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

21 december 2020 bijgewerkt door: Octapharma

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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

57

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Bulgarije
      • Sofia, Bulgarije
        • Specialized Hospital for Active Treatment "Joan Pavel"
  • Hongarije
      • Budapest, Hongarije
        • National Haemophilia Centre
  • Polen
      • Krakow, Polen
        • Krakowskie Centrum Medyczne
      • Rzeszow, Polen
        • Korczowski Bartosz Gabinet Lekarski
  • Roemenië
      • Bucharest, Roemenië
        • Centrul Medical Unirea -Policlinica Enescu
  • Russische Federatie
      • Barnaul, Russische Federatie
        • Barnaul Branch of RAMS hematology center
      • Moscow, Russische Federatie
        • Federal Scientific Hematology Center

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

12 jaar en ouder (Kind, Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Mannelijk

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: All patients
All patients will receive Wilate for prophylactic treatment
Geneesmiddel: Wilate
Andere namen:
  • von Willebrand-factor / Factor VIII (afgeleid uit plasma)

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Total Annualized Bleeding Rate (TABR)
Tijdsspanne: 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.
6 months

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Spontaneous Annualized Bleeding Rate (SABR)
Tijdsspanne: 6 months
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
Efficacy of Wilate in the Treatment of Breakthrough BEs
Tijdsspanne: 6 months
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
Wilate Consumption Data (Average Total Normdose of FVIII IU/kg Per Month of Study) for Prophylaxis
Tijdsspanne: 6 months
The average consumption of Wilate per month of study (IU/kg) for all patients receiving prophylaxis.
6 months
Pharmacokinetic (PK) Assessment (Area Under the Curve [AUC] Norm) of FVIII:C
Tijdsspanne: 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
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
Pharmacokinetic (PK) Assessment (in Vivo Half-Life (t1/2)) of FVIII:C
Tijdsspanne: 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
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
Pharmacokinetic (PK) Assessment (Maximum Plasma Concentration [Cmax]) of FVIII:C
Tijdsspanne: Initial PK assessment (Day -1) and 6 months
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
Incremental in Vivo Recovery (IVR) of Wilate Over Time
Tijdsspanne: Baseline, 3 and 6 months
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
Association Between ABO Blood Type and the FVIII:C Half-life of Wilate (OS Assay)
Tijdsspanne: 6 months
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
Association Between VWF:Ag Concentration and the FVIII:C Half-life of Wilate
Tijdsspanne: 6 months
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
Safety and Tolerability of Wilate by Monitoring Adverse Events (AEs) Throughout the Study
Tijdsspanne: 6 months
At each (scheduled or unscheduled) study visit, AEs were documented by the investigator throughout the study.
6 months
Immunogenicity of Wilate by Testing for FVIII Inhibitors
Tijdsspanne: 6 months
FVIII inhibitor activity was determined at each study visit before the injection of Wilate using the modified Bethesda assay (Nijmegen modification).
6 months
Virus Safety Measured by the Number of Parvovirus B19 Seroconversions Between Baseline (BL) and End of Study
Tijdsspanne: 6 months
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

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Efficacy of Wilate in Surgical Prophylaxis
Tijdsspanne: 6 months
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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Octapharma

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

1 december 2016

Primaire voltooiing (Werkelijk)

29 maart 2018

Studie voltooiing (Werkelijk)

29 maart 2018

Studieregistratiedata

Eerst ingediend

27 oktober 2016

Eerst ingediend dat voldeed aan de QC-criteria

1 november 2016

Eerst geplaatst (Schatting)

3 november 2016

Updates van studierecords

Laatste update geplaatst (Werkelijk)

19 januari 2021

Laatste update ingediend die voldeed aan QC-criteria

21 december 2020

Laatst geverifieerd

1 december 2020

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • WIL-27

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

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