A Safety, Tolerability, and Efficacy Study of Veligrotug, a Humanized Monoclonal Antibody Directed Against the IGF-1 Receptor in Subjects With Thyroid Eye Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 113
- 试验地点
- 102
- 主要终点
- Proptosis Responder Rate
研究概览
简要总结
The investigational drug, veligrotug (VRDN-001), is a monoclonal antibody that inhibits the activity of a cell surface receptor called insulin-like growth factor-1 receptor (IGF-1R). Inhibition of IGF-1R may help to reduce the inflammation and associated tissue swelling that occurs in participants with thyroid eye disease (TED). The primary objective of this clinical trial is to establish the safety, tolerability, and efficacy of veligrotug, and the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of veligrotug in active TED participants who received 10 milligrams (mg)/kilogram (kg).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for Active TED Participants (THRIVE):
- •Must have moderate to severe active TED with documented evidence of ocular symptoms or signs that began within 15 months prior to screening
- •Must have Clinical Activity Score (CAS) of ≥ 3 on the 7-item scale for the study eye
- •Must agree to use highly effective contraception as specified in the protocol
- •Female TED participants must have a negative serum pregnancy test at screening
排除标准
- •for Active TED Participants (THRIVE):
- •Must not have received prior treatment with another anti-IGF-1R therapy or any investigational agent for TED
- •Must not have used systemic corticosteroids or selenium within 2 weeks prior to Day 1
- •Must not have received rituximab, tocilizumab or other immunosuppressive agents or any other therapy for TED within 8 weeks prior to Day 1
- •Must not have received an investigational agent for any condition within 8 weeks prior to Day 1
- •Must not have a pre-existing ophthalmic condition in the study eye that in the opinion of the Investigator would confound interpretation of the study results
- •Must not have had previous orbital irradiation or surgery for TED in the study eye
- •Must not have a history of inflammatory bowel disease
- •Must not have a history of or screening audiometry assessment of clinically significant (as determined by investigator) ear pathology, relevant ear surgery, or hearing loss
- •Female TED participants must not be pregnant or lactating
- •Note: Prior thyroidectomy, radioactive iodine (RAI) treatment, or orbital decompression surgery limited to bone only are NOT exclusions.
研究组 & 干预措施
Placebo
Participants will receive placebo matched to veligrotug as an IV infusion Q3W for 12 weeks.
干预措施: Placebo (Drug)
Veligrotug
Participants will receive veligrotug 10 mg/kg as an intravenous (IV) infusion every 3 weeks (Q3W) for 12 weeks.
干预措施: Veligrotug (Drug)
结局指标
主要结局
Proptosis Responder Rate
时间窗: Week 15
Proptosis Responder Rate in the study eye (i.e., reduction of proptosis of ≥ 2 mm from baseline \[without a corresponding increase of ≥ 2 mm in the fellow eye\] as measured by exophthalmometer)
Proptosis Responder Rate (PRR) in the Study Eye As Measured by Exophthalmometer
时间窗: Baseline to Week 15
Proptosis responder in the study eye was defined as a reduction of proptosis of ≥2 millimeters (mm) from baseline in the study eye (without a corresponding increase of ≥2 mm in the fellow eye) as measured by exophthalmometer. Missing data were imputed with the Multiple Imputation method.
次要结局
- Diplopia Responder Rate(Week 15)
- Change from baseline in proptosis in the study eye(Week 15)
- Proptosis Responder Rate in the most proptotic eye(Week 15)
- Change from baseline in proptosis in the most proptotic eye(Week 15)
- Change from baseline in CAS(Week 15)
- Overall Responder Rate(Week 15)
- Clinical Activity Responder Rate in the study eye(Week 15)
- Proportion of participants with a CAS score of zero or one in the study eye(Week 15)
- Diplopia Resolution Rate(Week 15)
- Change From Baseline in Proptosis in the Study Eye As Measured by Exophthalmometer(Baseline, Week 15)
- PRR in the Most Proptotic Eye As Measured by Magnetic Resonance Imaging (MRI)/Computed Tomography (CT)(Week 15)
- Change From Baseline in Proptosis in the Most Proptotic Eye As Measured by MRI/CT(Baseline, Week 15)
- Change From Baseline in CAS in the Study Eye(Baseline, Week 15)
- Overall Responder Rate (ORR) Comprising of PRR and Clinical Activity Responder Rate in the Study Eye(Baseline to Week 15)
- Clinical Activity Responder Rate in the Study Eye(Week 15)
- Percentage of Participants With a CAS of 0 or 1 in the Study Eye(Week 15)