XTEND-ed: Long-term Safety and Efficacy of Efanesoctocog Alfa (BIVV001) in Previously Treated Patients With Hemophilia A

Sponsor

Bioverativ, a Sanofi company (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04644575

Collaborator

(none)

262

Enrollment

Locations

Arms

71.6

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objective:

To evaluate the long-term safety of BIVV001 in previously treated subjects 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 safety and tolerability of BIVV001 treatment.
To assess the PK of BIVV001 based on the one stage activated partial thromboplastin time (aPTT) and two-stage chromogenic FVIII activity assays (only applicable to Arm B).
To evaluate the efficacy of BIVV001 for perioperative management

Condition or Disease	Intervention/Treatment	Phase
Hemophilia A	Drug: efanesoctocog alfa (BIVV001)	Phase 3

Detailed Description

Participants will receive BIVV001 once weekly for a total of at least 100 exposure days to BIVV001 (including exposure during a BIVV001 parent study, if applicable). Participants will have the opportunity to continue in this study for up to 4 years, unless BIVV001 is commercially available in their applicable participating country.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

262 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

It is a 3-arm study with single interventionIt is a 3-arm study with single intervention

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3 Open-label, Multicenter Study of the Long-term Safety and Efficacy of Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein (rFVIIIFc-VWF-XTEN; BIVV001) in Previously Treated Patients With Severe Hemophilia A

Actual Study Start Date :

Feb 23, 2021

Anticipated Primary Completion Date :

Feb 12, 2027

Anticipated Study Completion Date :

Feb 12, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Previously treated in BIVV001 study This arm includes all participants who have completed the previous phase 3 studies on BIVV001, as well as participants who have completed Arm B or Arm C of this study rolling over in Arm A, and participants who will have completed any future BIVV001 study who will be proposed to continue BIVV001 treatment. Participants in this arm will continue receiving BIVV001 prophylaxis treatment once-weekly (QW) for a total of 100 exposure days (EDs) cumulative from the parent study and this study. Participants will have the opportunity to continue in this study for up to 4 years, unless BIVV001 is commercially available in their applicable participating country.	Drug: efanesoctocog alfa (BIVV001) Pharmaceutical form:Solution for Injection Route of administration: Intravenous
Experimental: Arm B: Newly initiated (China Only) in BIVV001 This arm includes Chinese participants of any age who will be newly initiated on BIVV001 prophylaxis treatment once-weekly (QW) for 52 weeks. After 52 weeks of treatment in this arm B, participants will be able to roll into arm A.	Drug: efanesoctocog alfa (BIVV001) Pharmaceutical form:Solution for Injection Route of administration: Intravenous
Experimental: Arm C: Newly initiated in BIVV001 with planned major surgery This arm includes participants of any age who will be newly initiated on BIVV001 prophylaxis treatment once-weekly (QW) and will undergo planned major surgery after at least 6 initial EDs with BIVV001, and within 26 weeks from Day 1. After 52 weeks of treatment in arm C, participants will be able to roll into arm A.	Drug: efanesoctocog alfa (BIVV001) Pharmaceutical form:Solution for Injection Route of administration: Intravenous

Arm

Intervention/Treatment

Experimental: Arm A: Previously treated in BIVV001 study

This arm includes all participants who have completed the previous phase 3 studies on BIVV001, as well as participants who have completed Arm B or Arm C of this study rolling over in Arm A, and participants who will have completed any future BIVV001 study who will be proposed to continue BIVV001 treatment. Participants in this arm will continue receiving BIVV001 prophylaxis treatment once-weekly (QW) for a total of 100 exposure days (EDs) cumulative from the parent study and this study. Participants will have the opportunity to continue in this study for up to 4 years, unless BIVV001 is commercially available in their applicable participating country.

Drug: efanesoctocog alfa (BIVV001)

Pharmaceutical form:Solution for Injection Route of administration: Intravenous

Experimental: Arm B: Newly initiated (China Only) in BIVV001

This arm includes Chinese participants of any age who will be newly initiated on BIVV001 prophylaxis treatment once-weekly (QW) for 52 weeks. After 52 weeks of treatment in this arm B, participants will be able to roll into arm A.

Drug: efanesoctocog alfa (BIVV001)

Pharmaceutical form:Solution for Injection Route of administration: Intravenous

Experimental: Arm C: Newly initiated in BIVV001 with planned major surgery

This arm includes participants of any age who will be newly initiated on BIVV001 prophylaxis treatment once-weekly (QW) and will undergo planned major surgery after at least 6 initial EDs with BIVV001, and within 26 weeks from Day 1. After 52 weeks of treatment in arm C, participants will be able to roll into arm A.

