Clinical trial NCT06281704: A Study of AK101 in Subjects With Moderately to Severely Active Ulcerative Colitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ulcerative Colitis
Keywords: AK101
safety
pharmacokinetics
efficacy
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2024-02-28
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Key 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.

Key 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.

Primary outcomes:
measure: Adverse Events
timeFrame: From the time of signing the informed consent form till last follow-up visit (Up to Week 12 or Week36)
measure: Adverse Events
timeFrame: From the time of signing the informed consent form till last follow-up visit (Up to Week 12 or Week36)
measure: Elimination half-life (T1/2) of AK101
timeFrame: Baseline till last follow-up visit (Up to Week12 or Week36)
measure: Mean residence time (MRT) of AK101
timeFrame: Baseline till last follow-up visit (Up to Week12 or Week36)
measure: Area under curve (AUC) of AK101
timeFrame: Baseline till last follow-up visit (Up to Week12 or Week36)
measure: Apparent distribution volume (VD/F) of AK101
timeFrame: Baseline till last follow-up visit (Up to Week12 or Week36)
measure: Systemic clearance (CL/F) of AK101
timeFrame: Baseline till last follow-up visit (Up to Week12 or Week36)
measure: Maximum (peak) plasma concentration (Cmax) of AK101
timeFrame: Baseline till last follow-up visit (Up to Week12 or Week36)
measure: Time to maximum plasma concentration (Tmax) of AK101
timeFrame: Baseline till last follow-up visit (Up to Week12 or Week36)
Secondary outcomes:
measure: Proportion of subjects with clinical response at Week8(per Adapted Mayo Score without physician's global assessment).
timeFrame: At week 8
measure: Proportion of subjects with clinical response at Week8(per the Mayo score).
timeFrame: At week 8
measure: Immunogenicity index
timeFrame: Baseline till last follow-up visit (Up to Week 12 or Week36)
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Guanzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Wuhan
country: China
facility: People's Hospital of Wuhan University
state: Hubei
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Shengyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Tianjing
country: China
facility: Tianjing People's Hospital
state: Tianjing
Study officials:
References: