A Phase Ib Study to Evaluate the Safety, Tolerance, Pharmacokinetics and Preliminary Efficacy of Single and Multiple Administration of AK101 in Subjects With Moderately to Severely Active Ulcerative Colitis

Akeso13 个研究点分布在 1 个国家目标入组 34 人开始时间: 2020年11月26日最近更新: 2024年2月28日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方
入组人数: 34
试验地点: 13
主要终点: Mean residence time (MRT) of AK101

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a Phase Ib clinical study to evaluate the safety, tolerance, pharmacokinetics and efficacy of AK101 in subjects with moderately to severely active ulcerative colitis.

详细描述

This is a phase Ib, randomized, double-blind, placebo-controlled, dose-escalation, two-phase study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of AK101 in subjects with moderately to severely active ulcerative colitis. The study consists of two parts. Part 1 is single-ascending-dose induction phase study, and Part 2 is a multiple subcutaneous maintenance therapy study followed by a single-dose induction treatment.

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 65 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Body mass index (BMI) ≥ 18 and ≤ 28 kg /m2 for male or female patients aged between 18 and 65 years (including upper and lower limits).
•Confirmed diagnosis of ulcerative colitis (UC) for at least 3 months before screening, and the diagnosis of UC must be confirmed by endoscopic and histological evidence.
•Has moderately to severely active UC,defined as the adapted Mayo score (excluding PGA) of 5-9 (including upper and lower limits), Mayo endoscopic subscore ≥ 2 within 10 days before the first administrationof study drug and rectal bleeding subscore ≥
•Have evidence of ulcerative colitis extending proximal to the rectum (≥15 cm of involved colon).
•Demonstrated intolerance or inadequate response to conventional therapy and tofacitinib (not a biologic) and biologic therapies.
•For women with fertility, the serum pregnancy test must be negative during the screening period; Or women without fertility.If male and female subjects with sexual life and fertility voluntarily take contraceptive measures during the treatment and at least 6 months after the last Administration.

排除标准

•Suspected or confirmed Crohn's disease (CD), undiagnosed type of colitis.
•Suffering from severe generalized colitis.
•Previous colectomy (total or subtotal resection) with ileal pouch, Kock pouch or ileostomy for ulcerative colitis.
•Patients who have received IL-12 / 23 or IL-23 target drug treatment.
•Received Natalizumab or other drugs that regulate B cells or T cells within 12 months before randomization, such as Rituximab, Alemtuzumab, Abatacept treatment.
•Received infliximab and adalimumab 2 months before randomization, and received Vedolizumab and other biological treatments 3 months before randomization.
•Patients with active hepatitis B virus (HBV) infection or active hepatitis C virus (HCV).
•Suffering from human immunodeficiency virus (HIV) or syphilis.
•Active tuberculosis or Latent tuberculosis infection.
•Has a history of, or ongoing, chronic or recurrent infectious disease.,
•Suffering from any mental illness, or suffer from a serious or active disease, the investigators think may interfere with the subject's treatment, evaluation or compliance with the study protocol.
•Patients with malignant tumors (except skin basal cell carcinoma and cervical carcinoma in situ that have been cured and have no signs of recurrence) or lymphoproliferative diseases, and cervical diseases caused by HPV.

研究组 & 干预措施

Part 1 : AK101 IV

Experimental

Subjects will be enrolled in sequential cohorts treated with successively higher doses of AK101 via intravenous injection on Day1.

干预措施: AK101 IV (Biological)

Part 1 : AK101 SC

Experimental

Subjects will be enrolled in sequential cohorts treated with successively higher doses of AK101 via subcutaneous injection on Day1.

干预措施: AK101 SC (Biological)

Part 1 :Placebo

Placebo Comparator

Subjects will be received matching placebo intravenously or subcutaneously on Day1.

干预措施: Placebo (Biological)

Part 2:AK101-AK101 low-dose SC every 8 weeks

Experimental

Subjects received single IV infusion of AK101 on Day1 will be randomized to receive low-dose AK101 subcutaneously every 8 weeks along with matching placebo subcutaneously (to maintain the blind).

干预措施: AK101 SC (Biological)

Part 2: AK101-AK101 high-dose SC every 8 weeks

Experimental

Subjects received single IV infusion of AK101 on Day1 will be randomized at Week8 to receive high-dose AK101 subcutaneously every 8 weeks.

干预措施: AK101 SC (Biological)

Part 2: Placebo-AK101 low-dose SC every 8 weeks

Experimental

Subjects received placebo on Day1 will receive a single IV infusion of AK101 at Week8 along with matching subcutaneous placebo (to maintain the blind). And subjects will be randomized at Week8 to receive low-dose AK101 subcutaneously every 8 weeks along with matching placebo subcutaneously (to maintain the blind).

干预措施: AK101 IV/AK101 SC (Biological)

Part 2:Placebo-AK101 high-dose SC every 8 weeks

Experimental

干预措施: AK101 IV/AK101 SC (Biological)