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).
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
36
New Hope Research Development
Corona, California, United States
RECRUITINGGuardian Angel Research Center
Tampa, Florida, United States
RECRUITINGTandem Clinical Research
Marrero, Louisiana, United States
RECRUITINGNumber 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
Time frame: 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.
Time frame: 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.
Time frame: Up to 30 days after the last dose
Cmax
Maximum observed plasma concentration
Time frame: Day 1 through Day 28
Tmax
Time to maximum plasma concentration
Time frame: Day 1 through Day 28
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Meridian Clinical Research
Rockville, Maryland, United States
RECRUITINGT1/2
Plasma half-life
Time frame: Day 1 through Day 28
AUClast
Area under the plasma concentration-time curve from 0 to last measurable concentration
Time frame: Day 1 through Day 28
AUC0-24
Area under the plasma concentration-time curve from 0 to 24 hours
Time frame: Day 1 through Day 28
AUC
Area under the plasma concentration-time curve from 0 to infinity
Time frame: Day 1 through Day 28
Cave
Average plasma concentration (steady state)
Time frame: Day 1 through Day 28
Cmin
Minimum plasma concentration at time of dosing (steady state)
Time frame: Day 1 through Day 28
Cmax/Cmin
Peak to minimum plasma concentration (steady state)
Time frame: Day 1 through Day 28
Cmax/Cave
Peak to average plasma concentration (steady state)
Time frame: Day 1 through Day 28
Fluctuation
100 (Cmax-Cmin)/Cave-percent fluctuation about average plasma concentration (steady state)
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Day 1 through Day 28