Trial Outcomes & Findings for Study To Compare On-Demand Treatment To A Prophylaxis Regimen Of BeneFIX In Subjects With Moderately Severe to Severe Hemophilia B (NCT NCT01335061)

Last Updated: 2015-06-08

Results Overview

The annualized bleed rate (ABR) or the annualized number of bleeding episodes per year, will be derived for each participant for each treatment period by using the following formula: ABR = number of bleeds / (Days on treatment period / 365.25) The number of bleeds for the ABR calculation includes all bleeds requiring treatment with factor IX product during the time on treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

25 participants

Primary outcome timeframe

2 years

Results posted on

2015-06-08

Participant Flow

Participation included 25 enrolled participants from 15 study centers and 9 countries.

The duration of participation was approximately 86 weeks, consisting of a Screening period (1 day to 4 weeks), Period 1 (on-demand treatment for 26 weeks), Period 2 (prophylaxis therapy for 52 weeks), and a follow-up safety period (4 weeks).

Participant milestones

Participant milestones
Measure	All Participants The data for all the participants is presented.
Overall Study STARTED	25
Overall Study COMPLETED	25
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study To Compare On-Demand Treatment To A Prophylaxis Regimen Of BeneFIX In Subjects With Moderately Severe to Severe Hemophilia B

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=25 Participants The data for all the participants is presented.
Age, Continuous	31.3 Years STANDARD_DEVIATION 12.6 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

Population: The efficacy analysis set (EAS) was used for the primary efficacy analyses with respect to ABR. It includes all participants who participated in at least one day of the routine prophylaxis period (ie, in the study through at least Visit 4).

Outcome measures

Outcome measures
Measure	On-Demand Therapy n=25 Participants Participants were treated for the bleeding events at the discretion of the study physician according to BeneFIX label.	Prophylaxis Therapy n=25 Participants The prophylaxis regimen of approximately 100 IU/kg once weekly was initiated at Visit 4.
Annualized Number of Bleeding Episodes.	32.9 Number of bleeds per year Standard Deviation 17.4	3.6 Number of bleeds per year Standard Deviation 4.6

SECONDARY outcome

Timeframe: 2 years

Population: The safety analysis set (SAS) was any participant who received at least one dose of BeneFIX, including the dose given during the enrollment visit (Visit 2) for the factor IX (FIX) recovery study. Follow-up infusion was only required for 18 participants.

Assessment scores on a 4-point Response Scale for an on-demand bleeding episode, as assessed by participant/caregiver or investigator/qualified staff. The 4-point scale assessments are Excellent, Good, Moderate or No response. Responses to number of observations were noted.

Outcome measures

Outcome measures
Measure	On-Demand Therapy n=507 bleeds Participants were treated for the bleeding events at the discretion of the study physician according to BeneFIX label.	Prophylaxis Therapy n=152 bleeds The prophylaxis regimen of approximately 100 IU/kg once weekly was initiated at Visit 4.
Response to On-Demand Treatment for All Bleeding Episodes. Excellent	271 Number of observations with response	39 Number of observations with response
Response to On-Demand Treatment for All Bleeding Episodes. Good	177 Number of observations with response	80 Number of observations with response
Response to On-Demand Treatment for All Bleeding Episodes. Moderate	55 Number of observations with response	33 Number of observations with response
Response to On-Demand Treatment for All Bleeding Episodes. No response	3 Number of observations with response	0 Number of observations with response
Response to On-Demand Treatment for All Bleeding Episodes. Data not recorded	1 Number of observations with response	0 Number of observations with response

SECONDARY outcome

Timeframe: 2 years

The number of study drug infusions administered to treat a bleed will be calculated by adding the initial (on-demand) infusion to any subsequent (on-demand) infusions for the same bleed (same bleed start date/time). The number of infusions needed to treat a bleed will be classified into the following categories: 1, 2, 3, 4 and \>4 infusions. If there were more than one bleed location (e.g., ankle and joint) with identical bleed start date and time, it was treated as one bleed occurrence.

