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

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

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).

Study Overview

• Status: Unknown
• Conditions: Thrombotic Microangiopathies; Atypical Hemolytic Uremic Syndrome
• Intervention / Treatment: Biological: OMS721

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • Not yet recruiting
      • Omeros Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Recruiting
      • Omeros Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: OMS721; Administration of OMS721	Biological: OMS721; Intravenous loading dose followed by daily subcutaneous injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Increase in eGFR	Increase of greater than 15 ml/min/1.73 m2 in eGFR calculated by the MDRD Equation	26 weeks
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
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
Incidence of antidrug antibodies (ADA)	Incidences of ADA in subjects with aHUS, administered OMS721	771 days post-dose
Change from baseline in serum creatinine	Assessment of subject's change from baseline in serum creatinine	26 weeks
Change from baseline in serum LDH	Assessment of subject's change from baseline in serum LDH	26 weeks
Change from baseline in haptoglobin	Assessment of subject's change from baseline in haptoglobin	26 weeks
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Omeros Corporation
• Investigators: Study Director: Eckhard Leifke, M.D., Omeros Corporation

Publications and helpful links

General Publications

• Pugh D, O'Sullivan ED, Duthie FA, Masson P, Kavanagh D. Interventions for atypical haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2021 Mar 23;3(3):CD012862. doi: 10.1002/14651858.CD012862.pub2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 23, 2017
• Primary Completion (ANTICIPATED): February 1, 2020
• Study Completion (ANTICIPATED): February 1, 2020

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: June 28, 2017
• First Posted (ACTUAL): July 2, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 18, 2018
• Last Update Submitted That Met QC Criteria: October 17, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: aHUS; TMA
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Hematologic Diseases; Anemia; Thrombocytopenia; Blood Platelet Disorders; Anemia, Hemolytic; Uremia; Syndrome; Thrombotic Microangiopathies; Azotemia; Hemolysis; Hemolytic-Uremic Syndrome; Atypical Hemolytic Uremic Syndrome
• Other Study ID Numbers: OMS721-HUS-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No