Severe Hemophilia APhase 1NCT02083965

Pharmacokinetics of rFVIIIFc at Two Vial Strengths

A Phase 1 study testing rFVIIIFc in people with Severe Hemophilia A, run by Bioverativ Therapeutics Inc. at 8 sites in 3 countries.

Completed

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

Official record

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Trial summary

Who is it for?: Ages 12 years and older, men only
Conditions the study is for: Severe Hemophilia A
What is being tested?: rFVIIIFc
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 19 participants
Where: 8 sitesin 3 countries
Study dates: Mar 2014to May 2015
Phase: Phase 1
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
Men only
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Have severe hemophilia A
Previously treated subject, defined as having at least 150 documented prior exposure days to any recombinant and/or plasma-derived FVIII and/or cryoprecipitate products (other than any use of rFVIIIFc- study drug or commercial product) at Day 1. Fresh frozen plasma treatment must not be considered in the count for documented exposure days.
No history of a positive inhibitor test or clinical signs of decreased response to FVIII administrations. Family history of inhibitors will not exclude subjects.
No measurable inhibitor activity using the Nijmegen-modified Bethesda assay at Screening.
Platelet count ≥100,000 platelets/μL at screening
CD4 lymphocytes >200 mm3 if known as HIV antibody positive at screening.
Viral load of <400 copies/mL if known HIV antibody positive at screening.

Who cannot join

Subject is at high risk of bleeding during the 5-day period between the first and second injections for PK analyses, as per Investigator discretion.
Previous treatment with rFVIIIFc as study drug or commercial product.
Other coagulation disorder(s) in addition to hemophilia A.
History of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration.
Currently taking (or likely to require during the study) acetylsalicylic acid (ASA), except for low-dose ASA as prophylaxis (other nonsteroidal anti-inflammatory drugs are permitted).
Concurrent systemic treatment with immunosuppressive drugs within 12 weeks prior to Day 1. Exceptions to this include: ribavirin for treatment of hepatitis C virus (HCV), and/or systemic steroids (a total of 2 courses of pulse treatments lasting no more than 7 days at a dose of ≤1 mg/kg within 12 weeks prior to Day 1) and/or inhaled steroids.
NOTE: Other protocol-defined inclusion/exclusion Criteria May Apply

Trial locations and contacts

8 sites in 3 countries.

Country

City, postcode or hospital

8 sites in 3 countries

United States3 sites

Research Site
Los Angeles, California
Research Site
Salt Lake City, Utah, 84101
Research Site
Seattle, Washington

Other trials in United States

United Kingdom3 sites

Research Site
Basingstoke
Research Site
Cambridge
Research Site
London

Other trials in United Kingdom

Australia2 sites

Research Site
Herston
Research Site
Perth

Other trials in Australia

About this study

Official title: A Randomized, Open-Label, Crossover Study to Evaluate the Pharmacokinetics of 2 Vial Strengths of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc; BIIB031) in Previously Treated Subjects With Severe Hemophilia A

The primary objective of the study is to characterize the pharmacokinetics (PK) of rFVIIIFc administered at vial strengths of 1000 and 3000 IU in subjects with severe hemophilia A. The secondary objective of the study is to evaluate the safety of rFVIIIFc beyond the PK assessment for up to 6 months for a continued treatment period.

Read the detailed description

This is a randomized, open-label, crossover study during which each participant receives a single injection of rFVIIIFc from 2 different vial concentrations (PK assessment). After the PK assessment, participants are provided with rFVIIIFc for either prophylactic or episodic (on-demand) treatment for up to 6 months.

Conditions: Severe Hemophilia A
Being tested: rFVIIIFc
Medical subject headings: Hemophilia A

What participants receive

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

rFVIIIFcBiological
Also called Eloctate, antihemophilic factor [recombinant] FC fusion protein, recombinant coagulation factor VIII Fc fusion protein, efmoroctocog alfa
Administered as specified in the treatment arm.

Study groups in NCT02083965
Study group	Role	What they receive
rFVIIIFc 1000 / 3000 PK Assessment	Experimental	A single intravenous (IV) injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial. Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator. Receives: Biological: rFVIIIFc
rFVIIIFc 3000 / 1000 PK Assessment	Experimental	A single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial. Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator. Receives: Biological: rFVIIIFc

What is being measured

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

Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by Activated Partial Thromboplastin Time (aPTT) Clotting Assay
Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞).
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Incremental Recovery (IR, K Value) as Estimated From the FVIII Activity Data Measured by aPTT Clotting Assay
The rise in FVIII activity in IU/dL per unit dose administered in IU/kg (IR, K value), as estimated from the FVIII activity data.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

Secondary outcomes (25)

Maximum Activity (Cmax) as Measured by the aPTT Clotting Assay
Maximum measured concentration of rFVIIIFc.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Half-life (t½) as Measured by aPTT Clotting Assay
Time required for the concentration of the drug to reach half of its original value.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Clearance (CL) as Measured by the aPTT Clotting Assay
The measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Volume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay
The apparent volume of distribution at steady state. (Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.)
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Mean Residence Time (MRT) as Measured by the aPTT Clotting Assay
The average time at which the number of absorbed molecules reside in the body, after single-dose administration.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Time of Cmax (Tmax) as Measured by aPTT Clotting Assay
Time at which maximum activity (Cmax) is observed.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Area Under the Curve to the Last Measurable Time Point (AUClast) as Measured by aPTT Clotting Assay
Area under the plasma concentration time-curve from zero to the last measured concentration.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Terminal Exponential Rate Constant (Lambda Z) as Measured by aPTT Clotting Assay
First order rate constant associated with the terminal portion of the curve (lambda z) .
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Percentage of AUCinf From the Last Data Point to Infinity (AUCext) as Measured by aPTT Clotting Assay
Percentage of AUCinf extrapolated from the last data point to infinity.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Dose Normalized Area Under the Curve (DNAUC) as Measured by aPTT Clotting Assay
Dose normalized area under the FVIII activity-time curve.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Terminal Exponential Volume of Distribution (Vz) as Measured by aPTT
The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
AUCinf as Estimated From the FVIII Activity Data as Measured by Two-Stage Chromogenic Clotting Assay
Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞).
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
IR, K Value as Measured by Two-Stage Chromogenic Clotting Assay
The rise in FVIII activity in IU/dL per unit dose administered in IU/kg (IR, K value), as estimated from the FVIII activity data.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Cmax as Measured by Two-Stage Chromogenic Clotting Assay
Maximum measured concentration of rFVIIIFc.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
t½ as Measured by Two-Stage Chromogenic Clotting Assay
Time required for the concentration of the drug to reach half of its original value.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
CL as Measured by Two-Stage Chromogenic Clotting Assay
The measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Vss as Measured by Two-Stage Chromogenic Clotting Assay
The apparent volume of distribution at steady state. (Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.)
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
MRT as Measured by Two-Stage Chromogenic Clotting Assay
The average time at which the number of absorbed molecules reside in the body, after single-dose administration.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Tmax as Measured by Two-Stage Chromogenic Clotting Assay
Time at which maximum activity (Cmax) is observed.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
AUClast as Measured by Two-Stage Chromogenic Clotting Assay
Area under the plasma concentration time-curve from zero to the last measured concentration.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Lambda Z as Measured by Two-Stage Chromogenic Clotting Assay
First order rate constant associated with the terminal portion of the curve (lambda z).
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
AUCext as Measured by Two-Stage Chromogenic Clotting Assay
Percentage of AUCinf extrapolated from the last data point to infinity.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
DNAUC as Measured by Two-Stage Chromogenic Clotting Assay
Dose normalized area under the FVIII activity-time curve.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Vz as Measured by Two-Stage Chromogenic Clotting Assay
The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Measured: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Development of Inhibitor as Measured by the Nijmegen-Modified Bethesda Assay
An inhibitor test result ≥0.6 Bethesda units (BU)/mL, confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. Both tests were to be performed by the central laboratory using the Nijmegen-modified Bethesda Assay. An exact 95% confidence interval (CI) for the proportion of subjects with a confirmed inhibitor was calculated using the Clopper-Pearson method for a binomial proportion. Percentage of participants with confirmed inhibitor development was summarized overall.
Measured: Predose, Month 3, Month 6/early withdrawal. Additionally: If inhibitor suspected; at 10-15 EDs; 2-4 weeks prior to scheduled surgery; preoperatively on day of surgery; 1-2 weeks post-surgery; at last postoperative visit (last 2 for major surgery only)

Timeline

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

Mar 2014May 2015

First posted11 Mar 2014 (estimated)
Study startMar 2014
Primary completionOct 2014
Study completionMay 2015

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 Severe Hemophilia AStudies 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 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02083965
Sponsor's protocol ID: 997HA307
Other IDs: 2013-003013-18
Status last verified: May 2017
First submitted: 7 Mar 2014
Last updated: 19 Dec 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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

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Severe Hemophilia A

All Severe Hemophilia A trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Open-Label, Crossover Study to Evaluate the Pharmacokinetics of 2 Vial Strengths of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc; BIIB031) in Previously Treated Subjects With Severe Hemophilia A
ClinicalTrials.gov ID: NCT02083965
Acronym / sponsor ID: 997HA307
Conditions: Severe Hemophilia A
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 19 participants (actual)
Lead sponsor: Bioverativ Therapeutics Inc.Industry (pharma, biotech, devices)
Study start: Mar 2014
Primary completion: Oct 2014 (actual)
Study completion: May 2015 (actual)
First posted: 11 Mar 2014 (estimated)
Results: Posted 19 Aug 2016

Clinical summary

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
rFVIIIFc 1000 / 3000 PK Assessment	Experimental	Biological: rFVIIIFcA single intravenous (IV) injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial. Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator.
rFVIIIFc 3000 / 1000 PK Assessment	Experimental	Biological: rFVIIIFcA single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial. Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator.

Who may qualify

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

Key inclusion criteria (7 listed)

Have severe hemophilia A
Previously treated subject, defined as having at least 150 documented prior exposure days to any recombinant and/or plasma-derived FVIII and/or cryoprecipitate products (other than any use of rFVIIIFc- study drug or commercial product) at Day 1. Fresh frozen plasma treatment must not be considered in the count for documented exposure days.
No history of a positive inhibitor test or clinical signs of decreased response to FVIII administrations. Family history of inhibitors will not exclude subjects.
No measurable inhibitor activity using the Nijmegen-modified Bethesda assay at Screening.
Platelet count ≥100,000 platelets/μL at screening

Key exclusion criteria (7 listed)

Subject is at high risk of bleeding during the 5-day period between the first and second injections for PK analyses, as per Investigator discretion.
Previous treatment with rFVIIIFc as study drug or commercial product.
Other coagulation disorder(s) in addition to hemophilia A.
History of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration.
Currently taking (or likely to require during the study) acetylsalicylic acid (ASA), except for low-dose ASA as prophylaxis (other nonsteroidal anti-inflammatory drugs are permitted).

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
rFVIIIFcAlso: Eloctate, antihemophilic factor [recombinant] FC fusion protein, recombinant coagulation factor VIII Fc fusion protein, efmoroctocog alfaAdministered as specified in the treatment arm.	Biological	rFVIIIFc 1000 / 3000 PK Assessment, rFVIIIFc 3000 / 1000 PK Assessment

Primary outcome

Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by Activated Partial Thromboplastin Time (aPTT) Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞).
Incremental Recovery (IR, K Value) as Estimated From the FVIII Activity Data Measured by aPTT Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
The rise in FVIII activity in IU/dL per unit dose administered in IU/kg (IR, K value), as estimated from the FVIII activity data.

25 secondary outcomes

Maximum Activity (Cmax) as Measured by the aPTT Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Half-life (t½) as Measured by aPTT Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Clearance (CL) as Measured by the aPTT Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Volume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Mean Residence Time (MRT) as Measured by the aPTT Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Time of Cmax (Tmax) as Measured by aPTT Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Area Under the Curve to the Last Measurable Time Point (AUClast) as Measured by aPTT Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Terminal Exponential Rate Constant (Lambda Z) as Measured by aPTT Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Percentage of AUCinf From the Last Data Point to Infinity (AUCext) as Measured by aPTT Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Dose Normalized Area Under the Curve (DNAUC) as Measured by aPTT Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Terminal Exponential Volume of Distribution (Vz) as Measured by aPTT
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
AUCinf as Estimated From the FVIII Activity Data as Measured by Two-Stage Chromogenic Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
IR, K Value as Measured by Two-Stage Chromogenic Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Cmax as Measured by Two-Stage Chromogenic Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
t½ as Measured by Two-Stage Chromogenic Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
CL as Measured by Two-Stage Chromogenic Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Vss as Measured by Two-Stage Chromogenic Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
MRT as Measured by Two-Stage Chromogenic Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Tmax as Measured by Two-Stage Chromogenic Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
AUClast as Measured by Two-Stage Chromogenic Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Lambda Z as Measured by Two-Stage Chromogenic Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
AUCext as Measured by Two-Stage Chromogenic Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
DNAUC as Measured by Two-Stage Chromogenic Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Vz as Measured by Two-Stage Chromogenic Clotting Assay
Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Development of Inhibitor as Measured by the Nijmegen-Modified Bethesda Assay
Time frame: Predose, Month 3, Month 6/early withdrawal. Additionally: If inhibitor suspected; at 10-15 EDs; 2-4 weeks prior to scheduled surgery; preoperatively on day of surgery; 1-2 weeks post-surgery; at last postoperative visit (last 2 for major surgery only)

Results and safety

Results posted to the registry on 19 Aug 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
rFVIIIFc 1000 / 3000	10	10
rFVIIIFc 3000 / 1000	9	9

Primary outcome: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by Activated Partial Thromboplastin Time (aPTT) Clotting Assay

Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection. Geometric mean (95% Confidence Interval). Unit: IU*h/dL

Measure	rFVIIIFc 1000 IU n = 17	rFVIIIFc 3000 IU n = 18
Value	2888.9 (2440.0 to 3420.5)	2646.3 (2149.8 to 3257.5)

Population analysed: The Pharmacokinetic Analysis Set is defined as all eligible participants who received at least one dose of rFVIIIFc and had sufficient PK data points to calculate at least one of the PK parameters of interest from either the aPTT clotting assay or the two-stage chromogenic clotting assay.

Primary outcome: Incremental Recovery (IR, K Value) as Estimated From the FVIII Activity Data Measured by aPTT Clotting Assay

Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection. Geometric mean (95% Confidence Interval). Unit: IU/dL

Measure	rFVIIIFc 1000 IU n = 18	rFVIIIFc 3000 IU n = 18
Value	2.33 (2.182 to 2.487)	2.412 (2.169 to 2.682)

25 secondary outcomes are reported in the full results.

Adverse events

Time frame: From screening (for serious adverse events) or first dose of study drug (for adverse events) until end of study (up to approximately 6 months).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Total Active	2 of 19 (10.5%)	12 of 19 (63.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Medical Director study director

Bioverativ Therapeutics Inc.

8 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing rFVIIIFc in people with Severe Hemophilia A, run by Bioverativ Therapeutics Inc. at 8 sites in 3 countries.

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 7 inclusion and 7 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 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, United Kingdom, Australia. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 19 Aug 2016). 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?

Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by Activated Partial Thromboplastin Time (aPTT) Clotting Assay (time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection). The study lists 2 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 NCT02083965.

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 19 Dec 2020.