Outcome measures

Outcome measures
Measure	On-Demand Therapy n=507 bleeds Participants were treated for the bleeding events at the discretion of the study physician according to BeneFIX label.	Prophylaxis Therapy The prophylaxis regimen of approximately 100 IU/kg once weekly was initiated at Visit 4.
Number of Nonacog Alfa, Recombinant Factor IX (BeneFIX) Infusions Used to Treat Each Bleeding Episode. Number of Infusion: 1	416 Number of bleeds requiring infusion	—
Number of Nonacog Alfa, Recombinant Factor IX (BeneFIX) Infusions Used to Treat Each Bleeding Episode. Number of Infusions: 2	69 Number of bleeds requiring infusion	—
Number of Nonacog Alfa, Recombinant Factor IX (BeneFIX) Infusions Used to Treat Each Bleeding Episode. Number of Infusions: 3	9 Number of bleeds requiring infusion	—
Number of Nonacog Alfa, Recombinant Factor IX (BeneFIX) Infusions Used to Treat Each Bleeding Episode. Number of Infusions: 4	3 Number of bleeds requiring infusion	—
Number of Nonacog Alfa, Recombinant Factor IX (BeneFIX) Infusions Used to Treat Each Bleeding Episode. Number of Infusions: >4	10 Number of bleeds requiring infusion	—

SECONDARY outcome

Timeframe: 2 years

Population: The safety analysis set (SAS) was any participant who received at least one dose of BeneFIX, including the dose given during the enrollment visit (Visit 2) for the factor IX (FIX) recovery study. Three participants experienced 1 spontaneous bleeding episode each within 48 hours of a previous prophylaxis infusion.

The number of spontaneous, non-traumatic breakthrough bleeds within 48 hours following a prophylaxis dose of BeneFIX were summarized. If there was more than one bleed location (eg, ankle and joint) with identical bleed start date and time, it was treated as one bleed occurrence.

Outcome measures

Outcome measures
Measure	On-Demand Therapy n=3 breakthrough bleeds Participants were treated for the bleeding events at the discretion of the study physician according to BeneFIX label.	Prophylaxis Therapy The prophylaxis regimen of approximately 100 IU/kg once weekly was initiated at Visit 4.
Number of Breakthrough (Spontaneous/Non-Traumatic) Bleeds Within 48 Hours of a Prophylaxis Dose of BeneFIX.	1.0 Number of breakthrough bleeds Standard Deviation 0.0	—

SECONDARY outcome

Timeframe: 2 years

The mean dose by per infusion by weight (IU/kg) was reported for both prophylaxis and on demand infusions

Outcome measures

Outcome measures
Measure	On-Demand Therapy n=25 Participants Participants were treated for the bleeding events at the discretion of the study physician according to BeneFIX label.	Prophylaxis Therapy n=25 Participants The prophylaxis regimen of approximately 100 IU/kg once weekly was initiated at Visit 4.
Average Infusion Dose.	52 IU/Kg Standard Deviation 16 • Interval 20.0 to 54.0	99 IU/Kg Standard Deviation 2 • Interval 93.0 to 104.0

SECONDARY outcome

Timeframe: 2 years

The total amount (IU) infused for each infusion recorded were summed to calculate the total factor consumption for each participant. For each infusion, IU/kg was calculated, using the most recently recorded weight measurement and the total factor consumption, divided by number of infusions, and was summarized similarly to average infusion dose (IU). Annualized TFC by weight was reported. Annualized TFC by weight = (Total IU/kg / treatment interval duration)\*365.25.

Outcome measures

Outcome measures
Measure	On-Demand Therapy n=25 Participants Participants were treated for the bleeding events at the discretion of the study physician according to BeneFIX label.	Prophylaxis Therapy n=25 Participants The prophylaxis regimen of approximately 100 IU/kg once weekly was initiated at Visit 4.
Total Factor Consumption.	707 IU/Kg Standard Deviation 519	4985 IU/Kg Standard Deviation 233

SECONDARY outcome

Timeframe: 2 years

The following criteria are the definitions for LETE in this study: 1. LETE in the On-Demand Setting: LETE occurs in the on-demand setting if 2 successive "No Response" ratings are recorded after 2 successive BeneFIX drug infusions in the absence of confounding factors. 2. LETE in the Prophylaxis Setting: LETE occurs in the prophylaxis setting if there is a spontaneous bleed within 48 hours (≤ 48 hours) after a regularly scheduled prophylactic dose of BeneFIX in the absence of confounding factors. 3. LETE (Low Recovery): LETE can also be lower than expected recovery of FIX in the opinion of the investigator following infusion of BeneFIX in the absence of confounding factors. Each reported occurrence of low recovery LETE was listed.

