Health Condition 1: D50-D89- Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism
Conditions
Interventions
Intervention1: Fibrogen-I TM (Human Fibrinogen 0.5 gm/ 1 gm freeze-dried powder, manufactured
from human plasma): Dose: Sterile freeze-dried powder form in a single-dose vial. Approximately 0.5 gm of
Sponsors
Intas Pharmaceuticals Limited
Intas Pharmaceuticals Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1) Must sign an ICF (or their legally acceptable representative must sign) indicating that the participant understands the purpose of, and procedures required for the study as described in Appendix 10.1.3 and in this protocol and is willing to participate in the study. Parent(s) (preferably both if available or per local requirements) must sign an ICF indicating that they understand the purpose of, and procedures required for the study and is willing to allow the child to participate in the study. Assent is also required of children capable of understanding the nature of the study as described in Informed Consent Process in Appendix 10.1.3. 2) Male or female. 3) Age of 0 to 75 (completed years) at the time of signing the informed consent. 4) Documented diagnosis of congenital fibrinogen deficiency manifested as afibrinogenaemia or severe hypofibrinogenaemia: Participants with a fibrinogen level undetectable, or equal or less than 50 mg per dL determined by both Clauss and antigen methods at Screening Visit. 5) Expected to require treatment for acute bleeding episode (spontaneous or after trauma [defined as any accidental event leading to acute bleeding]) or prophylaxis of bleeding before a surgical intervention or invasive procedure.
Exclusion criteria
Exclusion criteria: 1) Known allergies or hypersensitivity to the investigational interventions, human plasma proteins, blood-derived products or components excipients thereof [human albumin, Larginine hydrochloride, sodium citrate, sodium chloride; refer to the prescribing information of Fibrogen-I that, either manifested as severe immediate hypersensitivity reactions, including anaphylaxis prohibiting the further treatment with fibrinogen concentrate or contraindicates participation in the study in the opinion of the investigator. 2) Documented history of immunoglobulin A (IgA) deficiency and antibodies against IgA. 3) Participants with dysfibrinogenaemia or acquired (secondary) fibrinogen deficiency. 4) Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months before the first dose of investigational intervention. For participants with evidence of chronic hepatitis B virus (HBV) infection who are HBsAg positive but are already established on highly effective viral suppression with HBV DNA below the Level of Quantification at screening, and when the intent is for viral suppression to continue throughout study participation are eligible to participate. 5) Positive hepatitis C antibody test result at screening or within 3 months before starting the investigational intervention. NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C Ribonucleic acid (RNA) test is obtained. Participants with HCV infection who are currently on treatment, are eligible if they have an undetectable HCV viral load. 6) Has known human immunodeficiency virus (HIV) seropositive status, or positive HIV antibody test at screening. For participants with unknown HIV status, HIV testing will be performed at screening unless prohibited by local regulations. HIV-infected participants on effective anti-retroviral therapy with an undetectable viral load within 6 months are eligible for this study. 7) Treatment with: a) Any fibrinogen concentrate or other fibrinogen-containing blood product within 2 weeks before the start of treatment for the pharmacokinetic period. b) Any coagulation-active drug (ie, non-steroidal anti-inflammatory drugs at doses know to have anticoagulant effects, warfarin, coumarin derivatives, platelet aggregation inhibitors) within 1 week before the start of the treatment for the bleeding episode or surgery, or as a planned or expected medication during the period from Day 1 until 24 hours (ie, 1 day) after the last Fibrogen-I infusion. c) Participants receiving immune-modulating drugs (other than anti-retroviral chemotherapy) such as alpha-interferon, prednisone (equivalent to greater than 10 mg per day), or similar drugs at the start of treatment for the pharmacokinetic period. 8) Documented medical history or current evidence of before the start of treatment for the pharmacokinetic period: Deep vein thrombosis or pulmonary embolism within 1 year. Arterial thrombosis within 1 year. Current evidence of oesophageal varicose bleeding. Current evidence of end-stage liver disease (ie, Child-Pugh score B or C). 9) Polytrauma 1 year before the start of treatment for the bleeding episode or surgery. 10) Diagnosis or suspicion of a neutralizing anti-fibrinogen in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate the haemostatic efficacy of Fibrogen-I for the first documented bleeding episode in participants with congenital fibrinogen deficiency requiring on-demand treatment of acute bleeding (spontaneous or after trauma) To determine the single-dose pharmacokinetics of Fibrogen-I in participants with congenital fibrinogen deficiency.Timepoint: Day 1, Immediately prior to the scheduled infusion Day 1, 1 hour post-infusion Day 1, 3 hour post-infusion Day 2, 24 hour post-infusion Day 4, 72 hours post-infusion Day 7, 144 hours post-infusion Day 10, 216 hours post-infusion Day 14, 312 hours post-infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| To characterize further the efficacy of Fibrogen-I in participants with congenital fibrinogen deficiency requiring on-demand treatment of acute bleeding (spontaneous or after trauma). To demonstrate the efficacy of Fibrogen-I in preventing bleeding during and after surgery in participants with congenital fibrinogen deficiency. To determine clot strength or clot firmness [referred to as maximum clot firmness (MCF) in this protocol] as a surrogate pharmacodynamic marker for haemostatic efficacy before and after administration of Fibrogen-I in participants with congenital fibrinogen deficiency To demonstrate the impact of Fibrogen-I on standard coagulation parameters in participants with congenital fibrinogen deficiency. To assess the immunogenicity and safety of Fibrogen-I in participants with congenital fibrinogen deficiency.Timepoint: Day 1, Immediately prior to the scheduled infusion Day 1, 1 hour post-infusion Day 1, 3 hour post-infusion Day 2, 24 hour post-infusion Day 4, 72 hours post-infusion Day 7, 144 hours post-infusion Day 10, 216 hours post-infusion Day 14, 312 hours post-infusion | — |
Countries
India
Contacts
Public ContactDr Jogesh Mahajan
Lambda Therapeutic Research Ltd
Outcome results
None listed