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

September 29, 2021 updated by: CSL Behring

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
246

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Melbourne, Australia, 3052
        • Study Site 0360014
      • Nedlands, Australia, WA 6009
        • Study Site 0360028
      • Perth, Australia, WA 6000
        • Study Site 0360031
  • Austria
      • Graz, Austria, 8036
        • Study Site 0400012
      • Linz, Austria, 4020
        • Study Site 0400003
      • Wien, Austria, 1090
        • Study Site 0400001
      • Wien, Austria, 1090
        • Study Site 0400002
  • Canada
      • Saint John, Canada, E2L 4L2
        • Study Site 1240022
  • Czechia
      • Hradec Kralove, Czechia, 500 05
        • Study Site 2030017
  • France
      • Brest, France, 29609
        • Study Site 2500015
      • Le Kremlin Bicetre, France, 94270
        • Study Site 2500017
      • Lille Cedex, France, 59037
        • Study Site 2500028
      • Nantes, France, 44093
        • Study Site 2500018
      • Paris, France, 75015
        • Study Site 2500002
  • Georgia
      • Tbilisi, Georgia, 0179
        • Study Site 2680001
  • Germany
      • Bonn, Germany, 53127
        • Study Site 2760034
      • Frankfurt, Germany, 60596
        • Study Site 2760091
      • Giessen, Germany, 35385
        • Study Site 2760087
      • Hannover, Germany, 30625
        • Study Site 2760066
  • Hungary
      • Debrecen, Hungary, 4032
        • Study Site 3480007
  • Ireland
      • Dublin, Ireland, 12
        • Study Site 3720002
  • Italy
      • Milano, Italy, 20122
        • Study Site 3800023
  • Japan
      • Hyogo, Japan, 663-8501
        • Study Site 3920031
      • Nagoya, Japan, 466-8550
        • Study Site 3920029
      • Okayama, Japan, 710-8602
        • Study Site 3920064
      • Saitama, Japan, 339-8551
        • Study Site 3920033
      • Tokyo, Japan, 160-0023
        • Study Site 3920025
  • Lebanon
      • Beirut, Lebanon, 165191
        • Study Site 4220007
  • Malaysia
      • Kuala Lumpur, Malaysia, 50400
        • Study Site 4580001
  • Netherlands
      • Amsterdam Zuidoost, Netherlands, 1105 AZ
        • Study Site 5280006
      • Nijmegen, Netherlands, 6500
        • Study Site 5280008
      • Utrecht, Netherlands, 3584
        • Study Site 5280007
  • Philippines
      • Cebu City, Philippines, 6000
        • Study Site 6080001
      • Davao City, Philippines, 8000
        • Study Site 6080002
  • Poland
      • Gdansk, Poland, 80-952
        • Study Site 6160013
      • Krakow, Poland, 31-531
        • Study Site 6160038
      • Rzeszow, Poland, 35-301
        • Study Site 6160035
      • Wroclaw, Poland, 50-367
        • Study Site 6160014
  • Portugal
      • Porto, Portugal, 4200-319
        • Study Site 6200001
  • Romania
      • Bucharest, Romania, 011026
        • Study Site 6420030
      • Timisoara, Romania, 300011
        • Study Site 6420037
  • South Africa
      • Parktown, South Africa, 2193
        • Study Site 7100001
  • Spain
      • A Coruna, Spain, 15006
        • Study Site 7240008
      • Barcelona, Spain, 08035
        • Study Site 7240021
      • Madrid, Spain, 28046
        • Study Site 7240007
      • Valencia, Spain, 46026
        • Study Site 7240023
  • Switzerland
      • Luzern, Switzerland, 6000
        • Study Site 7560010
  • Thailand
      • Bangkok, Thailand, 10330
        • Study Site 7640001
      • Bangkok, Thailand, 10700
        • Study Site 7640005
      • Chiang Mai, Thailand, 50200
        • Study Site 7640002
      • Khon Kaen, Thailand, 40002
        • Study Site 7640004
      • Songkhla, Thailand, 90110
        • Study Site 7640003
  • Ukraine
      • Dnipropetrovsk, Ukraine, 49102
        • Study Site 8040007
      • Lviv, Ukraine, 79044
        • Study Site 8040005
  • United Kingdom
      • London, United Kingdom, NW3 2QG
        • Study Site 8260008
  • United States
    • California
      • San Diego, California, United States, 92103-8651
        • Study Site 8400213
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Study Site 8400241
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Study Site 8400118
    • Florida
      • Miami, Florida, United States, 33136
        • Study Site 8400116
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Study Site 8400184
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Study Site 8400204
    • Texas
      • Dallas, Texas, United States, 75390-9016
        • Study Site 8400240
      • Houston, Texas, United States, 77030
        • Study Site 8400041
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Study Site 8400154

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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 Names:
  • CSL627

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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).
At the closest visit after 100 EDs (up to 5 years).
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.
At the closest visit after 50 EDs (up to 5 years).
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.
Up to 5 years
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.
Up to 5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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".
Up to 5 years
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
Up to 5 years
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
Up to 5 years
Mean Number of On-demand Infusions of CSL627
Time Frame: Up to 5 years
Up to 5 years
Mean On-demand Dose Administered of CSL627
Time Frame: Up to 5 years
Up to 5 years
Mean Prophylaxis Dose Administered of CSL627
Time Frame: Up to 5 years
Up to 5 years
Mean Total Amount of CSL627 Administered During Surgery Period in PTPs
Time Frame: Day of surgery up to 336 hours post-surgery
Day of surgery up to 336 hours post-surgery
Total Amount of CSL627 Administered During Surgery Period in PUPs
Time Frame: Day of surgery up to 336 hours post-surgery
Day of surgery up to 336 hours post-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)
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".
From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)
Incidence of Inhibitor Formation to FVIII in PTPs After 10 EDs and After 50 EDs
Time Frame: Up to 5 years
Up to 5 years
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).
PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).
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).
PTPs: At the closest visit after 100 EDs (up to 5 years). PUPs: At the closest visit after 50 EDs (up to 5 years).
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.
At the closest visit after 10 EDs (up to 5 years)
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.
At the closest visit after 10 and after 50 EDs (up to 5 years)
Incidence of Total Inhibitor Formation to FVIII in PUPs
Time Frame: Up to 5 years
Up to 5 years
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.
Up to 5 years
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.
Up to 6 hours after first infusion
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.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
CSL Behring

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 13, 2014

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 19, 2021

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 19, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 23, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 23, 2014

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 24, 2014

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 27, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 29, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CSL627_3001
  • 2013-003262-13 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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