Severe Haemophilia APhase 3NCT02256917

Assess the Efficacy and Safety of Personalized Prophylaxis Human-cl rhFVIII in Patients With Severe Haemophilia A

A Phase 3 study testing Human cl rhFVIII in people with Severe Haemophilia A, run by Octapharma at 30 sites in 9 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 18 years and older, men only
Conditions the study is for: Severe Haemophilia A
What is being tested?: Human cl rhFVIII
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 58 participants
Where: 30 sitesin 9 countries
Study dates: May 2015to Sep 2018
Phase: Phase 3
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 18 years and older
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

Severe Haemophilia A (FVIII:C < 1%)
Male patients >= 18 years of age
Previous treatment with a FVIII concentrate for at least 150 EDs
Good documentation regarding dosing and bleeding frequency in the 6 months preceding study start
Immunocompetence (CD4+ count > 200/uL)

Who cannot join

Any coagulation disorder other than Haemophilia A
Present of past FVIII inhibitor activity
Severe liver or kidney disease

Trial locations and contacts

30 sites in 9 countries.

Country

City, postcode or hospital

30 sites in 9 countries

United States9 sites

Octapharma Research Site
Aurora, Colorado, 80045
Octapharma Research Site
Chicago, Illinois, 60612
Octapharma Research Site
Houston, Texas, 77030
Octapharma Research Site
Indianapolis, Indiana, 46260
Octapharma Research Site
Memphis, Tennessee, 38163
Octapharma Research Site
Miami, Florida, 33136
Octapharma Research Site
Sacramento, California, 95817
Octapharma Research Site
Salt Lake City, Utah, 84112
Octapharma Research Site
Washington D.C., District of Columbia, 20057

Other trials in United States

Japan8 sites

Nara Medical University Hospital
Kashihara, Nara
St. Marianna Univ School of Medicine Hospital
Kawasaki, Kanagawa
Hospital of the Univ of Occupational and Environmental Health
Kitakyushu, Fukuoka
Gunma University Hospital
Maebashi
Nagoya University Hospital
Nagoya, Aichi-ken
Osaka National Hospital
Osaka
Ogikubo Hospital
Tokyo
Teikyo University Hospital
Tokyo

Other trials in Japan

France5 sites

Centre Régional de Traitement de l'Hémophilie
Bron, 69677
CHU Estaing
Clermont-Ferrand
Centre Hospitalier Universitaire Félix Guyon
La Réunion, 97400
Centre Régional de Traitement de l'hémophilie
Nantes, 44093
Hôpital Purpan - Centre de Traitment Regional de l'Hemophilie Pole
Toulouse, 31059

Other trials in France

Canada3 sites

Octapharma Research Site
Edmonton, Alberta, T6G1C9
McMaster University
Hamilton, Ontario, L8N 4K1
Octapharma Research Site
St. John's, Newfoundland and Labrador

Other trials in Canada

Croatia1 site

University Hospital Centre Zagreb
Zagreb

Other trials in Croatia

Finland1 site

Helsinki University Hospital
Helsinki, 00290

Other trials in Finland

Netherlands1 site

University Medical Center Groningen
Groningen, 9713

Other trials in Netherlands

North Macedonia1 site

PHI Institute of Transfusion Medicine of Republic of Macedonia
Skopje

Other trials in North Macedonia

Slovenia1 site

University Medical Centre Ljubljana
Ljubljana

Other trials in Slovenia

About this study

Official title: Prospective, Open-label, Multi-centre Phase 3b Study to Assess the Efficacy and Safety of Personalized Prophylaxis With Human-cl rhFVIII in Previously Treated Adult Patients With Severe Haemophilia A

The rationale of this study is to further fine-tune and individualize prophylactic treatment of patients with severe Haemophilia A with the goal of keeping the trough FVIII level above 1% between doses. Because trough FVIII levels are likely to be important predictors of the efficacy of prophylaxis, the focus of this study is on pharmacokinetic (PK) data.

Conditions: Severe Haemophilia A
Being tested: Human cl rhFVIII
Medical subject headings: Hemophilia A

What participants receive

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

Human cl rhFVIIIBiological

Study groups in NCT02256917
Study group	Role	What they receive
Human-cl rhFVIII	Experimental	Not described Receives: Biological: Human cl rhFVIII

What is being measured

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

Annualized Total Bleeding Rate of Individually Tailored Prophylaxis
Total annualized bleeding rate (ABR) of individually tailored prophylaxis (GENA-21b) compared to historical bleeding rate in patients having received on-demand treatment (GENA-01) with Human-cl rhFVIII
Measured: 6 months

Secondary outcomes (12)

Annualized Spontaneous Bleeding Rate of Individually Tailored Prophylaxis
Spontaneous annualized bleeding rate (ABR) of individually tailored prophylaxis (GENA-21b) compared to historical bleeding rate in patients having received on-demand treatment (GENA-01) with Human-cl rhFVIII
Measured: 6 months
Annualized Total Bleeding Rate in Patients With 2x/Week (or Less) Prophylaxis
Total annualized bleeding rate (ABR) in patients with 2x/week (or less) prophylaxis (GENA-21b) compared to historical bleeding rate in patients having received on-demand treatment (GENA-01) with Human-cl rhFVIII
Measured: 6 months
Median Prophylactic Dosing Interval
Median over median actual dosing intervals between two prophylactic treatments per patient. The median time (hours) between two prophylactic doses of Human-cl rhFVIII in the prophylactic treatment Phase II per patient
Measured: 6 months
Mean Prophylactic Dosing Interval
Mean over mean actual dosing intervals between two prophylactic treatments per patient. The mean time (hours) between two prophylactic doses of Human-cl rhFVIII in the prophylactic treatment Phase II per patient
Measured: 6 months
AUC Divided by the Dose (AUCnorm) of Human-cl rhFVIII
AUCnorm of Human-cl rhFVIII measured using the one-stage (OS) assay
Measured: Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
In-vivo Recovery (IVR) of Human-cl rhFVIII
IVR of Human-cl rhFVIII measured using the one-stage (OS) assay and will be determined from the FVIII level before the infusion and the peak level after the infusion of Human-cl rhFVIII
Measured: Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Half Life (t1/2) of Human-cl rhFVIII
T1/2 of Human-cl rhFVIII measured using the one-stage (OS) assay
Measured: Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Mean Residence Time (MRT) of Human-cl rhFVIII
MRT of Human-cl rhFVIII measured using the one-stage (OS) assay
Measured: Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Clearance (CL) of Human-cl rhFVIII
CL of Human-cl rhFVIII measured using the one-stage (OS) assay
Measured: Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Volume of Distribution at Steady State (Vss) of Human-cl rhFVIII
Vss of Human-cl rhFVIII measured using the one-stage (OS) assay
Measured: Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Usage of Human-cl rhFVIII (FVIII IU/kg BW Per Week Per Patient)
Average weekly consumption of Human-cl rhFVIII reported as IU/kg BW per week per patient was determined during individualized prophylactic treatment
Measured: 6 months
Number of Patients With Adverse Events (AEs)
AEs were documented at each (scheduled or unscheduled) study visit. Severity and seriousness of all AEs were documented by the investigator according to pre-defined criteria
Measured: At each study visit over the study duration (7-9 months)

Timeline

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

May 2015Sep 2018

First posted6 Oct 2014 (estimated)
Study startMay 2015
Primary completionSep 2018
Study completionSep 2018

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 Haemophilia AStudies of the same condition, open and under way.
More trials run by OctapharmaThe sponsor's other registered studies.
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 3
Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 58 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02256917
Sponsor's protocol ID: GENA-21B
Status last verified: Dec 2020
First submitted: 30 Sep 2014
Last updated: 19 Jan 2021
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

RecruitingPhase 1/2
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Hemophilia A
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
Hemophilia B
RecruitingPhase 3
Open-Label Extension Study of Marstacimab in Hemophilia Participants With or Without Inhibitors
Hemophilia A, Hemophilia B
Active, not recruitingPhase 4
A Study to Evaluate Overall Health, Physical Activity, and Joint Outcomes in Participants With Severe or Moderate Hemophilia A Without Factor VIII Inhibitors on Emicizumab Prophylaxis
Severe Hemophilia A, Moderate Hemophilia A
Not yet recruitingObservational study
Post Approval Phase 4 Study to Learn More About How Safe Octocog Alfa is, and How Well it Works in Patients With Severe Hemophilia A in India
Severe Hemophilia A

All Severe Haemophilia A trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Prospective, Open-label, Multi-centre Phase 3b Study to Assess the Efficacy and Safety of Personalized Prophylaxis With Human-cl rhFVIII in Previously Treated Adult Patients With Severe Haemophilia A
ClinicalTrials.gov ID: NCT02256917
Acronym / sponsor ID: GENA-21B
Conditions: Severe Haemophilia A
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 58 participants (actual)
Lead sponsor: OctapharmaIndustry (pharma, biotech, devices)
Study start: May 2015 (actual)
Primary completion: Sep 2018 (actual)
Study completion: Sep 2018 (actual)
First posted: 6 Oct 2014 (estimated)
Results: Posted 3 Dec 2019

Clinical summary

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

Study design

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

Arm	Type	Receives
Human-cl rhFVIII	Experimental	Biological: Human cl rhFVIII

Who may qualify

Ages: 18 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Severe Haemophilia A (FVIII:C < 1%)
Male patients >= 18 years of age
Previous treatment with a FVIII concentrate for at least 150 EDs
Good documentation regarding dosing and bleeding frequency in the 6 months preceding study start
Immunocompetence (CD4+ count > 200/uL)

Key exclusion criteria (3 listed)

Any coagulation disorder other than Haemophilia A
Present of past FVIII inhibitor activity
Severe liver or kidney disease

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
Human cl rhFVIII	Biological	Human-cl rhFVIII

Primary outcome

Annualized Total Bleeding Rate of Individually Tailored Prophylaxis
Time frame: 6 months
Total annualized bleeding rate (ABR) of individually tailored prophylaxis (GENA-21b) compared to historical bleeding rate in patients having received on-demand treatment (GENA-01) with Human-cl rhFVIII

12 secondary outcomes

Annualized Spontaneous Bleeding Rate of Individually Tailored Prophylaxis
Time frame: 6 months
Annualized Total Bleeding Rate in Patients With 2x/Week (or Less) Prophylaxis
Time frame: 6 months
Median Prophylactic Dosing Interval
Time frame: 6 months
Mean Prophylactic Dosing Interval
Time frame: 6 months
AUC Divided by the Dose (AUCnorm) of Human-cl rhFVIII
Time frame: Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
In-vivo Recovery (IVR) of Human-cl rhFVIII
Time frame: Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Half Life (t1/2) of Human-cl rhFVIII
Time frame: Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Mean Residence Time (MRT) of Human-cl rhFVIII
Time frame: Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Clearance (CL) of Human-cl rhFVIII
Time frame: Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Volume of Distribution at Steady State (Vss) of Human-cl rhFVIII
Time frame: Before injection (within 1 h before injection) and up to 72 h (± 2 h) after the end of injection
Usage of Human-cl rhFVIII (FVIII IU/kg BW Per Week Per Patient)
Time frame: 6 months
Number of Patients With Adverse Events (AEs)
Time frame: At each study visit over the study duration (7-9 months)

Results and safety

Results posted to the registry on 3 Dec 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Human-cl rhFVIII	58	58

Primary outcome: Annualized Total Bleeding Rate of Individually Tailored Prophylaxis

Time frame: 6 months. Mean (Standard Deviation). Unit: Bleeding events per year (ABR)

Measure	Individualized Prophylaxis in GENA-21b n = 56	GENA-01 n = 22
Value	4.67 (6.46)	58.08 (30.78)

Individualized Prophylaxis in GENA-21b vs GENA-01: ABR: 4.87 (95% CI 4.06 to 5.79), one-sided one-sample Poisson-test
Individualized Prophylaxis in GENA-21b vs GENA-01: Rate ratio: 11.89 (95% CI 7.50 to 18.86), p <0.0001, Negative binomial regression model
Individualized Prophylaxis in GENA-21b vs GENA-01: Rate ratio: 10.14 (95% CI 6.12 to 16.80), p <0.0001, Poisson regression model

Population analysed: The analysis population comprised 56 patients who received at least one infusion of Human-cI rhFVIII for individualized prophylaxis in the GENA-21b trial. Their annualized bleeding rate was compared with those in patients from the completed GENA-01 trial who received only on-demand treatment.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: At each study visit over the study duration (7-9 months). Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
SAF/ITT Population	4 of 58 (6.9%)	34 of 58 (58.6%)	0 of 58

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Severe Haemophilia A

RecruitingPhase 1/2
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Hemophilia A
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
Hemophilia B
RecruitingPhase 3
Open-Label Extension Study of Marstacimab in Hemophilia Participants With or Without Inhibitors
Hemophilia A, Hemophilia B
Active, not recruitingPhase 4
A Study to Evaluate Overall Health, Physical Activity, and Joint Outcomes in Participants With Severe or Moderate Hemophilia A Without Factor VIII Inhibitors on Emicizumab Prophylaxis
Severe Hemophilia A, Moderate Hemophilia A
Not yet recruitingObservational study
Post Approval Phase 4 Study to Learn More About How Safe Octocog Alfa is, and How Well it Works in Patients With Severe Hemophilia A in India
Severe Hemophilia A

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.

Craig M Kessler, MD principal investigator

Georgetown University

30 sites in 9 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Human cl rhFVIII in people with Severe Haemophilia A, run by Octapharma at 30 sites in 9 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 5 inclusion and 3 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 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in United States, Japan, France, Canada, Croatia and 4 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 3 Dec 2019). 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?

Annualized Total Bleeding Rate of Individually Tailored Prophylaxis (time frame: 6 months). 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 NCT02256917.

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 Jan 2021.