Severe Hemophilia APhase 3NCT02954575
Clinical Study to Investigate the PK, Efficacy, and Safety of Wilate in Patients With Severe Hemophilia A
A Phase 3 study testing Wilate in people with Severe Hemophilia A, run by Octapharma at 7 sites in 5 countries.
Trial summary
The purpose of this study is to obtain additional data on the safety and efficacy of Wilate in PTPs with hemophilia A with at least 150 previous exposure days (EDs) to a FVIII concentrate who undergo prophylactic treatment with Wilate for 6 months and at least 50 EDs, thus supplementing the existing database to obtain… Read more about this study
- Who is it for?
- Ages 12 years and older, men only
- Conditions the study is for
- Severe Hemophilia A
- What is being tested?
- Wilate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 7 sitesin 5 countries
- Study dates
- Dec 2016to 29 Mar 2018
- 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 12 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Severe hemophilia A (<1% FVIII:C) according to medical history
- Male patients aged ≥12 years
- Previous treatment with a FVIII concentrate for at least 150 exposure days (EDs)
- Immunocompetence (CD4+ count >200/µL)
- Good documentation of the historical bleeding rate (at least for the 6 months preceding study start)
- Voluntarily given, fully informed written and signed consent obtained by the patient (or parent/legal guardian in case of adolescents) before any study-related procedures are conducted
- Whenever possible, the interval between the Screening Visit and the PK or Non-PK Visit should not exceed 30 days. If the 30-day interval is exceeded, determination of the CD4+ count is to be repeated and must be >200/µL for patients to be enrolled (i.e., exclusion criterion no. 4).
Who cannot join
- Any coagulation disorders other than hemophilia A
- History of FVIII inhibitor activity (≥0.6 BU) or detectable FVIII inhibitory anti-bodies (≥0.6 BU using the Nijmegen modification of the Bethesda assay) at screening, as determined by the central laboratory
- Severe liver or kidney diseases (alanine aminotransferase [ALAT] and aspartate transaminase [ASAT] levels >5 times of upper limit of normal, creatinine>120 µmol/L)
- Patients receiving or scheduled to receive immunomodulating drugs (other than anti-retroviral chemotherapy) such as alpha-interferon, prednisone (equivalent to >10 mg/day), or similar drugs
- Treatment with any investigational medicinal product in another interventional clinical study currently or within 4 weeks before enrollment
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
Poland2 sites
Krakowskie Centrum Medyczne
Krakow
Korczowski Bartosz Gabinet Lekarski
Rzeszów
Russia2 sites
Barnaul Branch of RAMS hematology center
Barnaul
Federal Scientific Hematology Center
Moscow
About this study
Official title: Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Patients With Severe Hemophilia A
The purpose of this study is to obtain additional data on the safety and efficacy of Wilate in PTPs with hemophilia A with at least 150 previous exposure days (EDs) to a FVIII concentrate who undergo prophylactic treatment with Wilate for 6 months and at least 50 EDs, thus supplementing the existing database to obtain approval of Wilate for the indication hemophilia A in the USA.
- Conditions
- Severe Hemophilia A
- Being tested
- Wilate
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WilateDrug
Also called von Willebrand factor / Factor VIII (plasma derived)
| Study group | Role | What they receive |
|---|---|---|
| All patients | Experimental | All patients will receive Wilate for prophylactic treatment Receives: Drug: Wilate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Annualized Bleeding Rate (TABR)
The total number of bleeding events (BEs) was documented by patients in a patient diary (together with the investigator in case of on-site treatments), which was reviewed at each follow-up visit by site personnel.
Measured: 6 months
Secondary outcomes (12)
Spontaneous Annualized Bleeding Rate (SABR)
The number of spontaneous bleeding events (BEs) was documented by patients in a patient diary (together with the investigator in case of on-site treatments), which was reviewed at each follow-up visit by site personnel.
Measured: 6 months
Efficacy of Wilate in the Treatment of Breakthrough BEs
The proportion of BEs successfully treated with Wilate were documented by the patient (together with the investigator in case of on-site treatments) in the patient diary for all BEs according to a 4-point hemostatic efficacy scale including the four items: 'excellent,' 'good,' moderate,' and 'none', where 'excellent' was defined as "Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single injection" (best outcome) and 'none' was defined as "No improvement within 12 hours, or worsening of symptoms, requiring more than two injections for complete resolution" (worst outcome). All efficacy ratings assessed as either 'excellent' or 'good' were considered 'successfully treated.'
