2024-515090-96-00招募中4 期
A Phase 3b/4, Double-masked, Randomized, International, Parallel-assignment, Multicenter Trial in Patients with Thyroid Eye Disease to Evaluate the Safety and Tolerability of Different Dosing Durations of Teprotumumab
Horizon Therapeutics Ireland Designated Activity Company, Horizon Therapeutics USA Inc.16 个研究点 分布在 4 个国家目标入组 214 人开始时间: 2024年7月3日最近更新:
适应症
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 214
- 试验地点
- 16
- 主要终点
- The percentage of patients who experience at least 1 TEAE and the percentage of patients who experience at least 1 treatment-emergent AESI during treatment with teprotumumab. . The percentage of patients who receive re-treatment
研究概览
简要总结
"The overall objective is to investigate the safety, tolerability and need for re-treatment of 3 different teprotumumab treatment durations in patients with Thyroid Eye Disease (TED)."
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Initial Follow-up Period
- 盲法
- Double (Subject, Carer, Investigator, Monitor, Analyst)
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
- •Written informed consent.
- •Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.
- •Male or female between the ages of 18 and 80 years, inclusive, at Screening.
- •Initial diagnosis of TED within 7 years prior to Screening.
- •Initial diagnosis of TED within 7 years prior to Screening.
- •Proptosis ≥3 mm from baseline (prior to diagnosis of TED), as estimated by treating physician, and/or proptosis >3 mm above normal for race and gender (Note: For sites in France: Normal values for proptosis do vary by gender and race [de Juan et al, 1980; Fledelius and Stubgaard, 1986; Kashkouli et al, 2008]).
- •Patients must be euthyroid with the 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 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 patients must have HbA1c ≤8.0% at Screening.
- •Patients with a history of IBD (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 IBD 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 the patient's participation in the Follow-up Period); patients 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 teprotumumab. Highly effective contraceptive methods (with a failure rate <1% per year), when used consistently and correctly, include implants, injectables, bilateral tubal ligation, combination oral contraceptives, some intrauterine devices, vasectomized partner or sexual abstinence. Abstinence should only be used as a contraceptive method if it is in line with the patient's usual and preferred lifestyle and periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) is not an acceptable method of contraception. Periodic abstinence, withdrawal (coitus interruptus) or spermicides only are not acceptable methods of contraception. For sites in France, highly effective contraceptive methods (with a failure rate <1% per year), when used consistently and correctly, include: • combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral intravaginal transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation: oral injectable implantable • intrauterine device (IUD) • intrauterine hormone-releasing system (IUS) • bilateral tubal ligation • vasectomized partner • sexual abstinence (Abstinence should only be used as a contraceptive method if it is in line with the patient's usual and preferred lifestyle; periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] is not an acceptable method of contraception.)
排除标准
- •Decreased best-corrected visual acuity due to optic neuropathy, as 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.
- •Treatment with any monoclonal antibody 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 5 years (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 patient.
- •Known hypersensitivity to any of the components of teprotumumab or prior hypersensitivity reactions to monoclonal antibodies.
- •Human immunodeficiency virus, 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.
- •After 150 patients with a CAS <3 at Baseline have been randomized, an additional exclusion criterion will apply: CAS <3 at Baseline.
- •Corneal decompensation unresponsive to medical management.
- •Decrease in proptosis of ≥2 mm in the study eye between Screening and Baseline
- •Prior orbital irradiation, orbital decompression or strabismus surgery.
- •Planned eyelid surgery during the course of the trial.
- •Alanine aminotransferase or aspartate aminotransferase >3 × the upper limit of normal or estimated glomerular filtration rate ≤30 mL/min/1.73m2 at Screening.
- •Any systemic use of any steroid (intravenous [IV] or oral), or steroid eye drops for the treatment of TED or other conditions within 3 weeks prior to Screening. Such steroids cannot be initiated during the trial. Exceptions include local administration [excluding steroid eye drops], eg, topical (for skin only), intraarticular, and inhaled steroids, as well as allowance for systemic steroids (IV or oral) used to treat infusion reactions.
- •Any treatment with rituximab (Rituxan® or MabThera®) within 12 months prior to the first infusion of teprotumumab or tocilizumab (Actemra® or Roactemra®) within 6 months prior to the first infusion of teprotumumab. Use of any other non-steroid immunosuppressive agent within 3 months prior to the first infusion of teprotumumab.
- •Any previous treatment with teprotumumab, including previous enrollment in this trial or participation in a prior teprotumumab trial.
结局指标
主要结局
The percentage of patients who experience at least 1 TEAE and the percentage of patients who experience at least 1 treatment-emergent AESI during treatment with teprotumumab. . The percentage of patients who receive re-treatment
The percentage of patients who experience at least 1 TEAE and the percentage of patients who experience at least 1 treatment-emergent AESI during treatment with teprotumumab. . The percentage of patients who receive re-treatment
次要结局
- The binocular diplopia resolution rate (percentage of patients with baseline binocular diplopia >0 who have no binocular diplopia).
- Mean change from Baseline in the GO-QoL questionnaire appearance and visual functioning sub-scales.
- Mean change from Baseline in proptosis measurement in the study eye.
- Proptosis responder rate (percentage of patients with a ≥2-mm reduction from Baseline in proptosis in the study eye, without deterioration [≥2-mm increase] of proptosis in the fellow eye).
- The overall responder rate (percentage of patients with ≥2-point reduction in CAS AND ≥2-mm reduction in proptosis from Baseline in the study eye, provided there is no corresponding deterioration [≥2 point/mm increase] in CAS or proptosis in the fellow eye).
- The binocular diplopia responder rate (percentage of patients with baseline binocular diplopia >0 who have a reduction of ≥1 grade).
- Rate of flares at the end of the Initial Follow-up Period.
- Time to proptosis response from the first infusion until the end of the Initial Treatment Period.
- CAS: - Proportion of patients with a CAS ≥3 at Baseline who have a CAS of 0 or 1 at the end of the Initial Treatment Period - Proportion of patients who improve on individual questions on the CAS for - spontaneous orbital pain - gaze-evoked orbital pain.
- Proportion of patients with complete response at the end of the Initial Follow-up Period, as defined by durability of complete response
- Proportion of patients with response at the last assessment in the Initial Follow-up Period, as defined by durability of response at the last assessment in the Initial Follow-up Period.
- Mean change from Baseline over time in disease biomarkers for patients with a Baseline CAS ≥3.
- "All other endpoints, except the time to proptosis response, rate of flares at the end of the Initial Follow-up Period, durability of complete response and durability of response at the last assessment in the Initial Follow-up Period, will be assessed by randomized cohort at the end of the Initial Treatment Period, at the end of the Initial Follow-up Period.
- For patients who require re-treatment, the same endpoints will be estimated at the end of the 24-week Re-treatment Period.
- Safety and Tolerability Endpoints 1. Incidence of TEAEs, SAEs, TEAEs resulting in premature discontinuation of treatment and treatment-emergent AESIs (infusion reactions, hyperglycemia, hearing impairment, new onset IBD and exacerbation of IBD). "
- 2. Incidence of ≥Grade 3 TEAEs. 3. Incidence of ≥Grade 3 laboratory evaluations, in which CTCAE grading is available. 4. The results of best-corrected visual acuity. PK and ADA Endpoints 1. Peak and trough concentrations of teprotumumab. 2. ADA incidence and titers."
研究者
Medical Director
Scientific
Horizon Therapeutics USA Inc.
研究点 (16)
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