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

Ulcerative Colitis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06281704
• Other study ID #: AK101-102
• Status: Completed
• Phase: Phase 1
• Start date: November 26, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: February 2024
• Source: Akeso
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: December 31, 2022
• Est. primary completion date: May 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Biological:
• AK101 IV
AK101 will be administered intravenously.
• AK101 SC
AK101 will be administered subcutaneously.
• Placebo
Placebo will be administered subcutaneously or intravenously.
• AK101 IV/AK101 SC
AK101 will be administered as intravenous infusion at Week8, then subcutaneously every 8 weeks thereafter .

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui
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	Nanjing First Hospital	Nanjing	Jiangsu
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Shengjing Hospital of China Medical University	Shengyang	Liaoning
China	The Second Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Tianjing People's Hospital	Tianjing	Tianjing
China	People's Hospital of Wuhan University	Wuhan	Hubei
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Akeso

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events	Percentage of subjects with treatment-emergent adverse events (TEAEs) during the study.	From the time of signing the informed consent form till last follow-up visit (Up to Week 12 or Week36)
Primary	Adverse Events	Percentage of subjects with treatment-emergent serious adverse events (SAEs) during the study.	From the time of signing the informed consent form till last follow-up visit (Up to Week 12 or Week36)
Primary	Elimination half-life (T1/2) of AK101	Assessment of half-life (T1/2) of AK101	Baseline till last follow-up visit (Up to Week12 or Week36)
Primary	Mean residence time (MRT) of AK101	Assessment of mean residence time (MRT) of AK101	Baseline till last follow-up visit (Up to Week12 or Week36)
Primary	Area under curve (AUC) of AK101	Assessment of area under curve (AUC) of AK101	Baseline till last follow-up visit (Up to Week12 or Week36)
Primary	Apparent distribution volume (VD/F) of AK101	Assessment of apparent distribution volume (VD/F) of AK101	Baseline till last follow-up visit (Up to Week12 or Week36)
Primary	Systemic clearance (CL/F) of AK101	Assessment of systemic clearance (CL/F) of AK101	Baseline till last follow-up visit (Up to Week12 or Week36)
Primary	Maximum (peak) plasma concentration (Cmax) of AK101	Assessment of maximum (peak) plasma concentration (Cmax)	Baseline till last follow-up visit (Up to Week12 or Week36)
Primary	Time to maximum plasma concentration (Tmax) of AK101	Assessment of Time to maximum plasma concentration (Tmax)	Baseline till last follow-up visit (Up to Week12 or Week36)
Secondary	Proportion of subjects with clinical response at Week8(per Adapted Mayo Score without physician's global assessment).	Clinical response(per Adapted Mayo Score) was defined as a decrease from induction baseline in the adapted Mayo score by=30 percent (%) and = 2 points, with either a decrease from baseline in the rectal bleeding subscore =1 or a rectal bleeding subscore of 0 or 1. Adapted Mayo Score consists of 3 subscores (stool frequency, rectal bleeding and endoscopy findings), rated as 0 (normal) to 3 (severe). Total score was calculated as the sum of 3 subscores and values range from 0 to 9 scores.	At week 8
Secondary	Proportion of subjects with clinical response at Week8(per the Mayo score).	Clinical response(per the Mayo Score) was defined as a decrease from induction baseline in the Mayo score by =30 percent (%) and = 3 points, with either a decrease from baseline in the rectal bleeding subscore =1 or a rectal bleeding subscore of 0 or 1. The Mayo Score consists of 4 subscores (stool frequency, rectal bleeding, endoscopy findings, and physician's global assessment), rated as 0 (normal) to 3 (severe). Total score was calculated as the sum of 4 subscores and values range from 0 to 12 scores.	At week 8
Secondary	Immunogenicity index	Number and percentage of subjects with detectable anti-AK101 antibody (ADA).	Baseline till last follow-up visit (Up to Week 12 or Week36)