Drug: efanesoctocog alfa (BIVV001)

Pharmaceutical form:Solution for Injection Route of administration: Intravenous

Outcome Measures

Primary Outcome Measures

Number of participants with the occurrence of inhibitor development (neutralizing antibodies detected against factor VIII [FVIII]) [Baseline to month 48]
The number of participants with the occurrence of inhibitor development (neuatralizing antibodies detected against factor VIII [FVIII]) as determined via the Nijmegen modified Bethesda assay.

Secondary Outcome Measures

Annual bleeding rate (ABR) [Baseline to month 48]
Annualized bleeding rate (ABR) for treated bleeding episodes and all bleeding episodes (including untreated bleeds).
Annualized bleeding rate (ABR) by type of bleed [Baseline to month 48]
Annualized bleeding rate (ABR) by type during prophylaxis treatment per study arm and parent study.
Annualized bleeding rate (ABR) by location [Baseline to month 48]
Annualized bleeding rate (ABR) by location during prophylaxis treatment per study arm and parent study.
Percentage of patients who maintain factor VIII (FVIII) above prespecified activity levels [Baseline to month 48]
Percentage of participants who maintain factor VIII (FVIII) activity levels over 7 days post dose during prophylaxis treatment per study arm and per parent study or arm.
Number of injections and dose of BIVV0001 to treat a bleeding episode [Month 48]
Percentage of bleeding episode treated with a single injection of BIVV001 [Month 48]
Assessment of response to BIVV001 treatment of individual bleeding episodes [Baseline to month 48]
Assessment of response to BIVV001 treatment of individual bleeding episodes based on the International Society on Thrombosis and Haemostasis (ISTH) 4-point response scale
Physician's global assessment (PGA) of participants response to BIVV001 [Baseline to month 48]
Physician's global assessment (PGA) of participant's response to BIVV001 treatment based on a 4-point response scale .
Total annualized BIVV001 consumption [Baseline to month 48]
Total annualized BIVV001 consumption per participant during prophylaxis treatment
Annualized joint bleeding rate (AJBR) [Baseline to month 48]
Target joint resolution [Month 48]
Target joint development, resolution and maintenance of target joint resolution based on ISTH criteria.
Change from baseline in Hemophilia Joint Health Score (HJHS) [Baseline to month 48]
Change from Baseline to the end of study visit in total score and domain scores (eg, swelling and strength) assessed by the Hemophilia Joint Health Score (HJHS)
Change from baseline in PROMIS-SF Physical Function [Baseline to month 48]
Change in Quality of Life (QoL) measures from baseline to end of study visit per study arm and per parent study arm: PROMIS-SF Physical Function (participants aged ≥18 years old).)
Change from baseline in Haem-A-QoL total score and physical health score [Baseline to month 48]
Change from baseline in Haemophilia QoL Questionnaire for Adults (Haem-A-QoL) total and physical health domain score on participants aged ≥17 years old.
Change from baselin in Haemo-QoL total score and physical health score [Baseline to month 48]
Change from baseline in Haemophilia QoL Questionnaire for Children (Haemo-QoL) total and physical health domain score on participants aged ≥4 to 16 years old and parent proxy for participants aged ≥4 to to <12 years old.
Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Baseline to month 48]
Participants with occurrences of treatment emergent adverse events (AEs) and serious adverse events (SAEs).
Number of participants with the occurrence of embolic and thrombotic events [Baseline to month 48]
Participants with the occurrence of embolic and thrombotic events.
PK parameter: Maximum activity (Cmax) [Baseline to week 52]
PK parameter: Elimination half-life (t1/2) [Baseline to week 26]
PK parameter: Total clearance (CL) [Baseline to week 26]
PK parameter: Total clearance at steady state (CLss) [Baseline to week 26]
PK parameter: Accumulation index (AI) [Baseline to week 26]
PK parameter: Area under the activity time curve (AUC) [Baseline to week 26]
PK parameter: Volume of distribution at steady state (Vss) [Baseline to week 26]
PK parameter: Mean residence time (MRT) [Baseline to week 26]
PK parameter: Incremental recovery (IR) [Baseline to week 52]
PK parameter: Trough activity (Ctrough) [Baseline to week 52]
PK parameter: Time above FVIII activity levels [Baseline to week 26]
Investigators' or Surgeons' assessment of participant's hemostatic response to BIVV001 treatment [Baseline to month 48]
Investigators' or Surgeons' assessment of participant's hemostatic response to BIVV001 treatment on the ISTH 4 point response for surgical procedures scale.
Number of injections and dose to maintain hemostasis during perioperative period for major surgery [Baseline to month 48]
Total BIVV001 consumption during perioperative period for major surgery [Baseline to month 48]
Number and type of blood component transfusions used during perioperative period for major surgery [Baseline to month 48]
Estimated blood loss during perioperative period for major surgery [Baseline to month 48]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria :

For participants rolling over into Arm A

Participants who have completed the studies EFC16923, EFC16925, Arm B or Arm C of the current study, or any other potential BIVV001 study.
Male or Female For participants new to BIVV001 (Arm B and C)
Participants who have severe hemophilia A, defined as <1 IU/dL (<1%) endogenous FVIII activity as documented either by central laboratory testing at screening or in historical medical records from a clinical laboratory demonstrating <1% FVIII coagulant activity (FVIII:C) or a documented genotype known to produce severe hemophilia A.
Previous treatment for hemophilia A (prophylaxis or on-demand) with any recombinant and/or plasma-derived FVIII, or cryoprecipitate for at least 150 EDs or 50 EDs for participants aged <6 years.
Platelet count ≥100 000 cells/μL at screening.
A participant known to be human immunodeficiency virus (HIV) antibody positive, either previously documented or identified from screening assessments, must have the following results prior to enrollment: CD4 lymphocyte count >200 cells/mm³ and viral load of <400 000 copies/mL
Male
Only for Arm B: Chinese participants
Only for Arm C: planned major surgery within 6 months after Day 1.

Exclusion criteria:

For participants rolling over into Arm A

Positive inhibitor result, defined as ≥0.6 Bethesda units (BU)/mL.
Participation in another study. For participants new to BIVV001 (Arm B and Arm C)
Any concurrent clinically significant liver disease that, in the opinion of the Investigator, would make the participant unsuitable for enrollment. This may include, but is not limited to cirrhosis, portal hypertension, and acute hepatitis.
Serious active bacterial, fungal, 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.
History of a positive inhibitor (to FVIII) test defined as ≥0.6 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 will not exclude the participant.
Positive inhibitor test (FVIII) result, defined as ≥0.6 BU/mL at screening.
Treatment with acetylsalicylic acid (ASA) or antiplatelet agents that are not nonsteroidal anti-inflammatory drugs (NSAIDs) within 2 weeks prior to screening.
Treatment with NSAIDs greater than the maximum dose specified in the regional prescribing information within 2 weeks prior to screening.
Systemic treatment within 12 weeks prior to Screening with chemotherapy and/or other immunosuppressive drugs (except for the treatment of hepatitis C virus [HCV] or HIV).
Emicizumab use within the 20 weeks prior to screening.
Major surgery within 8 weeks prior to screening.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Orthopaedic Institute for Children-Site Number:8400003	Los Angeles	California	United States	90007
2	Children's Hospital Los Angeles-Site Number:8400009	Los Angeles	California	United States	90027
3	University of California San Diego-Site Number:8400007	San Diego	California	United States	92121
4	University of Florida Health-Site Number:8400008	Gainesville	Florida	United States	32608
5	Rush University Medical Center-Site Number:8400010	Chicago	Illinois	United States	60612-3833
6	Children's Hospital Of Iowa-Site Number:8400011	Iowa City	Iowa	United States	52242
7	University of Michigan Medical Center-Site Number:8400006	Ann Arbor	Michigan	United States	48109
8	Michigan State University School Of Med-Site Number:8400002	Lansing	Michigan	United States	00000
9	Hemostasis and Thrombosis Center of Nevada-Site Number:8400001	Las Vegas	Nevada	United States	89113
10	Cincinnati Children's Hospital Medical Center-Site Number:8400012	Cincinnati	Ohio	United States	45229
11	Bloodworks Northwest-Site Number:8400005	Seattle	Washington	United States	98104
12	Investigational Site Number :0320001	Caba	Ciudad De Buenos Aires	Argentina	C1425BWE
13	Investigational Site Number :0320002	Godoy Cruz	Mendoza	Argentina	M5504FKD
14	Investigational Site Number :0320003	Buenos Aires		Argentina	C1015ABO
15	Investigational Site Number :0360004	Camperdown	New South Wales	Australia	2050
16	Investigational Site Number :0360003	Murdoch	Western Australia	Australia	6961
17	Investigational Site Number :0560003	Bruxelles		Belgium	1200
18	Investigational Site Number :0760001	Campinas		Brazil	13083-970
19	Investigational Site Number :1000171	Plovdiv		Bulgaria	4002
20	Investigational Site Number :1000172	Sofia		Bulgaria	1756
21	Investigational Site Number :1240005	Hamilton	Ontario	Canada	L8L 8E7
22	Investigational Site Number :1240004	Hamilton	Ontario	Canada	L8N 3Z5
23	Investigational Site Number :1240002	Ottawa	Ontario	Canada	K1H 8L1
24	Investigational Site Number :1240001	Toronto	Ontario	Canada	M5G 1X8
25	Investigational Site Number :1560002	Beijing		China	100045
26	Investigational Site Number :1560006	Beijing		China	100730
27	Investigational Site Number :1560001	Guangzhou		China	510515
28	Investigational Site Number :1560003	Hangzhou		China	310003
29	Investigational Site Number :1560004	Hangzhou		China	310003
30	Investigational Site Number :1560005	Jinan		China	250013
31	Investigational Site Number :1560009	Kunming		China	650032
32	Investigational Site Number :1560010	Kunming		China	650101
33	Investigational Site Number :1560013	Lanzhou		China	730000
34	Investigational Site Number :1560007	Suzhou		China	215006
35	Investigational Site Number :2500005	Brest		France	29200
36	Investigational Site Number :2500004	Bron		France	69500
37	Investigational Site Number :2500001	Kremlin Bicetre		France	94275
38	Investigational Site Number :2500003	Lille		France	59037
39	Investigational Site Number :2500006	Marseille		France	13385
40	Investigational Site Number :2760304	Berlin		Germany	10249
41	Investigational Site Number :2760302	Bonn		Germany	53127
42	Investigational Site Number :2760001	Frankfurt am Main		Germany	60590
43	Investigational Site Number :3000001	Athens		Greece	11527
44	Investigational Site Number :3480002	Budapest		Hungary	1134
45	Investigational Site Number :3480004	Debrecen		Hungary	4093
46	Investigational Site Number :3800001	Milano		Italy	20121
47	Investigational Site Number :3800003	Vicenza		Italy	36100
48	Investigational Site Number :3920425	Nagoya-shi	Aichi	Japan	466-0065
49	Investigational Site Number :3920423	Kitakyushu-shi	Fukuoka	Japan	807-8555
50	Investigational Site Number :3920426	Kawasaki-shi	Kanagawa	Japan	216-8511
51	Investigational Site Number :3920422	Kashihara-Shi	Niigata	Japan	634-8521
52	Investigational Site Number :3920421	Shinjuku-ku	Tokyo	Japan	160-0023
53	Investigational Site Number :3920424	Suginami-ku	Tokyo	Japan	167-0035
54	Investigational Site Number :4100603	Daegu	Daegu-gwangyeoksi	Korea, Republic of	41404
55	Investigational Site Number :4100601	Seoul	Seoul-teukbyeolsi	Korea, Republic of	03722
56	Investigational Site Number :4100600	Seoul	Seoul-teukbyeolsi	Korea, Republic of	05278
57	Investigational Site Number :5280002	Amsterdam		Netherlands	1105 AZ
58	Investigational Site Number :5280001	Utrecht		Netherlands	3584 CX
59	Investigational Site Number :7240001	Madrid	Madrid, Comunidad De	Spain	28046
60	Investigational Site Number :7240002	Esplugues de Llobregat		Spain	08950
61	Investigational Site Number :7560001	Zürich		Switzerland	8032
62	Investigational Site Number :1580005	Changhua County		Taiwan	500
63	Investigational Site Number :1580002	Taipei		Taiwan	10002
64	Investigational Site Number :8260005	London	London, City Of	United Kingdom	NW3 2QG
65	Investigational Site Number :8260004	Hampshire		United Kingdom	RG24 9NA

Sponsors and Collaborators

Bioverativ, a Sanofi company

Investigators

Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Bioverativ, a Sanofi company

ClinicalTrials.gov Identifier:

NCT04644575

Other Study ID Numbers:

LTS16294
2020-002215-22
U1111-1244-0517

First Posted:

Nov 25, 2020

Last Update Posted:

Jul 13, 2022

Last Verified:

Jul 12, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Hemophilia A

Study Results

No Results Posted as of Jul 13, 2022