Phase 3
N=74
Safety, Efficacy and PK of BIVV001 in Pediatric Patients With Hemophilia A
Hemophilia A
Bottom Line
View on ClinicalTrials.gov: NCT04759131 ↗Enrolled (actual)
74
Serious AEs
12.2%
Results posted
Feb 2024
Primary outcome: Primary: Number of Participants With Neutralising Antibodies (Development of Inhibitors) Directed Against Factor VIII — 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- efanesoctocog alfa (BIVV001) (Drug)
- Age
- Pediatric
- Sex
- Male
- Sponsor
- Bioverativ, a Sanofi company
- Primary completion
- Jan 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Neutralising Antibodies (Development of Inhibitors) Directed Against Factor VIII |
0; 0 | — |
| SECONDARY Annualized Bleeding Rate (ABR): For Treated Bleeds |
0.48; 1.33 | — |
| SECONDARY Sensitivity Analysis: Annualized Bleeding Rate: For Treated Bleeds |
0.48; 0.75 | — |
| SECONDARY Annualized Bleeding Rate for All Bleeding Episodes |
2.78; 2.85 | — |
| SECONDARY Sensitivity Analysis: Annualized Bleeding Rate for All Bleeding Episodes |
2.78; 2.32 | — |
| SECONDARY Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type) |
0.17; 0.14; 0.28; 0.59; 0.03; 0.59 | — |
| SECONDARY Sensitivity Analysis: Annualized Bleeding Rate by Type of Bleed (Spontaneous, Traumatic and Unknown Type) |
0.17; 0.15; 0.28; 0.52; 0.03; 0.09 | — |
| SECONDARY Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) |
0.19; 0.99; 0.03; 0.17; 0.08; 0.06 | — |
| SECONDARY Sensitivity Analysis: Annualized Bleeding Rate by Location of Bleed (Joint, Muscle, Internal and Skin/Mucosa) |
0.19; 0.40; 0.03; 0.17; 0.08; 0.06 | — |
| SECONDARY Percentage of Participants Achieving FVIII Activity Levels Above 1%, 3%, 5%, 10%, 15%, and 20% |
100; 100; 100; 100; 75.0; 100 | — |
| SECONDARY Number of Injections of BIVV001 Required to Treat a Bleeding Episode |
1.12; 1.30 | — |
| SECONDARY Sensitivity Analysis: Number of Injections of BIVV001 Required to Treat a Bleeding Episode |
1.12; 1.00 | — |
| SECONDARY Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001 |
88.2; 78.7 | — |
| SECONDARY Sensitivity Analysis: Percentage of Bleeding Episodes Treated With a Single Injection of BIVV001 |
88.2; 100 | — |
| SECONDARY Total Dose of BIVV001 Required to Treat a Bleeding Episode |
52.29; 66.90 | — |
| SECONDARY Sensitivity Analysis: Total Dose of BIVV001 Required to Treat a Bleeding Episode |
52.29; 50.39 | — |
| SECONDARY Physicians' Global Assessment (PGA) of Participant's Response to BIVV001 Treatment Based on a 4-point Response Scale |
37; 34; 0; 2; 0; 0 | — |
| SECONDARY Participant's Response to BIVV001 Treatment Based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point Response Scale |
14; 22; 1; 2; 1; 0 | — |
| SECONDARY Total Annualized BIVV001 Consumption Per Participant |
3115.57; 2884.67 | — |
| SECONDARY Annualized Joint Bleeding Rate (AJBR) |
0.19; 0.99 | — |
| SECONDARY Sensitivity Analysis: Annualized Joint Bleeding Rate (AJBR) |
0.19; 0.41 | — |
| SECONDARY Change From Baseline in Hemophilia Joint Health Score Domain Score at Week 52 |
0.0; -0.1; 0.1; -0.0; 0.0; -0.1 | — |
| SECONDARY Change From Baseline in Hemophilia Quality of Life Questionnaire (Haemo-QoL) Kids Short Version Total Score at Week 52 for Children Participants (Aged 4 to 7 and 8 to <12 Years) |
-5.31; 4.69; -9.79 | — |
| SECONDARY Change From Baseline in Hemophilia Quality of Life Questionnaire Parent Proxy Short Version Total Score at Week 52 for Children Participants (Aged 4 to 7 and 8 to <12 Years): Parent's Evaluation |
-3.21; -1.17; -4.05 | — |
