NCT04322708已完成2 期
A Phase 2/3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Lirentelimab (AK002) in Adult and Adolescent Patients With Active Eosinophilic Esophagitis
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Allakos Inc.
- 入组人数
- 277
- 试验地点
- 1
- 主要终点
- Proportion of Subjects Who Achieve a Peak Esophageal Intraepithelial Count of ≤6 Eosinophils/Hpf at Week 24
研究概览
简要总结
This is a Phase 2/3, multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of lirentelimab (AK002) given monthly for 6 doses in adult and adolescent patients with active eosinophilic esophagitis. Subjects who complete the randomized, double-blind, placebo-controlled treatment may have the option to receive 6 doses of open-label lirentelimab (AK002) through the OLE Period of the study.
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
- 12 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged ≥12 and ≤80 years at the time of signing ICF.
- •Confirmed diagnosis of EoE and esophageal intraepithelial eosinophilic infiltration of ≥15 eosinophils/hpf in 1 hpf from a biopsy collected during the Screening EGD without any other cause for the esophageal eosinophilia.
- •History (by patient report) of an average of ≥2 episodes of dysphagia with intake of solid foods per week during the 4 weeks prior to Screening.
- •Subjects must have failed or not be adequately controlled on standard of care treatments for EoE symptoms, which could include PPI, systemic or topical corticosteroids, and/or diet, among others.
- •If on an allowed treatment for EoE, stable dose for at least 4 weeks prior to Screening and willingness to continue that dose for the study duration.
- •If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study, as much as possible.
- •Able and willing to comply with all study procedures.
- •Female subjects must be either post-menopausal for at least 1 year with FSH level >30 mIU/mL at Screening or surgically sterile (tubal ligation,hysterectomy, or bilateral oophorectomy) for at least 3 months, or if of childbearing potential, have a negative pregnancy test and agree to use dual methods of contraception, or abstain from sexual activity from screening until the end of the study, or for 120 days following the last dose of study drug, whichever is longer. Male subjects with female partners of childbearing potential must agree to use a highly effective method of contraception from Screening until the end of the study or for 120 days following the last dose of study drug,whichever is longer. All fertile men with female partners of childbearing potential should be instructed to contact the Investigator immediately if they suspect their partner might be pregnant at any time during study participation.
排除标准
- •Concomitant EG, EoD, or eosinophilic colitis (EC).
- •EG and/or EoD (≥30 eosinophils/hpf in 5 hpf in the stomach and/or ≥30 eosinophils/hpf in 3 hpf in the duodenum) as determined by central histology assessment of biopsies collected during the Screening EGD.
- •Causes of esophageal eosinophilia other than EoE or one the following: hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, or peripheral blood absolute eosinophil count of >1500 eosinophils/μL.
- •History of inflammatory bowel disease, celiac disease, achalasia, and/or esophageal surgery.
- •Any esophageal stricture unable to be passed with a standard diagnostic 9 mm to 10 mm upper endoscope or any critical esophageal stricture that requires dilation during screening.
- •History of bleeding disorders or esophageal varices.
- •History of malignancy; except carcinoma in situ, early stage prostate cancer, or non-melanoma skin cancers. However, cancers that have been in remission for more than 5 years and are considered cured, can be enrolled (with the exception of breast cancer). All history of malignancy (including diagnosis, dates, and compliance with cancer screening recommendations) must be documented and certified by the Investigator, along with the statement that in their clinical judgment the tissue eosinophilia is attributable to EGID, rather than recurrence of malignancy.
- •Active Helicobacter pylori infection (as determined by central histology staining of the biopsy collected during the Screening EGD), unless treated and confirmed to be negative prior to randomization and symptoms remain consistent.
- •Positive Ova and Parasite (O&P) test at Screening, seropositive for Strongyloides stercoralis at Screening, and/or treatment for a clinically significant helminthic parasitic infection within 6 months of Screening.
- •Seropositive for HIV or hepatitis at Screening, except for vaccinated patients or patients with a history of hepatitis that has since resolved.
- •Prior exposure to AK002 or hypersensitivity to any constituent of AK
- •Change in dose of inhaled corticosteroids, nasal corticosteroids, PPI, and/or diet therapy within 4 weeks prior to Screening.
- •Use of oral corticosteroids (swallowed topical or systemic corticosteroids) within 8 weeks prior to Screening.
- •Use of any biologics or medications that may interfere with the study, such as immunosuppressive or immunomodulatory drugs including azathioprine, JAK inhibitors, 6-mercaptopurine, methotrexate, cyclosporine, tacrolimus, anti-TNF, anti-IL-4 receptor, e.g., dupilumab), anti-IL-5 (e.g., mepolizumab), anti-IL-5 receptor (e.g., benralizumab), anti-IL-13 (e.g., lebrikizumab), anti-IgE (e.g., omalizumab), within 12 weeks prior to Screening.
- •Participation in a concurrent interventional study with the last intervention occurring within 30 days prior to administration of study drug or 90 days or 5 half-lives, whichever is longer, for biologic products.
- •Vaccination with live attenuated vaccines ≤30 days prior to initiation of treatment in the study, during the treatment period, or vaccination expected ≤5 half-lives (≤4 months) following study drug administration.
- •Treatment with chemotherapy or radiotherapy in the preceding 6 months.
- •Presence of abnormal laboratory values considered by the Investigator to be clinically significant.
- •Any disease, condition (medical or surgical), or cardiac abnormality, which in the opinion of the Investigator, would place the subject at increased risk.
- •Known history of alcohol, drug, or other substance abuse or dependence.
- •Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.
- •Any other reason that in the opinion of the Investigator or Medical Monitor makes the patient unsuitable for enrollment.
研究组 & 干预措施
Placebo
Placebo Comparator
Subjects in this arm will receive 6 monthly doses of placebo.
干预措施: Placebo (Other)
1 mg/kg of lirentelimab (AK002)
Experimental
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) (1mg/kg).
干预措施: lirentelimab (AK002) (Drug)
3 mg/kg of lirentelimab (AK002)
Experimental
Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): A first dose of 1 mg/kg, followed by 5 monthly doses of 3 mg/kg.
干预措施: lirentelimab (AK002) (Drug)
结局指标
主要结局
Proportion of Subjects Who Achieve a Peak Esophageal Intraepithelial Count of ≤6 Eosinophils/Hpf at Week 24
时间窗: At Week 24
Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies.
Change in Dysphagia Symptom Questionnaire (DSQ) Score From Baseline to Weeks 23-24.
时间窗: Baseline to Weeks 23-24
The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.
次要结局
- Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eosinophil/Hpf at Week 24(At Week 24)
- Subjects Who Achieve >50% Reduction in DSQ Score From Baseline to Weeks 23-24(Weeks 23-24)
- Percent Change in DSQ Score From Baseline to Weeks 23-24(Baseline to Weeks 23-24)
- Change in EoE Reference Score for Endoscopic Abnormalities (EREFS) From Baseline to Week 24(Baseline to Week 24)
- Percent Change in Peak Esophageal Intraepithelial Eosinophil Count From Baseline to Week 24(Baseline to Week 24)
- Number of Treatment Responders(At Weeks 23-24 and Week 24, Respectively)
- Change in Biweekly Mean DSQ Over Time Using MMRM(Baseline to Weeks 23-24)
- Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/Hpf at Week 24(At Week 24)
研究者
研究点 (1)
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