2025-522406-20-00招募中2 期
A Phase 1b/2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Investigate A) the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Doses of IM-101 in Adult Participants with Generalized Myasthenia Gravis, and B) the Efficacy and Safety of Treatment of IM-101 in Adult Participants with Generalized Myasthenia Gravis and Ocular Myasthenia Gravis
Immunabs Inc.12 个研究点 分布在 3 个国家目标入组 51 人开始时间: 2026年2月18日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 51
- 试验地点
- 12
- 主要终点
- [Part A, Multiple Ascending Dose Cohorts] Incidence of TEAEs, including clinically significant changes in physical examinations or ECGs during study treatment [Part B, Expansion Cohorts] Incidence of TEAEs including clinically significant changes in physical examinations or ECGs during study treatment
研究概览
简要总结
[Part A, Multiple Ascending Dose Cohorts] To assess the safety and tolerability of IM-101 across 3 ascending dose regimens (each with 3 administrations) in participants with AChR antibody-positive gMG [Part B, Expansion Cohorts] 1, To assess the safety and tolerability of IM-101, compared with placebo, in participants with AChR antibody-positive gMG, AChR antibody-negative gMG, and oMG 2. To evaluate the efficacy of IM-101, compared with placebo, in participants with AChR antibody-positive gMG, AChR antibody-negative gMG, and oMG
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
- 否
入选标准
- •All Participants Able and willing to provide signed informed consent and willing to travel to the investigational sites for study visits and fulfill logistical requirements of study
- •Female participants of childbearing potential (ie, women who are not postmenopausal or who have not had a hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) and male participants who have not been surgically sterilized by a vasectomy must use a reliable and highly effective contraception method throughout the study and for 3 months after the last dose of study intervention
- •Female participants of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to the first dose of study intervention
- •All gMG Participants Myasthenia Gravis – Activities of Daily Living (MG-ADL) total score ≥ 6 at both screening and randomization, with at least 50% of the score attributed to non-ocular elements
- •All gMG Participants Myasthenia Gravis Foundation of America (MGFA) Class II to IVa classification.
- •AChR Antibody-positive gMG Participants Only Must have anti-AChR binding antibody.
- •AChR Antibody-negative gMG Participants Only AChR-binding antibody negative.
- •oMG Participants Only MGFA Clinical Classification Class I
- •oMG Participants Only MG-ADL total score 3 to 6 at both screening and randomization, assigned exclusively to ocular elements.
- •Willingness to consent to screening for genetic muscular diseases (mitochondrial myopathy, oculopharyngeal muscular dystrophy, congenital myasthenia syndrome, and progressive external ophthalmoplegia)
- •Male or female aged ≥ 18 years and < 75 years
- •Has no known weakness in infancy and develop muscle weakness after aged 16 years and diagnosed with acquired MG at least 6 months (180 days) prior to the date of the screening visit (signing of informed consent)
- •Diagnosed with MG, confirmed through: a. Abnormal neuromuscular transmission demonstrated by single fiber electromyography or repetitive nerve stimulation, or b. Positive response to an AChEI test (eg, edrophonium chloride test), or c. Improvement of signs or symptoms related to MG during treatment with an oral acetylcholinesterase inhibitor, as determined by the treating physician (pyridostigmine or neostigmine or edrophonium test)
- •Body weight ≥ 40 kg at screening
- •On a stable dose of background therapy for the treatment of MG for the time periods specified below, with no changes to the regimen expected during the treatment period: a. Oral corticosteroids: stable for ≥ 4 weeks before Day 1 with the daily dose not exceeding 20 mg/day for prednisone/prednisolone or 16 mg/day for methylprednisolone. b. Acetylcholinesterase inhibitors: stable for ≥ 4 weeks prior to randomization c. Azathioprine, mycophenolate mofetil, methotrexate: receiving for ≥ 6 months prior to screening, with a stable dose for ≥ 3 month prior to randomization. If discontinued prior to screening, participants must have stopped azathioprine, mycophenolate mofetil or methotrexate ≥ 12 weeks prior to Day 1
- •Vaccinated against meningococcal infection (Neisseria meningitidis) within 1 year of screening, and at least 2 weeks prior to Day 1 (participants must have received 2 doses of vaccine to be considered vaccinated)
- •Vaccinated against streptococcus pneumoniae, and haemophilus influenzae type B according to local standard
排除标准
- •All Participants Previous exposure to IM-101
- •Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to screening
- •Evidence of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV-1 or HIV-2) viral infection at screening
- •Active systemic bacterial, viral, or fungal infection within 14 days prior to first dose of the study intervention
- •Presence of fever as documented by a temperature ≥ 37.8°C (100.04°F) by oral or ≥ 37.3°C (99.14°F) by skin (axillary) or ≥ 38.3°C (100.94°F) by tympanic within 7 days prior to the first dose of the study intervention
- •Use of the following within the time periods specified: a. Intravenous immunoglobulin (IVIg) or subcutaneous immunoglobulin within the 4 weeks prior to screening b. Use of plasma exchange (PLEX) within 4 weeks prior to screening c. Use of rituximab, tacrolimus, or cyclophosphamide within 6 months prior to screening d. Use of neonatal Fc receptor (FcRn) blocker within 6 weeks prior to screening e. Use of C5 inhibitor approved for the treatment of gMG at the recommended dose regimen for within 2 months (zilucoplan or eculizumab) or 3 months (ravulizumab) prior to screening
- •Has been treated with any complement inhibitor, but failed due to intolerability or lack of efficacy
- •Clinical laboratory abnormalities at screening, including: a. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2 × the upper limit of normal (ULN) b. Total bilirubin > 1.5 × ULN c. Estimated glomerular filtration rate < 60 mL/min/1.73 m2 based on the Modification of Diet in Renal Disease equation
- •Participation in another interventional treatment study or use of any experimental therapy within 30 days before screening or within 5 half-lives of the study drug, whichever is longer
- •Pregnant, breastfeeding, or intending to conceive during the course of the study
- •Planned surgical procedure requiring general anesthesia during the course of the study
- •Anti-MuSK antibody Positive
- •Any medical or psychological condition(s), clinically significant laboratory abnormality or risk factor that, in the opinion of the Investigator or the Medical Monitor, might interfere with participation in the study, pose any added risk to the participant, or confound the assessment of the participant or outcome of the study.
- •oMG Participants Only Participant with fixed ophthalmoplegia
- •oMG Participants Only History of eyelid retraction surgery
- •oMG Participants Only Family history of clinically meaningful ptosis or diplopia or other known diseases that lead to eyelid drooping, peripheral muscle weakness, or diplopia.
- •History of thymectomy, or any other thymic surgery within 12 months prior to screening or planned during the study
- •History of malignant thymoma (patients with Stage I may be enrolled), or history of cancer within the past 5 years of screening, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervix cancer
- •History of any immunologic disorder other than MG, or any other conditions that would interfere with an accurate assessment of clinical gMG or oMG or that would require chronic oral, intravenous, intramuscular, or intra-articular corticosteroid therapy. Well-controlled thyroid disease, as per the Investigator or the participant’s regular treating physician recorded in the source documents, is not exclusionary
- •History of, or current diagnosis of active tuberculosis (TB), or currently undergoing treatment for latent TB, or untreated latent TB infection as determined by results within 3 months of the screening visit of a positive TB skin test with purified protein derivative with induration ≥ 5 mm. Additionally, the participant should be excluded if they have current household contacts with active TB, or the participant has a positive QuantiFERON TB Gold test at screening unless they have completed chemoprophylaxis for the latent TB infection (as per applicable local guidelines) prior to the screening visit.
- •History of N. meningitidis infection
- •Clinical features that, in the opinion of the Investigator, are consistent with gMG crisis/exacerbation or clinical deterioration, within 28 days prior to randomization (Day 1)
- •History of hypersensitivity to any ingredient contained in the study intervention
结局指标
主要结局
[Part A, Multiple Ascending Dose Cohorts] Incidence of TEAEs, including clinically significant changes in physical examinations or ECGs during study treatment [Part B, Expansion Cohorts] Incidence of TEAEs including clinically significant changes in physical examinations or ECGs during study treatment
[Part A, Multiple Ascending Dose Cohorts] Incidence of TEAEs, including clinically significant changes in physical examinations or ECGs during study treatment [Part B, Expansion Cohorts] Incidence of TEAEs including clinically significant changes in physical examinations or ECGs during study treatment
[Part A, Multiple Ascending Dose Cohorts] Incidence of treatment-emergent SAEs [Part B, Expansion Cohorts] Incidence of SAEs during study treatment
[Part A, Multiple Ascending Dose Cohorts] Incidence of treatment-emergent SAEs [Part B, Expansion Cohorts] Incidence of SAEs during study treatment
[Part A, Multiple Ascending Dose Cohorts] Incidence of TEAEs leading to premature study intervention discontinuation [Part B, Expansion Cohorts] Incidence of AEs that led to premature discontinuation
[Part A, Multiple Ascending Dose Cohorts] Incidence of TEAEs leading to premature study intervention discontinuation [Part B, Expansion Cohorts] Incidence of AEs that led to premature discontinuation
[Part A, Multiple Ascending Dose Cohorts] Incidence of AESIs during study treatment period [Part B, Expansion Cohorts] Incidence of AESIs during study treatment period
[Part A, Multiple Ascending Dose Cohorts] Incidence of AESIs during study treatment period [Part B, Expansion Cohorts] Incidence of AESIs during study treatment period
[Part B, Expansion Cohorts] 1. gMG cohorts: Change from baseline to Week 16 in the MG-ADL total score 2. oMG cohort: Change from baseline to Week 16 in MGII ocular score
[Part B, Expansion Cohorts] 1. gMG cohorts: Change from baseline to Week 16 in the MG-ADL total score 2. oMG cohort: Change from baseline to Week 16 in MGII ocular score
次要结局
- [Part A, Multiple Ascending Dose Cohorts] Incidence and prevalence of ADAs and NAb to IM-101 [Part B, Expansion Cohorts] Incidence and prevalence of ADAs and NAb of IM-101 over time
- [Part A, Multiple Ascending Dose Cohorts] Changes from baseline in vital signs, laboratory assessments, and other safety variables [Part B, Expansion Cohorts] Changes from baseline in vital signs, laboratory assessments, and other safety variables
- Part A; Serum PK IM-101, Cmax, tmax, AUC0-tau, Ctrough, CL, Vz, t1/2, ratio for Cmax & AUC0-tau Part B [gMG] 1.Change from baseline to wk16 in QMG total; MGC scale; MG-QoL15r 2. %age participants with MG-ADL ≥ 2-point & ≥ 3-point change at Wk16 3. %age participants with MSE; MG-ADL of 0 or 1 [oMG] 1.Change from baseline to Wk16 in MG-ADL ocular domain & MGII total score 2.Quantitative change from baseline to Wk16 in QMG total score [All]1.%age requiring rescue therapy over 16-wk treatment period
- [Part A, Multiple Ascending Dose Cohorts] Obtain serum IM-101 concentration for modeling and simulation [Part B, Expansion Cohorts] CH50, AH50, and total C5 and free C5 at baseline and timepoints during and following treatment
- [Part A, Multiple Ascending Dose Cohorts] CH50, AH50, and total C5 and free C5 at baseline and timepoints during and following treatment [Part B, Expansion Cohorts] 1. Serum IM-101 concentrations over the treatment period 2. Sparse sample collections to support population PK modeling and simulations
研究者
Soonyoung Lee
Scientific
Immunabs Inc.
研究点 (12)
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