A Phase 4, Randomized, Double-masked, Placebo-controlled, Multicenter Trial to Evaluate the Efficacy and Safety of TEPEZZA® in Treating Patients With Chronic (Inactive) Thyroid Eye Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 62
- 试验地点
- 12
- 主要终点
- Change From Baseline in Proptosis of Study Eye at Week 24
研究概览
简要总结
The overall objective is to investigate the efficacy, safety and tolerability of TEPEZZA® in participants with chronic (inactive) TED (thyroid eye disease). Approximately 57 participants will be enrolled. There will be a treatment period (through Week 24) and a follow up period (where TEPEZZA will not be infused).
详细描述
This is a randomized, double-masked, placebo-controlled, parallel-group, multicenter trial. Participants will be screened for the trial within 4 weeks prior to Baseline (Day 1). Approximately 57 participants who meet the trial eligibility criteria will be randomized on Day 1 in a 2:1 ratio to receive 8 infusions of TEPEZZA or placebo once every 3 weeks.
All participants will enter a 24-week double-masked Treatment Period, during which trial drug will be infused on Day 1 (Baseline) and Weeks 3, 6, 9, 12, 15, 18 and 21 (with a final visit at Week 24 of the 24-week Treatment Period). At the end of the double-masked Treatment Period (Week 24), all patients will be assessed for treatment response. Non-responders may choose to receive 8 infusions of TEPEZZA in an open-label fashion q3W at Weeks 24, 27, 30, 33, 36, 39, 42 and 45.
Study acquired from Horizon in 2024.
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
- Quadruple (Participant, Care Provider, 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
- •Written informed consent.
- •Male or female at least 18 years old at Screening.
- •Initial diagnosis of TED ≥2 years but <10 years prior to Screening. Clinical diagnosis of stable, chronic (inactive) TED, as determined by participant medical records indicating a Clinical Activity Score (CAS) ≤1 in both eyes for at least 1 year prior to Screening or all of the following:
- •no progression in proptosis for at least 1 year prior to Screening
- •if participant has history of diplopia due to TED, no progression in diplopia for at least 1 year prior to Screening
- •no new inflammatory TED symptoms for at least 1 year prior to Screening
- •CAS ≤1 at the Screening and Baseline Visits.
- •Proptosis ≥3-mm increase from participant's Baseline (prior to diagnosis of TED), as estimated by treating physician and/or proptosis ≥3 mm above normal for race and gender.
- •Participants must be euthyroid with the participant's Baseline disease under control or have mild hypo- or hyperthyroidism (defined as free thyroxine and free triiodothyronine levels <50% above or below the normal limits) at Screening. Every effort should be made to correct the mild hypo- or hyperthyroidism promptly and to maintain the euthyroid state for the full duration of the trial.
- •Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the course of the trial.
- •Diabetic participants must have HbA1c ≤8.0% at Screening.
- •Participants with a history of inflammatory bowel disease, ulcerative colitis or Crohn's disease must be in clinical remission for at least 3 months, with no history of bowel surgery within 6 months prior to screening and no planned surgery during the trial. Concomitant stable therapies for inflammatory bowel disease without modifications in the 3 months prior to Screening are allowed.
- •Women of childbearing potential (including those with an onset of menopause <2 years prior to Screening, non-therapy-induced amenorrhea for <12 months prior to Screening, or not surgically sterile [absence of ovaries and/or uterus]) must have a negative serum pregnancy test at Screening and negative urine pregnancy tests at all protocol-specified time points (i.e., prior to each dose and throughout participant's participation); participants who are sexually active with a non-vasectomized male partner must agree to use 2 reliable forms of contraception during the trial, 1 of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started at least 1 full cycle prior to Baseline and continue for 180 days after the last dose of trial drug. Highly effective contraceptive methods (failure rate <1% per year), when used consistently and correctly, include implants, injectables, combination oral contraceptives, some intrauterine devices, sexual abstinence and vasectomized partner.
- •Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.
排除标准
- •Decreased best-corrected visual acuity due to optic neuropathy, defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect or color defect secondary to optic nerve involvement within the last 6 months.
- •Corneal decompensation unresponsive to medical management in the study eye
- •Decrease in proptosis of ≥2 mm in the study eye between Screening and Baseline.
- •Prior orbital irradiation, orbital decompression in the study eye.
- •Prior strabismus surgery.
- •Alanine aminotransferase or aspartate aminotransferase >3 × the upper limit of normal or estimated glomerular filtration rate ≤30 mL/min/1.73 m2 at Screening.
- •Use of any steroid (IV, oral, steroid eye drops) for the treatment of TED or other conditions within 3 weeks prior to Screening. Steroids cannot be initiated during the trial. Exceptions include topical and inhaled steroids and steroids used to treat infusion reactions.
- •Any treatment with rituximab (Rituxan® or MabThera®) within 12 months prior to the first infusion of trial drug or tocilizumab (Actemra® or Roactemra®) within 6 months prior to the first infusion of trial drug. Use of any other non-steroid immunosuppressive agent within 3 months prior to the first infusion of trial drug.
- •Any previous treatment with TEPEZZA, including previous enrollment in this trial or participation in a prior teprotumumab trial.
- •Treatment with any mAb within 3 months prior to Screening.
- •Identified pre-existing ophthalmic disease that, in the judgment of the Investigator, would preclude trial participation or complicate interpretation of trial results.
- •Use of an investigational agent for any condition within 60 days or 5 half-lives, whichever is longer, prior to Screening or anticipated use during the course of the trial.
- •Malignant condition in the past 12 months (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ).
- •Pregnant or lactating women.
- •Current drug or alcohol abuse or history of either within the previous 2 years, in the opinion of the Investigator or as reported by the participant.
- •Known hypersensitivity to any of the components of TEPEZZA or prior hypersensitivity reactions to mAbs.
- •Poorly controlled human immunodeficiency virus infection or untreated or positive viral load for hepatitis C or hepatitis B infections.
- •Any other condition that, in the opinion of the Investigator, would preclude inclusion in the trial.
研究组 & 干预措施
TEPEZZA
Participants received intravenous infusion of 10 milligrams per kilogram (mg/kg) teprotumumab at first infusion and then 20 mg/kg once every 3 weeks (Q3W) for next 7 infusions during the double masked treatment period. Proptosis non-responders who completed the double-masked treatment period had opted to receive 10 mg/kg teprotumumab at first infusion and then 20 mg/kg Q3W for next 7 infusions during open label treatment period.
干预措施: TEPEZZA (Biological)
Placebo
Participants received teprotumumab matching placebo by intravenous infusion, Q3W for 8 infusions during the double masked treatment period. Proptosis non-responders who completed the double-masked treatment period had opted to receive 10 mg/kg teprotumumab at first infusion and then 20 mg/kg Q3W for next 7 infusions during open label treatment period.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Proptosis of Study Eye at Week 24
时间窗: Baseline, week 24
Proptosis assessments were performed using a Hertel exophthalmometer. It measures the anterior projection of the eye from the lateral orbital rim to the cornea (proptosis).
次要结局
未报告次要终点