A Study of AK101 in Subjects With Moderately to Severely Active Ulcerative Colitis

NCT ID: NCT06281704

Last Updated: 2024-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-26
• Study Completion Date: 2022-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part 1 : AK101 IV

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

Group Type: EXPERIMENTAL

AK101 IV

Intervention Type: BIOLOGICAL

AK101 will be administered intravenously.

Part 1 : AK101 SC

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

Group Type: EXPERIMENTAL

AK101 SC

Intervention Type: BIOLOGICAL

AK101 will be administered subcutaneously.

Part 1 :Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Placebo will be administered subcutaneously or intravenously.

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

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).

Group Type: EXPERIMENTAL

AK101 SC

Intervention Type: BIOLOGICAL

AK101 will be administered subcutaneously.

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

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

Group Type: EXPERIMENTAL

AK101 SC

Intervention Type: BIOLOGICAL

AK101 will be administered subcutaneously.

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

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).

Group Type: EXPERIMENTAL

AK101 IV/AK101 SC

Intervention Type: BIOLOGICAL

AK101 will be administered as intravenous infusion at Week8, then subcutaneously every 8 weeks thereafter .

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

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 high-dose AK101 subcutaneously every 8 weeks.

Group Type: EXPERIMENTAL

AK101 IV/AK101 SC

Intervention Type: BIOLOGICAL

AK101 will be administered as intravenous infusion at Week8, then subcutaneously every 8 weeks thereafter .

Interventions

AK101 IV

AK101 will be administered intravenously.

Intervention Type: BIOLOGICAL

AK101 SC

AK101 will be administered subcutaneously.

Intervention Type: BIOLOGICAL

Placebo

Placebo will be administered subcutaneously or intravenously.

Intervention Type: BIOLOGICAL

AK101 IV/AK101 SC

AK101 will be administered as intravenous infusion at Week8, then subcutaneously every 8 weeks thereafter .

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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 ≥ 1.
• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Akeso

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, China

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

Nanfang Hospital

Guangzhou, Guangdong, China

The Sixth Affiliated Hospital of Sun Yat-Sen University

Guanzhou, Guangdong, China

The Second Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

People's Hospital of Wuhan University

Wuhan, Hubei, China

Nanjing First Hospital

Nanjing, Jiangsu, China

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, China

Shengjing Hospital of China Medical University

Shengyang, Liaoning, China

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

Tianjing People's Hospital

Tianjing, Tianjing, China

Countries

China

Other Identifiers

AK101-102

Identifier Type: -

Identifier Source: org_study_id