Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Marzeptacog alfa (activated) in Treatment of Episodic Bleeding in Subjects with Factor VII deficiency, Glanzmann thrombasthenia, and Haemophilia A with inhibitors on prophylaxis

Phase 1

• Conditions: Factor VII deficiency, Glanzmann thrombasthenia (GT) and Hemophilia A with inhibitors on emicizumab prophylaxis (HAwI-E); MedDRA version: 20.0Level: LLTClassification code 10060612Term: Hemophilia ASystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 20.0Level: PTClassification code 10016079Term: Factor VII deficiencySystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2020-003371-18-IT
• Lead Sponsor: Catalyst Biosciences, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-05-24
• Last Update Posted: 9 January 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1) Confirmed diagnosis of cohort:
a) Confirmed diagnosis of congential FVIID
b) Confirmed diagnosis of congenital GT (ie, platelet function analyzer, mutational analysis)
c) Confirmed diagnosis of congenital HAwI-E treated with the same dose of emicizumab for at least 4 weeks and with one of the following:
i) Titer =5 BU
ii) Titer =0.6 BU but expected to have a high anamnestic response to FVIII, as demonstrated from the subject’s medical history, precluding the use of FVIII products to treat bleeding as documented by the Investigator
iii) Titer =0.6 BU but expected to be refractory to increased dosing of FVIII, as demonstrated from the subject’s medical history, precluding the use of FVIII products to treat bleeding as documented by in the Investigator
Note: documentation of highest historic titer should be recorded.
2) History of bleeding with an
a) ABR of =8 for FVIID
b) ABR of =8 for GT
c) ABR of =1 for HAwI-E
3) Male or female, age =12 years
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 from age 12 to 17 years 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 subject’s ability to administer MarzAA SC at home
Are the trial subjects under 18? yes
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 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion Criteria

1) Cohort 1: genotype of FVIID subjects with following mutations:
a) P.A354V-p.464Hfs
b) P.Ser112-Stop (homozygous)
c) Ala294Val + Del C
d) 100GLN - ARG shift
e) Ser103 - Gly
Note: documentation of historic genotype would be acceptable
2) Inability to discontinue and washout any prophylactic (except Hemlibra) or episodic treatment for 5 days and 10 days for platelet transfusion prior to dosing
3) Previous participation in a clinical study involving SC administration of wt-rFVIIa (NovoSeven or MOD-5014) or any study using a modified amino-acid sequence FVIIa (other than MarzAA) such as: NN1731 or BAY86-6150.
Note: Prior participation in a study of intravenous (IV) LR769, rFVIIa-FP (CSL689), or MarzAA is permissible
4) Previous participation in a clinical study with treatment within the previous 30 days or =5 half-lives (of the investigation product) or absence of clinical effect, whichever is longer
5) Known positive antibody to FVIIa or variants thereof detected during screening or prior to Day 1
6) Known hypersensitivity to pd-FVIIa, pd-FVII, wt-rFVIIa, or MarzAA or any of the excipients or related products
7) Treatment with anticoagulants or antiplatelet therapy within 1 week of enrollment or anticipated need during the study
8) Planned elective surgery within 12 months following study entry
9) History of clinically relevant coagulation blood disorders
10) CD 4 T cell count of <200 cells/mm3
11) Platelet count <50,000 /µL based on screening laboratory assessments
12) Current or history of advanced atherosclerotic disease (ie, known history of coronary artery disease, ischemic stroke, etc), or deep venous thrombosis (DVT) within 24 months of dosing or considered to be at a high risk of venous thromboembolic event (VTE) as judged by the Investigator
13) Compromised hepatic or renal function:
a) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels =5 × 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 level >1.25 × ULN
14) 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
15) Weight =105 kg

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified