A Phase 3 Study to Evaluate Claseprubart in Adults With Generalized Myasthenia Gravis (EMERGE)

Официальное название

A Phase 3 Global, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Demonstrate the Efficacy, Safety, and Tolerability of Claseprubart (DNTH103) in Patients With Generalized Myasthenia Gravis (EMERGE)

Обзор

The purpose of this Phase 3 study is to demonstrate the efficacy, safety, and tolerability of claseprubart in participants with generalized myasthenia gravis (gMG).

Подробное описание

The study includes the following periods:

* Screening (up to 12 weeks) * Randomized, blinded, controlled treatment (RCT) period (17 weeks) * Extended treatment period (ETP) (104 weeks) (optional) for eligible participants \[includes blinded extension period (BEP) and open-label extension (OLE) period\] * Safety Follow-Up period (40 weeks)

Вмешательства

• Препарат Claseprubart
  IV loading dose on Day 1
• Препарат Placebo
  IV infusion on Day 1
• Комбинированный продукт Claseprubart
  Prefilled syringe containing claseprubart for SC administration
• Комбинированный продукт Placebo
  Prefilled syringe containing placebo for SC administration

Первичные конечные точки

• Change from Baseline to Week 17 in Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale Score [Срок оценки: Baseline (Day 1) to Week 17]

Вторичные конечные точки (10)

• Change from Baseline to Week 17 in Quantitative Myasthenia Gravis (QMG) Scale Score [Срок оценки: Baseline (Day 1) to Week 17]
• Change from Baseline to Week 17 in Myasthenia Gravis Composite (MGC) Scale Score [Срок оценки: Baseline (Day 1) to Week 17]
• Proportion of Participants with Greater Than or Equal to (≥) a 5-point Reduction in MG-ADL Scale Score at Week 17 Compared to Baseline [Срок оценки: Baseline (Day 1) to Week 17]
• Proportion of Participants Who Reach Minimal Symptom Expression (MSE), Defined as MG-ADL 0 or 1 at Week 17, Without Use of Rescue Therapy [Срок оценки: Baseline (Day 1) to Week 17]
• Proportion of Participants with a ≥ 5-point Reduction in QMG Scale Score at Week 17 Compared to Baseline [Срок оценки: Baseline (Day 1) to Week 17]
• Incidence of Treatment-emergent Adverse Events (TEAEs) and Treatment-Emergent and Treatment-Emergent Serious Adverse Events (SAEs) in the RCT period, BEP, OLE, and Safety Follow-Up [Срок оценки: Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks)]
• Serum Concentrations of Claseprubart [Срок оценки: Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks)]
• Change from Baseline in Complement Total Blood Test (CH50) in Serum ex vivo [Срок оценки: Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks)]
• Incidence of Antidrug Antibody (ADAs) Against Claseprubart in the RCT Period, BEP, OLE, and Safety Follow-Up [Срок оценки: Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks)]
• Titer of ADAs Against Claseprubart in the RCT Period, BEP, OLE, and Safety Follow-Up [Срок оценки: Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks)]

Критерии участия

Критерии включения

• Must have given written informed consent before any study-related activities are carried out
• Weight range between 40-130 kg at Screening
• Diagnosis of gMG by the following tests:

• Acetylcholine receptor antibody (AChR Ab) positive, and
• One of the following:

i. History of abnormal neuromuscular transmission test; ii. History of positive anticholinesterase test; iii. Clinical response to acetylcholinesterase inhibitors.

• Myasthenia Gravis Foundation of America (MGFA) Class II-IVa
• MG-ADL scale score of 6 or more
• QMG scale score of 10 or more
• Documented vaccinations against encapsulated bacteria in accordance with local requirements and based on vaccine availability
• Female participants must be of non-childbearing potential, or if of childbearing potential, must agree not to donate ova, not to attempt to become pregnant and, if engaging in sexual intercourse with a male partner, must agree to use a highly effective method of contraception
• Male participants agree not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception

Критерии исключения

• History or presence of significant medical/surgical condition including any acute illness, mental illness, or major surgery considered to be clinically significant or that could have potential impact on safety/efficacy or study procedures
• Known complement deficiency
• Prior history (at any time) of N. meningitidis infection
• Participants with known seropositivity or who test positive for an active viral infection with human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B (HBV; except participants who are seropositive because of HBV vaccination) or hepatitis C virus (HCV) during Screening
• Previous treatment with claseprubart (DNTH103) or participation in a clinical trial with claseprubart. \[
• Any thymic surgery/biopsy within 1 year of Screening
• Any known or untreated thymoma.
• Any history of thymic carcinoma or thymic malignancy
• History of active malignancy within 5 years prior to Screening, except basal cell carcinoma of the skin, curatively resected squamous cell carcinoma of the skin, cervical carcinoma in situ curatively treated or low-grade prostate adenocarcinoma for which appropriate management is observation alone
• Concurrent or previous use of the following medication within the time periods specified below.

• Rituximab or other B-cell targeting therapies (ie, inebilizumab) within 6 months (180 days) prior to randomization (Day 1);
• Intravenous immunoglobulin (IVIg) and plasma exchange (PLEX) within 4 weeks (28 days) prior to randomization (Day 1)
• Participation in another clinical study of an investigational drug within 90 days or 5 half-lives of the investigational agent
• Diagnosis of systemic lupus erythematosus (SLE) or family history (defined as a parent, sibling, or child) of SLE

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Cinical Study Site — Fayetteville

Идентификаторы

NCT: NCT07647510 · DNTH103-MG-301 · 2026-525298-38-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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