Trial Outcomes & Findings for A Safety and Efficacy Study of a Recombinant Factor IX in Patients With Severe Hemophilia B (NCT NCT01361126)

NCT ID: NCT01361126

Last Updated: 2016-05-09

Results Overview

The causal relationship of each adverse event to rIX-FP was assessed by the Investigator.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 17 participants
• Primary outcome timeframe: Approximately 20 weeks
• Results posted on: 2016-05-09

Participant Flow

A total of 17 subjects were screened and enrolled in the study. Fifteen subjects participated in the pharmacokinetic (PK) evaluation period and were administered a dose of 25 IU/kg rIX-FP. Two subjects did not participate in the PK evaluation period because PK data for these 2 subjects were available from the previous phase 1 study (CSL654_2001).

Participant milestones

Measure	Prophylactic For the PK evaluation, subjects received a single intravenous (IV) infusion of Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) at a dose of 25 IU/kg. After completion of the PK evaluation period, subjects entered the treatment period and were administered a single IV infusion of rIX-FP once a week at a dose of 15 to 35 IU/kg, or at a dose determined by the investigator. The dose was adjusted up to 75 IU/kg to maintain the trough FIX activity level \> 1% between infusions.	On-demand For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg. After completion of the PK evaluation period, subjects entered the treatment period and were administered 1 or more IV infusions of rIX-FP at a dose of at least 25 IU/kg to treat minor, moderate or major bleeding episodes. The dose of rIX-FP was calculated by the investigator.
Overall Study STARTED	13	4
Overall Study COMPLETED	13	2
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Measure	Prophylactic For the PK evaluation, subjects received a single intravenous (IV) infusion of Recombinant Coagulation Factor IX Albumin Fusion Protein (rIX-FP) at a dose of 25 IU/kg. After completion of the PK evaluation period, subjects entered the treatment period and were administered a single IV infusion of rIX-FP once a week at a dose of 15 to 35 IU/kg, or at a dose determined by the investigator. The dose was adjusted up to 75 IU/kg to maintain the trough FIX activity level \> 1% between infusions.	On-demand For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg. After completion of the PK evaluation period, subjects entered the treatment period and were administered 1 or more IV infusions of rIX-FP at a dose of at least 25 IU/kg to treat minor, moderate or major bleeding episodes. The dose of rIX-FP was calculated by the investigator.
Overall Study Sponsor decision	0	2

Baseline Characteristics

A Safety and Efficacy Study of a Recombinant Factor IX in Patients With Severe Hemophilia B

Baseline characteristics by cohort

Measure	Prophylactic n=13 Participants For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg. After completion of the PK evaluation period, subjects entered the treatment period and were administered a single IV infusion of rIX-FP once a week at a dose of 15 to 35 IU/kg, or at a dose determined by the investigator. The dose was adjusted up to 75 IU/kg to maintain the trough FIX activity level \> 1% between infusions.	On-demand n=4 Participants For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg. After completion of the PK evaluation period, subjects entered the treatment period and were administered 1 or more IV infusions of rIX-FP at a dose of at least 25 IU/kg to treat minor, moderate or major bleeding episodes. The dose of rIX-FP was calculated by the investigator.	Total n=17 Participants Total of all reporting groups
Age, Continuous	23.2 years STANDARD_DEVIATION 9.4 • n=5 Participants	35.8 years STANDARD_DEVIATION 9.7 • n=7 Participants	26.1 years STANDARD_DEVIATION 10.7 • n=5 Participants
Age, Customized < 18 years	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Age, Customized ≥ 18 years	10 participants n=5 Participants	4 participants n=7 Participants	14 participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	4 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 20 weeks

Population: Safety Population

The causal relationship of each adverse event to rIX-FP was assessed by the Investigator.

Outcome measures

Measure	All Subjects n=17 Participants Subjects received rIX-FP as prophylactic treatment once a week or on-demand to treat bleeding episodes administered by IV infusion for 20 weeks.	On-demand For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg.
Number of Subjects With Treatment-related Adverse Events	0 participants	—

PRIMARY outcome

Timeframe: Baseline, Day 10 and Weeks 4, 12 and 20

Population: Safety Population

The presence of inhibitors against FIX was assessed by the central laboratory by a FIX potency assay. To quantify anti-FIX neutralizing antibodies, the Bethesda assay with the Nijmegen modification was used, and the results expressed as Bethesda Units per mL (BU/mL). A positive inhibitor test is >=0.6 BU/mL.

Outcome measures

Measure	All Subjects n=17 Participants Subjects received rIX-FP as prophylactic treatment once a week or on-demand to treat bleeding episodes administered by IV infusion for 20 weeks.	On-demand For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg.
Number of Subjects With Inhibitors Against Factor IX (FIX)	0 participants	—

PRIMARY outcome

Timeframe: Pre-dose, Day 10 and Weeks 4, 12, and 20

Population: Safety Population

Antibodies against rIX-FP were detected using a direct binding enzyme-linked immunosorbent assay (ELISA).

Outcome measures

Measure	All Subjects n=17 Participants Subjects received rIX-FP as prophylactic treatment once a week or on-demand to treat bleeding episodes administered by IV infusion for 20 weeks.	On-demand For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg.
Number of Subjects Who Developed Antibodies to rIX-FP	0 participants	—

SECONDARY outcome

Timeframe: Pre-dose and up to 14 days after rIX-FP infusion.

Population: PK population

The plasma concentrations of rIX-FP were measured as FIX activity using a validated, 1-stage assay in a central laboratory for a quantification range from 0.25 to 150% (or 0.25 IU/dL to 150 IU/dL). The PK population comprised all subjects who received at least 1 dose of rIX-FP and for whom a sufficient number of analyzable PK samples had been obtained in order to permit the evaluation of the PK profile of rIX-FP, and who did not receive a dose of rIX-FP or any other FIX product for the treatment of a bleed during the PK sampling period.

Outcome measures

Measure	All Subjects n=10 Participants Subjects received rIX-FP as prophylactic treatment once a week or on-demand to treat bleeding episodes administered by IV infusion for 20 weeks.	On-demand n=3 Participants For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg.
Area Under the Curve to the Last Sample With Quantifiable Drug Concentration (AUC0-t) After a Single Dose of rIX-FP	2915 h*IU/dL Geometric Coefficient of Variation 11.3	2960 h*IU/dL Geometric Coefficient of Variation 12.4

SECONDARY outcome

Timeframe: Pre-dose and up to 14 days after infusion

Population: PK population

Outcome measures

Measure	All Subjects n=10 Participants Subjects received rIX-FP as prophylactic treatment once a week or on-demand to treat bleeding episodes administered by IV infusion for 20 weeks.	On-demand n=3 Participants For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg.
Half-life (t1/2) of a Single Dose of rIX-FP	77.7 hours Geometric Coefficient of Variation 25.2	138 hours Geometric Coefficient of Variation 37.1

SECONDARY outcome

Timeframe: 30 minutes after infusion

Population: PK population

Incremental recovery (IU/mL/IU/kg) is defined as FIX activity (IU/mL) obtained 30 minutes following infusion, per dose of (IU/kg) infusion. FIX activity was measured at a central laboratory using validated one-stage clotting method.

Outcome measures

Measure	All Subjects n=10 Participants Subjects received rIX-FP as prophylactic treatment once a week or on-demand to treat bleeding episodes administered by IV infusion for 20 weeks.	On-demand n=3 Participants For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg.
Incremental Recovery of rIX-FP at 30 Minutes Following Infusion of rIX-FP	1.47 IU/dL/IU/kg Geometric Coefficient of Variation 8.2	1.35 IU/dL/IU/kg Geometric Coefficient of Variation 4.9

SECONDARY outcome

Timeframe: Pre-dose and up to 14 days after rIX-FP infusion

Population: PK population

Outcome measures

Measure	All Subjects n=10 Participants Subjects received rIX-FP as prophylactic treatment once a week or on-demand to treat bleeding episodes administered by IV infusion for 20 weeks.	On-demand n=3 Participants For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg.
Clearance of a Single Dose of rIX-FP	0.749 mL/h/kg Geometric Coefficient of Variation 14.0	0.699 mL/h/kg Geometric Coefficient of Variation 10.6

SECONDARY outcome

Timeframe: Week 9 to approximately Week 20

Population: Per protocol population

Number of breakthrough bleeding events (spontaneous bleeding events) requiring treatment per subject in subjects receiving prophylactic treatment regimen with rIX-FP

Outcome measures

Measure	All Subjects n=13 Participants Subjects received rIX-FP as prophylactic treatment once a week or on-demand to treat bleeding episodes administered by IV infusion for 20 weeks.	On-demand For the PK evaluation, subjects received a single IV infusion of rIX-FP at a dose of 25 IU/kg.
Breakthrough Bleeding Events	0.2 Events per subject Standard Deviation 0.38	—

Adverse Events

All Subjects

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	All Subjects n=17 participants at risk Subjects received rIX-FP administered by IV infusion as prophylactic treatment once a week or on demand to treat bleeding episodes for 20 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	29.4% 5/17 • Number of events 11 • 20 weeks
Musculoskeletal and connective tissue disorders Synovitis	5.9% 1/17 • Number of events 2 • 20 weeks
Musculoskeletal and connective tissue disorders Bone pain	5.9% 1/17 • Number of events 1 • 20 weeks
Musculoskeletal and connective tissue disorders Chondropathy	5.9% 1/17 • Number of events 1 • 20 weeks
Musculoskeletal and connective tissue disorders Joint range of motion decreased	5.9% 1/17 • Number of events 1 • 20 weeks
Musculoskeletal and connective tissue disorders Muscle spasms	5.9% 1/17 • Number of events 1 • 20 weeks
Injury, poisoning and procedural complications Hand fracture	11.8% 2/17 • Number of events 2 • 20 weeks
Injury, poisoning and procedural complications Laceration	11.8% 2/17 • Number of events 2 • 20 weeks
Injury, poisoning and procedural complications Contusion	5.9% 1/17 • Number of events 1 • 20 weeks
Injury, poisoning and procedural complications Head injury	5.9% 1/17 • Number of events 1 • 20 weeks
Injury, poisoning and procedural complications Injury	5.9% 1/17 • Number of events 1 • 20 weeks
Injury, poisoning and procedural complications Limb injury	5.9% 1/17 • Number of events 1 • 20 weeks
Injury, poisoning and procedural complications Radius fracture	5.9% 1/17 • Number of events 1 • 20 weeks
Infections and infestations Upper respiratory tract infection	11.8% 2/17 • Number of events 4 • 20 weeks
Infections and infestations Pharyngitis	5.9% 1/17 • Number of events 1 • 20 weeks
Infections and infestations Tonsillitis	5.9% 1/17 • Number of events 1 • 20 weeks
General disorders Injection site swelling	5.9% 1/17 • Number of events 3 • 20 weeks
General disorders Injection site erythema	5.9% 1/17 • Number of events 1 • 20 weeks
General disorders Injection site haemorrhage	5.9% 1/17 • Number of events 1 • 20 weeks
Nervous system disorders Headache	17.6% 3/17 • Number of events 3 • 20 weeks
Nervous system disorders Dizziness	5.9% 1/17 • Number of events 1 • 20 weeks
Eye disorders Conjunctivitis	5.9% 1/17 • Number of events 1 • 20 weeks
Eye disorders Eye pain	5.9% 1/17 • Number of events 1 • 20 weeks
Gastrointestinal disorders Dyspepsia	5.9% 1/17 • Number of events 1 • 20 weeks
Investigations Weight decreased	5.9% 1/17 • Number of events 1 • 20 weeks
Skin and subcutaneous tissue disorders Rash follicular	5.9% 1/17 • Number of events 1 • 20 weeks

Additional Information

Clinical Trial Disclosure Manager

CSL Behring

Phone: Use email contact

Email: clinicaltrials@cslbehring.com

Results disclosure agreements

• Principal investigator is a sponsor employee CSL agreements and restrictions on publishing may vary with individual investigators; however, CSL will not prohibit any investigator from publishing. CSL supports the publication of results from all centers of a multi-center trial and generally requires that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER