Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01193348




Registration number
NCT01193348
Ethics application status
Date submitted
31/08/2010
Date registered
1/09/2010
Date last updated
29/04/2015

Titles & IDs
Public title
An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric Patients With Atypical Hemolytic-Uremic Syndrome
Scientific title
An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric Patients With Atypical Hemolytic-Uremic Syndrome
Secondary ID [1] 0 0
C10-003
Universal Trial Number (UTN)
Trial acronym
aHUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atypical Hemolytic-Uremic Syndrome 0 0
Condition category
Condition code
Blood 0 0 0 0
Other blood disorders
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Blood 0 0 0 0
Anaemia
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Eculizumab

Experimental: Eculizumab -


Treatment: Drugs: Eculizumab
Fixed dosing is based on body weight cohorts. Adjustment of dose to accommodate patient growth is possible.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of Patients With Complete TMA Response
Timepoint [1] 0 0
Through 26 weeks
Secondary outcome [1] 0 0
Proportion of Patients With Complete Hematologic Response
Timepoint [1] 0 0
Through 26 weeks
Secondary outcome [2] 0 0
Proportion of Patients With Platelet Count Normalization
Timepoint [2] 0 0
Through 26 weeks
Secondary outcome [3] 0 0
Proportion of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement
Timepoint [3] 0 0
Through 26 weeks
Secondary outcome [4] 0 0
Platelet Count Change From Baseline to 26 Weeks
Timepoint [4] 0 0
Through 26 weeks
Secondary outcome [5] 0 0
Proportion of Patients With Complete TMA Response
Timepoint [5] 0 0
Through End of Study, Median Exposure 55 Weeks
Secondary outcome [6] 0 0
Proportion of Patients With Complete Hematologic Response
Timepoint [6] 0 0
Through End of Study, Median Exposure 55 Weeks
Secondary outcome [7] 0 0
Proportion of Patients With Platelet Count Normalization
Timepoint [7] 0 0
Through End of Study, Median Exposure 55 Weeks
Secondary outcome [8] 0 0
Proportion of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement
Timepoint [8] 0 0
Through End of Study, Median Exposure 55 Weeks
Secondary outcome [9] 0 0
Platelet Count Change From Baseline to 52 Weeks
Timepoint [9] 0 0
Through 52 Weeks
Secondary outcome [10] 0 0
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 5 - <10kg) N=3
Timepoint [10] 0 0
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
Secondary outcome [11] 0 0
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 10 - <20kg) N=7
Timepoint [11] 0 0
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
Secondary outcome [12] 0 0
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 20 - <30kg)
Timepoint [12] 0 0
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
Secondary outcome [13] 0 0
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort 30 - <40kg) N=1
Timepoint [13] 0 0
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
Secondary outcome [14] 0 0
Pharmacokinetics (PK) and Pharmacodynamics (PD); Minimum and Maximum Blood Concentration (Body Weight Cohort =40kg) N=5
Timepoint [14] 0 0
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

Eligibility
Key inclusion 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 (<LLN). If screening visit and baseline visit are combined into one day, an
additional platelet count value obtained at least 24 hours before screening/baseline
sample must also be <LLN.

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
Minimum age
1 Month
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2014
Sample size
Target
Accrual to date
Final
22
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
- North Adelaide
Recruitment postcode(s) [1] 0 0
5006 - North Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
New Jersey
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
United States of America
State/province [4] 0 0
Washington
Country [5] 0 0
Belgium
State/province [5] 0 0
Gent
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
France
State/province [7] 0 0
Lille
Country [8] 0 0
France
State/province [8] 0 0
Marseille
Country [9] 0 0
France
State/province [9] 0 0
Paris
Country [10] 0 0
France
State/province [10] 0 0
Rouen
Country [11] 0 0
Germany
State/province [11] 0 0
Hannover
Country [12] 0 0
Italy
State/province [12] 0 0
Milano
Country [13] 0 0
Italy
State/province [13] 0 0
Palermo
Country [14] 0 0
Netherlands
State/province [14] 0 0
Nijmegen
Country [15] 0 0
United Kingdom
State/province [15] 0 0
London
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alexion Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary purpose is to assess the efficacy and safety of eculizumab in pediatric patients
with aHUS to control TMA as characterized by thrombocytopenia, hemolysis and renal
impairment.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01193348
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01193348