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NCT Number: NCT02172950

An Open-label Safety and Efficacy Study of Recombinant FVIII in Patients With Severe Hemophilia A

This multicenter, open-label, phase 3 extension study will investigate the safety and efficacy of rVIII-SingleChain for prophylaxis and on-demand treatment of bleeding episodes in at least 200 previously treated patients (PTPs) with severe congenital hemophilia A and previous exposure to FVIII products who achieve at least 100 exposure days (EDs) to rVIII-SingleChain in this study, as well as in previously untreated patients (PUPs) with no previous exposure to any FVIII product who achieve at least 50 EDs to rVIII-SingleChain in this study. A substudy (open to both PTPs and PUPs) will investigate the use of rVIII-SingleChain in surgery. A substudy (open to PUPs who develop an inhibitor to rVIII-SingleChain) will investigate the use of rVIII-SingleChain in immune tolerance induction (ITI) therapy.

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Key information

Conditions

Hemophilia A Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Coagulation Protein Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Severe Hemophilia A

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

Study Site 0360014, Melbourne, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

PTPs:

  • Males of any age who have been diagnosed with severe congenital hemophilia A (FVIII activity levels < 1%) and who participated in a previous CSL-sponsored clinical study with rVIII-SingleChain.
  • Males 0 to <65 years age who have been diagnosed with severe congenital hemophilia A (FVIII activity levels < 1%), who have at least 50 EDs to any FVIII product, and who are not currently enrolled in a CSL-sponsored clinical study with rVIII-SingleChain.

PUPs:

  • Males 0 to <18 years of who have been diagnosed with severe congenital hemophilia A (FVIII activity levels < 1%)
  • No prior exposure to any Factor VIII product (with the exception of short-term use of blood products).

ITI substudy:

  • PUPs who have developed a confirmed inhibitor to rVIII-SingleChain in the main study.

Exclusion criteria

  • Known or suspected hypersensitivity to rVIII-SingleChain or to any excipients of rVIII-SingleChain or Chinese hamster ovary (CHO) proteins.
  • Currently receiving a therapy not permitted during the study.
  • Serum creatinine > 2 x upper limit of normal, alanine aminotransferase or aspartate aminotransferase > 5 x upper limit of normal at Screening (if specified)
  • Any first-order family (eg, siblings) history of FVIII inhibitors
  • For PTPs not rolling over directly from a CSL-sponsored clinical study with rVIII-SingleChain: any history of or current FVIII inhibitors

Treatment and study plan

rVIII-SingleChain

Biological

Recombinant single-chain coagulation factor VIII

Other names: CSL627

Primary outcomes

  1. Incidence of Inhibitor Formation to FVIII in Previously Treated Patients (PTPs) With 100 Exposure Days (EDs) to CSL627

    Time frame: At the closest visit after 100 EDs (up to 5 years).

  2. Number of Previously Untreated Patients (PUPs) With High-titer Inhibitor Formation to FVIII With at Least 50 EDs to CSL627

    Time frame: At the closest visit after 50 EDs (up to 5 years).

    High-titer inhibitor is defined as an inhibitor titer of ≥ 5 Bethesda units/mL.

  3. Percent Treatment Success for Major Bleeding Episodes in PUPs

    Time frame: Up to 5 years

    Percentage of major bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of "excellent" or "good" on the investigator's clinical assessment of hemostatic efficacy 4-point scale "excellent, good, moderate or poor/no response". Major bleeding episodes are defined as bleeding episodes for which a subject is required to seek treatment at the hemophilia center or that threatens the subject's life or loss of limb.

  4. Annualized Spontaneous Bleeding Rate in PUPs

    Time frame: Up to 5 years

    The annualized spontaneous bleeding rate for PUPs taking prophylaxis and on-demand treatment regimens.

Secondary outcomes

  1. Percentage of Bleeding Episodes Treated Successfully in PTPs

    Time frame: Up to 5 years

    Percentage of bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of "excellent" or "good" on the investigator's clinical assessment of hemostatic efficacy 4-point scale "excellent, good, moderate or poor/no response".

  2. Annualized Bleeding Rate in PTPs and PUPs

    Time frame: Up to 5 years

    The annualized bleeding rate for PTPs and PUPs taking prophylaxis and on-demand treatment regimens

  3. Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs

    Time frame: Up to 5 years

  4. Mean Number of On-demand Infusions of CSL627

    Time frame: Up to 5 years

  5. Mean On-demand Dose Administered of CSL627

    Time frame: Up to 5 years

  6. Mean Prophylaxis Dose Administered of CSL627

    Time frame: Up to 5 years

  7. Mean Total Amount of CSL627 Administered During Surgery Period in PTPs

    Time frame: Day of surgery up to 336 hours post-surgery

  8. Total Amount of CSL627 Administered During Surgery Period in PUPs

    Time frame: Day of surgery up to 336 hours post-surgery

  9. Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery

    Time frame: From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)

    The investigator will rate the efficacy of the rVIII-SingleChain treatment during surgery based on a hemostatic efficacy four point rating scale of "excellent, good, moderate or poor/no response".

  10. Incidence of Inhibitor Formation to FVIII in PTPs After 10 EDs and After 50 EDs

    Time frame: Up to 5 years

  11. Percentage of PTPs and PUPs Developing Antibodies Against CSL627

    Time frame: PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).

  12. Percentage of PTPs and PUPs Developing Antibodies to Chinese Hamster Ovary (CHO) Proteins

    Time frame: PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).

  13. Number of PUPs With High-titer Inhibitor Formation to FVIII After 10 EDs With CSL627

    Time frame: At the closest visit after 10 EDs (up to 5 years)

    High-titer inhibitor is defined as an inhibitor titer of ≥ 5 Bethesda units/mL.

  14. Number of PUPs With Low-titer Inhibitor Formation to FVIII After 10 EDs and After 50 EDs With CSL627

    Time frame: At the closest visit after 10 and after 50 EDs (up to 5 years)

    Low-titer inhibitor is defined as an inhibitor titer of less than 5 Bethesda units/mL.

  15. Incidence of Total Inhibitor Formation to FVIII in PUPs

    Time frame: Up to 5 years

  16. Percent Treatment Success for Non-major Bleeding Episodes in PUPs

    Time frame: Up to 5 years

    Percentage of bleeding episodes treated successfully where treatment success for a bleeding episode is defined as a rating of "excellent" or "good" on the investigator's clinical assessment of hemostatic efficacy 4-point scale "excellent, good, moderate or poor/no response". Non-major bleeding episodes are those not requiring treatment at the hemophilia center or not threatening subject's life or loss of limb.

  17. Percentage of PUPs With Clinically Significant Abnormal Vital Signs Values After First Infusion of CSL627

    Time frame: Up to 6 hours after first infusion

    Vital signs assessments include heart rate, blood pressure, and body temperature. Clinical significance of an abnormality will be assessed by the investigator.

  18. Percentage of PUPs With Treatment-emergent Clinically Significant Abnormal Vital Signs Values

    Time frame: Up to 5 years

    Vital signs assessments include heart rate, blood pressure, and body temperature. Clinical significance of an abnormality will be assessed by the investigator.

Sponsors and collaborators

Lead sponsor

CSL Behring

Industry

Registry information

Official study title

A Phase III Open Label, Multicenter, Extension Study to Assess the Safety and Efficacy of Recombinant Coagulation Factor VIII (rVIII-SingleChain, CSL627) in Subjects With Severe Hemophilia A

Important dates

Study start
2014
Primary completion
2021
Study completion
2021
First posted
Jun 24, 2014
Registry last updated
Oct 27, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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