Efficacy and safety of a new human fibrinogen concentrate in patients with congenital fibrinogen deficiency: An interim analysis of a Phase III trial

Toshko Lissitchkov, Bella Madan, Claudia Djambas Khayat, Nadezhda Zozulya, Cecil Ross, Mehran Karimi, Kaan Kavakli, Guillermo R. De Angulo, Abdulkareem Almomen, Bruce A. Schwartz, Cristina Solomon, Sigurd Knaub, Flora Peyvandi

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Fibrinogen concentrate is the preferred choice for fibrinogen replacement in congenital fibrinogen deficiency. This study investigated hemostatic efficacy of a new plasma-derived, double virus-inactivated (using two dedicated virus inactivation/elimination steps) human fibrinogen concentrate for on-demand treatment of bleeding episodes (BEs) and surgical prophylaxis. STUDY DESIGN AND METHODS: In this planned interim analysis of a prospective, multinational Phase III study (NCT02267226), 13 patients with afibrinogenemia (≥12 years) received fibrinogen concentrate (FIBRYGA, Octapharma AG). Hemostatic efficacy was assessed by investigators and an independent data monitoring and endpoint adjudication committee (IDMEAC) using objective four-point criteria and by thromboelastometry maximum clot firmness (MCF). RESULTS: Fibrinogen concentrate was used on-demand to treat 23 BEs in 11 patients, with 21 (91.3%) requiring a single infusion only. Treatment success was 95.7% (90% confidence interval [CI], 0.81-1.00; assessment missing for one BE) by investigators and 100% (90% CI, 0.88-1.00) by IDMEAC. Mean MCF increased significantly from 0.0 to 6.5 mm (95% CI, 5.65-7.40; p<0.0001) at 1 hour postinfusion of a median (range) dose of 58.8 (33.9-101.7) mg/kg per BE. Four patients received fibrinogen concentrate as surgical prophylaxis, with intraoperative and postoperative treatment success rated 100% (90% CI, 0.50-1.00) by investigators and IDMEAC (median [range] dose per surgery 93.5 [34.1-225.4] mg/kg). No additional hemostatic interventions were required. No deaths, thromboses, or seroconversions were reported. CONCLUSION: These data showed that the new fibrinogen concentrate was efficacious for on-demand treatment of acute bleeding and surgical prophylaxis in congenital afibrinogenemia patients.

Original languageEnglish
Pages (from-to)413-422
JournalTransfusion
Volume58
Issue number2
DOIs
Publication statusPublished - 2018

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Afibrinogenemia
Fibrinogen
Safety
Hemorrhage
Hemostatics
Confidence Intervals
Research Personnel
Virus Inactivation
Thrombelastography
Therapeutics
Thrombosis
Viruses

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

Cite this

Efficacy and safety of a new human fibrinogen concentrate in patients with congenital fibrinogen deficiency : An interim analysis of a Phase III trial. / Lissitchkov, Toshko; Madan, Bella; Djambas Khayat, Claudia; Zozulya, Nadezhda; Ross, Cecil; Karimi, Mehran; Kavakli, Kaan; De Angulo, Guillermo R.; Almomen, Abdulkareem; Schwartz, Bruce A.; Solomon, Cristina; Knaub, Sigurd; Peyvandi, Flora.

In: Transfusion, Vol. 58, No. 2, 2018, p. 413-422.

Research output: Contribution to journalArticle

Lissitchkov, T, Madan, B, Djambas Khayat, C, Zozulya, N, Ross, C, Karimi, M, Kavakli, K, De Angulo, GR, Almomen, A, Schwartz, BA, Solomon, C, Knaub, S & Peyvandi, F 2018, 'Efficacy and safety of a new human fibrinogen concentrate in patients with congenital fibrinogen deficiency: An interim analysis of a Phase III trial', Transfusion, vol. 58, no. 2, pp. 413-422. https://doi.org/10.1111/trf.14421
Lissitchkov, Toshko ; Madan, Bella ; Djambas Khayat, Claudia ; Zozulya, Nadezhda ; Ross, Cecil ; Karimi, Mehran ; Kavakli, Kaan ; De Angulo, Guillermo R. ; Almomen, Abdulkareem ; Schwartz, Bruce A. ; Solomon, Cristina ; Knaub, Sigurd ; Peyvandi, Flora. / Efficacy and safety of a new human fibrinogen concentrate in patients with congenital fibrinogen deficiency : An interim analysis of a Phase III trial. In: Transfusion. 2018 ; Vol. 58, No. 2. pp. 413-422.
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abstract = "BACKGROUND: Fibrinogen concentrate is the preferred choice for fibrinogen replacement in congenital fibrinogen deficiency. This study investigated hemostatic efficacy of a new plasma-derived, double virus-inactivated (using two dedicated virus inactivation/elimination steps) human fibrinogen concentrate for on-demand treatment of bleeding episodes (BEs) and surgical prophylaxis. STUDY DESIGN AND METHODS: In this planned interim analysis of a prospective, multinational Phase III study (NCT02267226), 13 patients with afibrinogenemia (≥12 years) received fibrinogen concentrate (FIBRYGA, Octapharma AG). Hemostatic efficacy was assessed by investigators and an independent data monitoring and endpoint adjudication committee (IDMEAC) using objective four-point criteria and by thromboelastometry maximum clot firmness (MCF). RESULTS: Fibrinogen concentrate was used on-demand to treat 23 BEs in 11 patients, with 21 (91.3{\%}) requiring a single infusion only. Treatment success was 95.7{\%} (90{\%} confidence interval [CI], 0.81-1.00; assessment missing for one BE) by investigators and 100{\%} (90{\%} CI, 0.88-1.00) by IDMEAC. Mean MCF increased significantly from 0.0 to 6.5 mm (95{\%} CI, 5.65-7.40; p<0.0001) at 1 hour postinfusion of a median (range) dose of 58.8 (33.9-101.7) mg/kg per BE. Four patients received fibrinogen concentrate as surgical prophylaxis, with intraoperative and postoperative treatment success rated 100{\%} (90{\%} CI, 0.50-1.00) by investigators and IDMEAC (median [range] dose per surgery 93.5 [34.1-225.4] mg/kg). No additional hemostatic interventions were required. No deaths, thromboses, or seroconversions were reported. CONCLUSION: These data showed that the new fibrinogen concentrate was efficacious for on-demand treatment of acute bleeding and surgical prophylaxis in congenital afibrinogenemia patients.",
author = "Toshko Lissitchkov and Bella Madan and {Djambas Khayat}, Claudia and Nadezhda Zozulya and Cecil Ross and Mehran Karimi and Kaan Kavakli and {De Angulo}, {Guillermo R.} and Abdulkareem Almomen and Schwartz, {Bruce A.} and Cristina Solomon and Sigurd Knaub and Flora Peyvandi",
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T2 - An interim analysis of a Phase III trial

AU - Lissitchkov, Toshko

AU - Madan, Bella

AU - Djambas Khayat, Claudia

AU - Zozulya, Nadezhda

AU - Ross, Cecil

AU - Karimi, Mehran

AU - Kavakli, Kaan

AU - De Angulo, Guillermo R.

AU - Almomen, Abdulkareem

AU - Schwartz, Bruce A.

AU - Solomon, Cristina

AU - Knaub, Sigurd

AU - Peyvandi, Flora

PY - 2018

Y1 - 2018

N2 - BACKGROUND: Fibrinogen concentrate is the preferred choice for fibrinogen replacement in congenital fibrinogen deficiency. This study investigated hemostatic efficacy of a new plasma-derived, double virus-inactivated (using two dedicated virus inactivation/elimination steps) human fibrinogen concentrate for on-demand treatment of bleeding episodes (BEs) and surgical prophylaxis. STUDY DESIGN AND METHODS: In this planned interim analysis of a prospective, multinational Phase III study (NCT02267226), 13 patients with afibrinogenemia (≥12 years) received fibrinogen concentrate (FIBRYGA, Octapharma AG). Hemostatic efficacy was assessed by investigators and an independent data monitoring and endpoint adjudication committee (IDMEAC) using objective four-point criteria and by thromboelastometry maximum clot firmness (MCF). RESULTS: Fibrinogen concentrate was used on-demand to treat 23 BEs in 11 patients, with 21 (91.3%) requiring a single infusion only. Treatment success was 95.7% (90% confidence interval [CI], 0.81-1.00; assessment missing for one BE) by investigators and 100% (90% CI, 0.88-1.00) by IDMEAC. Mean MCF increased significantly from 0.0 to 6.5 mm (95% CI, 5.65-7.40; p<0.0001) at 1 hour postinfusion of a median (range) dose of 58.8 (33.9-101.7) mg/kg per BE. Four patients received fibrinogen concentrate as surgical prophylaxis, with intraoperative and postoperative treatment success rated 100% (90% CI, 0.50-1.00) by investigators and IDMEAC (median [range] dose per surgery 93.5 [34.1-225.4] mg/kg). No additional hemostatic interventions were required. No deaths, thromboses, or seroconversions were reported. CONCLUSION: These data showed that the new fibrinogen concentrate was efficacious for on-demand treatment of acute bleeding and surgical prophylaxis in congenital afibrinogenemia patients.

AB - BACKGROUND: Fibrinogen concentrate is the preferred choice for fibrinogen replacement in congenital fibrinogen deficiency. This study investigated hemostatic efficacy of a new plasma-derived, double virus-inactivated (using two dedicated virus inactivation/elimination steps) human fibrinogen concentrate for on-demand treatment of bleeding episodes (BEs) and surgical prophylaxis. STUDY DESIGN AND METHODS: In this planned interim analysis of a prospective, multinational Phase III study (NCT02267226), 13 patients with afibrinogenemia (≥12 years) received fibrinogen concentrate (FIBRYGA, Octapharma AG). Hemostatic efficacy was assessed by investigators and an independent data monitoring and endpoint adjudication committee (IDMEAC) using objective four-point criteria and by thromboelastometry maximum clot firmness (MCF). RESULTS: Fibrinogen concentrate was used on-demand to treat 23 BEs in 11 patients, with 21 (91.3%) requiring a single infusion only. Treatment success was 95.7% (90% confidence interval [CI], 0.81-1.00; assessment missing for one BE) by investigators and 100% (90% CI, 0.88-1.00) by IDMEAC. Mean MCF increased significantly from 0.0 to 6.5 mm (95% CI, 5.65-7.40; p<0.0001) at 1 hour postinfusion of a median (range) dose of 58.8 (33.9-101.7) mg/kg per BE. Four patients received fibrinogen concentrate as surgical prophylaxis, with intraoperative and postoperative treatment success rated 100% (90% CI, 0.50-1.00) by investigators and IDMEAC (median [range] dose per surgery 93.5 [34.1-225.4] mg/kg). No additional hemostatic interventions were required. No deaths, thromboses, or seroconversions were reported. CONCLUSION: These data showed that the new fibrinogen concentrate was efficacious for on-demand treatment of acute bleeding and surgical prophylaxis in congenital afibrinogenemia patients.

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