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FORMA 01 Trial
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FORMA-01 was a prospective, randomized, controlled, crossover phase II study evaluating the pharmacokinetics, surrogate efficacy, and safety of fibryga® compared to an active control (alternative fibrinogen concentrate) in 22 patients aged ≥12 years with congenital fibrinogen deficiency (afibrinogenaemia)​.
Patients were randomized to receive a single intravenous infusion of 70 mg/kg body weight of either fibryga® or the active control across two 45-day study periods, with crossover occurring at the end of the first period.
Primary objective
To determine the single-dose PK profiles and MCF as a surrogate marker for haemostatic efficacy for fibryga® versus active control.
Efficacy
PK Profile
The primary endpoint, mean area under the concentration–time curve normalized to the dose administered (AUCnorm), was significantly higher for fibryga® compared to the active control (1.62 vs 1.38 h·kg·g/L/mg; p=0.0001).
Clearance
No significant differences were found for secondary PK parameters except mean clearance, which was significantly slower for fibryga® than active control (0.67 vs 0.80 mL/h/kg; p=0.0002), and volume of distribution at steady state (70.16 vs 76.63 mL/kg)
Maximum Clot Firmness
Mean (± SD) MCF was substantially increased at 1 hour following infusion with fibryga® (9.68 ± 2.95 mm) and active control (10.00 ± 4.35 mm) (both p<0.0001); the mean difference between treatments of −0.32 (95% confidence interval [CI]: −1.70, 1.07) mm was not significant.
Figure 1: Mean (±SD) fibrinogen activity (g/L) during pharmacokinetic assessment after administration of fibryga® or active control (n = 21).
Safety
There were no safety concerns with the single-dose administration of fibryga® compared to the active control.
A total of 25 adverse events (AEs) were reported in 11 patients in the fibryga® group, while 30 AEs occurred in 11 patients in the active control group. Most AEs were mild, isolated events (Figure).
No deaths, thrombotic events, severe allergic reactions, or seroconversions (HIV, HAV, HBV, HCV, or parvovirus B19) occurred with either treatment.
Figure 2: Number of Adverse Events
Reference
Ross C, Rangarajan S, Karimi M, Toogeh G, Apte S, Lissitchkov T, Acharya S, Manco-Johnson MJ, Srivastava A, Brand B, Schwartz BA, Knaub S, Peyvandi F. Pharmacokinetics, clot strength and safety of a new fibrinogen concentrate: randomized comparison with active control in congenital fibrinogen deficiency. J Thromb Haemost. 2018 Feb;16(2):253-261. doi: 10.1111/jth.13923. Epub 2018 Jan 22. PMID: 29220876. [PubMed]
