Ulcerative Colitis
Conditions
Keywords
AK101, safety, pharmacokinetics, efficacy
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.
Interventions
BIOLOGICALAK101 IV
AK101 will be administered intravenously.
BIOLOGICALAK101 SC
AK101 will be administered subcutaneously.
BIOLOGICALPlacebo
Placebo will be administered subcutaneously or intravenously.
BIOLOGICALAK101 IV/AK101 SC
AK101 will be administered as intravenous infusion at Week8, then subcutaneously every 8 weeks thereafter .
Sponsors
Akeso
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to maximum plasma concentration (Tmax) of AK101 | Baseline till last follow-up visit (Up to Week12 or Week36) | Assessment of Time to maximum plasma concentration (Tmax) |
| Apparent distribution volume (VD/F) of AK101 | Baseline till last follow-up visit (Up to Week12 or Week36) | Assessment of apparent distribution volume (VD/F) of AK101 |
| Systemic clearance (CL/F) of AK101 | Baseline till last follow-up visit (Up to Week12 or Week36) | Assessment of systemic clearance (CL/F) of AK101 |
| Maximum (peak) plasma concentration (Cmax) of AK101 | Baseline till last follow-up visit (Up to Week12 or Week36) | Assessment of maximum (peak) plasma concentration (Cmax) |
| Adverse Events | From the time of signing the informed consent form till last follow-up visit (Up to Week 12 or Week36) | Percentage of subjects with treatment-emergent adverse events (TEAEs) during the study. |
| Elimination half-life (T1/2) of AK101 | Baseline till last follow-up visit (Up to Week12 or Week36) | Assessment of half-life (T1/2) of AK101 |
| Mean residence time (MRT) of AK101 | Baseline till last follow-up visit (Up to Week12 or Week36) | Assessment of mean residence time (MRT) of AK101 |
| Area under curve (AUC) of AK101 | Baseline till last follow-up visit (Up to Week12 or Week36) | Assessment of area under curve (AUC) of AK101 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects with clinical response at Week8(per the Mayo score). | At week 8 | 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. |
| Immunogenicity index | Baseline till last follow-up visit (Up to Week 12 or Week36) | Number and percentage of subjects with detectable anti-AK101 antibody (ADA). |
| Proportion of subjects with clinical response at Week8(per Adapted Mayo Score without physician's global assessment). | At week 8 | 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. |
Countries
China
Outcome results
None listed