Clinical Trials Register

Summary
EudraCT Number:	2014-001032-11
Sponsor's Protocol Code Number:	OMS721-TMA-001
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-08-21
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2014-001032-11

A.3

Full title of the trial

A Phase 2, uncontrolled, three-stage, dose-escalation cohort study to evaluate the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and clinical activity of OMS721 in adults with thrombotic microangiopathies.

A.3.1

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

A study to investigate the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and clinical activity of study drug OMS721 in adults with thrombotic microangiopathies.

A.4.1

Sponsor's protocol code number

OMS721-TMA-001

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	+4822210 02 004808
B.5.5	Fax number	+4822210 02 20
B.5.6	E-mail	Pawel.Szczesniak@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
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous 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	OMS721 100 mg/ml Injection solution, 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	100
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	Yes
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
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous 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	OMS721 185 mg/ml Injection solution, 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	Yes
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

Three forms of thrombotic microangiopathies (TMA):
- atypical hemolytic uremic syndrome (aHUS)
- hematopoietic stem cell transplant (HSCT)-associated TMA
- thrombotic thrombocytopenic purpura (TTP)

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	PT
E.1.2	Classification code	10043645
E.1.2	Term	Thrombotic microangiopathy
E.1.2	System Organ Class	10005329 - Blood and lymphatic system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The co-primary objectives of this study are to:
• Assess the safety and tolerability of multiple-dose administration of OMS721 in subjects with TMA
• Evaluate the clinical activity of multiple-dose administration of OMS721 in subjects with TMA

E.2.2

Secondary objectives of the trial

• Determine the pharmacokinetics (PK) of multiple-dose administration of OMS721 in subjects with TMA
• Determine the pharmacodynamics (PD) of multiple-dose administration of OMS721 in subjects with TMA
• Determine the immunogenicity of multiple-dose administration of OMS721 in subjects with TMA

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Competent to provide informed consent.
2. 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.
3. Are age ≥18 at screening (Visit 1).
4. Have a diagnosis of TMA in accordance with one of the following three categories:
• As of Amendment 10 of the Study Protocol, enrollment of aHUS
subjects is closed. Primary aHUS, diagnosed clinically and having ADAMTS13 activity >10% in plasma. Subjects are eligible with or without a documented complement mutation or anti-CFH antibody. Subjects are categorized according to their response to plasma therapy (plasma exchange or plasma infusion):
o Plasma therapy-resistant aHUS subjects must have all of the following: 1) screening platelet count < 150,000/μL despite at least four plasma therapy treatments prior to screening; 2) evidence of microangiopathic hemolysis (presence of schistocytes, serum lactate dehydrogenase (LDH) > upper limit of normal (ULN), or haptoglobin < LLN) and 3) serum creatinine > ULN.
o Chronic plasma therapy-responsive aHUS subjects (plasma therapy-sensitive) must require at least once-per-week plasma therapy for four weeks before first dose of OMS721 with serum creatinine >ULN.
• As of Amendment 10 of the Study Protocol, enrollment of TTP subjects
is closed. TTP defined as having all of the following:
o Platelet count < 150,000/μL
o Evidence of microangiopathic hemolysis (presence of schistocytes, serum LDH > ULN, or haptoglobin < LLN)
o ADAMTS13 activity ≤ 10% during the current episode of TTP or historically.
• Persistent HSCT-associated TMA defined as having all of the following at least two weeks following modification or discontinuation of
calcineurin inhibitor treatment or at least 30 days after the transplant:
o Platelet count < 150,000/μL
o Evidence of microangiopathic hemolysis (presence of schistocytes, serum LDH > ULN, or haptoglobin < LLN)
o Renal dysfunction (doubling of serum creatinine from pre-transplant).
5. No clinically apparent alternative explanation for thrombocytopenia and anemia.
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.

E.4

Principal exclusion criteria

Subjects will be excluded from the study for any of the following reasons:
1. Had eculizumab therapy within three months prior to screening.
2. Have STEC-HUS.
3. Have a positive direct Coombs test.
4. Have an active systemic bacterial or fungal infection requiring antimicrobial therapy (prophylactic antimicrobial therapy administered as standard of care is allowed).
5. Baseline resting heart rate < 45 beats per minute or > 115 beats per minute.
6. Baseline QTcF > 470 milliseconds.
7. Have malignant hypertension (diastolic blood pressure [BP] > 120 mm Hg with bilateral hemorrhages or “cotton-wool” exudates on funduscopic examination).
8. Have a poor prognosis with a life expectancy of less than three months in the opinion of the investigator.
9. Are pregnant or lactating.
10. Have received treatment with an investigational drug or device within four weeks prior to screening.
11. Have abnormal liver function tests defined as ALT or AST > five times ULN.
12. Have a positive test for human immunodeficiency virus (HIV) antibodies.
13. Are an employee of Omeros, an investigator, a study staff member, or their immediate family member.
14. Have a known hypersensitivity to any constituent of the product.
15. Presence of any condition that the Investigator believes would put the subject at risk.

E.5 End points

E.5.1

Primary end point(s)

• Safety as assessed by AEs, vital signs, ECGs and clinical laboratory tests
• Clinical activity as assessed by platelet count

E.5.1.1

Timepoint(s) of evaluation of this end point

from baseline across all evaluations/visits

E.5.2

Secondary end point(s)

• TMA clinical activity
o Serum LDH
o Serum haptoglobin
o Hemoglobin
o Serum creatinine
o TMA-related symptoms
o Need for plasma therapy (plasma exchange or plasma infusion)
o Need for dialysis
• PK parameters including maximum concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (t½), area under time-concentration curve (AUC), clearance (CL), and volume of distribution (Vz)
• PD measure of inhibition of ex vivo lectin pathway activation
• Presence of ADA response

E.5.2.1

Timepoint(s) of evaluation of this end point

pre-dose, 5 min, 2 hours, 24 hours, 48 hours, 72 hours

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

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Yes

E.8.1.7.1

Other trial design description

ascending-dose-escalation study

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in 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

Belgium

Bulgaria

Hong Kong

Italy

Lithuania

Malaysia

New Zealand

Poland

Singapore

Taiwan

Thailand

United States

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

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)

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

2014-10-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-09-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-10-16

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