Congenital Hemophilia APhase 3NCT02093897
Pharmacokinetic, Efficacy, and Safety Study of Recombinant Factor VIII Single Chain (rVIII-SingleChain) in Children With Severe Hemophilia A
A Phase 3 study testing rVIII-SingleChain in people with Congenital Hemophilia A, run by CSL Behring at 37 sites in 19 countries.
Trial summary
This is an international, multicenter, open-label study to assess the efficacy, safety, and pharmacokinetic (PK) profile of rVIII-SingleChain in pediatric patients with severe hemophilia A. Read more about this study
- Who is it for?
- Ages Up to 11 years, men only
- Conditions the study is for
- Congenital Hemophilia A
- What is being tested?
- rVIII-SingleChain
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 37 sitesin 19 countries
- Study dates
- Mar 2014to Aug 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 11 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Diagnosis of severe hemophilia A defined as < 1% Factor VIII (FVIII) concentration (FVIII:C) documented in medical records,
- Males < 12 years of age,
- Subjects who have received > 50 EDs with a FVIII product,
- Prior PK data (at least incremental recovery and half-life) from previous FVIII exposure for subjects participating in the PK part
- Investigator believes that the subject is willing and able to adhere to all protocol requirements. Investigator believes that the subject's parent(s) or legally acceptable representative(s) is / are willing and able to adhere to all protocol requirements.
Who cannot join
- Any history of or current FVIII inhibitors
- Use of an Investigational Medical Product (IMP) within 30 days prior to the first rVIII-SingleChain administration,
- Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of rVIII-SingleChain,
- Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein,
- Subject currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment,
- Subject with serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) values >5 times (x) the upper limit of normal (ULN) at Screening,
Show all 9Show fewer
- Subjects with serum creatinine values >2 x ULN at Screening,
- Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction and arterial embolus within 3 months before Day 1,
- Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months before rVIII-SingleChain administration.
Trial locations and contacts
37 sites in 19 countries.
37 sites in 19 countries
France5 sites
Study Site
Brest, 29609
Study Site
Le Kremlin-Bicêtre, 94270
Study Site
Lille, 59037
Study Site
Nantes, 44093
Study Site
Paris, 75015
Thailand5 sites
Study Site
Bangkok, 10330
Study Site
Bangkok, 10700
Study Site
Chiang Mai, 50200
Study Site
Khon Kaen, 40002
Study Site
Songkhla, 90110
Germany4 sites
Study Site
Bonn, 53127
Study Site
Bremen, 28177
Study Site
Frankfurt am Main, 60590
Study Site
Hanover, 30159
Netherlands3 sites
Study Site
Amsterdam, 1105 AZ
Study Site
Njmegen, 6525 GA
Study Site
Utrecht, 3584 CX
Turkey (Türkiye)3 sites
Study Site
Adana, 01330
Study Site
Istanbul, 34098
Study Site
Izmir, 35100
United States2 sites
Study Site
Aurora, Colorado, 80045
Study Site
Chicago, Illinois, 60612
About this study
Official title: A Phase III Open-label Pharmacokinetic, Efficacy and Safety Study of rVIII-SingleChain in a Pediatric Population With Severe Hemophilia A
This is an international, multicenter, open-label study to assess the efficacy, safety, and pharmacokinetic (PK) profile of rVIII-SingleChain in pediatric patients with severe hemophilia A. A minimum of 25 previously treated subjects ≥ 6 to < 12 years of age and at least 25 subjects < 6 years of age who have undergone > 50 exposure days (EDs) with a previous Factor VIII (FVIII) product are planned to be enrolled. Subjects will be assigned to either an on-demand or prophylaxis treatment regimen and will receive rVIII-SingleChain at a dose to be determined by the investigator. Hemostatic efficacy will be assessed by the subject/caregiver and the investigator who will assess overall efficacy by a 4-point scale.
