Clinical Trials Register

Summary
EudraCT Number:	2020-000996-19
Sponsor's Protocol Code Number:	MAA-304
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-09-21
Trial results	View 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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2020-000996-19

A.3

Full title of the trial

Phase 3 Study to Evaluate the Efficacy and Safety of Subcutaneous Marzeptacog Alfa (Activated) For On-Demand Treatment and Control of Bleeding Episodes in Subjects with Haemophilia A or Haemophilia B, with Inhibitors: The Crimson 1 Study

III. fázisú vizsgálat a szubkután alkalmazott Marzeptacog alfa (aktivált) biztonságosságának és hatásosságának értékelésére az A vagy B típusú hemofíliában szenvedő, inhibitorokat termelő betegek vérzéses epizódjainak szükség esetén történő kezelésében és betegségkontrolljában (Crimson 1 vizsgálat)

A.3.1

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

Study to evaluate the efficacy and safety of MarzAA for the control of bleeding episodes in subjects with Haemophilia A or Haemophilia B, with Inhibitors

Klinikai vizsgálat a MarzAA hatásosságának és biztonságosságának értékelésére az A vagy B típusú hemofíliában szenvedő, inhibitorokat termelő betegek vérzéses epizódjainak kontrollálásában

A.3.2

Name or abbreviated title of the trial where available

The Crimson 1 Study

A.4.1

Sponsor's protocol code number

MAA-304

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	Catalyst Biosciences, Inc.
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	Catalyst Biosciences, Inc.
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	Catalyst Biosciences, Inc.
B.5.2	Functional name of contact point	Dr. Linda Neuman
B.5.3	Address:
B.5.3.1	Street Address	611 Gateway Blvd., Suite 710
B.5.3.2	Town/ city	South San Francisco, California
B.5.3.3	Post code	94080
B.5.3.4	Country	United States
B.5.4	Telephone number	+1650266-8667
B.5.5	Fax number	+1650871-2475
B.5.6	E-mail	lneuman@catbio.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	Yes
D.2.5.1	Orphan drug designation number	EU/3/19/2151 for MarzAA (Haemophilia B only)
D.3 Description of the IMP
D.3.1	Product name	Marzeptacog alfa (activated)
D.3.2	Product code	MarzAA or CB813d
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Marzeptacog alfa (activated)
D.3.9.1	CAS number	1600492-21-4
D.3.9.2	Current sponsor code	MarzAA or CB813d
D.3.9.3	Other descriptive name	FACTOR VII A
D.3.9.4	EV Substance Code	SUB13812MIG
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	4,6 mg/vials
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	No
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

Marzeptacog alfa (activated) (MarzAA), a novel activated recombinant Factor VII (rFVIIa) variant, is being developed by Catalyst Biosciences to address the unmet need in haemophilia and other bleeding disorders.

E.1.1.1

Medical condition in easily understood language

Haemophilia and other bleeding disorders

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	10066439
E.1.2	Term	Hemophilia
E.1.2	System Organ Class	100000004850

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

To evaluate the efficacy of MarzAA for the on-demand treatment and control of bleeding episodes at 24 hours after the initial dose

E.2.2

Secondary objectives of the trial

• To determine the time needed to achieve haemostasis after the initial dose
• To assess the ability of MarzAA to achieve and maintain haemostasis in the treatment of bleeds at fixed timepoints after the initial dose
• To assess the number of doses and the cumulative dose needed to achieve adequate haemostasis for individual bleeds
• To assess the percentage of bleeds with treatment success at 24 hours that maintain haemostatic efficacy at 48 hours after the initial dose
• To assess the use and amount of rescue therapy required
• To assess the subcutaneous population PK of MarzAA

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Confirmed diagnosis of congenital Haemophilia A or B with inhibitors with one of the following:
a) Titer of ≥5BU
b) Titer of ≥0.6 BU but expected to have a high anamnestic response to FVIII or FIX, as demonstrated from the subject’s medical history, precluding the use of FVIII or FIX products to treat bleeding as documented by the Investigator
c) Titer ≥0.6 BU but expected to be refractory to increased dosing of FVIII or FIX, as demonstrated from the subject’s medical history, precluding the use of FVIII or FIX products to treat bleeding as documented by the Investigator
Note: Documentation of highest historic titer should be recorded.
2) History of bleeding with a historic ABR of ≥8
3) Male or Female, Age ≥12 years of age
4) Agreement to use highly effective birth control throughout the study if the subject has childbearing potential
5) If female the subject must meet the following criteria:
a) Not currently be breastfeeding
b) Not plan on becoming pregnant during the study
c) Be surgically sterile, or at least 2-years postmenopausal, or have a negative serum pregnancy test at Screening (Visit 1)
6) Affirmation of informed consent with signature confirmation and assent for children between ages 12 to 17 before any study-related activities Note: study-related activities are any procedure that would not have been performed during normal clinical management of the subject
7) Stated willingness to comply with all study procedures and availability for the duration of the study
8) Investigator confirmed subject’s ability to rapidly assess a bleeding episode and respond appropriately
9) Investigator confirmed subjects’ ability to administer MarzAA SC and infuse standard of care at home

