Clinical Trials Register

Summary
EudraCT Number:	2018-003660-31
Sponsor's Protocol Code Number:	B7841005
National Competent Authority:	Croatia - MIZ
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-12-02
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Croatia - MIZ

A.2

EudraCT number

2018-003660-31

A.3

Full title of the trial

An Open-Label Study in Adolescent and Adult Severe (Coagulation Factor Activity <1%) Hemophilia A or B Patients With or Without Inhibitors Comparing Standard Treatment to PF-06741086 Prophylaxis

A.3.1

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

PROPHYLAXIS STUDY OF PF-06741086 IN ADOLESCENT AND ADULT HEMOPHILIA PATIENTS WITH OR WITHOUT INHIBITORS

A.4.1

Sponsor's protocol code number

B7841005

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/292/2020

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Pfizer Inc., 235 East 42nd Street, New York, NY 10017
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	Pfizer Inc, 235 East 42nd Street, New York, NY 10017
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	Pfizer Inc.
B.5.2	Functional name of contact point	Clinical Trials.gov Call Centre
B.5.3	Address:
B.5.3.1	Street Address	235 East 42nd Street,
B.5.3.2	Town/ city	New York
B.5.3.3	Post code	NY 10017
B.5.3.4	Country	United States
B.5.4	Telephone number	+18007181021
B.5.6	E-mail	ClinicalTrials.gov_Inquiries@pfizer.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/3/16/1752
D.3 Description of the IMP
D.3.1	Product name	PF-06741086, MARSTACIMAB 150mg/ml
D.3.2	Product code	PF-06741086
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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	Marstacimab
D.3.9.2	Current sponsor code	PF-06741086
D.3.9.3	Other descriptive name	anti-TFPI mAb, , BLU-C002
D.3.9.4	EV Substance Code	SUB187130
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	150
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

Hemophilia A or B

E.1.1.1

Medical condition in easily understood language

Severe Hemophilia A or B

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	10060613
E.1.2	Term	Hemophilia A (Factor VIII)
E.1.2	System Organ Class	100000004850

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	10060612
E.1.2	Term	Hemophilia A
E.1.2	System Organ Class	100000004850

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	10060614
E.1.2	Term	Hemophilia B (Factor IX)
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 demonstrate the efficacy and safety of PF-06741086 for routine prophylaxis in severe (FVIII or FIX activity <1%) hemophilia A or B participants 12 to <75 years of age with or without inhibitors

E.2.2

Secondary objectives of the trial

To evaluate additional efficacy of PF-06741086

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. Participant must be male and 12 to <75 years of age with a minimum body weight of 30 kg at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2. Participants with a diagnosis of severe hemophilia A or B (FVIII or FIX activity <1%, respectively).
3. Participants who are enrolled into the Non-Inhibitor Cohort must also meet the following criteria:
• No detectable or documented history of inhibitors (≥0.6 BU/mL or greater than the upper limit of normal [ULN] for the testing laboratory) against FVIII or FIX prior to enrollment (Baseline of Observational Phase).
• Participants receiving routine prophylaxis (defined as treatment by IV injection of factor concentrate to prevent bleeding) treatment with FVIII/FIX replacement, have demonstrated at least 80% compliance with scheduled prophylaxis regimen during 6 months prior to enrollment, and willing to continue to receive routine prophylaxis treatment with FVIII/FIX replacement during the Observational Phase.
(OR)
• Participants with on-demand treatment regimen with ≥6 acute bleeding episodes (spontaneous or traumatic) that required coagulation factor infusion during the 6 months period prior to Enrollment into Observational Phase and willing to continue to receive on demand treatment during the Observational Phase. Surgical bleeding episodes do not apply to this criterion.
4. Participants who are enrolled into the Inhibitor Cohort must also meet the following criteria:
• Documentation of current high titer inhibitor (≥5 BU/mL); or current low titer inhibitor (<5 BU/mL) refractory to FVIII or FIX replacement and with FVIII or FIX recovery <60% of expected within previous 6 months prior to Enrollment into Observational Phase.
• Participants who have documented inhibitors while on factor-replacement therapy but who do not meet the quantitative inhibitor criteria described in the prior bullet at the time of Screening (eg, participant with a previously documented high-titer inhibitor (≥5 BU/mL) and whose condition precludes re-challenge with FVIII or FIX replacement) may be considered for eligibility on a case-by-case basis with prior approval from the Pfizer Medical Monitor.
• Participants with on-demand treatment regimen with ≥6 bleeding episodes (spontaneous or traumatic) necessitating treatment with bypass factor during the 6 months prior to Enrollment into Observational Phase and willing to continue to receive on-demand treatment during the Observational Phase. Surgical bleeding episodes do not apply to this criterion.
Sex
5. Male
Informed Consent
6. Participant or legally authorized representative, or participant’s caregiver capable of giving signed informed consent (or minor assent, when applicable) as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Previous or current treatment for or history of coronary artery diseases, venous or arterial thrombosis (Common Terminology Criteria for Adverse Events [CTCAE] Grade >1), or ischemic disease (except treatment for catheter associated thrombosis).
2. Known planned surgical procedure during the planned study period.
3. Known hemostatic defect other than hemophilia A or B.
4. Abnormal renal or hepatic function as defined by the following laboratory results at Screening:
a. Alanine transaminase (ALT) >2 × upper limit of normal (ULN)
b. Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
c. Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable chronic liver disease (including Gilbert’s syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C -eg, presence of hepatitis B surface antigen [HBsAg] or positive hepatitis C antibody test result at screening or within 3 months prior to starting study intervention) is acceptable if the participant otherwise meets entry criteria
d. Serum albumin less than the lower limit of normal (LLN).
e. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (see Appendix 10.2.1 for formulas used in eGFR calculation).
5. Abnormal hematology values as defined by the following laboratory tests at Screening:
a. Platelet count <100,000/uL
b. Hemoglobin level <10 g/dL
6. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
7. QTc >450 msec for male participants or QTc >480 msec in participants with bundle branch block.
8. Individuals with hypersensitivity or an allergic reaction to hamster protein or other components of the study intervention.
Prior/Concomitant Therapy
9. Current routine prophylaxis with bypassing agent (eg, aPCC, BYCLOT, Prothrombin Complex Concentrates [PCC], or rFVIIa) or non-coagulation non-factor replacement therapy (eg, emicizumab).
10. Regular, concomitant therapy with immunomodulatory drugs (eg, IV immunoglobulin [IVIG], and routine systemic corticosteroids, rituximab).
11. Ongoing or planned use of immune tolerance induction during the Observational Phase or Active Treatment Phase, or prophylaxis with FVIII or FIX replacement during the Active Treatment Phase.
Prior/Concurrent Clinical Study Experience
12. Participation in other studies involving investigational drug(s) within 30 days (or as determined by local requirements) or 5 half-lives prior to study entry or during study participation.
13. Previous exposure to PF 06741086 during to participation in studies B7841002 and B7841003.
Diagnostic assessments
14. CD4 cell count ≤200/uL if human immunodeficiency virus (HIV)-positive
15. Screening 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
Other Exclusions
16. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or participants who are Pfizer employees, including their family members, directly involved in the conduct of the study.

