Safety and Efficacy Study of OMS721 in Patients With Atypical Hemolytic Uremic Syndrome

Atypical Hemolytic Uremic Syndrome Clinical Trial

— aHUS  

Official title:

A Phase 3 Study to Evaluate the Safety and Efficacy of OMS721 for the Treatment of Atypical Hemolytic Uremic Syndrome (aHUS) in Adults and Adolescents

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03205995
• Other study ID #: OMS721-HUS-002
• Status: Recruiting
• Phase: Phase 3
• Start date: February 23, 2017
• Est. completion date: February 2020

Study information

• Verified date: October 2018
• Source: Omeros Corporation
• Contact: Alan Lew
• Phone: 206-676-5000
• Email: alew[@]omeros.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the platelet count change from baseline and safety of OMS721 in adults and adolescents with atypical hemolytic uremic syndrome (aHUS). The study will also evaluate pharmacokinetics (PK), pharmacodynamics (PD), and anti-drug antibody response (ADA).

Description:

This is a Phase 3, multicenter study of OMS721 in adults and adolescents with atypical hemolytic uremic syndrome (aHUS). The uncontrolled, open-label study will evaluate the effect of OMS721 in subjects with plasma therapy-resistant aHUS and plasma therapy-responsive aHUS. This study has four periods: Screening, Treatment Induction, Treatment Maintenance, and Follow-up. Approximate enrollment is 80 subjects. An interim analysis will be performed after 40 subjects have completed 26 weeks of treatment for potential registration.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: February 2020
• Est. primary completion date: February 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Competent to provide informed consent, or if a minor, have at least one parent or legal guardian to provide informed consent with written assent from the subject.

• Are at least 12 years old at screening (Visit 1).

• Have a clinically diagnosis of primary atypical hemolytic uremic syndrome (aHUS), with ADAMTS13 activity greater than 5% in plasma.

• Plasma therapy-resistant aHUS patients must have a screening platelet count less than 150,000/uL, evidence of microangiopathic hemolysis, and serum creatinine greater than upper limit of normal.

• Plasma therapy-responsive aHUS patients must have documented history of requiring plasma therapy to prevent aHUS exacerbation and received plasma therapy at least once every 2 weeks at an unchanged frequency for at least 8 weeks before first dose of OMS721.

Exclusion Criteria:

• Have STEC-HUS, a direct positive Coombs test, history of hematopoietic stem cell transplant, and/or HUS from an identified drug.

• History of vitamin B12 deficiency-related HUS, systemic lupus erythematosus, and/or antiphospholipid syndrome.

• Active cancer or history of cancer (except non-melanoma skin cancers) within 5 years of screening.

• Have been on hemodialysis or peritoneal dialysis for greater than or equal to 12 weeks.

• Have an active systemic bacterial or fungal infection requiring systemic antimicrobial therapy (prophylactic antimicrobial therapy administered as standard of care is allowed).

• Baseline resting heart rate less than 45 beats per minute or greater than 115 beats per minute.

• Baseline QTcF greater than 470 milliseconds.

• Have malignant hypertension (diastolic blood pressure [BP] greater than 120 mm Hg with bilateral hemorrhages or "cotton-wool" exudates on funduscopic examination).

• Have a poor prognosis with a life expectancy of less than three months in the opinion of the Investigator.

• Are pregnant or lactating.

• Have received treatment with an investigational drug or device within four weeks prior to screening.

• Have abnormal liver function tests defined as ALT or AST > five times ULN.

• Have HIV infection.

• History of cirrhosis of the liver.

• Have previously completed treatment in an OMS721study.

Related Conditions & MeSH terms

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

Intervention

Biological:
• OMS721
Intravenous loading dose followed by daily subcutaneous injections

Locations

Country	Name	City	State
United States	Omeros Investigational Site	Chicago	Illinois
United States	Omeros Investigational Site	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Omeros Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The effect of OMS721 as measured by platelet count change from baseline	The effect of OMS721 will be evaluated in subjects with aHUS by changes in platelet count from baseline	26 weeks
Secondary	Safety as measured by incidences of Adverse Events, vital signs, ECG, and clinical laboratory tests	Assessment of safety of OMS721 in subjects with aHUS by incidence of Adverse Events, clinically significant vital sign abnormalities, ECG abnormalities, and clinical laboratory test abnormalities	Pre-dose and up to 771 days post-dose
Secondary	TMA Response	Complete TMA response defined as normalization of platelet count, normalization of serum LDH, and > 25% decrease in serum creatinine by at least 2 consecutive measures over at least 4 consecutive weeks, within the initial 26-week period	26 weeks
Secondary	TMA event-free status	No decrease in platelet count of > 25% from baseline, no plasma exchange or plasma infusion, and no initiation of new dialysis over at least 12 consecutive weeks, within the initial 26-week period	26 weeks
Secondary	Increase in eGFR	Increase of greater than 15 ml/min/1.73 m2 in eGFR calculated by the MDRD Equation	26 weeks
Secondary	Hematological Normalization	Normalization of platelet count and normalization of serum LDH by 2 consecutive measurements over at least 4 consecutive weeks, within the initial 26-week period	26 weeks
Secondary	TMA Remission	Platelet count greater than or equal to 150,000/µL over at least 2 consecutive weeks, within the initial 26-week period	26 weeks
Secondary	Incidence of antidrug antibodies (ADA)	Incidences of ADA in subjects with aHUS, administered OMS721	771 days post-dose
Secondary	Change from baseline in serum creatinine	Assessment of subject's change from baseline in serum creatinine	26 weeks
Secondary	Change from baseline in serum LDH	Assessment of subject's change from baseline in serum LDH	26 weeks
Secondary	Change from baseline in haptoglobin	Assessment of subject's change from baseline in haptoglobin	26 weeks
Secondary	Pharmacokinetics (PK): Trough plasma concentration, lower limit of quantification (LLOQ)		Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (if occurs): RT Days 1-4; Follow-Up at Day 771
Secondary	Pharmacokinetics (PK): Maximum plasma concentrations (Cmax)		Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (if occurs): RT Days 1-4; Follow-Up at Day 771
Secondary	Pharmacokinetics (PK): Area under time-concentration curve (AUC)		Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (if occurs): RT Days 1-4; Follow-Up at Day 771
Secondary	Pharmacodynamics (PD): Inhibition of C3 activity		Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (if occurs): RT Days 1-4; Follow-Up at Day 771
Secondary	Pharmacodynamics (PD): Inhibition of C4 activity		Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (if occurs): RT Days 1-4; Follow-Up at Day 771