Measured: 6 months
Wilate Consumption Data (Average Total Normdose of FVIII IU/kg Per Month of Study) for Prophylaxis
The average consumption of Wilate per month of study (IU/kg) for all patients receiving prophylaxis.
Measured: 6 months
Pharmacokinetic (PK) Assessment (Area Under the Curve [AUC] Norm) of FVIII:C
PK assessments of FVIII:C were conducted using the one-stage (OS) assay. The value of the AUCnorm of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study.
Measured: Initial PK visit (Day -1) and PK study completion visit (6 months); data collected 1 h prior to injection and 15 min, 1 h, 3 h, 6 h, 9 h, 24 h, 30 h and 48 h after the end of injection
Pharmacokinetic (PK) Assessment (in Vivo Half-Life (t1/2)) of FVIII:C
PK assessments of FVIII:C were conducted using the one-stage (OS) assay. The in vivo half-life of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study.
Measured: Initial PK assessment (Day -1) and PK study completion visit (6 months); data collected 1 h prior to infusion and 15 min, 1 h, 3 h, 6 h, 9 h, 24 h, 30 h and 48 h after the end of injection
Pharmacokinetic (PK) Assessment (Maximum Plasma Concentration [Cmax]) of FVIII:C
PK assessments of FVIII:C were conducted using the one-stage (OS) assay. The maximum plasma concentration of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study.
Measured: Initial PK assessment (Day -1) and 6 months
Incremental in Vivo Recovery (IVR) of Wilate Over Time
The rise in FVIII activity in IU/dl per unit dose administered in IU/kg was determined from all patients at baseline, 3 and 6 months, using the OS assay.
Measured: Baseline, 3 and 6 months
Association Between ABO Blood Type and the FVIII:C Half-life of Wilate (OS Assay)
Analysis of variance (ANOVA) was used in an exploratory sense to assess an association between ABO blood type and the FVIII:C half-life of Wilate. This was analyzed by calculating the mean square in a one-stage assay.
Measured: 6 months
Association Between VWF:Ag Concentration and the FVIII:C Half-life of Wilate
ANOVA was used in an exploratory sense to assess an association between VWF:Ag with the FVIII:C half-life of Wilate. This was analyzed by calculating the mean square in a one-stage assay.
Measured: 6 months
Safety and Tolerability of Wilate by Monitoring Adverse Events (AEs) Throughout the Study
At each (scheduled or unscheduled) study visit, AEs were documented by the investigator throughout the study.
Measured: 6 months
Immunogenicity of Wilate by Testing for FVIII Inhibitors
FVIII inhibitor activity was determined at each study visit before the injection of Wilate using the modified Bethesda assay (Nijmegen modification).
Measured: 6 months
Virus Safety Measured by the Number of Parvovirus B19 Seroconversions Between Baseline (BL) and End of Study
Virus safety was evaluated by taking a plasma sample for parvovirus B19 antibody testing before the first injection of Wilate. All patients negative at screening were tested again at the study completion visit. The number with Parvovirus B19 seroconversions between BL and end of study was recorded.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2016 (estimated)
- Study startDec 2016
- Primary completion29 Mar 2018
- Study completion29 Mar 2018
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 Severe Hemophilia AStudies of the same condition, open and under way.
