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NCT02973087

rVWF IN PROPHYLAXIS

Completed Phase 3 Results posted Last updated 6 August 2021
What this trial tests

Phase 3 trial testing von Willebrand factor (Recombinant) in Von Willebrand Disease in 29 participants. Completed in 6 July 2020.

Timeline
16 November 2017
Primary endpoint
6 July 2020
6 July 2020

Quick facts

Lead sponsorTakeda
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposeprevention
Enrollment29
Start date16 November 2017
Primary completion6 July 2020
Estimated completion6 July 2020
Sites35 locations across France, Italy, Netherlands, Russia, Germany, Canada, United States, Turkey (Türkiye)

Drugs / interventions tested

Conditions studied

Sponsor

Takeda — full company profile →

Who can join

18 and older, any sex, with Von Willebrand Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Ratio of Annualized Bleeding Rate (ABR) for Spontaneous Bleeding Episodes (BEs) (On-study ABR / Historical ABR) Assessed by Investigator During Prophylactic Treatment With rVWF Through Month 12 Primary · Up to 12 months

ABR for treated spontaneous BEs while on prophylactic treatment with rVWF through month 12 of treatment period/observation period (in years), where an observation period = (date of completion/termination - date of first dose + 1)/365.2425. Bleeds occurred at the same anatomical location with the same etiology within 24 hours after onset of the first bleed were considered a single bleed. Bleeding occurred at multiple locations related to the same injury were considered as a single bleeding episode. Historical observation period for historical BEs was 365 days prior to first dose of study drug.

GroupValue95% CI
Prior On-demand Participants0.0850.021 – 0.346
Switch Participants0.5500.086 – 3.523
Percentage of Prior On-demand Participants Achieved Spontaneous ABR Percent Reduction Success Through Month 12 Secondary · Up to 12 months

For prior on-demand participants, spontaneous ABR percent reduction success was defined as at least 25% reduction of the ABR for treated spontaneous (not related to trauma) BEs during the first 12 months of rVWF (vonicog alfa) prophylaxis relative to the participant's own historical treated spontaneous ABR. Percentage of participants with ABR percent reduction success for on-demand cohort was reported.

GroupValue95% CI
Prior On-demand Participants92.364.0 – 99.8
Percentage of Switch Participants With Spontaneous ABR Preservation Success Through Month 12 Secondary · Up to 12 months

For switch participants, spontaneous ABR preservation success was defined as achieving an ABR for treated spontaneous BEs during first 12 months of rVWF (vonicog alfa) prophylaxis that was no greater than the participant's own historical ABR for treated spontaneous BEs during prophylactic treatment with pdVWF. Percentage of participants with ABR preservation success in switch cohort was reported.

GroupValue95% CI
Switch Participants90.055.5 – 99.7
Number of Participants Based on Categorized Spontaneous ABR (sABR) Through Month 12 Secondary · Baseline through Month 12

The sABR was the number of spontaneous bleeds divided by the observation period in years, where an observation period = (date of completion/termination-date of first dose+1)/365.2425.sABR was categorized based on number of BEs as 0, greater than (\>) 0 through 2,\>2 through 5,\>5 during the prophylactic treatment with rVWF (vonicog alfa) through 12 months. Bleeding at multiple locations related to the same injury was counted as single bleeding episode. BEs of unknown cause were counted as spontaneous bleeds. Observation period for historical BEs was 365 days prior to first dose of study drug.

Historical
GroupValue95% CI
Prior On-demand Participants0
Switch Participants6
Prior On-demand Participants0
Switch Participants3
Prior On-demand Participants10
Switch Participants0
Prior On-demand Participants3
Switch Participants1
On-Study Through Month 12
GroupValue95% CI
Prior On-demand Participants11
Switch Participants7
Prior On-demand Participants0
Switch Participants1
Prior On-demand Participants1
Switch Participants1
Prior On-demand Participants1
Switch Participants1
Total Number of Infusions Administered Per Participant During Prophylactic Treatment With rVWF Through Month 12 Secondary · Up to 12 months

For each participant, the total number of infusions was counted as the total number of unique infusions of rVWF which were administered between the dates of informed consent and termination from the study, inclusive, regardless of the date and time of administration. The total number of infusions administered during the study was entered in electronic case record form (eCRF), and recorded in ERT system. Total number of infusions administered per participant during prophylactic treatment With rVWF through 12 months was calculated.

GroupValue95% CI
Prior On-demand Participants65.1± 38.4
Switch Participants87.8± 30.2
Average Number of Infusions Per Week Per Participant During Prophylactic Treatment With rVWF Through Month 12 Secondary · Up to 12 months

Average number of infusions per week per participant during prophylactic treatment With rVWF through 12 months was calculated.

GroupValue95% CI
Prior On-demand Participants1.88± 0.7
Switch Participants1.85± 0.4
Total Weight Adjusted Consumption of rVWF Per Participant During Prophylactic Treatment Through Month 12 Secondary · Up to 12 months

For each participant, the body weight-adjusted dose (IU/kg) was derived as the number of units of rVWF infused (IU) divided by the last available body weight (kilogram \[kg\]) prior to the infusion. Total weight adjusted consumption of rVWF (vonicog alfa) per participant during prophylactic treatment was reported.

GroupValue95% CI
Prior On-demand Participants3431.584± 2117.6562
Switch Participants4433.752± 1844.8761
Number of Treated Spontaneous BEs by Location of Bleeding While on Prophylactic Treatment With rVWF Through Month 12 Secondary · Up to 12 months

Number of treated spontaneous BEs by location of bleeding (for example: oral and other mucosa, menorrhagia, hemarthrosis, etc.) while on prophylactic treatment with rVWF was reported.

Oral and other mucosa
GroupValue95% CI
Prior On-demand Participants5
Switch Participants14
Menorrhagia
GroupValue95% CI
Prior On-demand Participants3
Switch Participants0
Hemarthrosis
GroupValue95% CI
Prior On-demand Participants0
Switch Participants1
Other
GroupValue95% CI
Prior On-demand Participants1
Switch Participants0
Unknown
GroupValue95% CI
Prior On-demand Participants0
Switch Participants3
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Secondary · From first dose of study drug up to end of study (approximately 32 months)

An adverse event (AE) is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Number of participants with TEAEs and serious TEAEs were reported.

Participants With TEAEs
GroupValue95% CI
Prior On-demand Participants10
Switch Participants7
Participants with serious TEAEs
GroupValue95% CI
Prior On-demand Participants1
Switch Participants2
Number of Participants Based on Severity of TEAEs Secondary · From first dose of study drug up to end of study (approximately 32 months)

An AE is defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. Severity of TEAEs was determined by following definitions: Mild: No limitation of usual activities; Moderate: Some limitation of usual activities and may required therapeutic intervention; Severe: Inability to carry out usual activities with sequelae, which required th

Mild
GroupValue95% CI
Prior On-demand Participants7
Switch Participants4
Moderate
GroupValue95% CI
Prior On-demand Participants1
Switch Participants2
Severe
GroupValue95% CI
Prior On-demand Participants2
Switch Participants1
Number of Participants With TEAEs Based Causality Secondary · From first dose of study drug up to end of study (approximately 32 months)

An AE was defined as any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. TEAEs were events which occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious AEs and non-serious AEs. For each AE, the investigator assessed the causal relationship between the IP and the AE based on clinical expertise and judgment according to the following circumstances of the AE: Not related, Unlikely related, Possibly related, or Probably related. A related TEAE w

GroupValue95% CI
Prior On-demand Participants1
Switch Participants0
Number of Participants With Thromboembolic Events Secondary · From first dose of study drug up to end of study (approximately 32 months)

Thromboembolism defined as formation in a blood vessel of a clot (thrombus) that breaks loose and carried by the blood stream and could plug another vessel. Number of participants with thromboembolic events as TEAEs of special interest was reported. A broad standard search query approach was used (broad SMQ) to identify all potential thromboembolic events of interest which were then medically assessed. Number of participants with thromboembolic events as TEAEs of special interest was reported.

GroupValue95% CI
Prior On-demand Participants1
Switch Participants0

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug up to end of study (approximately 32 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Prior On-demand Participants
Serious: 1/13 (8%)
Deaths: 0/13
Switch Participants
Serious: 2/10 (20%)
Deaths: 0/10

Serious adverse events (3 terms)

ReactionSystemPrior On-demand ParticipantsSwitch Participants
Urinary tract infectionInfections and infestations
Multiple injuriesInjury, poisoning and procedural complications
Rheumatoid arthritisMusculoskeletal and connective tissue disorders
Other adverse events (29 terms — click to expand)

ReactionSystemPrior On-demand ParticipantsSwitch Participants
HeadacheNervous system disorders
Ear infectionInfections and infestations
GastroenteritisInfections and infestations
Joint injuryInjury, poisoning and procedural complications
ArthralgiaMusculoskeletal and connective tissue disorders
Supraventricular tachycardiaCardiac disorders
Ventricular extrasystolesCardiac disorders
DiarrhoeaGastrointestinal disorders
FlatulenceGastrointestinal disorders
ToothacheGastrointestinal disorders
Injection site irritationGeneral disorders
Herpes virus infectionInfections and infestations
NasopharyngitisInfections and infestations
Oral herpesInfections and infestations
PharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
FallInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
GoutMetabolism and nutrition disorders
Increased appetiteMetabolism and nutrition disorders
Iron deficiencyMetabolism and nutrition disorders
Vitamin B12 deficiencyMetabolism and nutrition disorders
Neck painMusculoskeletal and connective tissue disorders
Seronegative arthritisMusculoskeletal and connective tissue disorders
Sleep disorderPsychiatric disorders
PurpuraSkin and subcutaneous tissue disorders
Rash pruriticSkin and subcutaneous tissue disorders

Most-reported serious reactions: Urinary tract infection, Multiple injuries, Rheumatoid arthritis.

Data from ClinicalTrials.gov NCT02973087 adverse events section.

Sponsor's own description

The purpose of this phase 3 study is to investigate the efficacy and safety, including immunogenicity, thrombogenicity and hypersensitivity reactions, as well as pharmacokinetics (PK), health related quality of life (HRQoL) and pharmacoeconomics of prophylactic treatment with recombinant von Willebrand factor (rVWF) (vonicog alfa) in adult participants with severe von Willebrand disease (VWD).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Recombinant von Willebrand factor prophylaxis in patients with severe von Willebrand disease: phase 3 study results.
    Leebeek FWG, Peyvandi F, Escobar M, Tiede A, et al · · 2022 · cited 28× · PMID 35439298 · DOI 10.1182/blood.2021014810
  2. How I manage severe von Willebrand disease.
    Leebeek FWG, Atiq F. · · 2019 · cited 27× · PMID 31498884 · DOI 10.1111/bjh.16186
  3. New therapies for von Willebrand disease.
    Mannucci PM. · · 2019 · cited 25× · PMID 31714963 · DOI 10.1182/bloodadvances.2019000368
  4. von Willebrand factor/factor VIII concentrate (Wilate) prophylaxis in children and adults with von Willebrand disease.
    Sidonio RF, Boban A, Dubey L, Inati A, et al · · 2024 · cited 15× · PMID 38237075 · DOI 10.1182/bloodadvances.2023011742
  5. Prophylactic management of patients with von Willebrand disease.
    Franchini M, Seidizadeh O, Mannucci PM. · · 2021 · cited 14× · PMID 34987743 · DOI 10.1177/20406207211064064
  6. New therapies for von Willebrand disease.
    Mannucci PM. · · 2019 · cited 7× · PMID 31808884 · DOI 10.1182/hematology.2019000368
  7. 2025 ASH ISTH NBDF WFH monitoring report on the 2021 clinical guidelines on the diagnosis and management of von Willebrand disease.
    James PD, Flood VH, Connell NT. · · 2025 · cited 4× · PMID 40273329 · DOI 10.1182/bloodadvances.2025016512
  8. Prophylaxis in von Willebrand disease with von Willebrand factor concentrate and nonfactor therapies.
    van Kwawegen CB, Leebeek FWG. · · 2024 · cited 3× · PMID 39628990 · DOI 10.1016/j.rpth.2024.102599

Verify or expand the search:

Other recruiting trials for Von Willebrand Disease

Currently open trials in the same condition.

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Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing