| CTRI Number |
CTRI/2021/03/032089 [Registered on: 17/03/2021] Trial Registered Prospectively |
| Last Modified On: |
28/01/2022 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
Study of Coagulation Factor VIIa Marzeptacog Alfa (Activated) in Subjects With Inherited Bleeding Disorders |
|
Scientific Title of Study
|
Phase 1/2 Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Marzeptacog alfa (activated) in Treatment of Episodic Bleeding in Subjects with Inherited Bleeding Disorders. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 2020-003371-18 |
EudraCT |
| MAA-202 Original Protocol Dated 19-Jun-2020 |
Protocol Number |
| NCT04548791 |
ClinicalTrials.gov |
| US IND Number: 14789 |
Other |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Radhika Bobba |
| Designation |
Regional Director, India and Far East |
| Affiliation |
PSI CRO pharma India Pvt Ltd |
| Address |
PSI CRO Pharma India Pvt Ltd, 414 Shree complex, 73, St Johns Road, Bangalore, India- 560042
Bangalore
KARNATAKA
560042
India |
| Phone |
|
| Fax |
|
| Email |
Radhika.Bobba@psi-cro.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Radhika Bobba |
| Designation |
Regional Director, India and Far East |
| Affiliation |
PSI CRO pharma India Pvt Ltd |
| Address |
PSI CRO Pharma India Pvt Ltd, 414 Shree complex, 73, St Johns Road, Bangalore, India- 560042
Bangalore
KARNATAKA
560042
India |
| Phone |
|
| Fax |
|
| Email |
Radhika.Bobba@psi-cro.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Radhika Bobba |
| Designation |
Regional Director, India and Far East |
| Affiliation |
PSI CRO pharma India Pvt Ltd |
| Address |
PSI CRO Pharma India Pvt Ltd, 414 Shree complex, 73, St Johns Road, Bangalore, India- 560042
Bangalore
KARNATAKA
560042
India |
| Phone |
|
| Fax |
|
| Email |
Radhika.Bobba@psi-cro.com |
|
|
Source of Monetary or Material Support
|
| Catalyst Biosciences, Inc, 611 Gateway Blvd., Suite 710 South San Francisco, CA 94080, USA |
|
|
Primary Sponsor
|
| Name |
Catalyst Biosciences Inc |
| Address |
611 Gateway Blvd., Suite 710 South San Francisco, CA 94080, USA |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India
Italy
Russian Federation
Ukraine
United States of America |
|
Sites of Study
|
| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Neeraj Sidharthan |
Amrita Institute of Medical Sciences |
Department of Clinical Haematology & Stem Cell Transplant Unit
Amrita Institute of Medical Sciences Ponekkara, AIMS (P.O.) Kochi - 682041, Kerala,India
Ernakulam
KERALA |
9946047464
neerajsidharthan@aims.amrita.edu |
| Dr Savita Rangarajan |
K. J. Somaiya Hospital & Research Centre |
K. J. Somaiya Hospital & Research Centre
Somaiya Ayurvihar Complex, Eastern Express Highway,Sion (E)
Mumbai
MAHARASHTRA |
9619525341
rangarajansavita@gmail.com |
| Dr Sharath Damodar |
Mazumdar Shaw Medical Centre |
7 Floor, Department of
Haemato-oncology,
Mazumdar Shaw Medical Centre
Narayana Hrudayalaya Ltd, 258/A, Bommasandra Industrial Area,Hosur Road, Anekal Taluk
Bangalore
KARNATAKA |
9880437134
sharat.damodar.dr@narayanahealth.org |
| Dr Shashikant Janardan Apte |
Sahyadri Super Specialty Hospital |
Department of Haematology and BMT.
Sahyadri Super Specialty Hospital
30c, Erandwane,Karve Road, Pune-411004
Pune
MAHARASHTRA |
912025403040
shashikant.apte@gmail.com |
| Dr Ross Cecil Reuben |
St.John’s Medical College and Hospital |
Dept. of Medicine and Hematology
St.Johns Medical College Hospital
Sarjapur Main Road, Koramangala
Bangalore
KARNATAKA |
9448493705
cecilrross@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 5 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee, K. J. Somaiya Medical College & Research Centre |
Approved |
| Institutional Ethics Committee, St. Johns Medical College Hospital |
Approved |
| Institutional Ethics Committee:- Amrita Institute of Medical Sciences |
Submittted/Under Review |
| Narayana Health Medical Ethics Committee |
Approved |
| Sahyadri Hospital Ltd. Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: D66||Hereditary factor VIII deficiency, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Factor VIIa, marzeptacog alfa (activated) [MarzAA] |
Phase1- Single dose- 1A- 18ug/kg IV administration
Ascending dose given subcutaneously as be the below dose 1B-10ug/kg, 1C-20ug/Kg, 1D-30ug/Kg, 1E- 40ug/kg, 1F- 60ug/kg.
Based on the PK, PD analysis dose for phase 2 is confirmed as following and will administered subcutaneously (1) FVIID- 20ug/kg. (2) GT-60ug/kg. (3) HAwI-E-60ug/kg.
|
| Comparator Agent |
Not Applicable |
Not Applicable |
|
|
Inclusion Criteria
|
| Age From |
12.00 Year(s) |
| Age To |
90.00 Year(s) |
| Gender |
Both |
| Details |
Study candidates must meet all the following inclusion criteria to be eligible for participation in this study:
1) Confirmed diagnosis of cohort:
a) Confirmed diagnosis of congential Factor VII deficiency (FVIID)
b) Confirmed diagnosis of congenital Glanzmann thrombasthenia (GT) (ie, platelet function analyzer, mutational analysis)
c) Confirmed diagnosis of congenital Hemophilia A with inhibitors on emicizumab (HAwI-E) treated with the same dose of emicizumab
2) History of bleeding with an (a) Annualized bleeding rate (ABR) of ≥8 for FVIID. (b) Annualized bleeding rate (ABR) of ≥8 for GT. (c) Annualized bleeding rate (ABR) of ≥1 for HAwI-E
3) Agreement to use highly effective birth control throughout the study if the subject has childbearing potential
4) 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 during Screening.
5) Subject’s ability to rapidly assess a bleeding episode and respond appropriately
6) Affirmation of informed consent with signature confirmation and assent for children from age 12 to 17 years before any study-related activities
7) Subject’s ability to administer MarzAA SC at home
|
|
| ExclusionCriteria |
| Details |
Subjects who meet any of the following criteria will not be eligible for participation in this study:
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) or pulmonary embolism 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 (231 lbs)
|
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
Phase 1 by Cohort
1- Pharmacokinetics of ascending SC doses of MarzAA by dose level/stage and confirm the Phase 2 dose
Phase 2 by Cohort
2- Percentage of bleed treatments resulting in effective hemostasis at 24 hours.
|
For Phase 1:- Blood samples for PK will be obtained at predose and at specified time intervals post dosing at Phase 1A, 1B, 1C, 1D, 1F and 1E. PK analysis to determine the dosing for phase 2
For Phase 2:- e-Diaries provided to subject where potential bleeds can be recorded. The bleeds are adjudicated and assessed for effective hemostasis at 24 hours
|
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Phase 1 by Cohort
1-Pharmacokinetics of IV and SC MarzAA
2-Pharmacokinetic assessment of dose proportionality
3-Pharmacodynamics of IV and SC MarzAA |
Blood samples for PK will be obtained at predose and at specified time intervals post dosing at Phase 1A, 1B, 1C, 1D, 1F and 1E and analyzed. |
Phase 2 by Cohort
1-The time to cessation of bleeding after the initial dose
2-Percentage of bleed treatment resulting in effective hemostasis at the time points after initial dose
3-Number of doses and cumulative dose needed to achieve hemostasis for individual bleeds
4-Percentage of bleeds with treatment success at 24 hours that demonstrated maintenance of efficacy at 48 hours after the initial dose
|
For Phase 2:- e-Diaries provided to subject where potential bleeds can be recorded. The bleeds are adjudicated and assessed to confirm the following.
1-The time to cessation of bleeding after the initial dose
2-Percentage of bleed treatment resulting in effective hemostasis
3-Number of doses and cumulative dose needed to achieve haemostasis for individual bleeds
|
1-Use and amount of rescue therapy needed in treatment failures
2-Pharmacokinetics and pharmacodynamics of MarzAA in the bleeding state
|
1-Rescue therapy is required after dosing with maximum protocol guided doses of MarzAA to control bleeding
2-Subjects should attempt to get an unscheduled visit based on number of dosing of MarzAA |
1-Occurrence of clinical thromboembolic events (TEs)
2-Occurrence of ADA and whether they are neutralizing or cross-reactive to FVIIa or FVII or variants there of.
|
Lab Thrombogenicity and Immunogenicity sampling will be done at screening, predose for Stage A, Stage C, Stage E, Stage G (Cohort 1), monthly in the Phase 2, and at end of study |
|
|
Target Sample Size
|
Total Sample Size="24"
Sample Size from India="9"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 1/ Phase 2 |
|
Date of First Enrollment (India)
|
30/04/2021 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
31/03/2021 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Other (Terminated) |
| Recruitment Status of Trial (India) |
Other (Terminated) |
|
Publication Details
|
Nil |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Phase 1/2 Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of Marzeptacog alfa (activated) in Treatment of Episodic Bleeding in Subjects with Inherited Bleeding Disorders.
Marzeptacog alfa (activated) (MarzAA), a novel activated recombinant Factor VII (rFVIIa) variant, to address the unmet need for medical management of Factor VII deficiency (FVIID), Glanszmann thrombasthenia (GT), and Hemophilia A with inhibitors on emicizumab prophylaxis (HAwI-E)
|