Ulcerative ColitisPhase 1NCT05743010
A Phase 1b Study to Evaluate APL-1401 in Patients With Moderately to Severely Active Ulcerative Colitis
A Phase 1 study testing APL-1401 in people with Ulcerative Colitis, run by Jiangsu Yahong Meditech Co., Ltd aka Asieris at 4 sites in United States.
Trial summary
This is a randomized, double-blind, placebo-controlled, phase 1b study designed to evaluate safety, tolerability, PK, and preliminary efficacy of APL-1401 in patients with moderately to severely active UC. 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?
- APL-1401
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 4 sitesUnited States
- Study dates
- 26 Jan 2023to Apr 2025
- 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
- Willing and able to provide written informed consent.
- Age 18-65 years (inclusive).
- With a history of UC diagnosis at least 3 months prior to screening.
- Currently has active UC, defined as a Total Mayo Score of 6 to 12 (inclusive), at baseline, and with a Mayo Endoscopic Sub-Score (MESS) ≥ 2 confirmed by a site reader.
- Has a rectal bleeding score ≥1 and a stool frequency Score ≥1 and in addition to MESS ≥2 during screening.
- May be receiving the following drugs:
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- Oral 5-ammosahcylate (5-ASA) class of medications (mesalamine, olsalazine, balsalazide, sulfasalazine), provided the prescribed dose has been stable for at least 4 weeks prior to randomization; dose must be stable during the treatment period.
- Oral corticosteroid therapy (prednisone prescribed at a stable dose ≤ 30 mg/day or budesonide prescribed at a stable dose of ≤ 9 mg/day), provided the prescribed dose has been stable for at least 2 weeks prior to randomization; during the treatment period, the same dose should be maintained but can be tapered by the investigators.
- Women of childbearing potential must have a negative pregnancy test at screening visit and agree to use 2 highly effective methods of birth control at the same time during entire study period.
- Male subjects must agree to use protocol specified method(s) of contraception from screening visit until 3 months after last dose.
Who cannot join
- Has fulminant colitis, toxic megacolon, primary sclerosing cholangitis, Crohn's disease, history of colitis-associated colonic dysplasia, active peptic ulcer disease.
- Has a current clinically significant bacterial, parasitic, fungal, or viral infection.
- Is positive for hepatitis A, B or C, human immunodeficiency virus (HIV), or tuberculosis.
- Uses any of the following medications:
- Intravenous corticosteroids 1 week prior to randomization;
- Topical 5-ASA compounds or topical steroid (i.e., enemas or suppositories) 2 weeks prior to randomization;
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- Anti-diarrheal medications 2 weeks prior to randomization;
- Sphingosine 1-phosphate receptor (S1PR) modulator including ozanimod 9 prior to randomization;
- JAK inhibitors including tofacitinib and upadacitinib 4 weeks prior to randomization;
- TNF-α antagonist including (but not limited to) infliximab, adalimumab, golimumab, certolizumab, or biosimilar agents 10 weeks prior to randomization;
- Integrin antagonist, including vedolizumab 18 weeks prior to screening and natalizumab 10 weeks prior to screening;
- Interleukin antagonist including ustekinumab 14 weeks prior to screening;
- Patients receiving any of the following medications, if they were not discontinued at least 2 weeks prior to randomization: azathioprine, 6-mercaptopurine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, sirolimus, thalidomide. See Table 1;
- Prohibited concomitant medications as described in Section 6.5.2 Table 1.
- Participated in another clinical study of an investigational drug (or medical device) within 30 days prior to screening or is currently participating in another study of an investigational drug (or medical device).
- Has clinically significant abnormalities in laboratory tests (complete blood count, chemistry panel, TSH, total T3, free T4, urinalysis
- Hepatic panel (AST, ALT, total bilirubin) >2 times the upper limits of normal (ULN)
- Estimated CrCl <60 mL/min as calculated by the Cockcroft-Gault equation
- Thyroid stimulating hormone (TSH) <2.5 mIU/L or >4.2 mIU/L
- Has a resting heart rate (HR) of <50 bpm or >120 bpm.
- Has a resting systolic blood pressure >160 mmHg or <90 mmHg.
- With thyroid disease or history thyroid surgery or on thyroid medications
- Has orthostatic hypotension (decrease in systolic blood pressure >20 mmHg or decrease in diastolic blood pressure >10 mmHg when going from supine to standing) or a history of clinically significant orthostatic dizziness.
