Trial Outcomes & Findings for Assess the Safety and Efficacy of Individually Tailored Prophylaxis With Human-cl rhFVIII in Patients With Severe Haemophilia A (NCT NCT01863758)

NCT ID: NCT01863758

Last Updated: 2018-01-30

Results Overview

The annualized number of total BEs was calculated for each participant as follows: d\*y/t, where y = the number of BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A bleeding episode (BE) was defined as any BE whether treated or not during Phase II of the study; BEs related to surgery were not included. This study was considered as showing efficacy if the annualized number of BEs was reduced by 50% compared to the number of BEs observed in study GENA-01 where patient where severe Hemophilia A patients were treated on-demand (NCT00989196).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 66 participants
• Primary outcome timeframe: Beginning to the end of Phase II (6 months)
• Results posted on: 2018-01-30

Participant Flow

Participant milestones

Measure	Human-cl rhFVIII Up to 60-80 IU/kg of intravenous human-cl rhFVIII (human cell line recombinant Factor VIII) was administered at an individually determined dose and dose interval.
Pharmacokinetic Assessment STARTED	66
Pharmacokinetic Assessment COMPLETED	66
Pharmacokinetic Assessment NOT COMPLETED	0
Prophylactic Treatment-Phase I STARTED	66
Prophylactic Treatment-Phase I COMPLETED	66
Prophylactic Treatment-Phase I NOT COMPLETED	0
Prophylactic Treatment-Phase II STARTED	66
Prophylactic Treatment-Phase II COMPLETED	64
Prophylactic Treatment-Phase II NOT COMPLETED	2

Reasons for withdrawal

Measure	Human-cl rhFVIII Up to 60-80 IU/kg of intravenous human-cl rhFVIII (human cell line recombinant Factor VIII) was administered at an individually determined dose and dose interval.
Prophylactic Treatment-Phase II investigator Error of Early Termination	1
Prophylactic Treatment-Phase II Lost to Follow-up	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Human-cl rhFVIII n=66 Participants Up to 60-80 IU/kg of intravenous human-cl rhFVIII (human cell line recombinant Factor VIII) was administered at an individually determined dose and dose interval.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	65 Participants n=93 Participants
Age, Categorical >=65 years	1 Participants n=93 Participants
Sex: Female, Male Female	0 Participants n=93 Participants
Sex: Female, Male Male	66 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants
Race (NIH/OMB) White	65 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment Austria	1 participants n=93 Participants
Region of Enrollment Romania	9 participants n=93 Participants
Region of Enrollment Hungary	4 participants n=93 Participants
Region of Enrollment Poland	9 participants n=93 Participants
Region of Enrollment United Kingdom	6 participants n=93 Participants
Region of Enrollment Slovakia	2 participants n=93 Participants
Region of Enrollment Bulgaria	31 participants n=93 Participants
Region of Enrollment Germany	4 participants n=93 Participants
Age	33.6 years STANDARD_DEVIATION 9.9 • n=93 Participants
Weight	80.5 kg STANDARD_DEVIATION 19.9 • n=93 Participants
BMI	25.4 kg/m^2 STANDARD_DEVIATION 5.4 • n=93 Participants
Hemophilia Joint Health Score (HJHS)	37.4 Units on a scale STANDARD_DEVIATION 25.3 • n=93 Participants

PRIMARY outcome

Timeframe: Beginning to the end of Phase II (6 months)

Population: Prophylactic treatment population: All participants who received at least 1 dose of Human-cl rhFVIII in Phase II and had any data collected after treatment with Human-cl rhFVIII.

The annualized number of total BEs was calculated for each participant as follows: d*y/t, where y = the number of BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A bleeding episode (BE) was defined as any BE whether treated or not during Phase II of the study; BEs related to surgery were not included. This study was considered as showing efficacy if the annualized number of BEs was reduced by 50% compared to the number of BEs observed in study GENA-01 where patient where severe Hemophilia A patients were treated on-demand (NCT00989196).

Outcome measures

Measure	Human-cl rhFVIII n=66 Participants Up to 60-80 IU/kg of intravenous human-cl rhFVIII (human cell line recombinant Factor VIII) was administered at an individually determined dose and dose interval.
Annualized Number of Bleeding Episodes (BE) in Phase II	3.05 Annualized number of bleeding episodes Standard Deviation 13.43

SECONDARY outcome

Timeframe: Beginning to the end of Phase II (6 months)

Population: Prophylactic treatment population: All participants who received at least 1 dose of Human-cl rhFVIII in Phase II and had any data collected after treatment with Human-cl rhFVIII.

The annualized number of spontaneous BEs was calculated for each participant as follows: d*y/t, where y = the number of spontaneous BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A spontaneous bleeding episode (BE) was defined as a BE whether treated or not during Phase II of the study. BEs related to surgery and BEs due to trauma or due to other causes were not included.

Outcome measures

Measure	Human-cl rhFVIII n=66 Participants Up to 60-80 IU/kg of intravenous human-cl rhFVIII (human cell line recombinant Factor VIII) was administered at an individually determined dose and dose interval.
Annualized Number of Spontaneous Bleeding Episodes (BE) in Phase II	1.84 Annualized number of bleeding episodes Standard Deviation 8.81

SECONDARY outcome

Timeframe: Beginning to the end of Phase II (6 months)

Population: Prophylactic treatment population: All participants who received at least 1 dose of Human-cl rhFVIII in Phase II and had any data collected after treatment with Human-cl rhFVIII. Only participants who received ≤ 2 treatments/week were included in the analysis.

The annualized number of BEs was calculated for each participant as follows: d*y/t, where y = the number of BEs documented in Phase II, t = the number of treatment periods in days, and d = 365.25, the number of days per year. A bleeding episode (BE) was defined as a BE whether treated or not during Phase II of the study. BEs related to surgery were not included.

Outcome measures

Measure	Human-cl rhFVIII n=38 Participants Up to 60-80 IU/kg of intravenous human-cl rhFVIII (human cell line recombinant Factor VIII) was administered at an individually determined dose and dose interval.
Annualized Number of Bleeding Episodes (BE) in Phase II in Participants With ≤ 2 Treatments/Week	4.1 Annualized number of bleeding episodes Standard Deviation 17.4

SECONDARY outcome

Timeframe: Beginning to the end of Phase II (6 months)

Population: Prophylactic treatment population: All participants who received at least 1 dose of Human-cl rhFVIII in Phase II and had any data collected after treatment with Human-cl rhFVIII.

The median time between 2 prophylactic doses of Human-cl rhFVIII in the prophylactic treatment phase II were determined per patient

Outcome measures

Measure	Human-cl rhFVIII n=66 Participants Up to 60-80 IU/kg of intravenous human-cl rhFVIII (human cell line recombinant Factor VIII) was administered at an individually determined dose and dose interval.
Median Dosing Interval During Individually Tailored Prophylaxis End of Phase II	83.3 Hours Interval 56.2 to 95.6
Median Dosing Interval During Individually Tailored Prophylaxis Beginning of Phase II	83.1 Hours Interval 56.2 to 94.4

SECONDARY outcome

Timeframe: Beginning to the end of Phase II (6 months)

Population: Prophylactic treatment population: All participants who received at least 1 dose of Human-cl rhFVIII in Phase II and had any data collected after treatment with Human-cl rhFVIII.

The mean dosage per week during Phase II of the study are reported.

Outcome measures

Measure	Human-cl rhFVIII n=66 Participants Up to 60-80 IU/kg of intravenous human-cl rhFVIII (human cell line recombinant Factor VIII) was administered at an individually determined dose and dose interval.
Dosage Per Week in Phase II	97.7 IU/kg Standard Deviation 23.1

Adverse Events

Human-cl rhFVIII

Serious events: 5 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Measure	Human-cl rhFVIII n=66 participants at risk All subject who received at least one dose of intravenous Human-cl rhFVIII (human cell line recombinant Factor VIII).
Gastrointestinal disorders Haematemesis	1.5% 1/66 • Number of events 1 Safety population: All participants who received at least 1 dose of Human-cl rhFVIII.
Injury, poisoning and procedural complications Fracture of Lower Leg	1.5% 1/66 • Number of events 1 Safety population: All participants who received at least 1 dose of Human-cl rhFVIII.
Surgical and medical procedures Tenotomy of muculus gastrocnemius medialis	1.5% 1/66 • Number of events 1 Safety population: All participants who received at least 1 dose of Human-cl rhFVIII.
Infections and infestations Appendicitis Acuta	1.5% 1/66 • Number of events 1 Safety population: All participants who received at least 1 dose of Human-cl rhFVIII.
Infections and infestations wound inflammation due to surgery	1.5% 1/66 • Number of events 1 Safety population: All participants who received at least 1 dose of Human-cl rhFVIII.
Musculoskeletal and connective tissue disorders Pain of lumbar spine	1.5% 1/66 • Number of events 1 Safety population: All participants who received at least 1 dose of Human-cl rhFVIII.

Other adverse events

Measure	Human-cl rhFVIII n=66 participants at risk All subject who received at least one dose of intravenous Human-cl rhFVIII (human cell line recombinant Factor VIII).
Infections and infestations Nasopharyngitis	7.6% 5/66 • Number of events 5 Safety population: All participants who received at least 1 dose of Human-cl rhFVIII.
Infections and infestations Tonsillitis	3.0% 2/66 • Number of events 2 Safety population: All participants who received at least 1 dose of Human-cl rhFVIII.
Musculoskeletal and connective tissue disorders Arthralgia	6.1% 4/66 • Number of events 4 Safety population: All participants who received at least 1 dose of Human-cl rhFVIII.
Musculoskeletal and connective tissue disorders Back pain	3.0% 2/66 • Number of events 2 Safety population: All participants who received at least 1 dose of Human-cl rhFVIII.
Nervous system disorders Headache	7.6% 5/66 • Number of events 5 Safety population: All participants who received at least 1 dose of Human-cl rhFVIII.
Gastrointestinal disorders Toothache	3.0% 2/66 • Number of events 2 Safety population: All participants who received at least 1 dose of Human-cl rhFVIII.
General disorders Malaise	3.0% 2/66 • Number of events 2 Safety population: All participants who received at least 1 dose of Human-cl rhFVIII.
General disorders Pyrexia	3.0% 2/66 • Number of events 2 Safety population: All participants who received at least 1 dose of Human-cl rhFVIII.

Additional Information

Sylvia Werner

Octapharma

Phone: 415 260-9577

Email: sylvia.werner@octapharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee Octapharma agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Octapharma supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial. Octapharma also reserves the right to review data prior to publishing and provide comments/changes within a certain time period.
• Publication restrictions are in place

Restriction type: OTHER