Assess the Efficacy and Safety of Personalized Prophylaxis Human-cl rhFVIII in Patients With Severe Haemophilia A

Severe Haemophilia A Clinical Trial

Official title:

Prospective, Open-label, Multi-centre Phase 3b Study to Assess the Efficacy and Safety of Personalized Prophylaxis With Human-cl rhFVIII in Previously Treated Adult Patients With Severe Haemophilia A

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02256917
• Other study ID #: GENA-21B
• Status: Completed
• Phase: Phase 3
• Start date: May 2015
• Est. completion date: September 2018

Study information

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

Clinical Trial Summary

The rationale of this study is to further fine-tune and individualize prophylactic treatment of patients with severe Haemophilia A with the goal of keeping the trough FVIII level above 1% between doses. Because trough FVIII levels are likely to be important predictors of the efficacy of prophylaxis, the focus of this study is on pharmacokinetic (PK) data.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: September 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Severe Haemophilia A (FVIII:C < 1%)
• Male patients >= 18 years of age
• Previous treatment with a FVIII concentrate for at least 150 EDs
• Good documentation regarding dosing and bleeding frequency in the 6 months preceding study start
• Immunocompetence (CD4+ count > 200/uL)

Exclusion Criteria:

• Any coagulation disorder other than Haemophilia A
• Present of past FVIII inhibitor activity
• Severe liver or kidney disease

Related Conditions & MeSH terms

• Hemophilia A
• Severe Haemophilia A

Intervention

Biological:
• Human cl rhFVIII

Locations

Country	Name	City	State
Canada	Octapharma Research Site	Edmonton	Alberta
Canada	McMaster University	Hamilton	Ontario
Canada	Octapharma Research Site	St. John's	Newfoundland and Labrador
Croatia	University Hospital Centre Zagreb	Zagreb
Finland	Helsinki University Hospital	Helsinki
France	Centre Régional de Traitement de l'Hémophilie	Bron
France	CHU Estaing	Clermont-Ferrand
France	Centre Hospitalier Universitaire Félix Guyon	La Réunion
France	Centre Régional de Traitement de l'hémophilie	Nantes
France	Hôpital Purpan - Centre de Traitment Regional de l'Hemophilie Pole	Toulouse
Japan	Nara Medical University Hospital	Kashihara	Nara
Japan	St. Marianna Univ School of Medicine Hospital	Kawasaki	Kanagawa
Japan	Hospital of the Univ of Occupational and Environmental Health	Kitakyushu	Fukuoka
Japan	Gunma University Hospital	Maebashi
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	Osaka National Hospital	Osaka
Japan	Ogikubo Hospital	Tokyo
Japan	Teikyo University Hospital	Tokyo
Netherlands	University Medical Center Groningen	Groningen
North Macedonia	PHI Institute of Transfusion Medicine of Republic of Macedonia	Skopje
Slovenia	University Medical Centre Ljubljana	Ljubljana
United States	Octapharma Research Site	Aurora	Colorado
United States	Octapharma Research Site	Chicago	Illinois
United States	Octapharma Research Site	Houston	Texas
United States	Octapharma Research Site	Indianapolis	Indiana
United States	Octapharma Research Site	Memphis	Tennessee
United States	Octapharma Research Site	Miami	Florida
United States	Octapharma Research Site	Sacramento	California
United States	Octapharma Research Site	Salt Lake City	Utah
United States	Octapharma Research Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Octapharma

Countries where clinical trial is conducted

United States,  Canada,  Croatia,  Finland,  France,  Japan,  Netherlands,  North Macedonia,  Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Total Bleeding Rate of Individually Tailored Prophylaxis	Total annualized bleeding rate (ABR) of individually tailored prophylaxis (GENA-21b) compared to historical bleeding rate in patients having received on-demand treatment (GENA-01) with Human-cl rhFVIII	6 months
Secondary	Annualized Spontaneous Bleeding Rate of Individually Tailored Prophylaxis	Spontaneous annualized bleeding rate (ABR) of individually tailored prophylaxis (GENA-21b) compared to historical bleeding rate in patients having received on-demand treatment (GENA-01) with Human-cl rhFVIII	6 months
Secondary	Annualized Total Bleeding Rate in Patients With 2x/Week (or Less) Prophylaxis	Total annualized bleeding rate (ABR) in patients with 2x/week (or less) prophylaxis (GENA-21b) compared to historical bleeding rate in patients having received on-demand treatment (GENA-01) with Human-cl rhFVIII	6 months
Secondary	Median Prophylactic Dosing Interval	Median over median actual dosing intervals between two prophylactic treatments per patient. The median time (hours) between two prophylactic doses of Human-cl rhFVIII in the prophylactic treatment Phase II per patient	6 months
Secondary	Mean Prophylactic Dosing Interval	Mean over mean actual dosing intervals between two prophylactic treatments per patient. The mean time (hours) between two prophylactic doses of Human-cl rhFVIII in the prophylactic treatment Phase II per patient	6 months
Secondary	AUC Divided by the Dose (AUCnorm) of Human-cl rhFVIII	AUCnorm of Human-cl rhFVIII measured using the one-stage (OS) assay	Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Secondary	In-vivo Recovery (IVR) of Human-cl rhFVIII	IVR of Human-cl rhFVIII measured using the one-stage (OS) assay and will be determined from the FVIII level before the infusion and the peak level after the infusion of Human-cl rhFVIII	Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Secondary	Half Life (t1/2) of Human-cl rhFVIII	T1/2 of Human-cl rhFVIII measured using the one-stage (OS) assay	Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Secondary	Mean Residence Time (MRT) of Human-cl rhFVIII	MRT of Human-cl rhFVIII measured using the one-stage (OS) assay	Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Secondary	Clearance (CL) of Human-cl rhFVIII	CL of Human-cl rhFVIII measured using the one-stage (OS) assay	Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Secondary	Volume of Distribution at Steady State (Vss) of Human-cl rhFVIII	Vss of Human-cl rhFVIII measured using the one-stage (OS) assay	Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Secondary	Usage of Human-cl rhFVIII (FVIII IU/kg BW Per Week Per Patient)	Average weekly consumption of Human-cl rhFVIII reported as IU/kg BW per week per patient was determined during individualized prophylactic treatment	6 months
Secondary	Number of Patients With Adverse Events (AEs)	AEs were documented at each (scheduled or unscheduled) study visit. Severity and seriousness of all AEs were documented by the investigator according to pre-defined criteria	At each study visit over the study duration (7-9 months)