| SECONDARY Change From Baseline in Hemophilia Quality of Life Questionnaire Kids Short Version Physical Health Domain Score at Week 52 for Children Participants (Aged 8 to <12 Years) |
-10.63 | — |
| SECONDARY Change From Baseline in Hemophilia Quality of Life Questionnaire Parent Proxy Short Version Physical Health Domain Score at Week 52 for Children Participants (Aged 8 to <12 Years): Parent's Evaluation |
-7.64 | — |
| SECONDARY Total Number of Target Joints Resolved in Participants at Week 52 |
2 | — |
| SECONDARY Change From Baseline in Hemophilia Joint Health Score (HJHS) Total Score at Week 52 |
0.2; -1.1 | — |
| SECONDARY Investigators' or Surgeons' Assessment of Participant's Hemostatic Response to BIVV001 Treatment |
2; 2; 0; 0; 0 | — |
| SECONDARY Number of Injections Per Surgery Required to Maintain Hemostasis During Perioperative Period for Major Surgery |
2; 0; 0; 0; 0 | — |
| SECONDARY Number of Blood Component Transfusions Used During Perioperative Period for Major Surgery |
2; 0; 0; 0; 0 | — |
| SECONDARY Total BIVV001 Consumption From Day -1 to 14 During Perioperative Period for Major Surgery |
201.97 | — |
| SECONDARY Type of Blood Component Transfusions Used During Perioperative Period for Major Surgery |
0; 0; 0; 0; 0 | — |
| SECONDARY Total Dose Required to Maintain Hemostasis From Day -1 to Day 0 During Perioperative Period for Major Surgery |
61.13 | — |
| SECONDARY Estimated Blood Loss During Major Surgery |
25.00 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse (TESAEs) |
33; 29; 5; 4 | — |
| SECONDARY Number of Participants With Occurrence of Embolic and Thrombotic Events |
0; 0 | — |
| SECONDARY Pharmacokinetics (PK): Maximum FVIII Activity (Cmax) |
128 | — |
| SECONDARY Pharmacokinetics: Clearance (CL) |
0.711 | — |
| SECONDARY Pharmacokinetics: Volume of Distribution at Steady State (Vss) |
37.3 | — |
| SECONDARY Pharmacokinetics: Elimination Half-life (t1/2z) |
40.2 | — |
| SECONDARY Pharmacokinetics: Area Under the Plasma FVIII Activity Versus Time Curve (AUC0-tau) |
7000 | — |
| SECONDARY Pharmacokinetics: Total Clearance at Steady State (CLss) |
— | — |
| SECONDARY Pharmacokinetics: Incremental Recovery (IR) |
2.53 | — |
| SECONDARY Pharmacokinetics: Trough Concentration for BIVV001 (Ctrough) |
0.00; 13.68 | — |
| SECONDARY Pharmacokinetics: Mean Residence Time (MRT) |
53.0 | — |
| SECONDARY Time Above Predefined (10% and 40%) FVIII Activity Levels |
160; 72.2 | — |
| SECONDARY Pharmacokinetics: Dose-normalized Area Under the Activity-time Curve (DNAUC0-tau) |
139 | — |
Summary
Primary Objective:
- To evaluate the safety of BIVV001 in previously treated pediatric participants with hemophilia A.
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 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 (QoL) 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.
Eligibility Criteria
Inclusion criteria
- Participant must be younger than 12 years of age, at the time of signing the informed consent.
- Severe hemophilia A defined as =) 0.6 Bethesda units (BU/mL), or any value greater than or equal to the lower sensitivity cut-off for laboratories with cut-offs for inhibitor detection between 0.7 and 1.0 BU/mL, or clinical signs or symptoms of decreased response to FVIII administrations. Family history of inhibitors would not exclude the participant.
- Positive inhibitor test result, defined as >=0.6 BU/mL at 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 (NCT04759131). 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.