- More trials run by OctapharmaThe 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
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Octapharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Cristina Solomon, MD, Study director, Octapharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02954575
- Sponsor's protocol ID
- WIL-27
- Status last verified
- Dec 2020
- First submitted
- 27 Oct 2016
- Last updated
- 19 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Patients With Severe Hemophilia A
- ClinicalTrials.gov ID
- NCT02954575
- Acronym / sponsor ID
- WIL-27
- Conditions
- Severe Hemophilia A
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- OctapharmaIndustry (pharma, biotech, devices)
- Study start
- Dec 2016 (actual)
- Primary completion
- 29 Mar 2018 (actual)
- Study completion
- 29 Mar 2018 (actual)
- First posted
- 3 Nov 2016 (estimated)
- Results
- Posted 3 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to obtain additional data on the safety and efficacy of Wilate in PTPs with hemophilia A with at least 150 previous exposure days (EDs) to a FVIII concentrate who undergo prophylactic treatment with Wilate for 6 months and at least 50 EDs, thus supplementing the existing database to obtain approval of Wilate for the indication hemophilia A in the USA.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All patients | Experimental | Drug: WilateAll patients will receive Wilate for prophylactic treatment |
Who may qualify
- Ages
- 12 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Severe hemophilia A (<1% FVIII:C) according to medical history
- Male patients aged ≥12 years
- Previous treatment with a FVIII concentrate for at least 150 exposure days (EDs)
- Immunocompetence (CD4+ count >200/µL)
- Good documentation of the historical bleeding rate (at least for the 6 months preceding study start)
Key exclusion criteria (5 listed)
- Any coagulation disorders other than hemophilia A
- History of FVIII inhibitor activity (≥0.6 BU) or detectable FVIII inhibitory anti-bodies (≥0.6 BU using the Nijmegen modification of the Bethesda assay) at screening, as determined by the central laboratory
- Severe liver or kidney diseases (alanine aminotransferase [ALAT] and aspartate transaminase [ASAT] levels >5 times of upper limit of normal, creatinine>120 µmol/L)
- Patients receiving or scheduled to receive immunomodulating drugs (other than anti-retroviral chemotherapy) such as alpha-interferon, prednisone (equivalent to >10 mg/day), or similar drugs
- Treatment with any investigational medicinal product in another interventional clinical study currently or within 4 weeks before enrollment
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 |
|---|---|---|
| WilateAlso: von Willebrand factor / Factor VIII (plasma derived) | Drug | All patients |
Primary outcome
Total Annualized Bleeding Rate (TABR)
Time frame: 6 months
The total number of bleeding events (BEs) was documented by patients in a patient diary (together with the investigator in case of on-site treatments), which was reviewed at each follow-up visit by site personnel.
12 secondary outcomes
Spontaneous Annualized Bleeding Rate (SABR)
Time frame: 6 months
Efficacy of Wilate in the Treatment of Breakthrough BEs
Time frame: 6 months
Wilate Consumption Data (Average Total Normdose of FVIII IU/kg Per Month of Study) for Prophylaxis
Time frame: 6 months
Pharmacokinetic (PK) Assessment (Area Under the Curve [AUC] Norm) of FVIII:C
Time frame: Initial PK visit (Day -1) and PK study completion visit (6 months); data collected 1 h prior to injection and 15 min, 1 h, 3 h, 6 h, 9 h, 24 h, 30 h and 48 h after the end of injection
Pharmacokinetic (PK) Assessment (in Vivo Half-Life (t1/2)) of FVIII:C
Time frame: Initial PK assessment (Day -1) and PK study completion visit (6 months); data collected 1 h prior to infusion and 15 min, 1 h, 3 h, 6 h, 9 h, 24 h, 30 h and 48 h after the end of injection
Pharmacokinetic (PK) Assessment (Maximum Plasma Concentration [Cmax]) of FVIII:C
Time frame: Initial PK assessment (Day -1) and 6 months
Incremental in Vivo Recovery (IVR) of Wilate Over Time
Time frame: Baseline, 3 and 6 months
Association Between ABO Blood Type and the FVIII:C Half-life of Wilate (OS Assay)
Time frame: 6 months
Association Between VWF:Ag Concentration and the FVIII:C Half-life of Wilate
Time frame: 6 months
Safety and Tolerability of Wilate by Monitoring Adverse Events (AEs) Throughout the Study
Time frame: 6 months
Immunogenicity of Wilate by Testing for FVIII Inhibitors
Time frame: 6 months
Virus Safety Measured by the Number of Parvovirus B19 Seroconversions Between Baseline (BL) and End of Study
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Cristina Solomon, MD study director
Octapharma
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Wilate in people with Severe Hemophilia A, run by Octapharma at 7 sites in 5 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 7 inclusion and 5 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 19 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Poland, Russia, Bulgaria, Hungary, Romania. 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 3 Dec 2019). 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?
Total Annualized Bleeding Rate (TABR) (time frame: 6 months). 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 19 Jan 2021.