- Treatment with Class Ia or Class III anti-arrhythmic drugs or treatment with two or more agents in combination known to prolong PR interval.
- Is taking concomitant beta-blockers (including ophthalmologic timolol), amiodarone, reserpine, clonidine, monoamine oxidase (MAO) inhibitors, alpha blocking drugs, vasodilators which could enhance the production of catecholamines (hydralazine and nitrates), substrates or inhibitors of N-acetyltransferase.
- Alcohol abuse or alcohol dependence at least 3 months prior to first dose.
- With history of drug-related rash or has clinically significant rash or pruritus.
- Has severe COVID-19 infection and needs to use ventilator or other treatments that make using of study drug impossible.
- With moderate to severe (Child-Pugh Class B and Class C) hepatic impairment.
Trial locations and contacts
4 sites in 1 country.
United States4 sites, 4 recruiting
- Recruiting
New Hope Research Development
Corona, California, 92882
Tarcisio Diaz, MD
Tarcisio Diaz
- Recruiting
Tandem Clinical Research
Marrero, Louisiana, 70072
Gary Reiss, MD
Gary Reiss, MD
- Recruiting
Meridian Clinical Research
Rockville, Maryland, 20854
Belen Ashber Tesfaye, MD
Belen Ashber Tesfaye, MD
- Recruiting
Guardian Angel Research Center
Tampa, Florida, 33614
Lopez Luls, MD
Lopez Luls, MD
About this study
Official title: A Phase 1b Randomized, Double-blind Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of APL-1401 in Patients With Moderately to Severely Active Ulcerative Colitis
This is a randomized, double-blind, placebo-controlled, phase 1b study designed to evaluate safety, tolerability, PK, and preliminary efficacy of APL-1401 in patients with moderately to severely active UC. This study comprises 3 periods including screening period (D-28~D-1), treatment period (D1-D28), and safety follow-up period(D29-D58).
Read the detailed description
On Day 1, patients who meet all entry criteria and none of the exclusion criteria will be randomized to receive either APL-1401 or placebo in a 5:1 ratio. Patients will receive APL-1401 orally once daily (QD) during the 28-day treatment period.
Three cohorts with increasing doses of APL-1401 will be explored. The dose of APL-1401 will start at 120 mg QD in Cohort 1 and sequentially increase to 160 mg QD and 200 mg QD in Cohort 2 and Cohort 3, respectively. Three cohorts with increasing doses of APL-1401 will be explored. 200mg QD is designed to be maximum dose in this study.
In one cohort, if dose stopping criteria of cohort is not met, Safety Monitoring Committee (SMC) will be held when last patient completes 28-day of study treatment. SMC will determine whether to continue the study to next cohort base on pre-defined dose escalation criteria, safety data, and available PK data. At this dose strength, if patients are well tolerated and SMC decides to escalate to a higher dose, the next cohort will be started.
- Conditions
- Ulcerative Colitis
- Being tested
- APL-1401, Placebo
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APL-1401Drug
Also called Nepicastat, SYN117
APL-1401 capsules orally once daily
PlaceboDrug
Placebo capsules orally once daily
| Study group | Role | What they receive |
|---|---|---|
| APL-1401 | Experimental | On Day 1, patients will be randomized to receive either APL-1401 or placebo in a 5:1 ratio. Patients will receive APL-1401 orally once daily (QD) during the 28-day treatment period. Receives: Drug: APL-1401 |
| Placebo | Placebo comparator | Identically matching placebo capsules once daily for 28 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants adverse events (AEs)
An AE was defined as any untoward and unintended medical experience (sign, symptom, appearance of new illness or deterioration of pre-existed disease, abnormal laboratory finding or other medical event) in a patient from obtaining informed consent form, but which did not necessarily have a causal relationship with the study intervention.
Incidence of serious adverse events (SAEs) Incidence of adverse events leading to investigational drug discontinuation Incidence of adverse events of special interest (AESI) Laboratory evaluation results Vital sign measurements Physical examination findings
Measured: Up to 30 days after the last dose
Number of Participants serious adverse events (SAEs)
An SAE is defined as any untoward medical occurrence that, at any dose, including results in death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, a congenital anomaly/birth defect, other situations.
