Phase 3
N=159
A Phase 3 Open-label Interventional Study of Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein, Efanesoctocog Alfa (BIVV001), in Patients With Severe Hemophilia A
Factor VIII Deficiency
Bottom Line
View on ClinicalTrials.gov: NCT04161495 ↗Enrolled (actual)
159
Serious AEs
8.7%
Results posted
May 2023
Primary outcome: Primary: Estimated Annualized Bleeding Rate (ABR) in Arm A: Prophylaxis — 0.71 episodes per participant per year
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- efanesoctocog alfa (BIVV001) (Biological)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- All
- Sponsor
- Bioverativ, a Sanofi company
- Primary completion
- Feb 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Estimated Annualized Bleeding Rate (ABR) in Arm A: Prophylaxis |
0.71 | — |
| PRIMARY Observed Annualized Bleeding Rate in Arm A: Prophylaxis |
0.71 | — |
| SECONDARY Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Non-inferiority Analysis |
2.99; 0.69 | — |
| SECONDARY Observed Annualized Bleeding Rate During the Efficacy Period in Prophylaxis - Non-inferiority Analysis |
2.98; 0.69 | — |
| SECONDARY Estimated Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis |
2.96; 0.69 | <0.0001 sig |
| SECONDARY Observed Annualized Bleeding Rate During the Efficacy Period in Arm A: Prophylaxis - Superiority Analysis |
2.95; 0.68 | — |
| SECONDARY Change From Baseline in Hemophilia-specific Health-related Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Domain Score at Week 52 in Arm A: Prophylaxis |
-6.79 | 0.0001 sig |
| SECONDARY Change From Baseline in Patient Reported Outcomes Measurements Information Systems (PROMIS) Pain Intensity 3a Score at Week 52 in Arm A: Prophylaxis |
-1.97 | 0.0042 sig |
| SECONDARY Change From Baseline in Hemophilia Joint Health Score (HJHS) Total Score at Week 52 in Arm A: Prophylaxis |
-1.5 | 0.0101 sig |
| SECONDARY Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type) |
0.00; 16.69; 0.00; 0.00; 3.95; 0.00 | — |
| SECONDARY Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) |
0.00; 18.42; 0.00; 0.00; 0.00; 0.00 | — |
| SECONDARY Annualized Bleeding Rate for All Bleeding Episodes |
0.00; 21.13; 0.00 | — |
| SECONDARY Annualized Bleeding Rate: Intra-participant Comparison of Arm B Participants |
21.13; 0.00 | — |
| SECONDARY Percentage of Participants Achieving Factor VIII (FVIII) Activity Levels Above 1%, 5%, 10%, 15%, and 20% in Arm A: Prophylaxis |
100; 99.0; 83.5; 40.8; 17.5 | — |
| SECONDARY Number of Injections of BIVV001 Required to Treat a Bleeding Episode |
1.0; 1.0; 1.0 | — |
| SECONDARY Total Dose of BIVV001 Required to Treat Bleeding Episode |
50.85; 50.96; 49.79 | — |
| SECONDARY Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001 |
94.2; 97.4; 100 | — |
| SECONDARY Percentage of Participants With Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale |
82.2; 98.4; 100; 53.4; 76.5; 83.3 | — |
| SECONDARY Physicians' Global Assessment of Participant's Response to BIVV001 Treatment |
95.7; 96.1; 93.2; 4.3; 3.9; 6.8 | — |
| SECONDARY Total Annualized BIVV001 Consumption Per Participant |
2756.99; 1212.27; 2737.53 | — |
| SECONDARY Change From Baseline in Hemophilia Joint Health Score (HJHS) Domain Score at Week 52 in Arm A: Prophylaxis |
-0.3; -0.2; -0.3; -0.3; -0.3; -0.2 | — |
| SECONDARY Estimated Annualized Joint Bleeding Rate (AJBR) |
0.51; 17.48; 0.62 | — |
| SECONDARY Observed Annualized Joint Bleeding Rate (AJBR) |
0.52; 17.45; 0.61 | — |
| SECONDARY Total Number of Target Joint Resolved in Participants at Week 52 in Arm A: Prophylaxis |
45 | — |
| SECONDARY Change From Baseline in Hemophilia-specific Health-related Quality of Life Questionnaire for Adults Total Score at Week 52 in Arm A: Prophylaxis |
-4.56 | — |
| SECONDARY Change From Baseline in Patient Reported Outcomes Measurements Information Systems Short Form (PROMIS-SF) Physical Function (PF) 6b at Week 52 in Arm A: Prophylaxis |
0.62 | — |
| SECONDARY Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment |
12; 12; 0; 0; 0 | — |
| SECONDARY Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery |
1; 11; 0; 0; 0; 0 | — |
| SECONDARY Total Dose Required to Maintain Hemostasis From Day -1 to Day 0 During Perioperative Period for Major Surgery |
41.65 | — |
| SECONDARY Total BIVV001 Consumption From Day -1 to 14 During Perioperative Period for Major Surgery |
166.71 | — |
| SECONDARY Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery |
12; 0; 0; 0; 0 | — |
| SECONDARY Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery |
0; 0; 0; 0; 0 | — |
| SECONDARY Estimated Blood Loss During Major Surgery |
143.33 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE) |
108; 12; 8; 13; 2; 0 | — |
| SECONDARY Number of Participants With Neutralizing Antibodies (Development of Inhibitors) Directed Against Factor VIII |
0; 0; 0 | — |
| SECONDARY Number of Participants With Occurrence of Embolic and Thrombotic Events |
0; 0; 0 | — |
| SECONDARY Pharmacokinetics (PK): Maximum FVIII Activity (Cmax) |
125.05; 138.36; 144.72; 149.42 | — |
| SECONDARY Pharmacokinetics: Elimination Half-life (t1/2z) |
46.5; 46.7 | — |
| SECONDARY Pharmacokinetics: Clearance (CL) |
0.508 | — |
| SECONDARY Pharmacokinetics: Total Clearance at Steady State (CLss) |
0.449 | — |
| SECONDARY Pharmacokinetics: Accumulation Index (AI) |
1.17 | — |
| SECONDARY Pharmacokinetics: Area Under the Plasma FVIII Activity Versus Time Curve (AUC0-tau) |
9600; 11800 | — |
| SECONDARY Pharmacokinetics: Volume of Distribution at Steady State (Vss) |
31.7; 29.6 | — |
| SECONDARY Pharmacokinetics: Mean Residence Time (MRT) |
61.9; 66.1 | — |
| SECONDARY Pharmacokinetics: Incremental Recovery (IR) |
2.60; 3.05 | — |
| SECONDARY Pharmacokinetics: Trough Concentration for BIVV001 (Ctrough) |
0.00; 0.00; 15.70; 21.14 | — |
| SECONDARY Pharmacokinetics: Time Above Predefined (10 and 40%) FVIII Activity Levels |
185; 85.1 | — |
Summary
Primary Objective:
- To evaluate the efficacy of BIVV001 as a prophylaxis treatment in prophylaxis treatment arm.
Secondary Objectives:
* To evaluate the efficacy of BIVV001 as a prophylaxis treatment.
* To evaluate the efficacy of BIVV001 in the treatment of bleeding episodes.
* To evaluate BIVV001 consumption for the prevention and treatment of bleeding episodes.
* To evaluate the effect of BIVV001 prophylaxis on joint health outcomes.
* To evaluate the effect of BIVV001 prophylaxis on Quality of Life outcomes.
* To evaluate the efficacy of BIVV001 for perioperative management.
* To evaluate the safety and tolerability of BIVV001 treatment.
* To assess the pharmacokinetics (PK) of BIVV001 based on the 1-stage activated partial thromboplastin time (aPTT) and 2-stage chromogenic coagulation factor VIII (FVIII) activity assays.
Eligibility Criteria
Inclusion criteria
- Participant, male or female, must be equal to or greater than 12 years of age inclusive, at the time of signing the informed consent.
- Severe hemophilia A, defined as less than ( =] 18 years of age) to complete training in the use of the study electronic Patient Diary (ePD) and to use the ePD throughout the study.
- Ability of the participant or his or her legally authorized representative (eg., parent or legal guardian) to understand the purpose and risks of the study, willing and able to comply with study requirements and provide signed and dated informed consent or assent (as applicable) and authorization to use protected health information in accordance with national and local participant privacy regulations.
Exclusion criteria
- Clinically significant liver disease.
- Serious active bacterial or viral infection (other than chronic hepatitis or HIV) present within 30 days of screening.
- Other known coagulation disorder(s) in addition to hemophilia A.
- History of hypersensitivity or anaphylaxis associated with any FVIII product.
- Positive inhibitor results, defined as >=0.6 Bethesda unit per milliliter (BU/mL) at screening. History of a positive inhibitor test defined as >=0.6 BU/mL. Family history of inhibitors would not exclude the participant.
- Use of Emicizumab within the 20 weeks prior to screening.
- Major surgery within 8 weeks prior to screening.
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Data sourced from ClinicalTrials.gov (NCT04161495). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.