target sample size: 1
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00844844
• 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 Criteria:

1. Male or female patients from 12 and up to 18 years weighing = 40 kg who have been
diagnosed with Atypical Hemolytic-Uremic Syndrome (aHUS).

2. Decrease in platelet count despite at least 4 plasma therapy (PT) treatments in the 1
week immediately prior to screening.

1. Screening platelet count , < 150 x10^9/L and at least 25% lower than the average
remission platelet count or

2. If remission counts not available, platelet count at onset of the current aHUS
episode must be =75x10^9/L and platelet count at screening must be = 100 x 10^9/L
despite PT treatment administration of at least 4 PT treatments in the 1 week
immediately prior to screening

3. Known complement regulatory protein genetic abnormality

4. Lactate dehydrogenase (LDH) level = ULN unless the patient has been receiving plasma
exchange 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 such as
haptoglobin, schistocytes should be evaluated and discussed with Sponsor

5. Creatinine level = ULN for age

6. 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 of eculizumab
treatment discontinuation.

7. Patient's parents/legal guardian must be willing and able to give written informed
consent and patient must be willing to give written informed assent.

8. 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. Renal function status requiring chronic dialysis

10. Patients with a confirmed diagnosis of sepsis

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 IVIG within 8 weeks or Rituximab therapy within 12 weeks of
screening.

18. 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 or [4] 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

22. Patients between ages from 12 and up to 18 years weighing < 40 kg



Age minimum: 12 Years
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Atypical Hemolytic Uremic Syndrome

Intervention(s)

Drug: Eculizumab

Primary Outcome(s)

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

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

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

Secondary Outcome(s)

Percentage of Patients With Platelet Count Normalization [Time Frame: Through End of Study, Median Exposure 100.29 Weeks]

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

TMA Intervention Rate [Time Frame: Through End of Study, Median Exposure 100.29 Weeks]

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

TMA Intervention Rate [Time Frame: Through 26 weeks]

Percentage of Patients With Complete TMA Response [Time Frame: Through End of Study, Median Exposure 100.29 Weeks]

Percentage of Patients With Hematologic Normalization [Time Frame: Through End of Study, Median Exposure 100.29 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]

Secondary ID(s)

BB-IND-11075

EudraCT Number 2008-006953-41

C08-002B

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 03/12/2014
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00844844