Measured: Up to 30 days after the last dose
Number of Participants adverse events of special interest (AESI)
An adverse event of special interest (AESI) is an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor is required, including rash, orthostatic hypotension, thyroid dysfunction.
Measured: Up to 30 days after the last dose
Secondary outcomes (14)
Cmax
Maximum observed plasma concentration
Measured: Day 1 through Day 28
Tmax
Time to maximum plasma concentration
Measured: Day 1 through Day 28
T1/2
Plasma half-life
Measured: Day 1 through Day 28
AUClast
Area under the plasma concentration-time curve from 0 to last measurable concentration
Measured: Day 1 through Day 28
AUC0-24
Area under the plasma concentration-time curve from 0 to 24 hours
Measured: Day 1 through Day 28
AUC
Area under the plasma concentration-time curve from 0 to infinity
Measured: Day 1 through Day 28
Cave
Average plasma concentration (steady state)
Measured: Day 1 through Day 28
Cmin
Minimum plasma concentration at time of dosing (steady state)
Measured: Day 1 through Day 28
Cmax/Cmin
Peak to minimum plasma concentration (steady state)
Measured: Day 1 through Day 28
Cmax/Cave
Peak to average plasma concentration (steady state)
Measured: Day 1 through Day 28
Fluctuation
100 (Cmax-Cmin)/Cave-percent fluctuation about average plasma concentration (steady state)
Measured: Day 1 through Day 28
Clinical response
Clinical response, as assessed by Mayo Score, defined as a decrease from baseline in Total Mayo Score of ≥3 points and ≥30%, and a decrease from baseline in the rectal bleeding sub-score of ≥1 point or an absolute rectal bleeding sub-score of 0 or 1 point, after 28 days of treatment compared to baseline.
The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, endoscopy findings, and physician's global assessment) with each item graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, with a result ranging from 0 to 12 points. Higher scores represent more severe disease.
Measured: Day 1 through Day 28
Endoscopic improvement
Endoscopic improvement, as assessed by the endoscopic sub-score of the Total Mayo Score, defined as an endoscopy sub-score of 0 or 1 point, after 28 days of treatment compared to baseline.
Measured: Day 1 through Day 28
Histologic remission
Histologic remission, as assessed by Geboes Score, defined as a Geboes Score <2.0, after 28 days of treatment compared to baseline.
Measured: Day 1 through Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2023
- Study start26 Jan 2023
- Primary completionMar 2025 (estimated)
- Study completionApr 2025 (estimated)
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.
- 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
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jiangsu Yahong Meditech Co., Ltd aka Asieris
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Qiuyue QU, Study director, Jiangsu Yahong Meditech Co., Ltd aka Asieris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05743010
- Sponsor's protocol ID
- YHGT-UC-01
- Status last verified
- Jan 2023
- First submitted
- 15 Nov 2022
- Last updated
- 6 Sep 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Randomized, Double-blind Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of APL-1401 in Patients With Moderately to Severely Active Ulcerative Colitis
- ClinicalTrials.gov ID
- NCT05743010
- Acronym / sponsor ID
- YHGT-UC-01
- Conditions
- Ulcerative Colitis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Jiangsu Yahong Meditech Co., Ltd aka AsierisIndustry (pharma, biotech, devices)
- Study start
- 26 Jan 2023 (actual)
- Primary completion
- Mar 2025 (estimated)
- Study completion
- Apr 2025 (estimated)
- First posted
- 24 Feb 2023 (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 randomized, double-blind, placebo-controlled, phase 1b study designed to evaluate safety, tolerability, PK, and preliminary efficacy of APL-1401 in patients with moderately to severely active UC. This study comprises 3 periods including screening period (D-28~D-1), treatment period (D1-D28), and safety follow-up period(D29-D58).
Detailed description
On Day 1, patients who meet all entry criteria and none of the exclusion criteria will be randomized to receive either APL-1401 or placebo in a 5:1 ratio. Patients will receive APL-1401 orally once daily (QD) during the 28-day treatment period.
Three cohorts with increasing doses of APL-1401 will be explored. The dose of APL-1401 will start at 120 mg QD in Cohort 1 and sequentially increase to 160 mg QD and 200 mg QD in Cohort 2 and Cohort 3, respectively. Three cohorts with increasing doses of APL-1401 will be explored. 200mg QD is designed to be maximum dose in this study.
In one cohort, if dose stopping criteria of cohort is not met, Safety Monitoring Committee (SMC) will be held when last patient completes 28-day of study treatment. SMC will determine whether to continue the study to next cohort base on pre-defined dose escalation criteria, safety data, and available PK data. At this dose strength, if patients are well tolerated and SMC decides to escalate to a higher dose, the next cohort will be started.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| APL-1401 | Experimental | Drug: APL-1401On Day 1, patients will be randomized to receive either APL-1401 or placebo in a 5:1 ratio. Patients will receive APL-1401 orally once daily (QD) during the 28-day treatment period. |
| Placebo | Placebo comparator | Drug: PlaceboIdentically matching placebo capsules once daily for 28 days |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Willing and able to provide written informed consent.
- Age 18-65 years (inclusive).
- With a history of UC diagnosis at least 3 months prior to screening.
- Currently has active UC, defined as a Total Mayo Score of 6 to 12 (inclusive), at baseline, and with a Mayo Endoscopic Sub-Score (MESS) ≥ 2 confirmed by a site reader.
- Has a rectal bleeding score ≥1 and a stool frequency Score ≥1 and in addition to MESS ≥2 during screening.
Key exclusion criteria (29 listed)
- Has fulminant colitis, toxic megacolon, primary sclerosing cholangitis, Crohn's disease, history of colitis-associated colonic dysplasia, active peptic ulcer disease.
- Has a current clinically significant bacterial, parasitic, fungal, or viral infection.
- Is positive for hepatitis A, B or C, human immunodeficiency virus (HIV), or tuberculosis.
- Uses any of the following medications:
- Participated in another clinical study of an investigational drug (or medical device) within 30 days prior to screening or is currently participating in another study of an investigational drug (or medical device).
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 |
|---|---|---|
| APL-1401Also: Nepicastat, SYN117APL-1401 capsules orally once daily | Drug | APL-1401 |
| PlaceboPlacebo capsules orally once daily | Drug | Placebo |
Primary outcome
Number of Participants adverse events (AEs)
Time frame: Up to 30 days after the last dose
An AE was defined as any untoward and unintended medical experience (sign, symptom, appearance of new illness or deterioration of pre-existed disease, abnormal laboratory finding or other medical event) in a patient from obtaining informed consent form, but which did not necessarily have a causal relationship with the study intervention. Incidence of serious adverse events (SAEs) Incidence of adverse events leading to investigational drug discontinuation Incidence of adverse events of special interest (AESI) Laboratory evaluation results Vital sign measurements Physical examination findings
Number of Participants serious adverse events (SAEs)
Time frame: Up to 30 days after the last dose
An SAE is defined as any untoward medical occurrence that, at any dose, including results in death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, a congenital anomaly/birth defect, other situations.
Number of Participants adverse events of special interest (AESI)
Time frame: Up to 30 days after the last dose
An adverse event of special interest (AESI) is an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor is required, including rash, orthostatic hypotension, thyroid dysfunction.
14 secondary outcomes
Cmax
Time frame: Day 1 through Day 28
Tmax
Time frame: Day 1 through Day 28
T1/2
Time frame: Day 1 through Day 28
AUClast
Time frame: Day 1 through Day 28
AUC0-24
Time frame: Day 1 through Day 28
AUC
Time frame: Day 1 through Day 28
Cave
Time frame: Day 1 through Day 28
Cmin
Time frame: Day 1 through Day 28
Cmax/Cmin
Time frame: Day 1 through Day 28
Cmax/Cave
Time frame: Day 1 through Day 28
Fluctuation
Time frame: Day 1 through Day 28
Clinical response
Time frame: Day 1 through Day 28
Endoscopic improvement
Time frame: Day 1 through Day 28
Histologic remission
Time frame: Day 1 through Day 28
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2023.
- Individual participant dataSharing planned: No
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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.
Qiuyue QU study director
Jiangsu Yahong Meditech Co., Ltd aka Asieris
4 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 APL-1401 in people with Ulcerative Colitis, run by Jiangsu Yahong Meditech Co., Ltd aka Asieris at 4 sites in United States.
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 10 inclusion and 29 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: status not confirmed, as of the sponsor's last update on 6 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Qiuyue QU (+86 021 68583863, qyqu@asieris.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants adverse events (AEs) (time frame: Up to 30 days after the last dose). The study lists 3 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 6 Sep 2023; AzTrials last refreshed its copy on 31 Oct 2026.