E.5 End points

E.5.1

Primary end point(s)

Primary Efficacy Endpoint
The primary efficacy endpoint is the annualized bleeding rate (ABR) of treated bleeding events, which is derived for each participant for each treatment period by using the following formula: ABR = number of bleeds requiring treatments/ (days on treatment period / 365.25). The statistical objective and strategy of demonstrating the efficacy in each cohort is shown below.

Inhibitor Cohort:
In all regions, to demonstrate superiority in ABR of PF-06741086 prophylaxis observed over the 12-month Active Treatment Phase versus on demand treatment with bypass therapy during the 6 months prior to receiving study intervention.
Non-Inhibitor Cohort:
For regions outside of the EU, superiority in ABR of PF-06741086 prophylaxis observed over the 12-month Active Treatment Phase versus on-demand treatment with FVIII- or FIX- replacement during the Observational Phase prior to receiving study intervention
For the EU, non-inferiority in ABR of PF-06741086 prophylaxis observed over the 12-month Active Treatment Phase versus prophylaxis treatment with FVIII- or FIX-replacement during the Observational Phase prior to receiving study intervention.
Safety Endpoints
Type I error control would not be applied to the following safety endpoints:
Adverse events (AEs) and Serious Adverse Events (SAEs)
Incidence and severity of thrombotic events
Incidence and severity of thrombotic microangiopathy
Disseminated intravascular coagulation/consumption coagulopathy
Immunogenicity (incidence of antidrug antibody [ADA] and clinically significantly persistent neutralizing antibody [NAb] against PF-06741086)
Incidence and severity of injection site reaction
Changes in physical examination and vital signs
Incidence of clinically significant laboratory value abnormalities
Incidence of severe hypersensitivity and anaphylactic reactions

E.5.1.1

Timepoint(s) of evaluation of this end point

Timepoints are all listed in the list of primary endpoints.

E.5.2

Secondary end point(s)

The following parameters will be assessed for comparison between PF-06741086 prophylaxis observed over the 12-month Active Treatment Phase versus a respective control group corresponding to each of the 3 statistical objectives (inhibitors, non-inhibitors for regions outside of the EU, and non-inhibitors for the EU). For the Non-Inhibitor Cohort, all the primary and secondary endpoints for regions outside of the EU will be part of the secondary endpoints for the EU and vice versa.
Total coagulation factor or bypass product consumption
Incidence of joint bleeds
Incidence of spontaneous bleeds
Incidence of target joint bleeds
Incidence of total bleeds (treated and untreated).
Percentage of participants with no bleeding episodes
Change in joints as measured by the Hemophilia Joint Health Score (HJHS)
HRQoL:
• Hemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) (≥17 years of age)/Hemophilia Quality of Life Questionnaire for Children (Haemo-QoL); (Adolescents 12 to <17 years of age);
• Hemophilia Activities List (HAL) (Adult ≥17 years of age)/Pediatric Hemophilia Activities List (pedHAL) (Adolescents 12 to <17 years of age);
• Patient Global Impression of Change – Hemophilia (PGIC-H) (Observational Phase and Active Treatment Phase)
• Health Utilities Measure (EuroQol 5 Dimensions 5 Level [EQ-5D-5L])

E.5.2.1

Timepoint(s) of evaluation of this end point

Timepoints are all listed in the list of primary endpoints.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

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

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

one way

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 for Hemophilia A or B

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

Australia

Brazil

Bulgaria

Canada

China

Croatia

France

Germany

Hong Kong

India

Ireland

Italy

Japan

Korea, Republic of

Mexico

Oman

Russian Federation

Saudi Arabia

Serbia

Spain

Switzerland

Taiwan

Turkey

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

A participant is considered to have completed the study if he has completed all phases of the study including the Day 390 Follow-up phone call during the Active Treatment Phase.
The end of the study is defined as the date of the last scheduled procedure shown in the Schedule of Activities for the last participant in the trial globally.

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:

104

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

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

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

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Minors 12-18 years old

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

145

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)

Study intervention will not be provided after conclusion of this study. A 12-month extension study (B7841007) to assess safety is available for participants who complete the B7841005 study. Participants who will participate in the B7841007 long-term extension study are not required to complete the Active Treatment Phase Day 390 Follow-up Phone Call.

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

2020-03-12

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

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