Clinical Trials Register

Summary
EudraCT Number:	2017-002057-11
Sponsor's Protocol Code Number:	OMS721-HUS-002
National Competent Authority:	Lithuania - SMCA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-08-10
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Lithuania - SMCA

A.2

EudraCT number

2017-002057-11

A.3

Full title of the trial

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.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to investigate the safety and efficacy of study drug OMS721 in adults and adolescents with Atypical Hemolytic Uremic Syndrome.

A.4.1

Sponsor's protocol code number

OMS721-HUS-002

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03205995

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Omeros Corporation
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Omeros Corporation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PSI CRO AG
B.5.2	Functional name of contact point	Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Baarestrasse 113a
B.5.3.2	Town/ city	Zug
B.5.3.3	Post code	6300
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+441865855 290 6335
B.5.5	Fax number	+441865855 295
B.5.6	E-mail	Nigel.Smeeton@psi-cro.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	OMS721 Drug Product 185 mg/mL
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	not yet available
D.3.9.2	Current sponsor code	OMS721
D.3.9.3	Other descriptive name	OMS00620646, OMS620646, MASP-2 Antibody
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	185
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	Yes
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	OMS721 Drug Product 185 mg/mL
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	not yet available
D.3.9.2	Current sponsor code	OMS721
D.3.9.3	Other descriptive name	OMS00620646, OMS620646, MASP-2 Antibody
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	185
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	Yes
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Atypical Hemolytic Uremic Syndrome (aHUS)

E.1.1.1

Medical condition in easily understood language

thrombosis in capillaries and arterioles

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10019515
E.1.2	Term	Hemolytic uremic syndrome
E.1.2	System Organ Class	100000004851

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to evaluate the effect of OMS721 in subjects with aHUS on:
• Platelet count change from baseline

E.2.2

Secondary objectives of the trial

• Safety and tolerability
• Proportion of subjects who achieve complete TMA response
• Duration of complete TMA response
• Time to complete TMA response
• Proportion of subjects who achieve TMA event-free status during treatment
• Time to TMA event-free status
• Proportion of subjects who achieve an increase of > 15 ml/min/1.73 m2 in the eGFR calculated by either the MDRD Equation for subjects aged ≥ 18 years and the Schwarz equation for subjects < 18 years
• Time to eGFR increase of > 15 ml/min/1.73 m2
• Proportion of subjects who achieve hematological normalization
• Time to hematological normalization
• Proportion of subjects who achieve TMA remission
• QoL as measured by EQ-5D-5L
• Serum creatinine change from baseline
• Serum LDH change from baseline
• Serum haptoglobin change from baseline
• Rate of TMA interventions defined as the number of dialysis events, plasma infusion events and plasma exchange events per subject per day
• PK, PD and immunogenicity

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. 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.
2. If an adult, voluntarily provide informed consent in accordance with regulations and governing ethics committee requirements prior to any procedures or evaluations performed specifically for the sole purpose of the study. If a minor, at least one parent or legal guardian must provide informed consent and the subject must provide assent in accordance with local regulations and governing ethics committee requirements prior to any procedures or evaluations performed specifically for the sole purpose of the study.
3. Willing and able to comply with study procedures.
4. Are age ≥12 at screening (Visit 1).
5. Have a primary aHUS, diagnosed clinically, and have ADAMTS13 activity > 5% in plasma. Patients are eligible with or without a documented complement mutation or anti-CFH antibody. Patients are categorized according to their response to plasma therapy (plasma exchange or plasma infusion):
o Plasma therapy-resistant aHUS patients must have all of the following:
 Screening platelet count < 150,000/μL despite at least four plasma therapy treatments in a 7-day period prior to screening
 Evidence of microangiopathic hemolysis (at least one of: (1) presence of schistocytes, (2) serum LDH > 1.5 times upper limit of normal (ULN), and (3) haptoglobin < LLN)
 Serum creatinine > ULN
o Plasma therapy-responsive aHUS patients must have all of the following:
 Have a documented history of requiring plasma therapy to prevent aHUS exacerbation defined as all of the following:
− decrease in platelet count > 25% when plasma therapy frequency has been decreased (including discontinuation of plasma therapy)
− LDH > 1.5 times ULN when plasma therapy frequency has been decreased (including discontinuation of plasma therapy)
 Have received plasma therapy at least once every 2 weeks at an unchanged frequency for at least 8 weeks before first dose of OMS721
6. If sexually active and of childbearing potential, must agree to practice a highly effective method of birth control until the end of the study, defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner.
7. Do not have access to eculizumab treatment, have not derived therapeutic benefit from eculizumab treatment, or have not been able to tolerate eculizumab treatment.

