Trial Outcomes & Findings for Post Marketing Surveillance To Observe Safety and Efficacy Of BeneFIX In Patients With Hemophilia B (NCT NCT00484185)

NCT ID: NCT00484185

Last Updated: 2013-08-12

Results Overview

AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. AE assessed by baseline characteristics (chr) included age, gender, pediatric/geriatric status, liver disorder, BeneFIX treatment (previously/newly), factor nine (FIX) gene mutation, prior exposure to plasma-derived FIX products, prior FIX regimen(s) utilized, personal history of FIX inhibitor, family history of hemophilia B, severity of bleeding, medical history, concomitant medication and therapy.

• Recruitment status: COMPLETED
• Target enrollment: 183 participants
• Primary outcome timeframe: Baseline up to 6 months
• Results posted on: 2013-08-12

Participant Flow

Participant milestones

Measure	BeneFIX Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Overall Study STARTED	183
Overall Study Treated	178
Overall Study COMPLETED	112
Overall Study NOT COMPLETED	71

Reasons for withdrawal

Measure	BeneFIX Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Overall Study Lost to Follow-up	44
Overall Study Other	20
Overall Study Randomized but not treated	5
Overall Study Death	2

Baseline Characteristics

Post Marketing Surveillance To Observe Safety and Efficacy Of BeneFIX In Patients With Hemophilia B

Baseline characteristics by cohort

Measure	BeneFIX n=178 Participants Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Age Continuous	25.1 years STANDARD_DEVIATION 16.1 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	177 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 6 months

Population: Safety analysis set included all participants who received at least 1 dose of study medication including dropouts due to AEs.

AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. AE assessed by baseline characteristics (chr) included age, gender, pediatric/geriatric status, liver disorder, BeneFIX treatment (previously/newly), factor nine (FIX) gene mutation, prior exposure to plasma-derived FIX products, prior FIX regimen(s) utilized, personal history of FIX inhibitor, family history of hemophilia B, severity of bleeding, medical history, concomitant medication and therapy.

Outcome measures

Measure	BeneFIX n=178 Participants Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Age: Less than (<) 10 years	0 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Age: 10 to 19 years	1 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Age: 20 to 29 years	2 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Age: 30 to 39 years	3 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Age: 40 to 49 years	1 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Age: Greater than or equal (>=) to 50 years	2 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Gender: Male	9 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Gender: Female	0 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Pediatric status: < 12 years	0 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Pediatric status: >= 12 years	9 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Geriatric status: < 65 years	8 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Geriatric status: >= 65 years	1 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Liver disorder: Yes	2 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Liver disorder: No	7 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics BeneFIX treatment: New	0 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics BeneFIX treatment: Previous	9 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Factor IX gene mutation: Yes	0 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Factor IX gene mutation: No	1 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Factor IX gene mutation: Unknown	8 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Exposed to plasma-derived FIX products: Yes	5 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Exposed to plasma-derived FIX products: No	1 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Exposed to plasma-derived FIX products: Unknown	3 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Prior FIX regimen: Yes	8 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Prior FIX regimen: No	1 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Personal history of FIX inhibitor: Yes	1 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Personal history of FIX inhibitor: No	8 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Family history of hemophilia B: Brother	1 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Family history of hemophilia B: Other	1 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Family history of hemophilia B: None	6 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Family history of hemophilia B: Unknown	1 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Severity: Mild	0 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Severity: Moderate	4 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Severity: Severe	4 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Severity: Unknown	1 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Medical history: Yes	6 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Medical history: No	3 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Concomitant medication: Yes	5 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Concomitant medication: No	4 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Concomitant therapy: Yes	2 participants
Number of Participants With Adverse Events (AEs) According to Baseline Characteristics Concomitant therapy: No	7 participants

PRIMARY outcome

Timeframe: Baseline up to 6 months

Population: Safety analysis set included all participants who received at least 1 dose of study medication including dropouts due to AEs. Same participant may be represented in more than 1 category.

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity; mild (not causing any significant problem, dose adjustment not required), moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event) and severe (caused problem that interferes significantly with usual activities or the clinical status, study drug stopped due to adverse event).

Outcome measures

Measure	BeneFIX n=178 Participants Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Number of Participants With Adverse Events (AEs) According to Severity Mild	6 participants
Number of Participants With Adverse Events (AEs) According to Severity Moderate	2 participants
Number of Participants With Adverse Events (AEs) According to Severity Severe	4 participants

PRIMARY outcome

Timeframe: Baseline up to 6 months

Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis.

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. After an onset of an AE, relevant actions were undertaken on the study drug or the participant. Actions related to study drug included: dosage reduced, dosage increased, stopped temporarily or permanently, no action taken; actions related to participants included: withdrawal from the study, concomitant medication, no action taken or any other as per physician's discretion.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline up to 6 months

Population: Safety analysis set included all participants who received at least 1 dose of study medication including dropouts due to AEs.

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Seriousness of an AE was assessed under the criteria of serious adverse event (SAE). An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Outcome measures

Measure	BeneFIX n=178 Participants Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Number of Participants With Adverse Events (AEs) According to Seriousness SAEs	4 participants
Number of Participants With Adverse Events (AEs) According to Seriousness Non-SAEs	5 participants

PRIMARY outcome

Timeframe: Baseline up to 6 months

Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis.

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Outcome of an AE was assessed based on response to a question 'Is the adverse event still present?' as 'yes', 'unknown' or 'no-resolved'.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline up to 6 months

Population: Safety analysis set included all participants who received at least 1 dose of study medication including dropouts due to AEs.

AE: untoward medical occurrence in participant who received study drug without regard to causal relationship. All causalities and drug-related AEs reported. Drug-related AEs based on physician's discretion: certain (AE after drug intake, not explained by other drugs, reaction on drug cessation [DC], relapse on re-intake of drug), probable/likely (AE after drug intake, not explained by other drugs, reaction on DC, no information on re-intake), possible (AE after drug intake, explained by other drugs, no information on DC), unlikely (not related to drug intake time, explained by other drugs).

Outcome measures

Measure	BeneFIX n=178 Participants Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Number of Participants With Adverse Events (AEs) by Relationship AEs (all-causalities)	9 participants
Number of Participants With Adverse Events (AEs) by Relationship AEs (drug-related)	1 participants

PRIMARY outcome

Timeframe: Baseline up to 6 months

Population: Safety analysis set included all participants who received at least 1 dose of study medication including dropouts due to AEs.

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Unexpected AEs were those that were not included in precaution of local product document.

Outcome measures

Measure	BeneFIX n=178 Participants Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Number of Participants With Unexpected Adverse Events (AEs)	0 participants

SECONDARY outcome

Timeframe: Baseline up to 6 months

Population: Efficacy analysis set included all participants who received at least 1 dose of study medication for the approved indications and were evaluated upon its related parameters at least once. Here 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

An annualized bleeding rate (ABR) was calculated as the number of bleeds requiring administration of BeneFIX (for on-demand therapy and surgery), divided by total period of bleeding multiplied by 365.25. Total period of bleeding is the number of days on treatment for prophylaxis purpose and on-demand therapy and surgery.

Outcome measures

Measure	BeneFIX n=135 Participants Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Mean Annualized Bleeding Rate (ABR)	84.25 bleeds per year Standard Deviation 125.35

SECONDARY outcome

Timeframe: Baseline up to 6 months

Population: Efficacy analysis set included all participants who received at least 1 dose of study medication for the approved indications and were evaluated upon its related parameters at least once. Here 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

Responses to on-demand treatment were rated by participant/caregiver or physician each time the drug was administered, on 4-point scale. Score 1=excellent (definite pain relief [PR] and improvement [imp] within 8 hours [h] of infusion [inf], no additional inf); score 2=good (definite PR and imp within 8h of inf, at least 1 additional inf for complete resolution [CR] of bleeding or starting after 8h of inf, no additional inf); score 3=moderate (probable or slight imp starting after 8h of inf, at least 1 additional inf for CR of bleeding); score 4=no imp at all, or condition worsens).

Outcome measures

Measure	BeneFIX n=135 Participants Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Number of Responses to On-demand Treatment With Study Medication Excellent	1145 responses
Number of Responses to On-demand Treatment With Study Medication Good	788 responses
Number of Responses to On-demand Treatment With Study Medication Moderate	65 responses
Number of Responses to On-demand Treatment With Study Medication No response	0 responses

SECONDARY outcome

Timeframe: Baseline up to 6 months

Population: Efficacy analysis set included all participants who received at least 1 dose of study medication for the approved indications and were evaluated upon its related parameters at least once. Here 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

Mean frequency of BeneFIX administration of each participant was calculated from number of BeneFIX infusions which each participant received for treatment of each new bleed. Mean frequency of BeneFIX administration for total participants was summarized.

