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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by CSL Behring
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT02172950
First received: June 23, 2014
Last updated: July 7, 2016
Last verified: July 2016
  Purpose
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 at least 50 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.

Condition Intervention Phase
Hemophilia A
Severe Hemophilia A
Biological: rVIII‑SingleChain
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • Incidence of inhibitor formation to FVIII in PTPs with 100 EDs to rVIII-SingleChain [ Time Frame: At the closest visit after 100 EDs (up to 3 years). ] [ Designated as safety issue: Yes ]
    Number of PTPs (with 100 EDs to rVIII-SingleChain) with inhibitor formation to FVIII

  • Incidence of high-titer inhibitor formation to FVIII in at least 50 PUPs with at least 50 EDs of rVIII-SingleChain [ Time Frame: At the closest visit after 50 EDs (up to 4 years). ] [ Designated as safety issue: Yes ]
    Number of PUPs (with at least 50 EDs of rVIII-SingleChain) with high-titer inhibitor formation to FVIII. High-titer inhibitor is defined as an inhibitor titer of ≥ 5 Bethesda units/mL.

  • Treatment success for major bleeding episodes in PUPs [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    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.

  • Annualized spontaneous bleeding rate in PUPs [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    The annualized spontaneous bleeding rate for PUPs taking prophylaxis and on-demand treatment regimens.


Secondary Outcome Measures:
  • Treatment success in PTPs [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    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".

  • Annualized bleeding rate in PTPs and PUPs [ Time Frame: PTPs: Up to 3 years. PUPs: Up to 4 years. ] [ Designated as safety issue: No ]
    The annualized bleeding rate for PTPs and PUPs taking prophylaxis and on-demand treatment regimens

  • Percentage of bleeding episodes requiring 1, 2, 3, or > 3 injections of rVIII-SingleChain to achieve hemostasis in PTPs and PUPs [ Time Frame: PTPs: Up to 3 years. PUPs: Up to 4 years. ] [ Designated as safety issue: No ]
  • Consumption of rVIII-SingleChain in PTPs and PUPs - injections [ Time Frame: PTPs: Up to 3 years. PUPs: Up to 4 years. ] [ Designated as safety issue: No ]
    The number of rVIII-SingleChain injections per month and per year

  • Consumption of rVIII-SingleChain in PTPs and PUPs - IU/kg [ Time Frame: PTPs: Up to 3 years. PUPs: Up to 4 years. ] [ Designated as safety issue: No ]
    rVIII-SingleChain consumption (IU/kg) per month and per year, and per event during prophylaxis, on-demand, and surgery.

  • 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) ] [ Designated as safety issue: No ]
    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".

  • Incidence of inhibitor formation to FVIII after 10 EDs and after 50 EDs in PTPs [ Time Frame: After 10 and after 50 exposure days ] [ Designated as safety issue: Yes ]
  • Percentage of PTPs and PUPs developing antibodies against rVIII-SingleChain [ Time Frame: PTPs: At the closest visit after 100 EDs (up to 3 years). PUPs: At the closest visit after 50 EDs (up to 4 years). ] [ Designated as safety issue: Yes ]
  • 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 3 years). PUPs: At the closest visit after 50 EDs (up to 4 years). ] [ Designated as safety issue: Yes ]
  • Incidence of high-titer inhibitor formation to FVIII in PUPs after 10 EDs with rVIII-SingleChain [ Time Frame: At the closest visit after 10 EDs ] [ Designated as safety issue: Yes ]
    Number of PUPs (after 10 EDs of rVIII-SingleChain) with high-titer inhibitor formation to FVIII. High-titer inhibitor is defined as an inhibitor titer of ≥ 5 Bethesda units/mL.

  • Incidence of low-titer inhibitor formation to FVIII in PUPs [ Time Frame: At the closest visit after 10 and after 50 EDs (up to 4 years) ] [ Designated as safety issue: Yes ]
    Number of PUPs (after 10 and 50 EDs of rVIII-SingleChain) with low-titer inhibitor formation to FVIII. Low-titer inhibitor is defined as an inhibitor titer of less than 5 Bethesda units/mL.

  • Incidence of total inhibitor formation to FVIII in PUPs [ Time Frame: At the closest visit after 50 EDs (up to 4 years). ] [ Designated as safety issue: Yes ]
    Number of PUPs (after 50 EDs) with inhibitor formation (both low- and high-titer inhibitors) to FVIII.

  • Treatment success for non-major bleeding episodes in PUPs [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    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.

  • Percentage of PUPs with clinically significant abnormal vital signs values after first rVIII-SingleChain injection [ Time Frame: At 1, 2, 3, and 6 hours after first rVIII-SingleChain injection ] [ Designated as safety issue: Yes ]
    Vital signs assessments include heart rate, blood pressure, and body temperature. Clinical significance of an abnormality will be assessed by the investigator

  • Percentage of PUPs with treatment-emergent clinically significant abnormal vital signs values [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
    Vital signs assessments include heart rate, blood pressure, and body temperature. Clinical significance of an abnormality will be assessed by the investigator


Estimated Enrollment: 250
Study Start Date: June 2014
Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Previously treated patients (PTPs)
The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII‑SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule for the subject based upon the subject's pharmacokinetic (PK) profile, rVIII-SingleChain PK data, previous FVIII treatment regimen, and bleeding phenotype, if available.
Biological: rVIII‑SingleChain
Recombinant single-chain coagulation factor VIII
Other Name: CSL627
Experimental: Previously untreated patients (PUPs)
The investigator will assign subjects to either prophylaxis or on-demand treatment regimens for rVIII‑SingleChain by intravenous injection. The investigator will determine the rVIII-SingleChain dose and dosing schedule at their discretion, taking into consideration the World Federation of Hemophilia (WFH) guidelines, the type of bleeding episode, location of the bleeding, subject's age, and other disease characteristics.
Biological: rVIII‑SingleChain
Recombinant single-chain coagulation factor VIII
Other Name: CSL627

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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).

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02172950

Contacts
Contact: Trial Registration Coordinator clinicaltrials@cslbehring.com

  Show 73 Study Locations
Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Program Director CSL Behring
  More Information

Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT02172950     History of Changes
Other Study ID Numbers: CSL627_3001  2013-003262-13 
Study First Received: June 23, 2014
Last Updated: July 7, 2016
Health Authority: United States: Food and Drug Administration
Germany: Paul-Ehrlich-Institut
Austria: Agency for Health and Food Safety
Austria: Federal Office for Safety in Health Care
Sweden: Medical Products Agency
Italy: Ministry of Health
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Poland: Ministry of Health
Japan: Pharmaceuticals and Medical Devices Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Czech Republic: State Institute for Drug Control
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants

ClinicalTrials.gov processed this record on July 21, 2016