E.4

Principal exclusion criteria

1. Have STEC-HUS.
2. Have a positive direct Coombs test.
3. Have a history of hematopoietic stem cell transplant.
4. Have HUS from an identified drug.
5. History of vitamin B12 deficiency-related HUS.
6. History of Systemic Lupus Erythematosus.
7. History of antiphospholipid syndrome.
8. Active cancer or history of cancer (except non-melanoma skin cancers) within 5 years of screening.
9. Have been on hemodialysis or peritoneal dialysis for ≥ 12 weeks.
10. Have an active systemic bacterial or fungal infection requiring systemic antimicrobial therapy (prophylactic antimicrobial therapy administered as standard of care is allowed).
11. Baseline resting heart rate < 45 beats per minute or > 115 beats per minute.
12. Baseline QTcF > 470 milliseconds.
13. Have malignant hypertension (diastolic blood pressure [BP] > 120 mm Hg with bilateral hemorrhages or “cotton-wool” exudates on funduscopic examination).
14. Have a poor prognosis with a life expectancy of less than three months in the opinion of the Investigator.
15. Are pregnant or lactating.
16. Have received treatment with an investigational drug or device within four weeks prior to screening.
17. Have abnormal liver function tests defined as ALT or AST > five times ULN.
18. Have HIV infection.
19. History of cirrhosis of the liver.
20. Are an employee of Omeros, an Investigator, a study staff member, or their immediate family member.
21. Have a known hypersensitivity to any constituent of the product.
22. Presence of any condition that the Investigator believes would put the subject at risk or confound the interpretation of the data.
23. Have previously completed treatment in an OMS721study.
24. Have received intravenous immunoglobulin (IVIG) treatment within 8 weeks of screening visit.
25. Have received rituximab within 24 weeks of screening visit.

E.5 End points

E.5.1

Primary end point(s)

Platelet count change from baseline at week 26

E.5.1.1

Timepoint(s) of evaluation of this end point

at week 26

E.5.2

Secondary end point(s)

• Safety as assessed by AEs, SAEs, vital signs, ECGs, physical examinations, and laboratory measures
• Complete TMA response defined as normalization of platelet count, normalization of serum LDH, and > 25% decrease in serum creatinine on at least 2 consecutive measures over at least 4 weeks
• Duration of complete TMA response measured from the time of the first measurement of complete TMA response to the last consecutive measurement of complete TMA response
• Time to complete TMA response measured by the time to reach the first measurement of complete TMA response
• TMA event-free status during treatment defined as no decrease in platelet count of > 25% from baseline, no plasma exchange or plasma infusion, and no initiation of new dialysis for at least 12 consecutive weeks
• Time to TMA event-free status measured by the time to reach the first documented TMA event-free status from the first dose of OMS721
• Increase of > 15 ml/min/1.73 m2 in eGFR calculated by the MDRD Equation for subjects aged ≥ 18 years and the Schwarz equation for subjects < 18 years
• Time to eGFR increase of > 15 ml/min/1.73 m2 measured by the time to reach the first measurement increase in eGFR of > 15 ml/min/1.73 m2 from the first dose of OMS721
• Hematological normalization defined as normalization of platelet count and normalization of serum LDH on at least 2 consecutive measurements over at least 4 weeks
• Time to hematological normalization measured by the time to reach the first measurement of hematological normalization from the first dose of OMS721
• TMA remission defined as platelet count ≥ 150,000/μL on at least 2 consecutive measures over at least 2 weeks
• Quality of life as measured by EQ-5D-5L
• Serum creatinine change from baseline
• Serum LDH change from baseline
• Serum haptoglobin change from baseline
• Rate of TMA interventions defined as the number of dialysis events, plasma infusion events and plasma exchange events per subject per day over the treatment period
• PK of OMS721
• PD of OMS721
• ADA

E.5.2.1

Timepoint(s) of evaluation of this end point

pre-dose, 15 min, 30 min, 1 hour, after start of dosing, and 5 min,15 min, 30 min, 1 hour, 24 hours, 48 hours, 72 hours , after end of dosing; at each visit

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Taiwan

United States

Lithuania

Poland

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Standard of Care

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-09-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-09-06

P. End of Trial
P.	End of Trial Status	Completed

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