Clinical Study to Investigate the PK, Efficacy, and Safety of Wilate in Patients With Severe Hemophilia A

Severe Hemophilia A Clinical Trial

Official title:

Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Patients With Severe Hemophilia A

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02954575
• Other study ID #: WIL-27
• Status: Completed
• Phase: Phase 3
• Start date: December 2016
• Est. completion date: March 29, 2018

Study information

• Verified date: December 2020
• Source: Octapharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 approval of Wilate for the indication hemophilia A in the USA.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: March 29, 2018
• Est. primary completion date: March 29, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

1. Severe hemophilia A (<1% FVIII:C) according to medical history

2. Male patients aged =12 years

3. Previous treatment with a FVIII concentrate for at least 150 exposure days (EDs)

4. Immunocompetence (CD4+ count >200/µL)

5. Good documentation of the historical bleeding rate (at least for the 6 months preceding study start)

6. 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).

Exclusion Criteria:

1. Any coagulation disorders other than hemophilia A

2. 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

3. Severe liver or kidney diseases (alanine aminotransferase [ALAT] and aspartate transaminase [ASAT] levels >5 times of upper limit of normal, creatinine>120 µmol/L)

4. 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

5. Treatment with any investigational medicinal product in another interventional clinical study currently or within 4 weeks before enrollment

Related Conditions & MeSH terms

• Hemophilia A
• Severe Hemophilia A

Intervention

Drug:
• Wilate

Locations

Country	Name	City	State
Bulgaria	Specialized Hospital for Active Treatment "Joan Pavel"	Sofia
Hungary	National Haemophilia Centre	Budapest
Poland	Krakowskie Centrum Medyczne	Krakow
Poland	Korczowski Bartosz Gabinet Lekarski	Rzeszow
Romania	Centrul Medical Unirea -Policlinica Enescu	Bucharest
Russian Federation	Barnaul Branch of RAMS hematology center	Barnaul
Russian Federation	Federal Scientific Hematology Center	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Octapharma

Countries where clinical trial is conducted

Bulgaria,  Hungary,  Poland,  Romania,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Efficacy of Wilate in Surgical Prophylaxis	Hemostatic efficacy was assessed at the end of surgery by the surgeon and at end of the postoperative period by the hematologist, using a 4-point hemostatic efficacy scale including the four items: 'excellent' (best possible outcome), 'good', 'moderate' and 'none' (worst outcome). Overall efficacy was assessed by the investigator, taking both the intra and postoperative assessments into account, and using the 'excellent,' 'good,' moderate,' and 'none' scale.	6 months
Primary	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.	6 months
Secondary	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.	6 months
Secondary	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.'	6 months
Secondary	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.	6 months
Secondary	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.	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
Secondary	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.	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
Secondary	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.	Initial PK assessment (Day -1) and 6 months
Secondary	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.	Baseline, 3 and 6 months
Secondary	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.	6 months
Secondary	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.	6 months
Secondary	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.	6 months
Secondary	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).	6 months
Secondary	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.	6 months