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Hemophilia APhase 2/3NCT01486927

An Open-label Safety, Efficacy and Pharmacokinetic Study of a Recombinant FVIII Compared to Recombinant Human Antihemophilic FVIII in Patients With Severe Hemophilia A

A Phase 2/3 study testing rVIII-SingleChain and Octocog alfa in people with Hemophilia A, run by CSL Behring at 56 sites in 20 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

This is an open-label, non-randomized, efficacy, safety and pharmacokinetic (PK) study comparing octocog alfa and rVIII-SingleChain. The study consists of three parts, a PK period (Part 1), a continuation of dosing safety and efficacy period (Part 2) and a safety, efficacy, and repeat PK period (Part 3) and also… Read more about this study

Who is it for?
Ages 12 to 65 years, men only
Conditions the study is for
Hemophilia A
What is being tested?
rVIII-SingleChain and Octocog alfa
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
175 participants
Where
56 sitesin 20 countries
Study dates
Feb 2012to Dec 2014
Phase
Phase 2/3
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 12 to 65 years
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Diagnosis of severe hemophilia A defined as <1% FVIII:C documented in medical records.
  • Males between 18 and 65 years of age (Parts 1 and 2).
  • Males between 12 and 65 years of age (Part 3).
  • Subjects who have received or are currently receiving FVIII products (plasma-derived and/or recombinant FVIII) and have had >150 exposure days (EDs) with a FVIII product
  • Written informed consent for study participation obtained before undergoing any study specific procedures.

Who cannot join

  • Any history of or current FVIII inhibitors
  • Any first order family history of FVIII inhibitors
  • Use of an Investigational Medicinal Product within 30 days prior to the first rVIII-SingleChain administration.
  • Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of rVIII-SingleChain or reference product.
  • Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein.
  • Any known congenital or acquired coagulation disorder other than congenital FVIII deficiency.
Show all 13Show fewer
  • Platelet count < 100,000/µL at screening.
  • Human immunodeficiency virus (HIV) positive subjects with a CD4 count < 200/mm3, in their medical history or at screening if available results are older than one year. (HIV positive subjects may participate in the study and antiviral therapy are permitted, at the discretion of the Investigator).
  • Subject currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment.
  • Subject with serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) values > 5 times (x) the upper limit of normal (ULN) at Screening.
  • Subjects with serum creatinine values > 2 x ULN at Screening.
  • Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction and arterial embolus within 3 months prior to Day 1.
  • Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months prior to Day 1.

Trial locations and contacts

56 sites in 20 countries.

56 sites in 20 countries

United States9 sites
  • Study Site

    Aurora, Colorado, 80045

  • Study Site

    Chicago, Illinois, 60612-3833

  • Study Site

    Hartford, Connecticut, 06106

  • Study Site

    Houston, Texas, 77030

  • Study Site

    Miami, Florida, 33136

  • Study Site

    Milwaukee, Wisconsin, 53226

  • Study Site

    New Orleans, Louisiana, 70112

  • Study Site

    Sacramento, California, 95817

  • Study Site

    San Diego, California, 92103

Other trials in United States

Japan8 sites
  • Study Site

    Kashihara, Nara

  • Study Site

    Kitakyushu, Fukuoka

  • Study Site

    Nagoya, 466-85660

  • Study Site

    Nishinomiya, Hyogo

  • Study Site

    Okayama, 710-8602

  • Study Site

    Saitama

  • Study Site

    Suginami-ku, Tokyo

  • Study Site

    Tokyo, 160-0023

Other trials in Japan

Germany7 sites
  • Study Site

    Berlin, 10249

  • Study Site

    Berlin, 13353

  • Study Site

    Bonn, 53127

  • Study Site

    Giessen, 35392

  • Study Site

    Hamburg, 20095

  • Study Site

    Hanover, 30159

  • Study Site

    Heidelberg, 69123

Other trials in Germany

Italy5 sites
  • Study Site

    Florence, 50134

  • Study Site

    Milan, 20122

  • Study Site

    Padova, 35123

  • Study Site

    Padova, 35128

  • Study Site

    Torino, 10126

Other trials in Italy

Poland3 sites
  • Study Site

    Gdansk, 80-952

  • Study Site

    Krakow, 31-501

  • Study Site

    Wroclaw, Silesian Voivodeship, 50-367

Other trials in Poland

Spain3 sites
  • Study Site

    A Coruña

  • Study Site

    Barcelona

  • Study Site

    Valencia, 46026

Other trials in Spain

Ukraine3 sites
  • Study Site

    Dnipropetrovsk, 49102

  • Study Site

    Donetsk, 830045

  • Study Site

    Lviv, 79044

Other trials in Ukraine

Australia2 sites
  • Study Site

    Nedlands, WA 6009

  • Study Site

    Perth, WA 6000

Other trials in Australia

Austria2 sites
  • Study Site

    Graz, 8036

  • Study Site

    Vienna, 1090

Other trials in Austria

Philippines2 sites
  • Study Site

    Cebu City, 6000

  • Study Site

    Davao City, 8000

Other trials in Philippines

Russia2 sites
  • Study Site

    Barnaul, 656038

  • Study Site

    Kemerovo, 650066

Other trials in Russia

South Africa2 sites
  • Study Site

    Cape Town, 7295

  • Study Site

    Johannesburg, 2193

Other trials in South Africa

Canada1 site
  • Study Site

    New Brunswick, E2L 4L2

Other trials in Canada

Czechia1 site
  • Study Site

    Hradec Králové, 500 05

Other trials in Czechia

Hungary1 site
  • Study Site

    Debrecen, H-4032

Other trials in Hungary

Lebanon1 site
  • Study Site

    Beirut

Other trials in Lebanon

Malaysia1 site
  • Study Site

    Kuala Lumpur, 50400

Other trials in Malaysia

Netherlands1 site
  • Study Site

    Utrecht, 3584 CX

Other trials in Netherlands

Romania1 site
  • Study Site

    Bucharest, 011026

Other trials in Romania

United Kingdom1 site
  • Study Site

    London, NW3 2QG

Other trials in United Kingdom

About this study

Official title: A Phase I/III Open-label, Multicenter, Crossover Safety, Efficacy and Pharmacokinetic Study of Recombinant Coagulation Factor VIII (rFVIII) Compared to Recombinant Human Antihaemophilic Factor VIII (rFVIII; INN: Octocog Alfa) in Subjects With Hemophilia A, and a Repeat PK, Safety and Efficacy Study

This is an open-label, non-randomized, efficacy, safety and pharmacokinetic (PK) study comparing octocog alfa and rVIII-SingleChain. The study consists of three parts, a PK period (Part 1), a continuation of dosing safety and efficacy period (Part 2) and a safety, efficacy, and repeat PK period (Part 3) and also includes a surgical sub-study for subjects enrolled in Parts 2 and 3.

Conditions
Hemophilia A
Being tested
rVIII-SingleChain, Octocog alfa
Medical subject headings
Hemophilia A

What participants receive

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

  • rVIII-SingleChainBiological

    Also called Recombinant Factor VIII (rFVIII), CSL627

    In Part 1 of the study, subjects received a single intravenous infusion of 50 IU/kg recombinant, single-chain coagulation factor VIII (rVIII-SingleChain) preceded by a 4-day washout period. In Parts 2 and 3 of the study, subjects received repeat injections of rVIII-SingleChain either as an on-demand or prophylaxis regimen at a dose and frequency determined by their study doctor. Subjects participating in the Part 3 PK analyses received a single infusion of 50 IU/kg rVIII-SingleChain and a repeat dose of the same strength of rVIII-SingleChain after 3 to 6 months. Subjects from Parts 2 and 3 participating in the surgical substudy received an individualized dose regimen of rVIII-SingleChain, based on the type of surgery and the clinical status of the subject.

  • Octocog alfaBiological

    Also called Human coagulation factor VIII (rDNA)

    In Part 1 of the study, subjects received a single intravenous infusion of 50 IU/kg of octocog alfa preceded by a 4-day washout period. Octocog alfa is the international nonproprietary name (INN) for recombinant human coagulation factor VIII.

Study groups in NCT01486927
Study groupRoleWhat they receive
Recombinant Factor VIII (rFVIII)ExperimentalNot described
Receives: Biological: rVIII-SingleChain; Biological: Octocog alfa

What is being measured

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

  1. Treatment Success

    The investigator rated the efficacy of the treatment based on a 4-point rating scale "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point; the percentage of bleeding events with a rating of excellent or good and the 95% confidence interval are presented. The denominator includes all treated bleeding events. The 95% confidence interval is based on a model to account for within-subject correlation.

    Measured: Up to 24 months

  2. Inhibitor Formation to FVIII

    Number of subjects who develop inhibitors to FVIII

    Measured: Up to 24 months

  3. Annualized Spontaneous Bleeding Rate

    The annualized spontaneous bleeding rate (AsBR) was derived for each subject as follows: 365.25*(number of spontaneous bleeding episodes requiring treatment) / (observed treatment period of interest).

    Measured: Up to 24 months

  4. Treatment Success During the Peri-operative Surgical Sub-study

    Subjects received rVIII-SingleChain before and during surgery based on the type of surgery and the clinical status of the subject. The investigator rated the efficacy of the treatment based on a 4-point surgical treatment rating scale of "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point. The rate of success, defined as the percentage of surgeries with a rating of excellent or good for hemostatic efficacy on the surgical treatment scale is presented for the Surgical Population, based on the total number of surgeries (N=16) as denominator.

    Measured: From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)

Secondary outcomes (10)
  1. AUC0-∞ (Part 1)

    AUC0-∞ (AUC from 0 extrapolated to infinity) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.

    Measured: Before infusion and at up to 10 time points within 72 hours of infusion

  2. Cmax (Part 1)

    Cmax of a single infusion of octocog alfa and rVIII-SingleChain with correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.

    Measured: Before infusion and at up to 10 time points within 72 hours of infusion

  3. Tmax (Part 1)

    Tmax = time of Cmax (with correction for subject's predose plasma FVIII activity) after a single infusion of octocog alfa and rVIII-SingleChain.

    Measured: Before infusion and at up to 10 time points within 72 hours of infusion

  4. Half-life (t1/2) (Part 1)

    Half-life (t1/2) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity.

    Measured: Before infusion and at up to 10 time points within 72 hours of infusion.

  5. Mean Residence Time (MRT) (Part 1)

    Mean residence time (MRT) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity.

    Measured: Before infusion and at up to 10 time points within 72 hours of infusion

  6. Clearance (Cl) (Part 1)

    Clearance (Cl) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.

    Measured: Before infusion and at up to 10 time points within 72 hours of infusion

  7. Volume of Distribution at Steady-state (Vss) (Part 1)

    Volume of distribution at steady-state (Vss) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.

    Measured: Before infusion and at up to 10 time points within 72 hours of infusion

  8. Incremental Recovery (Part 1)

    Incremental recovery of a single infusion of octocog alfa and rVIII-SingleChain with correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.

    Measured: At 30 minutes after infusion

  9. Annualized Bleeding Rate for Total Bleeds and Traumatic Bleeds

    The annualized bleeding rate was derived for each subject as follows: 365.25*(number of bleeding episodes requiring treatment) / (observed treatment period of interest).

    Measured: Up to 24 months

  10. Proportion of Bleeding Episodes Requiring 1, 2, 3 or > 3 Infusions of rVIII-SingleChain to Achieve Hemostasis

    Percentage of bleeding episodes requiring 1, 2, 3 or > 3 infusions of rVIII-SingleChain to achieve hemostasis. The denominator includes all treated bleeding episodes.

    Measured: During the study (up to 24 months; assessed at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24)

Timeline

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

  1. First posted7 Dec 2011 (estimated)
  2. Study startFeb 2012
  3. Primary completionDec 2014
  4. Study completionDec 2014

Resources

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 2/3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
175 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01486927
Sponsor's protocol ID
CSL627_1001
Other IDs
2011-002393-23
Status last verified
Jun 2016
First submitted
19 Nov 2011
Last updated
9 Aug 2016

Publications

  • Mahlangu J, Kuliczkowski K, Karim FA, Stasyshyn O, Kosinova MV, Lepatan LM, Skotnicki A, Boggio LN, Klamroth R, Oldenburg J, Hellmann A, Santagostino E, Baker RI, Fischer K, Gill JC, P'Ng S, Chowdary P, Escobar MA, Khayat CD, Rusen L, Bensen-Kennedy D, Blackman N, Limsakun T, Veldman A, St Ledger K, Pabinger I; AFFINITY Investigators. Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A. Blood. 2016 Aug 4;128(5):630-7. doi: 10.1182/blood-2016-01-687434. Epub 2016 Jun 21.

    PubMed 27330001

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing rVIII-SingleChain and Octocog alfa in people with Hemophilia A, run by CSL Behring at 56 sites in 20 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 13 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 9 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 sites in United States, Japan, Germany, Italy, Poland and 15 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 combined 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.

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 9 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?

Treatment Success (time frame: Up to 24 months). The study lists 4 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 NCT01486927, which also lists 1 linked publication.

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 9 Aug 2016.

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