| CTRI Number |
CTRI/2015/07/005953 [Registered on: 02/07/2015] Trial Registered Prospectively |
| Last Modified On: |
14/10/2019 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
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Type of Study
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Biological |
| Study Design |
Other |
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Public Title of Study
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To study the effect of Octafibrin (i.e. human plasma fibrinogen concentrate, which is a product derived from blood) in paediatric subjects with congenital fibrinogen deficiency (a rare bleeding disorder). |
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Scientific Title of Study
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Prospective, open-label, uncontrolled, phase III study to assess the efficacy, safety, and pharmacokinetics of Octafibrin for on-demand treatment of acute bleeding and to prevent bleeding during and after surgery in paediatric subjects with congenital fibrinogen deficiency. |
| Trial Acronym |
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Secondary IDs if Any
Modification(s)
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| Secondary ID |
Identifier |
| FORMA-04, Version 4.0 dated 30 May 2017 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
Modification(s)
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| Name |
Dr Sonika Newar |
| Designation |
Medical Monitor |
| Affiliation |
JSS Medical Research India Private Limited |
| Address |
Plot No. 12/2, 6th Floor,
Vatika Mindscapes (Tower B), Sector 27 D
Faridabad
HARYANA
121003
India |
| Phone |
91-8800799887 |
| Fax |
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| Email |
sonika.newar@jssresearch.com |
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Details of Contact Person
Public Query
Modification(s)
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| Name |
Dr Shariq Anwar |
| Designation |
Head Operations |
| Affiliation |
JSS Medical Research India Ltd. |
| Address |
Plot No. 12/2, 6th Floor,
Vatika Mindscapes (Tower B)
near Sarai Khwaja Metro Station, Sector 27 D, Mathura Road, India
Faridabad
HARYANA
121003
India |
| Phone |
91-9810979215 |
| Fax |
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| Email |
Shariq.Anwar@jssresearch.com |
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Source of Monetary or Material Support
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| Octapharma AG,
Address: Octapharma AG Seidenstrasse 2 8853 Lachen Switzerland |
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Primary Sponsor
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| Name |
Octapharma AG |
| Address |
Octapharma AG Seidenstrasse 2 8853 Lachen Switzerland |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
Modification(s)
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| Name |
Address |
| JSS Medical Research India Private Limited |
Plot No. 12/2, 6th Floor, Vatika Mindscapes (Tower B), Sector 27D, Faridabad - 121003, Haryana, India |
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Countries of Recruitment
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India
Lebanon
United States of America |
Sites of Study
Modification(s)
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| No of Sites = 2 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Latha GS |
S.S Institute of Medical Sciences and Research Centre |
NH4-Bypass Road, 577 005,
Davanagere
KARNATAKA |
91-9448614364
91-8192266307
lathags@hotmail.com |
| Dr Fulton S DSouza |
St. John’s Medical College Hospital |
Department of Pediatrics, Room no. 8, Ground floor, Sarjapur road–560034
Bangalore
KARNATAKA |
91-9449534220
91-80-25503697
fultondsouza@gmail.com |
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Details of Ethics Committee
Modification(s)
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| No of Ethics Committees= 2 |
| Name of Committee |
Approval Status |
| Institutional Ethical Review Board Ground Floor St. John’s Medical College & Hospital Sarjapur Road Banagalore-560034 India |
Approved |
| Institutional Ethics Review Board S.S Institute of Medical Sciences and Research Centre |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
Modification(s)
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| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: D682||Hereditary deficiency of other clotting factors, |
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Intervention / Comparator Agent
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| Type |
Name |
Details |
| Comparator Agent |
Not Applicable |
Not Applicable |
| Intervention |
Octafibrin (a highly purified, lyophilised, human plasma fibrinogen concentrate, without added albumins) |
Dosage form: Freeze dried powder with active ingredient to be reconstituted with 50 ml water for injection (WFI)
Dose: For PK assessment dose will be 70mg/kg
For on demand & Surgical prophylaxis period; Octafibrin will be individually dosed to achieve a recommended target fibrinogen plasma level dependent on the bleeding type (minor or major)
Duration of treatment: The individual observation period by subject starts with the first dose of Octafibrin administered for on-demand treatment of an acute bleeding episode or prior to elective surgery (Day 1). Patients enrolled will be treated for any bleeding episodes or planned surgeries during the study observation period. They may remain in the study until the 6th patient has at least one documented bleeding episode.
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Inclusion Criteria
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| Age From |
0.00 Day(s) |
| Age To |
12.00 Year(s) |
| Gender |
Both |
| Details |
1. Aged <12 years (at the start of treatment). This will include two subgroups of subjects aged between 0 and <6 years and between 6 and <12 years of either gender.
2. Documented diagnosis of congenital fibrinogen deficiency, expected to require on-demand treatment for bleeding or surgical prophylaxis:
− Fibrinogen deficiency manifested as afibrinogenaemia or severe hypofibrino-genaemia.
− Historical plasma fibrinogen activity of <50 mg/dL or levels below the limit of detection of the local assay method.
3. Expected to have an acute bleeding episode (spontaneous or after trauma) or plan-ning to undergo elective surgery.
4. Informed consent signed by the subject’s legal guardian.
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| ExclusionCriteria |
| Details |
1. Life expectancy <6 months.
2. Bleeding disorder other than congenital fibrinogen deficiency, including dysfi-brinogenaemia.
3. Prophylactic treatment with a fibrinogen concentrate.
4. Treatment with:
− Any fibrinogen concentrate or other fibrinogen-containing blood product within 2 weeks prior to start of treatment for the PK phase, a bleeding episode, or sur-gery.
