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

NCT06281704 | Completed Phase 1

• 1 other identifier: AK101-102
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 12

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.

Conditions

Ulcerative Colitis

Keywords

AK101; safety; pharmacokinetics; efficacy

Outcome Measures

Primary Outcomes (9)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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 Outcomes (3)

• Proportion of subjects with clinical response at Week8(per Adapted Mayo Score without physician's global assessment).

  At week 8

• Proportion of subjects with clinical response at Week8(per the Mayo score).

  At week 8

• Immunogenicity index

  Baseline till last follow-up visit (Up to Week 12 or Week36)

Study Arms (7)

Part 1 : AK101 IV

EXPERIMENTAL

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

Biological: AK101 IV

Part 1 : AK101 SC

EXPERIMENTAL

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

Biological: AK101 SC

Part 1 :Placebo

PLACEBO COMPARATOR

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

Biological: Placebo

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).

Biological: AK101 SC

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.

Biological: AK101 SC

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).

Biological: AK101 IV/AK101 SC

Part 2:Placebo-AK101 high-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 high-dose AK101 subcutaneously every 8 weeks.

Biological: AK101 IV/AK101 SC

Interventions

AK101 IV BIOLOGICAL

AK101 will be administered intravenously.

Part 1 : AK101 IV

AK101 SC BIOLOGICAL

AK101 will be administered subcutaneously.

Part 1 : AK101 SC; Part 2: AK101-AK101 high-dose SC every 8 weeks; Part 2:AK101-AK101 low-dose SC every 8 weeks

Placebo BIOLOGICAL

Placebo will be administered subcutaneously or intravenously.

Part 1 :Placebo

AK101 IV/AK101 SC BIOLOGICAL

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

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Akeso: lead

Study Sites (12)

The First Affiliated Hospital of Bengbu Medical College

Bengbu, Anhui, 233099, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, 350004, China

Location

Nanfang Hospital

Guangzhou, Guangdong, 510515, China

Location

The Sixth Affiliated Hospital of Sun Yat-Sen University

Guanzhou, Guangdong, 510665, China

Location

The Second Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050004, China

Location

People's Hospital of Wuhan University

Wuhan, Hubei, 430060, China

Location

Nanjing First Hospital

Nanjing, Jiangsu, 210012, China

Location

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221004, China

Location

Shengjing Hospital of China Medical University

Shengyang, Liaoning, 110000, China

Location

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

Tianjing People's Hospital

Tianjing, Tianjing, 300122, China

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2021
• First Posted: February 28, 2024
• Study Start: November 26, 2020
• Primary Completion: May 17, 2022
• Study Completion: December 31, 2022
• Last Updated: February 28, 2024

Record last verified: 2024-02

Locations

CN (12)