Ulcerative ColitisPhase 1NCT06281704
A Study of AK101 in Subjects With Moderately to Severely Active Ulcerative Colitis
A Phase 1 study testing AK101 IV, AK101 SC and AK101 IV/AK101 SC in people with Ulcerative Colitis, run by Akeso at 12 sites in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- AK101 IV, AK101 SC and AK101 IV/AK101 SC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 12 sitesChina
- Study dates
- 26 Nov 2020to 31 Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
China12 sites
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
The First Affiliated Hospital of Bengbu Medical College
Bengbu, Anhui, 233099
The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, 350004
Nanfang Hospital
Guangzhou, Guangdong, 510515
The Sixth Affiliated Hospital of Sun Yat-Sen University
Guanzhou, Guangdong, 510665
Nanjing First Hospital
Nanjing, Jiangsu, 210012
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai Municipality, 200025
Shengjing Hospital of China Medical University
Shengyang, Liaoning, 110000
The Second Hospital of Hebei Medical University
Shijiazhuang, Hebei, 050004
Tianjing People's Hospital
Tianjing, Tianjing, 300122
People's Hospital of Wuhan University
Wuhan, Hubei, 430060
The Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, 221004
About this study
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
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.
Read the 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
- Being tested
- AK101 IV, AK101 SC, Placebo, AK101 IV/AK101 SC
- Keywords
- AK101, safety, pharmacokinetics, efficacy
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AK101 IVBiological
AK101 will be administered intravenously.
AK101 SCBiological
AK101 will be administered subcutaneously.
PlaceboBiological
Placebo will be administered subcutaneously or intravenously.
AK101 IV/AK101 SCBiological
AK101 will be administered as intravenous infusion at Week8, then subcutaneously every 8 weeks thereafter .
| Study group | Role | What they receive |
|---|---|---|
| Part 1 : AK101 IV | Experimental | Subjects will be enrolled in sequential cohorts treated with successively higher doses of AK101 via intravenous injection on Day1. Receives: 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. Receives: Biological: AK101 SC |
| Part 1 :Placebo | Placebo comparator | Subjects will be received matching placebo intravenously or subcutaneously on Day1. Receives: 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). Receives: 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. Receives: 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). Receives: 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. Receives: Biological: AK101 IV/AK101 SC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Percentage of subjects with treatment-emergent adverse events (TEAEs) during the study.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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).
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.
Measured: At week 8
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.
Measured: At week 8
Immunogenicity index
Number and percentage of subjects with detectable anti-AK101 antibody (ADA).
Measured: Baseline till last follow-up visit (Up to Week 12 or Week36)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2024
- Study start26 Nov 2020
- Primary completion17 May 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- More trials run by AkesoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akeso
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06281704
- Sponsor's protocol ID
- AK101-102
- Status last verified
- Feb 2024
- First submitted
- 25 Nov 2021
- Last updated
- 28 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06281704
- Acronym / sponsor ID
- AK101-102
- Conditions
- Ulcerative Colitis
- Keywords
- AK101, safety, pharmacokinetics, efficacy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- AkesoIndustry (pharma, biotech, devices)
- Study start
- 26 Nov 2020 (actual)
- Primary completion
- 17 May 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 28 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Part 1 : AK101 IV | Experimental | Biological: AK101 IVSubjects will be enrolled in sequential cohorts treated with successively higher doses of AK101 via intravenous injection on Day1. |
| Part 1 : AK101 SC | Experimental | Biological: AK101 SCSubjects will be enrolled in sequential cohorts treated with successively higher doses of AK101 via subcutaneous injection on Day1. |
| Part 1 :Placebo | Placebo comparator | Biological: PlaceboSubjects will be received matching placebo intravenously or subcutaneously on Day1. |
| Part 2:AK101-AK101 low-dose SC every 8 weeks | Experimental | Biological: AK101 SCSubjects 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). |
| Part 2: AK101-AK101 high-dose SC every 8 weeks | Experimental | Biological: AK101 SCSubjects received single IV infusion of AK101 on Day1 will be randomized at Week8 to receive high-dose AK101 subcutaneously every 8 weeks. |
| Part 2: Placebo-AK101 low-dose SC every 8 weeks | Experimental | Biological: AK101 IV/AK101 SCSubjects 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). |
| Part 2:Placebo-AK101 high-dose SC every 8 weeks | Experimental | Biological: AK101 IV/AK101 SCSubjects 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AK101 IVAK101 will be administered intravenously. | Biological | Part 1 : AK101 IV |
| AK101 SCAK101 will be administered subcutaneously. | Biological | Part 1 : AK101 SC, Part 2: AK101-AK101 high-dose SC every 8 weeks, Part 2:AK101-AK101 low-dose SC every 8 weeks |
| PlaceboPlacebo will be administered subcutaneously or intravenously. | Biological | Part 1 :Placebo |
| AK101 IV/AK101 SCAK101 will be administered as intravenous infusion at Week8, then subcutaneously every 8 weeks thereafter . | Biological | Part 2: Placebo-AK101 low-dose SC every 8 weeks, Part 2:Placebo-AK101 high-dose SC every 8 weeks |
Primary outcome
Adverse Events
Time frame: 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.
Adverse Events
Time frame: 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 serious adverse events (SAEs) during the study.
Elimination half-life (T1/2) of AK101
Time frame: 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
Time frame: 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
Time frame: Baseline till last follow-up visit (Up to Week12 or Week36)
Assessment of area under curve (AUC) of AK101
Apparent distribution volume (VD/F) of AK101
Time frame: 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
Time frame: 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
Time frame: Baseline till last follow-up visit (Up to Week12 or Week36)
Assessment of maximum (peak) plasma concentration (Cmax)
Time to maximum plasma concentration (Tmax) of AK101
Time frame: Baseline till last follow-up visit (Up to Week12 or Week36)
Assessment of Time to maximum plasma concentration (Tmax)
3 secondary outcomes
Proportion of subjects with clinical response at Week8(per Adapted Mayo Score without physician's global assessment).
Time frame: At week 8
Proportion of subjects with clinical response at Week8(per the Mayo score).
Time frame: At week 8
Immunogenicity index
Time frame: Baseline till last follow-up visit (Up to Week 12 or Week36)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AK101 IV, AK101 SC and AK101 IV/AK101 SC in people with Ulcerative Colitis, run by Akeso at 12 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (time frame: From the time of signing the informed consent form till last follow-up visit (Up to Week 12 or Week36)). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2024.