Outcome measures

Outcome measures
Measure	On-Demand Therapy n=25 Participants Participants were treated for the bleeding events at the discretion of the study physician according to BeneFIX label.	Prophylaxis Therapy The prophylaxis regimen of approximately 100 IU/kg once weekly was initiated at Visit 4.
Incidence of Less Than Expected Therapeutic Effect (LETE) LETE in On-Demand setting	0 Percentage of occurence	—
Incidence of Less Than Expected Therapeutic Effect (LETE) LETE in prophylaxis setting	0 Percentage of occurence	—
Incidence of Less Than Expected Therapeutic Effect (LETE) LETE (Low recovery)	0 Percentage of occurence	—

Adverse Events

On-Demand Therapy

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Prophylaxis Therapy

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	On-Demand Therapy n=25 participants at risk Participants were treated for the bleeding events at the discretion of the study physician according to BeneFIX label.	Prophylaxis Therapy n=25 participants at risk The prophylaxis regimen of approximately 100IU/kg once weekly was initiated at Visit 4.
General disorders Pain	0.00% 0/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	4.0% 1/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Infections and infestations Varicella	0.00% 0/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	4.0% 1/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Investigations Blood pressure decreased	4.0% 1/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	0.00% 0/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.00% 0/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	4.0% 1/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Renal and urinary disorders Nephrolithiasis	0.00% 0/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	4.0% 1/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	On-Demand Therapy n=25 participants at risk Participants were treated for the bleeding events at the discretion of the study physician according to BeneFIX label.	Prophylaxis Therapy n=25 participants at risk The prophylaxis regimen of approximately 100IU/kg once weekly was initiated at Visit 4.
Infections and infestations Upper respiratory tract infection	16.0% 4/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	20.0% 5/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Infections and infestations Pharyngitis	8.0% 2/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	12.0% 3/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Infections and infestations Nasopharyngitis	12.0% 3/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	4.0% 1/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Infections and infestations Influenza	8.0% 2/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	4.0% 1/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Injury, poisoning and procedural complications Inappropriate schedule of drug administration	0.00% 0/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	24.0% 6/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Injury, poisoning and procedural complications Drug dose omission	0.00% 0/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	16.0% 4/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Injury, poisoning and procedural complications Medication error	0.00% 0/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	12.0% 3/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Injury, poisoning and procedural complications Underdose	0.00% 0/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	12.0% 3/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Injury, poisoning and procedural complications Wrong dose administration	0.00% 0/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	12.0% 3/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Injury, poisoning and procedural complications Head injury	0.00% 0/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	8.0% 2/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 5/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	20.0% 5/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Musculoskeletal and connective tissue disorders Joint swelling	12.0% 3/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	8.0% 2/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Musculoskeletal and connective tissue disorders Back pain	4.0% 1/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	12.0% 3/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	8.0% 2/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Musculoskeletal and connective tissue disorders Pain in extremity	8.0% 2/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	4.0% 1/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Nervous system disorders Headache	32.0% 8/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	16.0% 4/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Gastrointestinal disorders Toothache	12.0% 3/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	20.0% 5/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Gastrointestinal disorders Gastritis	4.0% 1/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	8.0% 2/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Gastrointestinal disorders Abdominal pain upper	4.0% 1/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	8.0% 2/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
General disorders Pyrexia	16.0% 4/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	16.0% 4/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
General disorders Local swelling	4.0% 1/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	12.0% 3/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).	8.0% 2/25 • Until follow-up 82 weeks +/- 4 days. Five participants experienced six SAEs since one participant experienced the same event twice (nephrolithiasis).