Abstract Details

Title 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

Topic Autoimmune Neurology

Presentation(s) P1 - Poster Session 1 (8:00 AM-9:00 AM)

Poster/Presentation
Number 6-008

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.

Authors/Disclosures
James F. Howard, Jr., MD, FAAN (The University of North Carolina, Dept of Neurology, CB 7025) PRESENTER	Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for argenx . Dr. Howard has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Regeneron Pharmaceuticals. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion Pharmaceuticals. Dr. Howard has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AMGEN (Horizon Therapeutics). Dr. Howard has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Howard has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven Ltd. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CorEvitas. Dr. Howard has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck EMD Serono. Dr. Howard has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cartesian Therapeutics. Dr. Howard has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NMD Pharma. Dr. Howard has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for H. Lundbeck A/S. Dr. Howard has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Seismic Therapeutics. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Howard has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vor Biopharma. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Academic CME. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for PeerView CME. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Platform Q CME. Dr. Howard has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for MJH LifeSci. Dr. Howard has or had stock in Johnson & Johnson dividends.Dr. Howard has or had stock in Pfizer dividends. An immediate family member of Dr. Howard has or had stock in GlaxoSmithKline dividends.Dr. Howard has or had stock in Bristol Myer Squbb dividends.Dr. Howard has or had stock in AbbieVie Inc. The institution of Dr. Howard has received research support from Alexion Pharmaceuticals. The institution of Dr. Howard has received research support from argenx . The institution of Dr. Howard has received research support from UCB Biosciences. The institution of Dr. Howard has received research support from NIH. The institution of Dr. Howard has received research support from Centers for Disease Control/Research Triangle Institute. The institution of Dr. Howard has received research support from Cartestian Therapeutics. The institution of Dr. Howard has received research support from NMD Pharma. The institution of Dr. Howard has received research support from Ad Scientiam. The institution of Dr. Howard has received research support from Merck EMD Serono. Dr. Howard has a non-compensated relationship as a Scientific Advisiory Board member, Committee member with Myasthenia Gravis Foundation of America that is relevant to AAN interests or activities. Dr. Howard has a non-compensated relationship as a Committee member with American Assoc Neuromuscular and Electrodiagnostic Medicine that is relevant to AAN interests or activities.
Sanjay N. Rakhade, MBBS, PhD (Alexion Pharmaceuticals)	Dr. Rakhade has received personal compensation for serving as an employee of Alexion Pharmaceuticals . Dr. Rakhade has stock in Alexion Pharmaceuticals. Dr. Rakhade has stock in Astra Zeneca. Dr. Rakhade has received intellectual property interests from a discovery or technology relating to health care.
Joachim Scholz, MD (Alexion AstraZeneca Rare Disease)	Dr. Scholz has received personal compensation for serving as an employee of Alexion AstraZeneca Rare Disease. Dr. Scholz has stock in Alexion AstraZeneca Rare Disease. Dr. Scholz has stock in Biogen. Dr. Scholz has received intellectual property interests from a discovery or technology relating to health care.
Stephan Ortiz, PhD (Alexion, AstraZeneca Rare Disease)	Dr. Ortiz has received personal compensation for serving as an employee of Alexion/AstraZeneca Rare Disease. Dr. Ortiz has stock in Alexion.
	No disclosure on file
Tuan H. Vu, MD (University of South Florida)	Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Dianthus. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NMD Pharma. Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ARGENX. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Vu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen (Horizon). Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Johnson & Johnson. Dr. Vu has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Alexion. Dr. Vu has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for CSL Behring. Dr. Vu has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Argenx. The institution of Dr. Vu has received research support from CSL Behring. The institution of Dr. Vu has received research support from Alexion. The institution of Dr. Vu has received research support from RA Pharma/UCB. The institution of Dr. Vu has received research support from Mass Gen Hospital/Healy Platform Study. The institution of Dr. Vu has received research support from ARGENX. The institution of Dr. Vu has received research support from Horizon/Amgen. The institution of Dr. Vu has received research support from Woolsey Pharma. The institution of Dr. Vu has received research support from CSL Behring. The institution of Dr. Vu has received research support from Cartesian Therapeutics. The institution of Dr. Vu has received research support from Janssen/Johnson & Johnson. The institution of Dr. Vu has received research support from Immunovant. The institution of Dr. Vu has received research support from Regeneron. The institution of Dr. Vu has received research support from Dianthus. The institution of Dr. Vu has received research support from COUR.

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