Outcome measures

Measure	BeneFIX n=135 Participants Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Mean Number of Infusion of Study Medication	2.25 infusions Standard Deviation 4.33

SECONDARY outcome

Timeframe: Baseline up to 6 months

Population: Efficacy analysis set included all participants who received at least 1 dose of study medication for the approved indications and were evaluated upon its related parameters at least once. Here 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

Mean frequency of breakthrough (spontaneous/non-traumatic) bleeds of each participant within 48 hours of a preventive/prophylaxis dose of BeneFIX was calculated from number of irregular bleeding which occurred in each participant. Mean frequency breakthrough bleeds for total participants within 48 hours of a preventive/prophylaxis dose of BeneFIX was summarized.

Outcome measures

Measure	BeneFIX n=123 Participants Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Mean Number of Breakthrough Bleeds Within 48 Hours of Study Medication	0.27 breakthrough bleeds Standard Deviation 0.47

SECONDARY outcome

Timeframe: Baseline up to 6 months

Population: Efficacy analysis set included all participants who received at least 1 dose of study medication for the approved indications and were evaluated upon its related parameters at least once. Here 'N' (number of participants analyzed)= participants evaluable for this measure and 'n' = participants evaluable for the specified category.

Average of dose per infusion per kilogram (kg) body weight was reported for prophylaxis purpose or on-demand therapy and surgery.

Outcome measures

Measure	BeneFIX n=135 Participants Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Average Infusion Dose of Study Medication On-demand therapy and surgery: n= 135	38.79 international unit/kilogram (IU/kg) Standard Deviation 5.41
Average Infusion Dose of Study Medication Prophylaxis purpose: n= 123	32.92 international unit/kilogram (IU/kg) Standard Deviation 10.43

SECONDARY outcome

Timeframe: Baseline up to 6 months

Population: Efficacy analysis set included all participants who received at least 1 dose of study medication for the approved indications and were evaluated upon its related parameters at least once.

Total dose of study drug infused was calculated over the study duration.

Outcome measures

Measure	BeneFIX n=178 Participants Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Total Infusion of Study Medication	50356.11 IU Standard Deviation 42154.05

SECONDARY outcome

Timeframe: Baseline up to 6 months

Population: Efficacy analysis set included all participants who received at least 1 dose of study medication for the approved indications and were evaluated upon its related parameters at least once. Here 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.

The efficacy of study drug was rated as 'very effective', 'effective', 'slightly ineffective' and 'ineffective'.

Outcome measures

Measure	BeneFIX n=11 Participants Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Percentage of Participants With Efficacy Evaluation Very effective	81.82 percentage of participants
Percentage of Participants With Efficacy Evaluation Effective	18.18 percentage of participants
Percentage of Participants With Efficacy Evaluation Slightly ineffective	0.00 percentage of participants
Percentage of Participants With Efficacy Evaluation Ineffective	0.00 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 6 months

Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis.

Total time from onset of adverse event till the event is resolved. Duration of AE per event = AE stop date minus AE start date plus 1.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 6 months

Population: Safety analysis set included all participants who received at least 1 dose of study medication including dropouts due to AEs.

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Number of participants who discontinued the study due to AEs was reported.

Outcome measures

Measure	BeneFIX n=178 Participants Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Number of Participants Who Discontinued the Study Due to Adverse Events (AEs)	0 participants

Adverse Events

BeneFIX

Serious events: 4 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	BeneFIX n=178 participants at risk Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
General disorders Drug ineffective	0.56% 1/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Haemophilic arthropathy	0.56% 1/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal neoplasm	0.56% 1/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral haemorrhage	1.1% 2/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Measure	BeneFIX n=178 participants at risk Participants who received original or reformulated BeneFIX (recombinant coagulation factor IX) infusion intravenously as indicated according to the approved local product document, dosage solely adjusted as per physician's discretion, were observed for a period of 6 months.
Gastrointestinal disorders Stomatitis	0.56% 1/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Cellulitis	0.56% 1/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	0.56% 1/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Alanine aminotransferase increased	0.56% 1/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Aspartate aminotransferase increased	0.56% 1/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	0.56% 1/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	0.56% 1/178 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

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