2024-512865-15-00招募中2 期
A PHASE 2, RANDOMIZED, BLINDED, PLACEBOCONTROLLED, STUDY TO EVALUATE SAFETY, TOLERABILITY, PHARMACOMETRICS, AND EFFICACY OF DNTH103 IN ADULTS WITH GENERALIZED MYASTHENIA GRAVIS (MAGIC)
Dianthus Therapeutics Inc.23 个研究点 分布在 9 个国家目标入组 54 人开始时间: 2024年7月22日最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 54
- 试验地点
- 23
- 主要终点
- Safety and tolerability of DNTH103 up to Week 13: Incidence of TEAEs and treatment-emergent SAEs up to Week 13 (end of the RCT period)
研究概览
简要总结
To evaluate safety and tolerability of DNTH103 in patients with generalized myasthenia gravis (gMG) up to Week 13
研究设计
- 分配方式
- Not Applicable
- 主要目的
- 40-week Safety Follow-up Period
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects.
- •Participants must be receiving at least 1 but not more than 3 of the following immunosuppressant medications at Screening, provided they have a stable daily dose for the minimum periods outlined below and maintain throughout the study: a. If taking oral corticosteroids, must have been taking for at least 4 weeks (28 days) prior to randomization, with doses not to exceed an average of 40 mg/day (280 mg/week) of prednisone or its equivalent; b. If taking azathioprine, must have been taking for at least 6 months (180 days) at time of randomization with a stable dose for at least 2 months (60 days) prior to randomization; c. If taking other immunosuppressants, must have been on other immunosuppressants (such as cyclosporin, mycophenolate mofetil, cyclophosphamide, or methotrexate) for at least 3 months (90 days) at time of randomization with a stable dose for at least 1 month (30 days) prior to randomization.
- •Female participants must: a. Be of nonchildbearing potential, ie, surgically sterilized via laparoscopic methods at least 6 weeks before Screening, if surgically sterilized via open abdominal surgery, at least 12 weeks before Screening or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone [FSH] level ≥ 40 IU/L at Screening), or b. 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 from signing the informed consent form throughout the study until the end of the Safety Follow-up period, or longer if required in accordance with local requirements.
- •Male participants must be surgically sterile for at least 90 days prior to Screening or 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 from signing the informed consent form throughout the study until the end of the Safety Follow-up period, or longer if required in accordance with local requirements.
- •No clinically significant abnormalities (in the opinion of the Investigator) during Screening, including: a. No clinically significant findings in serum chemistry, hematology, coagulation, and urinalysis tests. b. Triplicate 12-lead electrocardiogram (ECG) with a mean QT interval corrected using the Fridericia method (QTcF) ≤ 450 msec for males and ≤ 460 msec for females and no clinically significant abnormalities. The triplicate 12-lead ECG assessment may be repeated once, if abnormal values were recorded in any of the 3 readings completed in the first instance, at the discretion of the PI. Electrocardiogram findings outside of normal ranges may be considered acceptable if determined by the Investigator to be not clinically significant.
- •Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
- •Adult males and females, 18 to 75 years of age (inclusive) at Screening.
- •Weight range between 40-120 kg at Screening.
- •Diagnosed with gMG at least 3 months (90 days) before the Screening visit, confirmed as specified in inclusion criterion #5 below.
- •Diagnosis of gMG by the following tests: a. Acetylcholine receptor antibody (AChR Ab) positive as confirmed during the Screening period prior to randomization, and b. One of the following: i. History of abnormal neuromuscular transmission test, consistent with gMG, as demonstrated by single-fiber electromyography or repetitive nerve stimulation; ii. History of positive anticholinesterase test (eg, edrophonium); iii. Clinical response to acetylcholinesterase inhibitors such as pyridostigmine (Mestinon®) as assessed by the treating physician.
- •Myasthenia Gravis Foundation of America (MGFA) Class II-IVa, at Screening and confirmed at randomization.
- •Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 6 or more, at Screening and confirmed at randomization.
- •Participants must have documented vaccinations against encapsulated bacterial pathogens N. meningitidis (including serogroup B meningococcus, where available) and S. pneumoniae within 3 years of enrollment or be vaccinated at least 2 weeks (14 days) prior to randomization. They should also have documented vaccinations against H. influenzae within 3 years prior to enrollment or be vaccinated at least 2 weeks (14 days) prior to randomization in accordance with local requirements and based on vaccine availability.
- •Participants using acetylcholinesterase inhibitors (eg, pyridostigmine, Mestinon) at Screening are allowed to continue provided they maintain a stable daily dose for a minimum period of 2 weeks (14 days) prior to randomization.
排除标准
- •History or presence of significant medical/surgical condition including any acute illness or major surgery considered to be clinically significant or that could have potential impact on safety/efficacy or study procedures in the opinion of the Investigator.
- •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.
- •History of hospitalization for 24 hours or longer, excluding elective procedures, within the 6 weeks (42 days) prior to Screening.
- •Liver test results elevated more than 2-fold above the upper limit of normal for gamma-glutamyl transferase, bilirubin (total), aspartate aminotransferase (AST) or alanine aminotransferase (ALT), unless a diagnosis of Gilbert syndrome. For history of Gilbert syndrome, the limit is extended to 3-fold above the upper limit of normal.
- •Concurrent or previous use of the following medications within the time periods specified below. a. Rituximab within 6 months (180 days) prior to randomization (Day 1); b. Intravenous immunoglobulin (IVIg) and plasma exchange (PLEX) within 4 weeks (28 days) prior to randomization (Day 1).
- •Receipt of any live vaccine within 30 days prior to randomization (Day 1) or expected to receive a live vaccine during the study.
- •Clinically significant drug or alcohol abuse in the opinion of the Investigator.
- •Known hypersensitivity to any of the study drug ingredients.
- •For persons of childbearing potential, a positive serum pregnancy test during Screening or a positive urine pregnancy test (with confirmatory serum pregnancy test) at randomization.
- •Females who are breastfeeding or planning to breastfeed at any time during the study.
- •Participation in another clinical study of an investigational drug within 90 days or 5 half-lives of the investigational agent (whichever is longer) prior to randomization (Day 1).
- •Clinical features that, in the opinion of the Investigator, are consistent with MG crisis/exacerbation at the time of the Screening visit or at any time between Screening and randomization.
- •Any other overlapping condition for which the condition or treatment of the condition may affect the study assessments or outcomes.
- •Any other condition, including mental illness or prior therapy that in the opinion of the Investigator would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.
- •Diagnosis of SLE or family history (defined as a parent or sibling) of SLE.
- •Diagnosis of an autoimmune disorder other than gMG. Exceptions for other autoimmune disorders (except SLE) may be granted following Medical Monitor review and approval on a case-by-case basis.
- •An antinuclear antibodies (ANA) titer of ≥ 1:320, or positive for both ANA (any titer) and anti-double stranded (ds) DNA antibodies.
- •Known complement deficiency or history of positive titer for anti-C1 antibodies.
- •Prior history (at any time) of N. meningitidis infection.
- •Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies during Screening. Participants who have no evidence of cirrhosis, have completed a curative intent regimen for HCV, and are deemed by a gastroenterologist to have no active HCV will not be excluded.
- •Currently or previously on complement inhibitors, or currently on antineonatal Fc receptor (FcRN) agents. Participants who were previously on anti-FcRN agents and took their last dose at least 5 half-lives or 90 days, whichever is greater, prior to randomization (Day 1) may be considered after review and approval by the Medical Monitor.
- •Any thymic surgery/biopsy within 1 year of Screening.
- •Any known or untreated thymoma. Past thymoma with resection (if surgery/resection done at least 1 year prior to Screening) is allowed, if no recurrence within 6 months prior to Screening or confirmed during Screening period (confirmed by computerized tomography scan or magnetic resonance imaging of the chest).
- •Any history of thymic carcinoma or thymic malignancy.
结局指标
主要结局
Safety and tolerability of DNTH103 up to Week 13: Incidence of TEAEs and treatment-emergent SAEs up to Week 13 (end of the RCT period)
Safety and tolerability of DNTH103 up to Week 13: Incidence of TEAEs and treatment-emergent SAEs up to Week 13 (end of the RCT period)
次要结局
- Efficacy: Change from baseline to Week 13 in MG-ADL scale score
- Efficacy: Change from baseline to Week 13 in Quantitative Myasthenia Gravis (QMG) scale score
- Efficacy: Change from baseline to Week 13 in Myasthenia Gravis Composite (MGC) scale score
- Pharmacokinetics/Pharmacodynamics: Serum concentrations and PK parameters, including Cmax and Cmin
- Pharmacokinetics/Pharmacodynamics: PD parameters (eg, CH50 [complement hemolysis 50%]) in serum ex vivo
- Immunogenicity: Incidence and titer of antidrug antibodies against DNTH103levels against DNTH103
- Safety and tolerability over 52 weeks in the OLE: Incidence of TEAEs and treatment-emergent SAEs up to Week 52 in the OLE
研究者
Scientific CTIS contact point
Scientific
Dianthus Therapeutics Inc.
研究点 (23)
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