Haemophilia APhase 3NCT01311648

BAY81-8973 Pediatric Safety and Efficacy Trial

A Phase 3 study testing Recombinant Factor VIII (Kovaltry, BAY81-8973) in people with Haemophilia A, run by Bayer at 43 sites in 17 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

The primary objective was to evaluate the safety and efficacy of the treatment with BAY81-8973 for prophylaxis and treatment of breakthrough bleeds in children with severe hemophilia A. The secondary objectives were To assess the safety and efficacy of BAY81-8973 during surgeries. Read more about this study

Who is it for?: Ages 0 to 12 years, men only
Conditions the study is for: Haemophilia A
What is being tested?: Recombinant Factor VIII (Kovaltry, BAY81-8973)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 94 participants
Where: 43 sitesin 17 countries
Study dates: 9 Jun 2011to 27 Oct 2020
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 0 to 12 years
Men only
No healthy volunteers
Child

Who may be able to join

Male
PTPs (previously treated patients): aged <= 12 years
PUPs (previously untreated patients) / MTPs (minimally treated patients): aged < 6 years
Severe hemophilia A defined as < 1% FVIII concentration (FVIII:C)
PTPs: >= 50 exposure days (EDs) with any FVIII concentrate, no current evidence of inhibitory antibody, and no history of FVIII inhibitor formation
PUPs: no prior exposure to any FVIII product
MTPs: having no more than 3 EDs with any FVIII product, no current evidence of inhibitory antibody and no history of FVIII inhibitor formation

Who cannot join

With another bleeding disorder that is different from Hemophilia A
With thrombocytopenia (platelet count < 100 000/mm^3)
Creatinine > 2x upper limit of normal or Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) > 5x upper limit of normal
Without a negative inhibitor testing at screening (except for PUPs)
Receiving chemotherapy, immune modulatory drugs, has received another investigational FVIII product within the last month, or received another experimental drug within the last 3 months
Requires any pre-medication to tolerate FVIII treatment
Known hypersensitivity to active substance, mouse, or hamster protein

Trial locations and contacts

43 sites in 17 countries.

Country

City, postcode or hospital

43 sites in 17 countries

Spain6 sites

Study site
A Coruña, 15006
Study site
Alicante, 03010
Study site
Cáceres, 10003
Study site
Esplugues de Llobregat, Barcelona, 8950
Study site
Madrid, 28046
Study site
Valencia, 46026

Other trials in Spain

Italy5 sites

Study site
Bari, Apulia, 70126
Study site
Catania, Sicily, 95123
Study site
Milan, Lombardy, 20122
Study site
Padova, Veneto, 35128
Study site
Rome, Lazio, 00165

Other trials in Italy

United States4 sites

Study site
Cincinnati, Ohio, 45229
Study site
Cleveland, Ohio, 44106
Study site
Columbus, Ohio, 43205-2696
Study site
New Orleans, Louisiana, 70112

Other trials in United States

Romania4 sites

Study site
Bucharest, 011026
Study site
Bucharest, 022328
Study site
Cluj-Napoca, 400177
Study site
Timișoara, 300011

Other trials in Romania

Canada3 sites

Study site
Edmonton, Alberta, T6G 2C8
Study site
Hamilton, Ontario, L8N 3Z5
Study site
Toronto, Ontario, M5G 1X8

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Hungary3 sites

Study site
Budapest, 1089
Study site
Debrecen, 4032
Study site
Mohács, 7700

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Mexico3 sites

Study site
Guadalajara, Jalisco, 44280
Study site
Oaxaca City, 68000
Study site
San Juan del Río, Querétaro, 76800

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Poland3 sites

Study site
Lodz, 91-738
Study site
Warsaw, 00-576
Study site
Wroclaw, 50-368

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Russia3 sites

Study site
Kazan', 139445
Study site
Kirov, 610027
Study site
Volgograd, 400138

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Bulgaria2 sites

Study site
Plovdiv, 4002
Study site
Varna, 9010

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Argentina1 site

Study site
Bahía Blanca, Buenos Aires, B8001HXM

Other trials in Argentina

Denmark1 site

Study site
Århus N, 8200

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Ireland1 site

Study site
Crumlin, Dublin, 12

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Israel1 site

Study site
Ramat Gan, 5262000

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Latvia1 site

Study site
Riga, LV-1004

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Lithuania1 site

Study site
Vilnius, 08406

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Norway1 site

Study site
Oslo

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About this study

Official title: A Multicenter Phase III Uncontrolled Open-label Trial to Evaluate Safety and Efficacy of BAY81-8973 in Children With Severe Hemophilia A Under Prophylaxis Therapy

The primary objective was to evaluate the safety and efficacy of the treatment with BAY81-8973 for prophylaxis and treatment of breakthrough bleeds in children with severe hemophilia A.

The secondary objectives were

To assess the safety and efficacy of BAY81-8973 during surgeries.
To assess incremental recovery of BAY81-8973.
To assess pharmacokinetic (PK) parameters in a subset of children (Previously treated patients [PTPs] and previously untreated patients [PUPs] / minimally treated patients [MTPs] - participation in PK sampling was voluntary and required consent).

Conditions: Haemophilia A
Being tested: Recombinant Factor VIII (Kovaltry, BAY81-8973)
Keywords: Recombinant factor VIII, Pediatric use
Medical subject headings: Hemophilia A

What participants receive

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

Recombinant Factor VIII (Kovaltry, BAY81-8973)Biological
Main study: 25-50 IU/kg at least 2x/week for 6 months and at least 50 EDs, IV infusion; Extension study: 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part A and extension study), IV infusion. Exposure day (ED): An ED is a unit of time (1 day) in which replacement treatment of Hemophilia is given to a patient.
Recombinant Factor VIII (Kovaltry, BAY81-8973)Biological
Main study: 15-50 IU/kg at least 1x/week for at least 50 EDs or until inhibitor development, IV infusion; Extension study: For participants having reached at least 50 EDs in main study - Part B: 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part B and extension study), IV infusion. For participants who developed an inhibitor in main study - Part B: up to 200 IU/kg per day or 100 IU/kg twice a day at the discretion of the investigator and coordinating investigator until successful eradication of the inhibitor, or until failure, for up to18 months (treatment beyond 18 months required an agreement with the sponsor and coordinating investigator), IV infusion

Study groups in NCT01311648
Study group	Role	What they receive
PTPs 0-12 years	Experimental	Previously treated patients (PTPs) aged below 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (EDs) in main study - Part A. Participants having reached at least 50 EDs in main study - Part A were offered participation in an open label extension study (optional). Participants who transitioned from main study - Part A to the extension study received BAY81-8973, 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part A and extension study). Receives: Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973)
PUPs/MTPs 0-<6 years	Experimental	Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days (EDs) with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for at least 50 EDs or until inhibitor development in main study - Part B. Participants having reached at least 50 EDs in main study - Part B were offered participation in an open label extension study and received BAY81-8973 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part B and extension study); participants who developed an inhibitor in main study - Part B were offered participation in open label extension study and received Immune Tolerance Induction (ITI) treatment with BAY81-8973 until successful eradication of the inhibitor, or until failure, for approximately 18 months. Receives: Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973)

What is being measured

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

Annualized Number of Total Bleeds Within 48 h
Annualized number (mean +/- standard deviation) of total bleeds that occurred within 48 hours after all prophylaxis infusions (Part A: 6 months and at least 50 exposure days [EDs]; Part B: at least 50 EDs or until inhibitor development) was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
Measured: Within 48 hours post infusion
Annualized Number of Total Bleeds Within 48 h
Annualized number (median [inter-quartile range (Q1-Q3)]) of total bleeds that occurred within 48 hours after all prophylaxis infusions (Part A: 6 months and at least 50 exposure days [EDs]; Part B: at least 50 EDs or until inhibitor development) was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
Measured: Within 48 hours post infusion

Secondary outcomes (12)

Annualized Number of Total Bleeds During Prophylaxis Treatment
Annualized number (mean +/- standard deviation) of total bleeds that occurred during prophylaxis treatment was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
Measured: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Annualized Number of Total Bleeds During Prophylaxis Treatment
Annualized number (median [inter-quartile range (Q1-Q3)]) of total bleeds that occurred during prophylaxis treatment was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
Measured: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Hemostatic Control During Major and Minor Surgeries
For participants who underwent major or minor surgeries during the study, hemostasis during the surgeries was assessed as excellent, good, moderate or poor. Number of surgeries per assessment was summarized and reported.
Measured: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Number of Participants With Inhibitor Development in Main Study
Number of participants with confirmed positive FVIII inhibitor titer (≥ 0.6 Bethesda unit [BU/mL]) during the main study was summarized and classified as participants developing low titer inhibitor (i.e. ≥ 0.6 to ≤ 5.0 BU/mL) and participants developing high titer inhibitor (i.e. > 5.0 BU/mL).
Measured: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Number of Participants With New Inhibitor Development in Extension Study
Number of participants who had not developed an inhibitor during the main study but developed an inhibitor (confirmed positive FVIII inhibitor titer [≥ 0.6 BU/mL]) during the extension study was summarized and classified as participants developing low titer inhibitor (i.e. ≥ 0.6 to ≤ 5.0 BU/mL) and participants developing high titer inhibitor (i.e. > 5.0 BU/mL).
Measured: From start of extension study to at least 100 cumulative exposure days (EDs) (median 421 EDs; median 3.8 years)
Factor VIII Recovery Values
Incremental recovery of Factor VIII (FVIII) at 20-30 min after end of infusions was determined and mean recovery values were reported.
Measured: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Consumption of Factor VIII in All Infusions
Factor VIII (FVIII) usage/consumption was summarized for all infusions. Consumption per participant's body weight per year was calculated and reported.
Measured: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Consumption of FVIII in Infusions for Prophylaxis
Factor VIII (FVIII) usage/consumption was summarized for prophylaxis infusions. Consumption per participant's body weight per year was calculated and reported.
Measured: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Consumption of FVIII in Infusions for the Treatment of Bleeds
Factor VIII (FVIII) usage/consumption was summarized for infusions used to treat breakthrough bleeds. Consumption per participant's body weight per year was calculated and reported.
Measured: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Number of Infusions Per Bleed
The number of infusions used to treat a bleed was defined as the first infusion to treat the bleed plus all follow-up infusions to treat the same bleed, if any. The mean value of number of infusions for each bleed was calculated and reported.
Measured: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Response to Treatment of Bleeds
Participants or caregivers were asked to assess the response to treatment of bleeds as excellent, good, moderate or poor. Percentage of bleeds per assessment was summarized and reported.
Measured: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Half-life (t1/2) of BAY81-8973 in Plasma
Half-life (t1/2) of BAY81-8973 in plasma was measured. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: Pre-infusion and until 24 hours post infusion

Timeline

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

9 Jun 201127 Oct 2020

First posted9 Mar 2011 (estimated)
Study start9 Jun 2011
Primary completion9 Sep 2019
Study completion27 Oct 2020

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.
Publications (11)Papers the sponsor has linked to this study.
Other trials for Haemophilia AStudies of the same condition, open and under way.
More trials run by BayerThe 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: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 94 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01311648
Sponsor's protocol ID: 13400
Other IDs: 2010-021781-29
Status last verified: Nov 2023
First submitted: 18 Feb 2011
Last updated: 5 Dec 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Oldenburg J, Windyga J, Hampton K, Lalezari S, Tseneklidou-Stoeter D, Beckmann H, Maas Enriquez M. Safety and efficacy of BAY 81-8973 for surgery in previously treated patients with haemophilia A: results of the LEOPOLD clinical trial programme. Haemophilia. 2016 May;22(3):349-53. doi: 10.1111/hae.12839. Epub 2016 Mar 1.
PubMed 26931631
Ljung R, Kenet G, Mancuso ME, Kaleva V, Rusen L, Tseneklidou-Stoeter D, Michaels LA, Shah A, Hong W, Maas Enriquez M; investigators of the LEOPOLD Kids Trial. BAY 81-8973 safety and efficacy for prophylaxis and treatment of bleeds in previously treated children with severe haemophilia A: results of the LEOPOLD Kids Trial. Haemophilia. 2016 May;22(3):354-60. doi: 10.1111/hae.12866. Epub 2015 Dec 9.
PubMed 26663410
Keating GM. BAY 81-8973 (Octocog Alfa; Kovaltry(R)): A Review in Haemophilia A. BioDrugs. 2016 Oct;30(5):453-459. doi: 10.1007/s40259-016-0191-4.
PubMed 27577234
Shah A, Delesen H, Garger S, Lalezari S. Pharmacokinetic properties of BAY 81-8973, a full-length recombinant factor VIII. Haemophilia. 2015 Nov;21(6):766-71. doi: 10.1111/hae.12691. Epub 2015 May 8.
PubMed 25952661
Maas Enriquez M, Thrift J, Garger S, Katterle Y. BAY 81-8973, a full-length recombinant factor VIII: Human heat shock protein 70 improves the manufacturing process without affecting clinical safety. Protein Expr Purif. 2016 Nov;127:111-115. doi: 10.1016/j.pep.2016.07.009. Epub 2016 Jul 18.
PubMed 27436242
Garmann D, McLeay S, Shah A, Vis P, Maas Enriquez M, Ploeger BA. Population pharmacokinetic characterization of BAY 81-8973, a full-length recombinant factor VIII: lessons learned - importance of including samples with factor VIII levels below the quantitation limit. Haemophilia. 2017 Jul;23(4):528-537. doi: 10.1111/hae.13192. Epub 2017 Feb 20.
PubMed 28220555
Mahlangu JN, Ahuja SP, Windyga J, Church N, Shah A, Schwartz L. BAY 81-8973, a full-length recombinant factor VIII for the treatment of hemophilia A: product review. Ther Adv Hematol. 2018 Jul;9(7):191-205. doi: 10.1177/2040620718777903. Epub 2018 Jun 12.
PubMed 30013766
Kenet G, Ljung R, Rusen L, Kerlin BA, Blanchette V, Saulyte Trakymiene S, Uscatescu V, Beckmann H, Tseneklidou-Stoeter D, Church N. Continued benefit demonstrated with BAY 81-8973 prophylaxis in previously treated children with severe haemophilia A: Interim analysis from the LEOPOLD Kids extension study. Thromb Res. 2020 May;189:96-101. doi: 10.1016/j.thromres.2020.03.005. Epub 2020 Mar 9.
PubMed 32197139
Kenet G, Moulton T, Wicklund BM, Ahuja SP, Escobar M, Mahlangu J. Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials. J Blood Med. 2023 Jun 7;14:379-388. doi: 10.2147/JBM.S405624. eCollection 2023.
PubMed 37309365
Ljung R, Chan AKC, Glosli H, Afonja O, Becker B, Tseneklidou-Stoeter D, Mancuso ME, Saulyte-Trakymiene S, Kenet G. BAY 81-8973 Efficacy and Safety in Previously Untreated and Minimally Treated Children with Severe Hemophilia A: The LEOPOLD Kids Trial. Thromb Haemost. 2023 Jan;123(1):27-39. doi: 10.1055/s-0042-1757876. Epub 2023 Jan 10.
PubMed 36626898
Ljung R, Chan AKC, Ahuja SP, Mancuso ME, Marquez JFC, Volk F, Blanchette V, Kerlin BA, Trakymiene SS, Glosli H, Kenet G. BAY 81-8973 Demonstrates Long-Term Safety and Efficacy in Children With Severe Haemophilia A: Results From the LEOPOLD Kids Extension Study. Eur J Haematol. 2025 Mar;114(3):556-565. doi: 10.1111/ejh.14362. Epub 2024 Dec 12.
PubMed 39667975

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?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter Phase III Uncontrolled Open-label Trial to Evaluate Safety and Efficacy of BAY81-8973 in Children With Severe Hemophilia A Under Prophylaxis Therapy
ClinicalTrials.gov ID: NCT01311648
Acronym / sponsor ID: 13400
Conditions: Haemophilia A
Keywords: Recombinant factor VIII, Pediatric use
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 94 participants (actual)
Lead sponsor: BayerIndustry (pharma, biotech, devices)
Study start: 9 Jun 2011 (actual)
Primary completion: 9 Sep 2019 (actual)
Study completion: 27 Oct 2020 (actual)
First posted: 9 Mar 2011 (estimated)
Results: Posted 3 Nov 2020

Clinical summary

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

The primary objective was to evaluate the safety and efficacy of the treatment with BAY81-8973 for prophylaxis and treatment of breakthrough bleeds in children with severe hemophilia A.

The secondary objectives were

To assess the safety and efficacy of BAY81-8973 during surgeries.
To assess incremental recovery of BAY81-8973.
To assess pharmacokinetic (PK) parameters in a subset of children (Previously treated patients [PTPs] and previously untreated patients [PUPs] / minimally treated patients [MTPs] - participation in PK sampling was voluntary and required consent).

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
PTPs 0-12 years	Experimental	Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973)Previously treated patients (PTPs) aged below 12 years received BAY81-8973 25-50 IU/kg at least 2x/week for 6 months and at least 50 exposure days (EDs) in main study - Part A. Participants having reached at least 50 EDs in main study - Part A were offered participation in an open label extension study (optional). Participants who transitioned from main study - Part A to the extension study received BAY81-8973, 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part A and extension study).
PUPs/MTPs 0-<6 years	Experimental	Biological: Recombinant Factor VIII (Kovaltry, BAY81-8973)Previously untreated patients (PUPs) or minimally treated patients (MTPs, patients who had no more than 3 exposure days (EDs) with any FVIII product) received BAY81-8973 15-50 IU/kg at least 1x/week for at least 50 EDs or until inhibitor development in main study - Part B. Participants having reached at least 50 EDs in main study - Part B were offered participation in an open label extension study and received BAY81-8973 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part B and extension study); participants who developed an inhibitor in main study - Part B were offered participation in open label extension study and received Immune Tolerance Induction (ITI) treatment with BAY81-8973 until successful eradication of the inhibitor, or until failure, for approximately 18 months.

Who may qualify

Ages: 0 to 12 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (7 listed)

Male
PTPs (previously treated patients): aged <= 12 years
PUPs (previously untreated patients) / MTPs (minimally treated patients): aged < 6 years
Severe hemophilia A defined as < 1% FVIII concentration (FVIII:C)
PTPs: >= 50 exposure days (EDs) with any FVIII concentrate, no current evidence of inhibitory antibody, and no history of FVIII inhibitor formation

Key exclusion criteria (7 listed)

With another bleeding disorder that is different from Hemophilia A
With thrombocytopenia (platelet count < 100 000/mm^3)
Creatinine > 2x upper limit of normal or Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) > 5x upper limit of normal
Without a negative inhibitor testing at screening (except for PUPs)
Receiving chemotherapy, immune modulatory drugs, has received another investigational FVIII product within the last month, or received another experimental drug within the last 3 months

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
Recombinant Factor VIII (Kovaltry, BAY81-8973)Main study: 25-50 IU/kg at least 2x/week for 6 months and at least 50 EDs, IV infusion; Extension study: 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part A and extension study), IV infusion. Exposure day (ED): An ED is a unit of time (1 day) in which replacement treatment of Hemophilia is given to a patient.	Biological	PTPs 0-12 years
Recombinant Factor VIII (Kovaltry, BAY81-8973)Main study: 15-50 IU/kg at least 1x/week for at least 50 EDs or until inhibitor development, IV infusion; Extension study: For participants having reached at least 50 EDs in main study - Part B: 25-50 IU/kg at least 2x/week for at least 100 cumulative EDs (main study - Part B and extension study), IV infusion. For participants who developed an inhibitor in main study - Part B: up to 200 IU/kg per day or 100 IU/kg twice a day at the discretion of the investigator and coordinating investigator until successful eradication of the inhibitor, or until failure, for up to18 months (treatment beyond 18 months required an agreement with the sponsor and coordinating investigator), IV infusion	Biological	PUPs/MTPs 0-<6 years

Primary outcome

Annualized Number of Total Bleeds Within 48 h
Time frame: Within 48 hours post infusion
Annualized number (mean +/- standard deviation) of total bleeds that occurred within 48 hours after all prophylaxis infusions (Part A: 6 months and at least 50 exposure days [EDs]; Part B: at least 50 EDs or until inhibitor development) was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').
Annualized Number of Total Bleeds Within 48 h
Time frame: Within 48 hours post infusion
Annualized number (median [inter-quartile range (Q1-Q3)]) of total bleeds that occurred within 48 hours after all prophylaxis infusions (Part A: 6 months and at least 50 exposure days [EDs]; Part B: at least 50 EDs or until inhibitor development) was summarized and reported. Total bleeds: sum of spontaneous bleeds, trauma bleeds (only treated bleeds were classified as spontaneous or trauma), untreated bleeds and 'other' bleeds ('other' bleeds were infusions with reason given as 'other').

12 secondary outcomes

Annualized Number of Total Bleeds During Prophylaxis Treatment
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Annualized Number of Total Bleeds During Prophylaxis Treatment
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Hemostatic Control During Major and Minor Surgeries
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Number of Participants With Inhibitor Development in Main Study
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Number of Participants With New Inhibitor Development in Extension Study
Time frame: From start of extension study to at least 100 cumulative exposure days (EDs) (median 421 EDs; median 3.8 years)
Factor VIII Recovery Values
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Consumption of Factor VIII in All Infusions
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Consumption of FVIII in Infusions for Prophylaxis
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Consumption of FVIII in Infusions for the Treatment of Bleeds
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Number of Infusions Per Bleed
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Response to Treatment of Bleeds
Time frame: Part A: 6 months and at least 50 exposure days (EDs) (median 73 EDs; median 6 months); Part B: at least 50 EDs or until inhibitor development (median 46 EDs; median 8 months)
Half-life (t1/2) of BAY81-8973 in Plasma
Time frame: Pre-infusion and until 24 hours post infusion

Results and safety

Results posted to the registry on 3 Nov 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PTPs 0-12 Years	51	51
PUPs/MTPs 0-<6 Years	43	22

Primary outcome: Annualized Number of Total Bleeds Within 48 h

Time frame: Within 48 hours post infusion. Mean (Standard Deviation). Unit: Bleeds

Measure	Main Study - Part A: PTPs 0-<6 Years n = 25	Main Study - Part A: PTPs 6-12 Years n = 26	Main Study - Part B: PUPs/MTPs 0-<6 Years n = 43
Value	2.23 (2.77)	1.86 (3.08)	1.9 (3.3)

Population analysed: Intent-to-treat (ITT) analysis set - main study: all participants of the SAF in main study who had infusion/bleeding data from the electronic patient diary (EPD)

Primary outcome: Annualized Number of Total Bleeds Within 48 h

Time frame: Within 48 hours post infusion. Median (Inter-Quartile Range). Unit: Bleeds

Measure	Main Study - Part A: PTPs 0-<6 Years n = 25	Main Study - Part A: PTPs 6-12 Years n = 26	Main Study - Part B: PUPs/MTPs 0-<6 Years n = 43
Value	1.88 (0.00)	0.00 (0.00)	0.0 (0.0)

Population analysed: Intent-to-treat (ITT) analysis set - main study: all participants of the SAF in main study who had infusion/bleeding data from the electronic patient diary (EPD)

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Main study - Part A: from the first BAY81-8973 infusion until 3 days after the last infusion (median 6 months); Main study - Part B: from the first BAY81-8973 infusion until 7 days after the last infusion (median 8 months); Extension: from start of extension study until 3 days after the last infusion in extension study (median 3.1 years). Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Main Study - Part A: PTPs 0-<6 Years	0 of 25 (0%)	16 of 25 (64%)	0 of 25
Main Study - Part A: PTPs 6-12 Years	5 of 26 (19.2%)	19 of 26 (73.1%)	0 of 26
Main Study - Part B: PUPs/MTPs 0-<6 Years	26 of 43 (60.5%)	28 of 43 (65.1%)	0 of 43
Extension Study - Former Part A Participants	23 of 46 (50%)	41 of 46 (89.1%)	0 of 46
Extension Study - Former Part B Participants	14 of 36 (38.9%)	24 of 36 (66.7%)	0 of 36

Limitations and caveats (from the sponsor): Due to the small number of participants per reporting group, all presented summary measures (e.g. mean and proportion) have to be evaluated with caution. If displayed standard deviation should be taken into account. The participant who had a low titer inhibitor detected after 549 EDs during the extension study was considered to have a false positive result due to cross reactivity with IgG anticardiolipin antibodies.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 26931631Oldenburg J, Windyga J, Hampton K, Lalezari S, Tseneklidou-Stoeter D, Beckmann H, Maas Enriquez M. Safety and efficacy of BAY 81-8973 for surgery in previously treated patients with haemophilia A: results of the LEOPOLD clinical trial programme. Haemophilia. 2016 May;22(3):349-53. doi: 10.1111/hae.12839. Epub 2016 Mar 1.
Results publication: PubMed 26663410Ljung R, Kenet G, Mancuso ME, Kaleva V, Rusen L, Tseneklidou-Stoeter D, Michaels LA, Shah A, Hong W, Maas Enriquez M; investigators of the LEOPOLD Kids Trial. BAY 81-8973 safety and efficacy for prophylaxis and treatment of bleeds in previously treated children with severe haemophilia A: results of the LEOPOLD Kids Trial. Haemophilia. 2016 May;22(3):354-60. doi: 10.1111/hae.12866. Epub 2015 Dec 9.
Results publication: PubMed 27577234Keating GM. BAY 81-8973 (Octocog Alfa; Kovaltry(R)): A Review in Haemophilia A. BioDrugs. 2016 Oct;30(5):453-459. doi: 10.1007/s40259-016-0191-4.
Results publication: PubMed 25952661Shah A, Delesen H, Garger S, Lalezari S. Pharmacokinetic properties of BAY 81-8973, a full-length recombinant factor VIII. Haemophilia. 2015 Nov;21(6):766-71. doi: 10.1111/hae.12691. Epub 2015 May 8.
Results publication: PubMed 27436242Maas Enriquez M, Thrift J, Garger S, Katterle Y. BAY 81-8973, a full-length recombinant factor VIII: Human heat shock protein 70 improves the manufacturing process without affecting clinical safety. Protein Expr Purif. 2016 Nov;127:111-115. doi: 10.1016/j.pep.2016.07.009. Epub 2016 Jul 18.
Results publication: PubMed 28220555Garmann D, McLeay S, Shah A, Vis P, Maas Enriquez M, Ploeger BA. Population pharmacokinetic characterization of BAY 81-8973, a full-length recombinant factor VIII: lessons learned - importance of including samples with factor VIII levels below the quantitation limit. Haemophilia. 2017 Jul;23(4):528-537. doi: 10.1111/hae.13192. Epub 2017 Feb 20.
Results publication: PubMed 30013766Mahlangu JN, Ahuja SP, Windyga J, Church N, Shah A, Schwartz L. BAY 81-8973, a full-length recombinant factor VIII for the treatment of hemophilia A: product review. Ther Adv Hematol. 2018 Jul;9(7):191-205. doi: 10.1177/2040620718777903. Epub 2018 Jun 12.
Results publication: PubMed 32197139Kenet G, Ljung R, Rusen L, Kerlin BA, Blanchette V, Saulyte Trakymiene S, Uscatescu V, Beckmann H, Tseneklidou-Stoeter D, Church N. Continued benefit demonstrated with BAY 81-8973 prophylaxis in previously treated children with severe haemophilia A: Interim analysis from the LEOPOLD Kids extension study. Thromb Res. 2020 May;189:96-101. doi: 10.1016/j.thromres.2020.03.005. Epub 2020 Mar 9.
Results publication: PubMed 37309365Kenet G, Moulton T, Wicklund BM, Ahuja SP, Escobar M, Mahlangu J. Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials. J Blood Med. 2023 Jun 7;14:379-388. doi: 10.2147/JBM.S405624. eCollection 2023.
Results publication: PubMed 36626898Ljung R, Chan AKC, Glosli H, Afonja O, Becker B, Tseneklidou-Stoeter D, Mancuso ME, Saulyte-Trakymiene S, Kenet G. BAY 81-8973 Efficacy and Safety in Previously Untreated and Minimally Treated Children with Severe Hemophilia A: The LEOPOLD Kids Trial. Thromb Haemost. 2023 Jan;123(1):27-39. doi: 10.1055/s-0042-1757876. Epub 2023 Jan 10.
Derived from this study: PubMed 39667975Ljung R, Chan AKC, Ahuja SP, Mancuso ME, Marquez JFC, Volk F, Blanchette V, Kerlin BA, Trakymiene SS, Glosli H, Kenet G. BAY 81-8973 Demonstrates Long-Term Safety and Efficacy in Children With Severe Haemophilia A: Results From the LEOPOLD Kids Extension Study. Eur J Haematol. 2025 Mar;114(3):556-565. doi: 10.1111/ejh.14362. Epub 2024 Dec 12.
Click here to find information about studies related to Bayer Healthcare products conducted in EuropeLink provided by the sponsor.

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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.

Bayer Study Director study director

Bayer

43 sites in 17 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Recombinant Factor VIII (Kovaltry, BAY81-8973) in people with Haemophilia A, run by Bayer at 43 sites in 17 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 5 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in Spain, Italy, United States, Romania, Canada and 12 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 Nov 2020). 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 Number of Total Bleeds Within 48 h (time frame: Within 48 hours post infusion). 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 NCT01311648, which also lists 11 linked publications.

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 5 Dec 2023.