A Multicenter, Randomized, Double-Masked Phase II Study Evaluating the Efficacy and Safety of IBI311 in Subjects With Inactive or Active Thyroid Eye Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Safety and Tolerability
研究概览
简要总结
This is a multicenter, randomized, double-masked phase II study evaluating the efficacy and safety of IBI311 in subjects with inactive or active thyroid eye disease. Approximately 36 subjects meeting the study eligibility criteria will be randomly assigned to the 3-10 mg group, 3-20 mg group, 10 mg group, or 20 mg group on day 1 in a 1:1:2:2 ratio. Dose conversion of the 3-10 mg or 3-20 mg group was performed at week 12. Active and inactive TED was a stratification factor in this study. Active and inactive TED subjects were enrolled in a 1:1 ratio.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent.
- •Male or female subject between the ages of 18 and 80 years at screening.
- •Weight between 50 kg and 100 kg.
- •Moderate-to-severe active TED:
- •CAS ≥ 3 in the study eye at screening and baseline;
- •Usually associated with at least two of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement, exophthalmos ≥ 3 mm above normal, and/or inconstant or constant diplopia;
- •≤ 12 months since the onset of active TED symptoms according to subjects' chief complaint or medical record at screening;
- •Inactive TED:
- •According to subjects' chief complaint or medical record at screening, initial diagnosis of TED > 12 months but < 10 years prior to screening.
- •CAS ≤ 2 in both eyes at screening and baseline and CAS ≤ 2 in both eyes for at least 6 months prior to screening or all of the following at least 6 months prior to screening: a. no progression in proptosis; b. no progression in diplopia; c. no new inflammatory TED symptoms.
- •Exophthalmos ≥ 3 mm above normal.
- •Exophthalmos ≥ 20 mm in the study eye at baseline.
- •Female subjects should be fertile women who are sterile or have a negative blood pregnancy test during the screening period and who agree to take contraceptive measures within 120 days from the screening period to the last medication; Male subjects should agree to use contraception from the screening period to 120 days after the last dose.
排除标准
- •Subjects will be ineligible for study participation if they meet any of the following criteria:
- •Baseline CAS decreased by ≥ 2 points, or baseline proptosis decreased by ≥ 2 mm as compared with screening.
- •Visual function impairment due to optic neuropathy, defined as ≥ 2 lines of vision loss, new visual field defect, or color vision impairment secondary to optic nerve involvement within the past 180 days;
- •Corneal ulcers with no relief after treatment as determined by the investigator;
- •TED patients who need immediate corticosteroid therapy, orbital radiotherapy, or orbital decompression;
- •At any time prior to baseline or during the study period planned to receive orbital radiation therapy or TED surgery, including orbital decompression, strabismus surgery, and eyelid retraction correction;
- •Poorly controlled thyroid function, which was defined as free triiodothyronine (FT3) or free tetraiodothyronine (FT4) deviated more than 50% from the normal reference range of the local research center laboratory at screening.
- •Either ear had a history of tinnitus or other hearing impairment; or abnormal pure tone audiometry (defined as mean bone conduction threshold [0.5, 1, 2, 4 kHz] ≥25 dB or any bone conduction threshold ≥ 40 dB);
- •Poorly controlled diabetes at screening, defined as HbA1C ≥ 9.0% at screening, or any new medication for diabetes within 60 days prior to screening, or any dose adjustment for diabetes drugs > 10%);
- •Systemic use of glucocorticoids ≤ 30 days prior to screening;
- •Periorbital use of glucocorticoids ≤ 90 days prior to screening;
- •Systemic use of immunosuppressants ≤ 90 days prior to screening;
- •Use glucocorticoid eye drops or immunosuppressive eye drops ≤ 30 days prior to screening
- •12. Use IBI311 or TEPEZZA at any time prior to screening; 13 Use CD20 antibody ≤ 1 year prior to screening, or IL-6R antibody ≤ 180 days prior to screening;
- •Subjects had participated in other interventional clinical trials ≤ 90 days prior to screening, or attempting to participate in other clinical trials during the study period.
研究组 & 干预措施
Arm 2: IBI311 (3-20 mg)
Arm 2: IBI311 (3-20 mg). Participants will receive 8 intravenous infusions of IBI311 with an interval of 3 weeks. Dose conversion was performed at week 12.
干预措施: IBI311 (3-20 mg) (Biological)
Arm 4: IBI311 (20 mg)
Arm 4: IBI311 (20 mg). Participants will receive 8 intravenous infusions of IBI311 with an interval of 3 weeks.
干预措施: IBI311 (20 mg) (Biological)
Arm 3: IBI311 (10 mg)
Arm 3: IBI311 (10 mg). Participants will receive 8 intravenous infusions of IBI311 with an interval of 3 weeks.
干预措施: IBI311 (10 mg) (Biological)
Arm 1: IBI311 (3-10 mg)
Arm 1: IBI311 (3-10 mg). Participants will receive 8 intravenous infusions of IBI311 with an interval of 3 weeks. Dose conversion was performed at week 12.
干预措施: IBI311 (3-10mg/kg) (Biological)
结局指标
主要结局
Safety and Tolerability
时间窗: After receiving IBI311 treatment for 48 weeks
Incidence, severity, and association with the study drug of ocular and systemic adverse events (AE), treatment-emergent adverse events (TEAE), and serious adverse events (SAE).
Mean change from Baseline in proptosis in the study eye.
时间窗: Week 12
Proptosis assessment: protrusion of the eye from the orbital rim as measured by Hertel exophthalmometer.
次要结局
- The proptosis responder rate in the study eye(Week 12, 24 and 48)
- Mean change from Baseline in CAS in the study eye.(Week 12, 24 and 48)
- The impact of IBI311 on the quality of life.(Week 12, 24 and 48)
- The diplopia responder rate(Week 12, 24 and 48)
- Mean change from Baseline in proptosis in the study eye.(Week 24 and 48)
- Change from Baseline in MRI in the study eye.(Week 12, 24 and 48)
- Positive responder rate to IBI311 treatment in the study eye.(Week 12, 24 and 48)
- The overall responder rate in the study eye.(Week 12, 24 and 48)
- Percentage of subjects with a CAS of 0 or 1 in the study eye.(Week 12, 24 and 48)
- The relapse rate after IBI311 treatment(Week 28, 36 and 48)
- Systemic Pharmacokinetics profile of IBI311(From Day 1 to week 24)