An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome

Atypical Hemolytic-Uremic Syndrome Clinical Trial

Official title:

An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01194973
• Other study ID #: C10-004
• Status: Completed
• Phase: Phase 2
• First received: August 31, 2010
• Last updated: April 7, 2015
• Start date: July 2010
• Est. completion date: February 2014

Study information

• Verified date: April 2015
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationEuropean Union: European Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The record Primary purpose is to assess the efficacy of eculizumab in adult patients with aHUS to control TMA as characterized by thrombocytopenia, hemolysis and renal impairment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: February 2014
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion:

1. Patient must be willing and able to give written informed consent.

2. Patient's age > 18 years.

3. Patients exhibit thrombocytopenia, hemolysis and elevated Serum Creatinine.

4. Patients with diagnosis of aHUS with or without an identified complement regulatory protein genetic abnormality or anti-complement factor antibody and for whom etiologies of hemolytic uremic syndrome have been ruled out as confirmed in the exclusion criteria

5. 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. At the time of the last follow-up visit, patients must agree to continue to use adequate contraception methods for up to 5 months following discontinuation of eculizumab treatment.

6. Able and willing to comply with study procedures

Exclusion:

1. Chronic dialysis.

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

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

4. Typical HUS (known Shiga toxin +).

5. History of malignancy within 5 years of screening.

6. Known human immunodeficiency virus (HIV) infection.

7. Identified drug exposure-related HUS.

8. Infection-related HUS.

9. HUS related to bone marrow transplant (BMT).

10. HUS related to vitamin B12 deficiency.

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

12. 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.

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. Unresolved systemic meningococcal 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 8 weeks or chronic Rituximab therapy within 12 weeks of 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 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 4 weeks prior to screening and throughout the entire trial.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atypical Hemolytic-Uremic Syndrome
• Azotemia
• Hemolysis
• Hemolytic-Uremic Syndrome
• Syndrome

Intervention

Drug:
• Eculizumab
All patients received open-label eculizumab administered intravenously on the following dose schedule: Induction dose - 900 mg per week for four weeks and a dose of 1200 mg one week later; Maintenance dose - 1200 mg every two weeks. Patients who received plasma exchange or infusion during the eculizumab treatment period received a supplemental dose of 600 mg within one hour before plasma infusion or within one hour after the completion of each plasma exchange.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients With Complete TMA Response	Proportion of Patients with Complete TMA response was determined and defined by normalization of hematological parameters (platelet count and LDH) and preservation of renal function (defined as < 25% increase in serum creatinine from baseline) which were sustained for at least two consecutive measurements obtained at least four weeks apart.	Through 26 weeks	No
Primary	Proportion of Patients With Modified Complete TMA Response	Proportion of Patients with Modified Complete TMA response through 26 weeks of treatment was determined and defined by normalization of hematological parameters (platelet count and LDH) and improvement in renal function (defined as = 25% reduction from the baseline value in serum creatinine, which were sustained for at least two consecutive measurements obtained at least four weeks apart.	Through 26 weeks	No
Secondary	Proportion of Patients With Complete Hematologic Response	Proportion of Patients with Complete Hematologic response through end of study was determined and defined by normalization of platelet count and LDH sustained for at least two consecutive measurements obtained at least four weeks apart.	Through 26 weeks	No
Secondary	Proportion of Patients With Platelet Count Normalization	Proportion of Patients with Platelet Count Normalization through 26 weeks of treatment was determined and defined as the platelet count observed to be = 150 x 109/L on at least two consecutive measurements which span a period of at least four weeks	Through 26 weeks	No
Secondary	Proportion of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement	Proportion of Patients with Estimated Glomerular Filtration Rate (eGFR) Improvement was determined and defined as an increase in eGFR by = 15 mL/min/1.73m2 from baseline, sustained for at least two consecutive measurements obtained at least four weeks apart.	Through 26 weeks	No
Secondary	Platelet Count Change From Baseline to 26 Weeks		Through 26 weeks	No
Secondary	Proportion of Patients With Complete TMA Response	Proportion of Patients with Complete TMA response through end of study was determined and defined by normalization of hematological parameters (platelet count and LDH) and preservation of renal function (defined as < 25% increase in serum creatinine from baseline) which were sustained for at least two consecutive measurements obtained at least four weeks apart.	Through End of Study, Median Exposure 52 Weeks	No
Secondary	Proportion of Patients With Modified Complete TMA Response	Proportion of Patients with Modified Complete TMA response through end of study was determined and defined by normalization of hematological parameters (platelet count and LDH) and improvement in renal function (defined as = 25% reduction from the baseline value in serum creatinine, which were sustained for at least two consecutive measurements obtained at least four weeks apart.	Through End of Study, Median Exposure 52 Weeks	No
Secondary	Proportion of Patients With Complete Hematologic Response	Proportion of Patients with Complete Hematologic response through end of study of treatment was determined and defined by normalization of platelet count and LDH sustained for at least two consecutive measurements obtained at least four weeks apart.	Through End of Study, Median Exposure 52 Weeks	No
Secondary	Proportion of Patients With Platelet Count Normalization	Proportion of Patients with Platelet Count Normalization through end of study of treatment was determined and defined as the platelet count observed to be = 150 x 109/L on at least two consecutive measurements which span a period of at least four weeks	Through End of Study, Median Exposure 52 Weeks	No
Secondary	Proportion of Patients With Estimated Glomerular Filtration Rate (eGFR) Improvement	Proportion of Patients with Estimated Glomerular Filtration Rate (eGFR) Improvement was determined and defined as an increase in eGFR by = 15 mL/min/1.73m2 from baseline sustained for at least two consecutive measurements obtained at least four weeks apart	Through End of Study, Median Exposure 52 Weeks	No
Secondary	Platelet Count Change From Baseline to 52 Weeks		Through 52 Weeks	No