NCT01181128

A-LONG: An Open-Label, Multicenter Evaluation of the Safety, Pharmacokinetics, and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in the Prevention and Treatment of Bleeding in Previously Treated Subjects With Severe Hemophilia A

Completed Phase 3 Results posted Last updated 16 December 2020

What this trial tests

Phase 3 trial testing Factor VIII (rFVIIIFc) in Severe Hemophilia A in 165 participants. Completed in 1 August 2012.

Timeline

1 November 2010

Primary endpoint
1 August 2012

1 August 2012

Quick facts

Lead sponsor	Bioverativ Therapeutics Inc.
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	165
Start date	1 November 2010
Primary completion	1 August 2012
Estimated completion	1 August 2012
Sites	64 locations across United States, Australia, Austria, Belgium, Brazil, Canada, France, Germany

Drugs / interventions tested

• Factor VIII (rFVIIIFc) — full drug profile →
• Advate® — full drug profile →

Conditions studied

• Severe Hemophilia A — all drugs for Severe Hemophilia A →

Sponsor

Bioverativ Therapeutics Inc. — full company profile →

Who can join

12 and older, male only, with Severe Hemophilia A. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Incidence Rate of FVIII Inhibitor Development
  Time frame: up to 52 weeks ± 2 weeks
  An inhibitor test result ≥0.6 Bethesda units (BU)/mL, identified and confirmed by re-testing of a second sample obtained within 2 to 4 weeks, was considered positive. Both tests were to be performed using the Nijmegen-modified Bethesda Assay by the central laboratory. The incidence rates along with the 95% confidence interval (CI) were summarized for all titers for subjects with 50 or more exposur
• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
  Time frame: up to 52 weeks + 30 days ± 1 week
  AE=any untoward medical occurrence that did not necessarily have a causal relationship with treatment, and could be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study product, whether related or not. TEAE=AE present prior to receiving the first injection of Advate or rFVIIIFc that subsequently worsened in severity or not present prior to receiving
• Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values From Baseline
  Time frame: up to 52 weeks ± 2 weeks
  Clinical laboratory evaluations included hematology and blood chemistry. Table does not include laboratory tests evaluated during the surgical/rehabilitation period. ULN=upper limit of normal.
• Number of Participants With Clinically Relevant Abnormalities in Vital Signs or Relevant Changes From Baseline in Vital Signs
  Time frame: up to 52 weeks ± 2 weeks
  Number of participants with clinically relevant abnormalities or relevant changes from baseline in temperature, pulse (beats per minute \[bpm\]), systolic blood pressure (SBP), and diastolic blood pressure (DBP) are presented. Baseline (BL) is defined as the last non-missing evaluable assessment taken prior and closest to the first rFVIIIFc dose. ↑ signifies increase and ↓ signifies decrease.
• Annualized Bleeding Rate
  Time frame: up to 52 weeks ± 2 weeks (efficacy period as defined in description)
  Annualized bleeding episodes = (number of bleeding episodes during the efficacy period / number of days during the efficacy period)\*365.25. The efficacy period in Arms 1 and 2 began with the first prophylactic dose of rFVIIIFc and ended with the last dose (regardless of reason for dosing). The efficacy period in Arm 3 began at the time of last PK rFVIIIFc sampling timepoint and ended at the date
• Comparison of Annualized Bleeding Rates: Arm 1 Versus Arm 3
  Time frame: up to 52 weeks ± 2 weeks (efficacy period as defined in description)
  Estimated using the negative binomial model with treatment arm as covariate, based on whole study duration for all participants. Annualized bleeding episodes = (number of bleeding episodes / number of days in the respective period)\*365.25.The efficacy period in Arm 1 began with the first prophylactic dose of rFVIIIFc and ended with the last dose (regardless of reason for dosing). The efficacy per

Sponsor's own description

The primary objectives of this study are: to evaluate the safety and tolerability of rFVIIIFc administered as a prophylaxis (Arm 1), weekly (Arm 2), on-demand (Arm 3), and surgical treatment regimen; to evaluate the efficacy of the rFVIIIFc tailored prophylaxis regimen (Arm 1); to evaluate the efficacy of rFVIIIFc administered as an on-demand (Arm 3) and surgical treatment regimen. The secondary objectives of this study are: to characterize the PK profile of rFVIIIFc and compare the PK of rFVIIIFc with the currently marketed product, Advate®; to characterize the range of dose and schedules required to adequately prevent bleeding in a prophylaxis regimen, maintain hemostasis in a surgical setting, or to treat bleeding episodes in an on-demand, weekly treatment, or prophylaxis setting.

Publications & conference data

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

1. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A.
   Mahlangu J, Powell JS, Ragni MV, Chowdary P, et al · · 2014 · cited 359× · PMID 24227821 · DOI 10.1182/blood-2013-10-529974
2. Antibody-based therapeutics to watch in 2011.
   Reichert JM. · · 2011 · cited 161× · PMID 21051951 · DOI 10.4161/mabs.3.1.13895
3. Outcome of Clinical Trials with New Extended Half-Life FVIII/IX Concentrates.
   Mancuso ME, Santagostino E. · · 2017 · cited 72× · PMID 28350322 · DOI 10.3390/jcm6040039
4. Recombinant factor VIII Fc fusion protein for the treatment of severe haemophilia A: Final results from the ASPIRE extension study.
   Nolan B, Mahlangu J, Pabinger I, Young G, et al · · 2020 · cited 54× · PMID 32227570 · DOI 10.1111/hae.13953
5. First study of extended half-life rFVIIIFc in previously untreated patients with hemophilia A: PUPs A-LONG final results.
   Königs C, Ozelo MC, Dunn A, Kulkarni R, et al · · 2022 · cited 24× · PMID 35421219 · DOI 10.1182/blood.2021013563
6. To what degree are orphan drugs patient-centered? A review of the current state of clinical research in rare diseases.
   Lanar S, Acquadro C, Seaton J, Savre I, et al · · 2020 · cited 22× · PMID 32493385 · DOI 10.1186/s13023-020-01400-0
7. Fc-fusion technology and recombinant FVIII and FIX in the management of the hemophilias.
   Mancuso ME, Mannucci PM. · · 2014 · cited 17× · PMID 24729686 · DOI 10.2147/dddt.s47312
8. Recombinant factor VIII Fc for the treatment of haemophilia A.
   Hermans C, Mancuso ME, Nolan B, Pasi KJ. · · 2021 · cited 16× · PMID 33650192 · DOI 10.1111/ejh.13610