Study design and methodology of the PREVAIL trial: a phase 3, randomized, double-blind, placebo-controlled study of the safety and efficacy of subcutaneous ALXN1720 in adults with generalized myasthenia gravis
James Howard1, Sanjay Rakhade2, Joachim Scholz2, Stephan Ortiz2, Shulian Shang2, Tuan Vu3
1University of North Carolina at Chapel Hill School of Medicine, 2Alexion, AstraZeneca Rare Disease, 3University of South Florida
Objective:

To present the rationale and design for the PREVAIL trial (ALXN1720-MG-301; NCT05556096), a phase 3 study of ALXN1720 in adults with anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG).

Background:

ALXN1720, a novel 28 kDa bispecific variable domain on a heavy chain antibody, binds complement component 5 (C5) inhibiting its cleavage of C5 into C5a and C5b and subsequent formation of the membrane attack complex. ALXN1720 also binds to albumin, which increases its half-life, facilitating weekly dosing. The low molecular weight of ALXN1720 enables its concentration in small volumes for subcutaneous (SC) delivery, allowing self-administration. Previous programs have demonstrated safety and efficacy of C5 inhibitors in gMG. A phase 3, randomized, double-blind, placebo-controlled study was designed to assess safety and efficacy of ALXN1720 in adults with AChR Ab+ gMG.

Design/Methods:

Approximately 200 patients will be randomized (1:1) to receive ALXN1720 or placebo. Patients will receive a weight-based loading dose of ALXN1720 or placebo, followed by weekly weight-based maintenance doses. PREVAIL consists of a 4-week screening period, a 26-week randomized controlled treatment phase and a 96-week open-label extension period. The efficacy of ALXN1720 versus placebo will be measured by changes from baseline at week 26 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total scores. Secondary outcome measures include changes from baseline at week 26 in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Composite total scores, and MG-ADL 3-point improvement and QMG 5-point improvement. The safety, pharmacokinetics, pharmacodynamics and immunogenicity of ALXN1720 will be assessed. Key eligibility criteria include documented diagnosis of gMG ≥3 months ago; positive serological test for AChR autoantibodies; Myasthenia Gravis Foundation of America disease classification II to IV; and MG-ADL total score ≥5.

Results:

PREVAIL is currently active and recruiting patients in multiple countries.

Conclusions:

PREVAIL will assess safety and efficacy of SC ALXN1720 in patients with AChR Ab+ gMG.

10.1212/WNL.0000000000202990