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
Overview
- Phase
- Phase 1
- Intervention
- APL-1401
- Conditions
- Ulcerative Colitis
- Sponsor
- Jiangsu Yahong Meditech Co., Ltd aka Asieris
- Enrollment
- 36
- Locations
- 4
- Primary Endpoint
- Number of Participants adverse events (AEs)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief 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. 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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:
- •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.
Exclusion Criteria
- •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;
- •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;
Arms & Interventions
APL-1401
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.
Intervention: APL-1401
Placebo
Identically matching placebo capsules once daily for 28 days
Intervention: Placebo
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Cmin(Day 1 through Day 28)
- Cmax/Cmin(Day 1 through Day 28)
- Cmax(Day 1 through Day 28)
- T1/2(Day 1 through Day 28)
- AUClast(Day 1 through Day 28)
- Tmax(Day 1 through Day 28)
- Cmax/Cave(Day 1 through Day 28)
- AUC0-24(Day 1 through Day 28)
- AUC(Day 1 through Day 28)
- Cave(Day 1 through Day 28)
- Fluctuation(Day 1 through Day 28)
- Clinical response(Day 1 through Day 28)
- Endoscopic improvement(Day 1 through Day 28)
- Histologic remission(Day 1 through Day 28)