E.4

Principal exclusion criteria

1) Previous participation in a study involving SC administration of rFVIIa (NovoSeven or MOD-5014) or any study using a modified amino-acid sequence FVIIa (other than MarzAA) such as: NN1731 or BAY86-6150. Prior participation in a study of IV LR769, rFVIIa-FP (CSL689), or MarzAA is permissible.
2) Previous participation in a clinical study with subsequent treatment within the previous 30 days or ≤5-half-lives or absence of clinical effect, whichever is longer
3) Known positive antibody to FVIIa or variants thereof wt-rFVIIa detected during screening and prior to Day 1
4) Known hypersensitivity to pd-FVIIa, pd-FVII, wt-rFVIIa or MarzAA or any of the excipients or related products
5) Treatment with anticoagulants or antiplatelet therapy within one week of enrolment or anticipated need during the study
6) Planned elective surgery within 12 months following study entry
7) History of other clinically relevant coagulation disorders
8) Platelet count <50,000 /μL based on screening laboratory assessments
9) Current or history of advanced atherosclerotic disease (i.e., known history of coronary artery disease, ischemic stroke, etc.), or deep venous thrombosis (DVT) or pulmonary embolism (PE) within 24 months of dosing or considered to be at a high risk of venous thromboembolic event (VTE) as judged by the Investigator
10) CD4 T Cell count <200 cells/mm3
11) Compromised hepatic or renal function:
a) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≥5 x the upper limit of normal (ULN)
b) Total bilirubin level ≥2 mg/dL (>35 μmol/L) unless there is a known history of Gilbert’s syndrome
c) Serum creatinine (Cr) level >1.25 × ULN
12) Inability or medical, psychosocial, or familial issues that might prevent full participation and cooperation with the procedures and requirements of the clinical study as determined by the potential subject and physician/Investigator
13) Weight ≥105 kg (231 lbs)

E.5 End points

E.5.1

Primary end point(s)

Percentage of bleed treatments resulting in effective (Excellent or Good) hemostasis at 24 hours after the initial dose

E.5.1.1

Timepoint(s) of evaluation of this end point

24 hours after dosing

E.5.2

Secondary end point(s)

• The time to cessation of bleeding after the initial dose
• Percentage of bleed treatment resulting in effective haemostasis at the timepoints (Hours 1, 3, 6, 9, 12, and 48) after the initial dose
• Number of doses and cumulative dose needed to achieve haemostasis for individual bleeds
• Percentage of bleeds with treatment success at 24 hours that maintain haemostatic efficacy at 48 hours after the initial dose
• Use and amount of rescue therapy needed
• Population pharmacokinetics of MarzAA

E.5.2.1

Timepoint(s) of evaluation of this end point

Percentage of bleed treatment resulting in effective haemostasis at the timepoints (Hours 1, 3, 6, 9, 12, and 48) after the initial dose;
Percentage of bleeds with treatment success at 24 hours that maintain haemostatic efficacy at 48 hours after the initial dose

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

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

Yes

E.8.1.1

Randomised

Yes

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

Yes

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

standard of care

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

Yes

E.8.2.3.1

Comparator description

Standard of care

E.8.2.4

Number of treatment arms in the trial

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

Armenia

Bulgaria

Denmark

France

Georgia

Hungary

India

Italy

Malaysia

Mexico

Poland

Russian Federation

South Africa

Spain

Taiwan

Turkey

Ukraine

United Kingdom

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

For subjects: A subject is considered to have completed the study if all assessments are completed including end of study visit.
For the study: when ≥244 bleeds have been treated with MarzAA (cumulative from both sequences) and ≥244 bleeds have been treated with SOC (cumulative from both sequences) and ≥80% of subjects have ≥3 eligible treated bleeds.

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 months

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)

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)

None

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

2020-11-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-11-05

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2021-11-15

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials