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

Primary Purpose

Thrombotic Microangiopathies, Atypical Hemolytic Uremic Syndrome

Status

Unknown status

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

OMS721

About this trial

This is an interventional treatment trial for Thrombotic Microangiopathies focused on measuring TMA, aHUS

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Omeros Investigational Site
Omeros Investigational SiteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

OMS721

Arm Description

Administration of OMS721

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

Increase in eGFR

Increase of greater than 15 ml/min/1.73 m2 in eGFR calculated by the MDRD Equation

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

TMA Remission

Platelet count greater than or equal to 150,000/μL over at least 2 consecutive weeks, within the initial 26-week period

Incidence of antidrug antibodies (ADA)

Incidences of ADA in subjects with aHUS, administered OMS721

Change from baseline in serum creatinine

Assessment of subject's change from baseline in serum creatinine

Change from baseline in serum LDH

Assessment of subject's change from baseline in serum LDH

Change from baseline in haptoglobin

Assessment of subject's change from baseline in haptoglobin

Pharmacokinetics (PK): Trough plasma concentration, lower limit of quantification (LLOQ)

Pharmacokinetics (PK): Maximum plasma concentrations (Cmax)

Pharmacokinetics (PK): Area under time-concentration curve (AUC)

Pharmacodynamics (PD): Inhibition of C3 activity

Pharmacodynamics (PD): Inhibition of C4 activity

Full Information

NCT ID

NCT03205995

First Posted

April 17, 2017

Last Updated

October 17, 2018

Sponsor

Omeros Corporation

1. Study Identification

Unique Protocol Identification Number

NCT03205995

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Unknown status

Study Start Date

February 23, 2017 (Actual)

Primary Completion Date

February 2020 (Anticipated)

Study Completion Date

February 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Omeros Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thrombotic Microangiopathies, Atypical Hemolytic Uremic Syndrome

Keywords

TMA, aHUS

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

OMS721

Arm Type

Experimental

Arm Description

Administration of OMS721

Intervention Type

Biological

Intervention Name(s)

OMS721

Intervention Description

Intravenous loading dose followed by daily subcutaneous injections

Primary Outcome Measure Information:

Title

The effect of OMS721 as measured by platelet count change from baseline

Description

The effect of OMS721 will be evaluated in subjects with aHUS by changes in platelet count from baseline

Time Frame

26 weeks

Secondary Outcome Measure Information:

Title

Safety as measured by incidences of Adverse Events, vital signs, ECG, and clinical laboratory tests

Description

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

Time Frame

Pre-dose and up to 771 days post-dose

Title

TMA Response

Description

Time Frame

26 weeks

Title

TMA event-free status

Description

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

Time Frame

26 weeks

Title

Increase in eGFR

Description

Increase of greater than 15 ml/min/1.73 m2 in eGFR calculated by the MDRD Equation

Time Frame

26 weeks

Title

Hematological Normalization

Description

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

Time Frame

26 weeks

Title

TMA Remission

Description

Platelet count greater than or equal to 150,000/μL over at least 2 consecutive weeks, within the initial 26-week period

Time Frame

26 weeks

Title

Incidence of antidrug antibodies (ADA)

Description

Incidences of ADA in subjects with aHUS, administered OMS721

Time Frame

771 days post-dose

Title

Change from baseline in serum creatinine

Description

Assessment of subject's change from baseline in serum creatinine

Time Frame

26 weeks

Title

Change from baseline in serum LDH

Description

Assessment of subject's change from baseline in serum LDH

Time Frame

26 weeks

Title

Change from baseline in haptoglobin

Description

Assessment of subject's change from baseline in haptoglobin

Time Frame

26 weeks

Title

Pharmacokinetics (PK): Trough plasma concentration, lower limit of quantification (LLOQ)

Time Frame