ADAPT Forward 2 - ISA2 - a Study to Evaluate the Safety, Tolerability and Efficacy of Empasiprubart IV Monotherapy in Participants With AChR-Ab Seropositive Generalized Myasthenia Gravis (ADAPT Forward2)

ISA2 to Master Protocol ARGX-999-2-MG-2000 - an Exploratory, Phase 2a, Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Empasiprubart IV Monotherapy in Participants With AChR-Ab Seropositive Generalized Myasthenia Gravis

This study is part of the ADAPT Forward platform study (NCT07294170). ADAPT Forward is a platform study with the aim to look at how safe different drugs are and how well they work for people with myasthenia gravis. The goal is to find the best therapeutic approach to reduce patients' side effects and improve their quality of life.

The aim of this ISA2 is to investigate the effects of empasiprubart in participants with AChR-Ab seropositive generalized myasthenia gravis (gMG).

The ADAPT Forward master protocol is registered on https://clinicaltrials.gov/study/NCT07294170

Study Overview

• Status: Not yet recruiting
• Conditions: gMG; MG - Myasthenia Gravis; AChR-Ab Seropositive Generalized Myasthenia Gravis; Myasthenia Gravis (MG)
• Intervention / Treatment: Biological: Empasiprubart IV; Other: Placebo IV; Combination product: Efgartigimod PH20 SC PFS

Detailed Description

Once the master protocol and ISA2 screening periods are completed, eligible participants will be randomized to receive empasiprubart IV or placebo in the double-blinded treatment period (DBTP). All participants will then receive open-label efgartigimod PH20 SC PFS in the safety follow-up period.

The study duration for each participant is approximately up to 45 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sabine Coppieters, MD; Phone Number: 857-350-4834; Email: clinicaltrials@argenx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is seropositive for anti-acetylcholine receptor antibodies (AChR-Ab).
• Has confirmed diagnosis of gMG and is Myasthenia Gravis Foundation of America (MGFA) Class II, III, IVa, or IVb.
• Has documented immunization against encapsulated bacterial pathogens (Neisseria meningitidis and Streptococcus pneumoniae) within 5 years before ISA screening or will complete immunization at least 14 days before the first IMP administration.

Exclusion Criteria:

• Clinical diagnosis of systemic lupus erythematosus (SLE).
• Is receiving concurrent complement inhibitors (eg, eculizumab, zilucoplan, ravulizumab, or others). Participants who received zilucoplan or eculizumab >2 months or ravulizumab >6 months before baseline are allowed to participate.
• Has received an FcRn antagonist, including efgartigimod, within 4 weeks before baseline.
• Had prior empasiprubart exposure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empasiprubart IV; Participants receive empasiprubart IV in the DBTP	Biological: Empasiprubart IV; Intravenous infusions of empasiprubart
Placebo Comparator: Placebo IV; Participants receive placebo IV in the DBTP	Other: Placebo IV; Intravenous infusions of placebo
Other: Efgartigimod PH20 SC PFS; Participants receive open-label efgartigimod PH20 SC PFS in the safety follow-up period	Combination product: Efgartigimod PH20 SC PFS; Subcutaneous administration of efgartigimod PH20 via pre-filled syringe (PFS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events and serious adverse events in the DBTP	Up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MG-ADL total score change from baseline at week 12	The Myasthenia Gravis Activities of Daily Living (MG-ADL) scale is an 8-item instrument used to assess MG symptoms and their effects on daily activities. The total score ranges from 0 (normal symptoms) to 24 (most severe symptoms)	Up to 12 weeks
QMG total score change from baseline at week 12	The Quantitative myasthenia gravis (QMG) includes 13 items that measure endurance or fatigability and accounts for fluctuations in disease state. The total score ranges from 0 (no disease severity) to 39 (highest disease severity)	Up to 12 weeks
MG-ADL total score change from baseline over time up to week 12	The Myasthenia Gravis Activities of Daily Living (MG- ADL) scale is an 8-item instrument used to assess MG symptoms and their effects on daily activities. The total score ranges from 0 (normal symptoms) to 24 (most severe symptoms)	Up to 12 weeks
QMG total score change from baseline over time up to week 12	The Quantitative myasthenia gravis (QMG) includes 13 items that measure endurance or fatigability and accounts for fluctuations in disease state. The total score ranges from 0 (no disease severity) to 39 (highest disease severity)	Up to 12 weeks
Proportion of participants reaching MSE at any point by week 12	MSE: Minimal symptom expression	Up to 12 weeks
Proportion of participants who have ≥3-point reduction in MG-ADL at week 12	The Myasthenia Gravis Activities of Daily Living (MG- ADL) scale is an 8-item instrument used to assess MG symptoms and their effects on daily activities. The total score ranges from 0 (normal symptoms) to 24 (most severe symptoms).	Up to 12 weeks
Proportion of participants who have ≥5-point reduction in QMG at week 12	The Quantitative myasthenia gravis (QMG) includes 13 items that measure endurance or fatigability and accounts for fluctuations in disease state. The total score ranges from 0 (no disease severity) to 39 (highest disease severity).	Up to 12 weeks
Proportion of participants who have a positive PASS at week 12	PASS: Patient acceptable symptom state	Up to 12 weeks
Proportion of participants who have a 50% MG-ADL total score improvement at week 12	The Myasthenia Gravis Activities of Daily Living (MG-ADL) scale is an 8-item instrument used to assess MG symptoms and their effects on daily activities. The total score ranges from 0 (normal symptoms) to 24 (most severe symptoms).	Up to 12 weeks

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Estimated): June 29, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: June 23, 2026
• First Submitted That Met QC Criteria: June 23, 2026
• First Posted (Actual): June 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myasthenia Gravis
• Other Study ID Numbers: ARGX-999-2-MG-20002; 2025-522939-33-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No