− Any coagulation-active drug (i.e., non-steroidal anti-inflammatory drugs, war-farin, coumarin derivatives, platelet aggregation inhibitors) within 1 week prior to start of the PK phase or treatment for the bleeding episode or surgery, or as a planned or expected medication during the time period from Day 1 until 24 hours.
5. Presence or history of:
− Hypersensitivity to study medication.
− Deep vein thrombosis or pulmonary embolism within 1 year prior to start of treatment for the bleeding episode or surgery.
− Arterial thrombosis within 1 year prior to start of treatment for the bleeding episode or surgery
− Hypersensitivity to human plasma proteins.
− Oesophageal varicose bleeding.
− End-stage liver disease (i.e., Child-Pugh score B or C).
6. Known positive HIV infection with a viral load >200 particles/μL or >400,000 copies/mL.
7. Polytrauma 1 year prior to start of treatment for the bleeding episode or surgery.
8. Diagnosis or suspicion of a neutralizing anti-fibrinogen inhibitor currently or any time in the past.
9. Acute or chronic medical condition which may, in the opinion of investigator, affect the conduct of the study, including subjects receiving immune-modulating drugs (other than anti-retroviral chemotherapy), such as alpha-interferon, predni-sone (equivalent to >10 mg/day), or similar drugs, at study start.
10. Treatment with IMP in another interventional clinical study currently or during the past 4 weeks.
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Method of Generating Random Sequence
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Not Applicable |
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Method of Concealment
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Not Applicable |
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Blinding/Masking
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Open Label |
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Primary Outcome
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| Outcome |
TimePoints |
| The primary endpoint is the overall clinical assessment of the haemostatic efficacy of Octafibrin in treating the first documented bleeding episode of each patient. |
The first bleed-ing episode covers the time period from the first Octafibrin infusion for the treatment of a bleeding episode until 24 hours (i.e., 1 day) after the last infusion |
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Secondary Outcome
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| Outcome |
TimePoints |
| MCF assessment before first infusion and 1 hour after end of first infusion of each documented bleeding episode. |
Before first infusion and 1 hour after end of first infusion of each documented bleeding episode. |
| Fibrinogen plasma level before and 1 hour after the end of each infusion as well as at the time of the overall clinical assessment of haemostatic efficacy |
Before and 1 hour after the end of each infusion as well as at the time of the overall clinical assessment of haemostatic efficacy. |
| Response after the first infusion of each bleeding episode as indicated by incremental IVR, calculated as the maximum increase in plasma fibrinogen between the pre-infusion and the 3-hour post-infusion. |
Between the pre-infusion and the 3-hour post-infusion. |
| Efficacy of Octafibrin in all bleeding episodes & surgical prophylaxis |
Clinical assessment of haemostatic efficacy for bleeding based on a 4-point haemostatic efficacy scale.
To be assessed at the end of surgery by the surgeon and post-operatively by the haematologist
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Target Sample Size
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Total Sample Size="6"
Sample Size from India="4"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
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Phase 3 |
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Date of First Enrollment (India)
|
15/07/2015 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
15/07/2015 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
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Estimated Duration of Trial
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Years="5"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
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Closed to Recruitment of Participants |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
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Publication Details
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Individual Participant Data (IPD) Sharing Statement
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Will individual participant data (IPD) be shared publicly (including data dictionaries)?
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Brief Summary
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This Study is a Prospective, open-label, uncontrolled, phase III study to assess the efficacy, safety, and pharmacokinetics of Octafibrin for on-demand treatment of acute bleeding and to prevent bleeding during and after surgery in paediatric subjects with congenital fibrinogen deficiency that will be conducted in Three Centres of India. Primary Endpoint The primary endpoint is the overall clinical assessment of the haemostatic efficacy of Octafibrin in treating the first documented bleeding episode of each patient. The first bleeding episode covers the time period from the first Octafibrin infusion for the treatment of a bleeding episode until 24 hours (i.e., 1 day) after the last infusion or the end of the treatment observation period. Secondary Endpoints: • MCF assessment before first infusion and 1 hour after end of first infusion of each documented bleeding episode. • Fibrinogen plasma level before and 1 hour after the end of each infusion as well as at the time of the overall clinical assessment of haemostatic efficacy (i.e., 24 hours after the last infusion or end of the observation period of each documented bleeding episode). • Response after the first infusion of each bleeding episode as indicated by incremental IVR, calculated as the maximum increase in plasma fibrinogen (Clauss data) between the pre-infusion and the 3-hour post-infusion measurement, divided by the exact dose of Octafibrin (expressed as mg/kg dosed). • Efficacy of Octafibrin in all bleeding episodes collected in the study using the investiga-tor’s overall clinical assessment of haemostatic efficacy for bleeding based on a 4-point haemostatic efficacy scale. • Efficacy of Octafibrin in surgical prophylaxis will be assessed at the end of surgery by the surgeon and post-operatively by the haematologist using the following scales: An overall efficacy assessment taking both the intra- and post-operative assessment into account will be adjudicated by the IDMEAC. The surgical observation period starts with the first dose of Octafibrin administered prior to elective surgery (Day 1) and, depending on the severity of the event, will last at least 3 post-operative days for minor and 7 post-operative days for major surgeries or until the day of the last post-operative infusion, whichever comes last. |