An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric Patients With Atypical Hemolytic-Uremic Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01193348
• Date of registration: 31/08/2010
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals
• Public title: An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric Patients With Atypical Hemolytic-Uremic Syndrome aHUS
• Scientific title: An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric Patients With Atypical Hemolytic-Uremic Syndrome
• Date of first enrolment: September 2010
• Target sample size: 22
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01193348
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Italy, Netherlands, United Kingdom, United States

Key inclusion & exclusion criteria

Inclusion:

1. Patient's parent/legal guardian must have been willing and able to give written
informed consent and the patient must have been willing to give written informed
assent (if applicable as determined by the central IRB/IEC).

2. Pediatric patients with aHUS: Patients could have been newly diagnosed, or with
previously diagnosed disease, or post-kidney transplant with the disease.

3. Patients one month to 18 years and body weight = 5kg.

4. Platelet count at screening and baseline visit must have been below lower limit of
normal ( additional platelet count value obtained at least 24 hours before screening/baseline
sample must also be
5. Exhibited signs or symptoms of hemolysis at start of current aHUS event (i.e., lactate
dehydrogenase (LDH) =1.5 x Upper Limit of Normal [ULN] and hemoglobin =LLN),
fragmented RBC with a negative Coombs test.

6. Serum Creatinine level =97 percentile for age at screening (patients requiring
dialysis for acute renal failure are also eligible).

7. Patients with aHUS due to complement regulatory protein genetic abnormality or
anti-complement factor antibody or those in whom known etiologies of hemolytic uremic
syndrome (HUS) have been ruled out as confirmed in the Exclusion Criteria.

8. Patients must have been vaccinated against N. meningitidis, pneumococcus and
haemophilus (per the vaccine label) at least 14 days prior to study drug initiation or
otherwise be protected by prophylactic antibiotics. Patients under age two years were
to receive antibiotic prophylaxis throughout the treatment period.

9. Female patients of childbearing potential (female patients who have achieved menarche)
must have been 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 must have agreed to continue to use
adequate contraception methods for up to five months following discontinuation of
eculizumab treatment.

10. Able and willing to comply with study procedures

Exclusion:

Any of the following was regarded as a criterion for exclusion from the study:

1. Known familial ADAMTS-13 deficiency (ADAMTS-13 <5%).

2. Shiga toxin E.coli-related hemolytic uremic syndrome (STEC-HUS [known Shiga toxin +
E.coli]).

3. History of malignancy within five years of screening.

4. Known human immunodeficiency virus (HIV) infection.

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

10. Plasma Therapy for >5 weeks prior to enrollment.

11. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy
for end-stage renal disease [ESRD]).

12. Patients with a confirmed diagnosis of sepsis defined as positive blood cultures
within seven days of the screening visit and not treated with antibiotics to which the
organism is sensitive.

13. 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.

14. Pregnancy or lactation.

15. History of meningococcal/pneumococcal/gonococcal disease.

16. 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.

17. Patients receiving chronic intravenous immunoglobulin (IVIg) within eight weeks unless
for unrelated medical condition (e.g., Hypogammaglobinemia), or chronic Rituximab
therapy within 12 weeks of the screening visit.

18. Patients receiving other immunosuppressive therapies such as steroids, mTOR
inhibitors, calcineurin inhibitors (e.g., cyclosporine or tacrolimus are excluded
unless: [1] part of an established post-transplant anti-rejection regime, or [2]
patient has confirmed anti-Complement Factor antibodies antibody requiring
immunosuppressive therapy or [3] steroids are being used for a condition other than
aHUS (example asthma).

19. Participation in any other investigational drug trial or device trial, or procedures
beginning four weeks prior to screening and throughout the entire trial

20. Prior use of eculizumab, hypersensitivity to eculizumab, to murine proteins or to one
of the excipients.



Age minimum: 1 Month
Age maximum: 18 Years
Gender: All

Health Condition(s) or Problem(s) studied

Atypical Hemolytic-Uremic Syndrome

Intervention(s)

Drug: Eculizumab

Primary Outcome(s)

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

Secondary Outcome(s)

Proportion of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement [Time Frame: Through End of Study, Median Exposure 55 Weeks]

Proportion of Patients With Complete Hematologic Response [Time Frame: Through 26 weeks]

Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 20 - <30kg) [Time Frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort. Maintenance Phase was started either 2 weeks or 3 weeks after induction phase depending on patient weight cohort]

Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 10 - <20kg) N=7 [Time Frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort.Maintenance Phase was started 1 week after induction phase and dosing of eculizumab administration was every 2 weeks or every 3 weeks depending on patient weight cohort]

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

Platelet Count Change From Baseline to 52 Weeks [Time Frame: Through 52 Weeks]

Proportion of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement [Time Frame: Through 26 weeks]

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

Proportion of Patients With Platelet Count Normalization [Time Frame: Through End of Study, Median Exposure 55 Weeks]

Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 30 - <40kg) N=1 [Time Frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort. Maintenance Phase was started either 2 weeks or 3 weeks after induction phase depending on patient weight cohort]

Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 5 - <10kg) N=3 [Time Frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort.Maintenance Phase was started 1 week after induction phase and dosing of eculizumab administration was every 2 weeks or every 3 weeks depending on patient weight cohort]

Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort =40kg) N=5 [Time Frame: Induction Phase was between 1 and 4 weeks in length depending on patient weight cohort. Maintenance Phase was started either 2 weeks or 3 weeks after induction phase depending on patient weight cohort]

Proportion of Patients With Complete TMA Response [Time Frame: Through End of Study, Median Exposure 55 Weeks]

Proportion of Patients With Complete Hematologic Response [Time Frame: Through End of Study, Median Exposure 55 Weeks]

Secondary ID(s)

C10-003

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 29/04/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01193348