Phase 3
N=246
An Open-label Safety and Efficacy Study of Recombinant FVIII in Patients With Severe Hemophilia A
Hemophilia A · Severe Hemophilia A
Bottom Line
View on ClinicalTrials.gov: NCT02172950 ↗Enrolled (actual)
246
Serious AEs
15.0%
Results posted
Oct 2021
Primary outcome: Primary: Incidence of Inhibitor Formation to FVIII in Previously Treated Patients (PTPs) With 100 Exposure Days (EDs) to CSL627 — 0 percentage of paticipants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- rVIII-SingleChain (Biological)
- Age
- Pediatric, Adult, Older Adult
- Sex
- Male
- Sponsor
- CSL Behring
- Primary completion
- Jan 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence of Inhibitor Formation to FVIII in Previously Treated Patients (PTPs) With 100 Exposure Days (EDs) to CSL627 |
— | — |
| PRIMARY Number of Previously Untreated Patients (PUPs) With High-titer Inhibitor Formation to FVIII With at Least 50 EDs to CSL627 |
5 | — |
| PRIMARY Percent Treatment Success for Major Bleeding Episodes in PUPs |
100 | — |
| PRIMARY Annualized Spontaneous Bleeding Rate in PUPs |
1.9; 4.04 | — |
| SECONDARY Percentage of Bleeding Episodes Treated Successfully in PTPs |
87.1 | — |
| SECONDARY Annualized Bleeding Rate in PTPs and PUPs |
28.32; 5.12; 2.84; 5.94 | — |
| SECONDARY Percentage of Bleeding Episodes Requiring 1, 2, 3, or > 3 Injections of CSL627 to Achieve Hemostasis in PTPs and PUPs |
71.5; 77.5; 14.8; 11.4; 6.9; 5.4 | — |
| SECONDARY Mean Number of On-demand Infusions of CSL627 |
6.26; 1.23; 75.18; 14.75 | — |
| SECONDARY Mean On-demand Dose Administered of CSL627 |
210.39; 41.93; 2524.69; 503.16 | — |
| SECONDARY Mean Prophylaxis Dose Administered of CSL627 |
380.95; 389.30; 4571.35; 4671.54 | — |
| SECONDARY Mean Total Amount of CSL627 Administered During Surgery Period in PTPs |
51663.0 | — |
| SECONDARY Total Amount of CSL627 Administered During Surgery Period in PUPs |
15693; 5631; 7330 | — |
| SECONDARY Hemostatic Efficacy of rVIII-SingleChain for PTPs and PUPs Who Undergo Surgery |
28; 3; 4; 0; 0; 0 | — |
| SECONDARY Incidence of Inhibitor Formation to FVIII in PTPs After 10 EDs and After 50 EDs |
0; 0 | — |
| SECONDARY Percentage of PTPs and PUPs Developing Antibodies Against CSL627 |
15.3; 70.8 | — |
| SECONDARY Percentage of PTPs and PUPs Developing Antibodies to Chinese Hamster Ovary (CHO) Proteins |
0; 0 | — |
| SECONDARY Number of PUPs With High-titer Inhibitor Formation to FVIII After 10 EDs With CSL627 |
4 | — |
| SECONDARY Number of PUPs With Low-titer Inhibitor Formation to FVIII After 10 EDs and After 50 EDs With CSL627 |
4; 0 | — |
| SECONDARY Incidence of Total Inhibitor Formation to FVIII in PUPs |
50.0 | — |
| SECONDARY Percent Treatment Success for Non-major Bleeding Episodes in PUPs |
92.1 | — |
| SECONDARY Percentage of PUPs With Clinically Significant Abnormal Vital Signs Values After First Infusion of CSL627 |
— | — |
| SECONDARY Percentage of PUPs With Treatment-emergent Clinically Significant Abnormal Vital Signs Values |
— | — |
Summary
This multicenter, open-label, phase 3 extension study will investigate the safety and efficacy of rVIII-SingleChain for prophylaxis and on-demand treatment of bleeding episodes in at least 200 previously treated patients (PTPs) with severe congenital hemophilia A and previous exposure to FVIII products who achieve at least 100 exposure days (EDs) to rVIII-SingleChain in this study, as well as in previously untreated patients (PUPs) with no previous exposure to any FVIII product who achieve at least 50 EDs to rVIII-SingleChain in this study. A substudy (open to both PTPs and PUPs) will investigate the use of rVIII-SingleChain in surgery. A substudy (open to PUPs who develop an inhibitor to rVIII-SingleChain) will investigate the use of rVIII-SingleChain in immune tolerance induction (ITI) therapy.
Eligibility Criteria
Inclusion Criteria
PTPs:
- Males of any age who have been diagnosed with severe congenital hemophilia A (FVIII activity levels 2 x upper limit of normal, alanine aminotransferase or aspartate aminotransferase > 5 x upper limit of normal at Screening (if specified)
- Any first-order family (eg, siblings) history of FVIII inhibitors
- For PTPs not rolling over directly from a CSL-sponsored clinical study with rVIII-SingleChain: any history of or current FVIII inhibitors
Data sourced from ClinicalTrials.gov (NCT02172950). 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.