Hemophilia BPhase 2NCT03091751

Efficacy and Safety of AlphaNine Versus BeneFIX in Patients With Severe Hereditary Haemophilia B

A Phase 2 study testing BeneFIX in people with Hemophilia B, run by Grifols Biologicals, LLC at 3 sites in Bulgaria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The goal of this non-randomized, multi-center study in subjects with severe hereditary haemophilia B was to determine and compare the pharmacokinetic and safety profiles of BeneFIX in subjects having had 2 prior pharmacokinetic assessments with AlphaNine. Read more about this study

Who is it for?: Ages 12 years and older
Conditions the study is for: Hemophilia B
What is being tested?: BeneFIX
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 3 sitesBulgaria
Study dates: Aug 2005to Oct 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Participated in the previous study "Efficacy and safety of factor IX (FIX) contained in Alphananine in patients with severe hereditary haemophilia B":
Congenital deficiency in Factor IX (FIX)
FIX residual activity of ≤2% of normal
Had required FIX-containing products in the past and in clinical records that were collected data to assess a reliable estimation of at least 150 treatment exposure days to previous products
Was able to receive treatment for more than 10 days for a 6-month period

Who cannot join

Received a dose of FIX in the 7 days prior to the infusion
FIX inhibitor level of >0.5 Bethesda units (BU) or clinically relevant presence in the past (≥5 BU)
Active bleeding at the moment of infusion
Had a known allergic reaction to any BeneFIX component
Exhibited symptoms of any intercurrent infection (ie, fever, chills, nausea) at the time of the first infusion
Had any disease that might affect the distribution or metabolism of FIX and which could affect interpretation of the study (such as non-controlled diabetes mellitus)

Show all 12Show fewer

Had non-controlled arterial hypertension
Had abnormal renal function (creatinine >1.5 mg/dL)
Had documented liver cirrhosis or any hepatic disorder with alanine aminotransferase (ALT) levels 2.5x upper limit of normal (ULN )
Prevision to be concomitantly treated with other FIX-containing products
Had conditions that might affect subject compliance (survival-limiting [in 2 year time] diseases, alcohol or other drug abuse, etc.)
Unable to provide a storage plasma sample before the first dose of BeneFIX

Trial locations and contacts

3 sites in 1 country.

Bulgaria3 sites

Medical University Pleven
Pleven, 5800
National Center of Haematology
Sofia, 1000
Medical University, University Hospital "Sveta Marina",
Varna, 9010

Other trials in Bulgaria

About this study

Official title: Efficacy and Safety of Factor IX (FIX) Contained in AlphaNine® and Its Pharmacokinetic Comparison With BeneFIX® in Patients With Severe Hereditary Haemophilia B

Read the detailed description

Two pharmacokinetic assessments (studies) were carried out in the same subjects during a previous clinical trial. The first pharmacokinetic study (PK1) was performed after a single dose of AlphaNine. The second pharmacokinetic study (PK2) was performed following 26 Weeks of AlphaNine treatment after PK1. To compare AlphaNine with BeneFIX, a third pharmacokinetic study (PK3) (current study) was performed after a single dose of BeneFIX administered following a 7- to 15-day wash-out period.

The main objective of the PK3 study was to assess the pharmacokinetic profile of BeneFIX and compare to the pharmacokinetic profile of AlphaNine from the PK2 study.

Conditions: Hemophilia B
Being tested: BeneFIX
Keywords: Factor IX (FIX)
Medical subject headings: Hemophilia B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BeneFIXDrug
Also called recombinant coagulation factor IX
BeneFIX is a recombinant FIX that contains nonacog alfa, reconstituted in solvent and administered as a single dose of 65-75 IU/kg.

Study groups in NCT03091751
Study group	Role	What they receive
BeneFIX	Experimental	BeneFIX is a recombinant FIX provided in a vial containing 100 IU/mL lyophilized nonacog alfa accompanied with solvent for reconstitution and injection. Receives: Drug: BeneFIX

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Difference of Area Under the Curve (AUC): BeneFIX Compared to AlphaNine
BeneFIX pharmacokinetic parameter of area under the curve (AUC 0-inf) was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 study).
Measured: Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.
Mean Difference of In Vivo Recovery: BeneFIX Compared to AlphaNine
BeneFIX pharmacokinetic parameter of in vivo recovery was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Measured: Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.
Mean Difference of Terminal Half-Life: BeneFIX Compared to AlphaNine
BeneFIX pharmacokinetic parameter of terminal half-life was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Measured: Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.
Mean Difference of Clearance: BeneFIX Compared to AlphaNine
BeneFIX pharmacokinetic parameter of clearance was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Measured: Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.
Mean Difference of Mean Residence Time (MRT): BeneFIX Compared to AlphaNine
BeneFIX pharmacokinetic parameter of mean residence time (MRT 0-inf) was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Measured: Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2005Oct 2009

First posted27 Mar 2017
Study startAug 2005
Primary completionOct 2009
Study completionOct 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Hemophilia BStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03091751
Sponsor's protocol ID: IG-404-1
Status last verified: Jun 2017
First submitted: 16 Mar 2017
Last updated: 25 Jul 2017
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingObservational study
A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
Hemophilia A or B
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
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Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
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All Hemophilia B trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Efficacy and Safety of Factor IX (FIX) Contained in AlphaNine® and Its Pharmacokinetic Comparison With BeneFIX® in Patients With Severe Hereditary Haemophilia B
ClinicalTrials.gov ID: NCT03091751
Acronym / sponsor ID: IG-404-1
Conditions: Hemophilia B
Keywords: Factor IX (FIX)
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: Grifols Biologicals, LLCIndustry (pharma, biotech, devices)
Study start: Aug 2005 (actual)
Primary completion: Oct 2009 (actual)
Study completion: Oct 2009 (actual)
First posted: 27 Mar 2017 (actual)
Results: Posted 25 Jul 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The main objective of the PK3 study was to assess the pharmacokinetic profile of BeneFIX and compare to the pharmacokinetic profile of AlphaNine from the PK2 study.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
BeneFIX	Experimental	Drug: BeneFIXBeneFIX is a recombinant FIX provided in a vial containing 100 IU/mL lyophilized nonacog alfa accompanied with solvent for reconstitution and injection.

Who may qualify

Ages: 12 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (5 listed)

Participated in the previous study "Efficacy and safety of factor IX (FIX) contained in Alphananine in patients with severe hereditary haemophilia B":
Congenital deficiency in Factor IX (FIX)
FIX residual activity of ≤2% of normal
Had required FIX-containing products in the past and in clinical records that were collected data to assess a reliable estimation of at least 150 treatment exposure days to previous products
Was able to receive treatment for more than 10 days for a 6-month period

Key exclusion criteria (12 listed)

Received a dose of FIX in the 7 days prior to the infusion
FIX inhibitor level of >0.5 Bethesda units (BU) or clinically relevant presence in the past (≥5 BU)
Active bleeding at the moment of infusion
Had a known allergic reaction to any BeneFIX component
Exhibited symptoms of any intercurrent infection (ie, fever, chills, nausea) at the time of the first infusion

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BeneFIXAlso: recombinant coagulation factor IXBeneFIX is a recombinant FIX that contains nonacog alfa, reconstituted in solvent and administered as a single dose of 65-75 IU/kg.	Drug	BeneFIX

Primary outcome

Mean Difference of Area Under the Curve (AUC): BeneFIX Compared to AlphaNine
Time frame: Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.
BeneFIX pharmacokinetic parameter of area under the curve (AUC 0-inf) was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 study).
Mean Difference of In Vivo Recovery: BeneFIX Compared to AlphaNine
Time frame: Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.
BeneFIX pharmacokinetic parameter of in vivo recovery was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Mean Difference of Terminal Half-Life: BeneFIX Compared to AlphaNine
Time frame: Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.
BeneFIX pharmacokinetic parameter of terminal half-life was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Mean Difference of Clearance: BeneFIX Compared to AlphaNine
Time frame: Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.
BeneFIX pharmacokinetic parameter of clearance was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).
Mean Difference of Mean Residence Time (MRT): BeneFIX Compared to AlphaNine
Time frame: Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.
BeneFIX pharmacokinetic parameter of mean residence time (MRT 0-inf) was assessed and compared to the AlphaNine pharmacokinetic parameter (PK2 Study).

Results and safety

Results posted to the registry on 25 Jul 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
BeneFIX	22	22

Primary outcome: Mean Difference of Area Under the Curve (AUC): BeneFIX Compared to AlphaNine

Time frame: Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.. Mean (Standard Deviation). Unit: IU x hour/dL

Measure	BeneFIX n = 22
Value	10.41 (563.081)

BeneFIX: Mean Difference (Final Values): 10.41 (95% CI -224.88 to 245.70), p = 0.77, t-test, 1 sided

Population analysed: Thirteen subjects with 2 prior pharmacokinetic assessments with AlphaNine (PK1, PK2) had a third PK assessment with BeneFIX (PK3). Nine subjects had PK3 analysis with BeneFIX as part of a previous study. In total, 22 subjects treated with BeneFIX (PK3) were analyzed jointly and compared to 25 subjects treated with AlphaNine (PK2).

Primary outcome: Mean Difference of In Vivo Recovery: BeneFIX Compared to AlphaNine

Measure	BeneFIX n = 22
Value	0.3068 (0.37505)

BeneFIX: Mean Difference (Final Values): 0.3068 (95% CI 0.1501 to 0.4635), p = 0.002, t-test, 1 sided

Primary outcome: Mean Difference of Terminal Half-Life: BeneFIX Compared to AlphaNine

Measure	BeneFIX n = 22
Value	-3.3 (13.48)

BeneFIX: Mean Difference (Final Values): -3.3 (95% CI -8.9 to 2.3), p = 0.30, t-test, 1 sided

Primary outcome: Mean Difference of Clearance: BeneFIX Compared to AlphaNine

Measure	BeneFIX n = 22
Value	-0.0058 (0.0145)

BeneFIX: Mean Difference (Final Values): -0.0058 (95% CI -0.0119 to 0.0003), p = 0.16, t-test, 1 sided

Adverse events

Time frame: Adverse events produced during and after treatment administration were recorded.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
BeneFIX	0 of 22 (0%)	0 of 22 (0%)	0 of 22

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Hemophilia B

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BeneFIX in people with Hemophilia B, run by Grifols Biologicals, LLC at 3 sites in Bulgaria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Bulgaria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Difference of Area Under the Curve (AUC): BeneFIX Compared to AlphaNine (time frame: Baseline (prior to the infusion), and at 15 and 30 minutes, 1, 3, 6, 9, 24, 48, 72, and 74 hours following a single dose infusion of BeneFIX administered following a 7 to 15 day wash-out period.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03091751.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2017.