- Conditions
- Congenital Hemophilia A
- Being tested
- rVIII-SingleChain
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rVIII-SingleChainBiological
Also called Recombinant Factor VIII single chain, CSL627
| Study group | Role | What they receive |
|---|---|---|
| rVIII-SingleChain | Experimental | Subjects will be assigned to either an on-demand or prophylaxis regimen and will receive rVIII-SingleChain as an intravenous (IV) infusion. Subjects assigned to a prophylaxis regimen will be treated with 15 to 50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based on available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose for on-demand treatment of a bleeding episode is based on the recommendations of the World Federation of Hemophilia (WFH), with a minimum dose of 15 IU/kg. All subjects were to be treated for a minimum of 50 EDs. For the PK evaluation, the subjects will receive a single IV dose of 50 IU/kg of rVIII-SingleChain on Day 1 at the start of the PK evaluation period. Receives: Biological: rVIII-SingleChain |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Success
Rate of treatment success where treatment success of a bleeding episode is defined as a rating of "excellent" or "good" based on the investigator's overall clinical assessment of hemostatic efficacy (using a 4-point scale of excellent, good, moderate or poor/no response) on the on-demand and prophylaxis regimens combined. The rate of success was based on the number of treated bleeding events; there were 347 treated bleeding events in the Efficacy Population.
Measured: Up to 1 year
Secondary outcomes (12)
Annualized Bleeding Rate
The annualized bleeding rate was defined as the number of bleeding episodes requiring treatment divided by the efficacy evaluation period in days, x 365.25, and is presented separately for the on-demand regimen and the prophylaxis regimens.
Measured: Up to 1 year
Percentage of Bleeding Episodes Requiring 1, 2, 3, or More Than 3 Infusions of rVIII-SingleChain to Achieve Hemostasis.
Measured: Up to 1 year
Consumption of rVIII-SingleChain - IU/kg Per Subject Per Month
Measured: Up to 1 year
Consumption of rVIII-SingleChain - IU/kg Per Subject Per Year
Measured: Up to 1 year
Consumption of rVIII-SingleChain - IU/kg Per Bleeding Event
Measured: Up to 1 year
Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Month
Measured: Up to 1 year
Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Year
Measured: Up to 1 year
Incremental Recovery
Incremental recovery expressed as (IU/dL)/(IU/kg) corrected for subject's predose plasma FVIII activity measured using the chromogenic substrate assay.
Measured: At 1 hour after the start of infusion
Half-life (t1/2) of rVIII-SingleChain
Half-life (t1/2) of rVIII-SingleChain, baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.
Measured: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
Area Under the Concentration Curve (AUC)
AUC to the last sample with quantifiable drug concentration (AUC0-t), baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.
Measured: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
Clearance (Cl) of rVIII-SingleChain
Clearance (Cl) of rVIII-SingleChain, baseline uncorrected; plasma FVIII activity measured using the chromogenic substrate assay.
Measured: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
Number of Subjects With Inhibitor Formation to rVIII-SingleChain
The number of subjects who develop inhibitors to rVIII-SingleChain, defined as a rVIII-SingleChain antibody titer of at least 0.6 Bethesda Units (BU) per mL after receiving study drug.
Measured: At screening, then after dosing at approximately monthly intervals for 6 months, then every 3 months until reaching 50 EDs, and at the end of study visit (up to approximately 12 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2014 (estimated)
- Study startMar 2014
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Congenital Hemophilia AStudies of the same condition, open and under way.
- More trials run by CSL BehringThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Program Director, Study director, CSL Behring
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02093897
- Sponsor's protocol ID
- CSL627_3002
- Other IDs
- 2012-001336-65
- Status last verified
- Dec 2016
- First submitted
- 19 Mar 2014
- Last updated
- 27 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Open-label Pharmacokinetic, Efficacy and Safety Study of rVIII-SingleChain in a Pediatric Population With Severe Hemophilia A
- ClinicalTrials.gov ID
- NCT02093897
- Acronym / sponsor ID
- CSL627_3002
- Conditions
- Congenital Hemophilia A
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Study start
- Mar 2014
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 21 Mar 2014 (estimated)
- Results
- Posted 27 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an international, multicenter, open-label study to assess the efficacy, safety, and pharmacokinetic (PK) profile of rVIII-SingleChain in pediatric patients with severe hemophilia A. A minimum of 25 previously treated subjects ≥ 6 to < 12 years of age and at least 25 subjects < 6 years of age who have undergone > 50 exposure days (EDs) with a previous Factor VIII (FVIII) product are planned to be enrolled. Subjects will be assigned to either an on-demand or prophylaxis treatment regimen and will receive rVIII-SingleChain at a dose to be determined by the investigator. Hemostatic efficacy will be assessed by the subject/caregiver and the investigator who will assess overall efficacy by a 4-point scale.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| rVIII-SingleChain | Experimental | Biological: rVIII-SingleChainSubjects will be assigned to either an on-demand or prophylaxis regimen and will receive rVIII-SingleChain as an intravenous (IV) infusion. Subjects assigned to a prophylaxis regimen will be treated with 15 to 50 IU/kg of rVIII-SingleChain every second day or 2 to 3 times per week, or at the investigator's discretion, based on available PK data, the FVIII treatment regimen used before enrollment and/or the subject's bleeding phenotype. The dose for on-demand treatment of a bleeding episode is based on the recommendations of the World Federation of Hemophilia (WFH), with a minimum dose of 15 IU/kg. All subjects were to be treated for a minimum of 50 EDs. For the PK evaluation, the subjects will receive a single IV dose of 50 IU/kg of rVIII-SingleChain on Day 1 at the start of the PK evaluation period. |
Who may qualify
- Ages
- Up to 11 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Diagnosis of severe hemophilia A defined as < 1% Factor VIII (FVIII) concentration (FVIII:C) documented in medical records,
- Males < 12 years of age,
- Subjects who have received > 50 EDs with a FVIII product,
- Prior PK data (at least incremental recovery and half-life) from previous FVIII exposure for subjects participating in the PK part
- Investigator believes that the subject is willing and able to adhere to all protocol requirements. Investigator believes that the subject's parent(s) or legally acceptable representative(s) is / are willing and able to adhere to all protocol requirements.
Key exclusion criteria (9 listed)
- Any history of or current FVIII inhibitors
- Use of an Investigational Medical Product (IMP) within 30 days prior to the first rVIII-SingleChain administration,
- Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of rVIII-SingleChain,
- Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein,
- Subject currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rVIII-SingleChainAlso: Recombinant Factor VIII single chain, CSL627 | Biological | rVIII-SingleChain |
Primary outcome
Treatment Success
Time frame: Up to 1 year
Rate of treatment success where treatment success of a bleeding episode is defined as a rating of "excellent" or "good" based on the investigator's overall clinical assessment of hemostatic efficacy (using a 4-point scale of excellent, good, moderate or poor/no response) on the on-demand and prophylaxis regimens combined. The rate of success was based on the number of treated bleeding events; there were 347 treated bleeding events in the Efficacy Population.
12 secondary outcomes
Annualized Bleeding Rate
Time frame: Up to 1 year
Percentage of Bleeding Episodes Requiring 1, 2, 3, or More Than 3 Infusions of rVIII-SingleChain to Achieve Hemostasis.
Time frame: Up to 1 year
Consumption of rVIII-SingleChain - IU/kg Per Subject Per Month
Time frame: Up to 1 year
Consumption of rVIII-SingleChain - IU/kg Per Subject Per Year
Time frame: Up to 1 year
Consumption of rVIII-SingleChain - IU/kg Per Bleeding Event
Time frame: Up to 1 year
Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Month
Time frame: Up to 1 year
Consumption of rVIII-SingleChain (On-demand Regimen) - Number of Infusions Per Subject Per Year
Time frame: Up to 1 year
Incremental Recovery
Time frame: At 1 hour after the start of infusion
Half-life (t1/2) of rVIII-SingleChain
Time frame: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
Area Under the Concentration Curve (AUC)
Time frame: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
Clearance (Cl) of rVIII-SingleChain
Time frame: Immediately before dosing, and at approximately 1, 5, 10, 24, and 48 hours after dosing.
Number of Subjects With Inhibitor Formation to rVIII-SingleChain
Time frame: At screening, then after dosing at approximately monthly intervals for 6 months, then every 3 months until reaching 50 EDs, and at the end of study visit (up to approximately 12 months).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Program Director study director
CSL Behring
37 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing rVIII-SingleChain in people with Congenital Hemophilia A, run by CSL Behring at 37 sites in 19 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in France, Thailand, Germany, Netherlands, Turkey (Türkiye) and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Success (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2017.