This study is a randomized, double-blind, placebo-controlled, multi-center phase II clinical study conducted in China to compare the efficacy and safety of two different dose groups of AK3280 in IPF patients compared to the placebo control group.
This study is a randomized, double-blind, placebo-controlled, multi-center phase II clinical study conducted in China to compare the efficacy and safety of two different dose groups of AK3280 in IPF patients compared to the placebo control group. One hundred and five IPF patients who have completed the screening assessment and meet the enrollment requirements will participate in this study and be randomized into 3 treatment groups in a 1:1:1 (35:35:35) ratio: AK3280 200 mg group, AK3280 100 mg group and placebo group; the frequency of medication for each treatment group is twice a day (BID). This study is divided into a main study and an extension study. The main study includes a 4-week screening period, a 24-week medication observation period, and a 4-week safety follow-up period. The extension study includes a 24-week medication observation period and a 4-week safety follow-up period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
105
China-Japan Friendship Hospital
Beijing, Beijing Municipality, China
After 24 weeks of continuous medication, the absolute decrease in percentage of the predicted FVC from baseline in the AK3280 treatment group compared to the placebo control group.
Change in percentage of the predicted FVC from baseline
Time frame: Up to 24 weeks
Assessment of whether AK3280 prolongs the progression-free survival of IPF subjects compared with the placebo control group within 24 weeks and 48 weeks of medication.
Progression-free survival is defined as the time from randomization to the first occurrence of any of the following events: * The percentage of FVC to the normal expected value (%FVC) achieves an absolute decrease of 10%, or * The percentage of DLco to the normal expected value (%DLco) achieves an absolute decrease of 15%, or * Non-elective hospitalization due to respiratory events * Death
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
The changes from baseline in %DLco, in the AK3280 treatment group compared to the placebo control group
\- After hemoglobin correction, the absolute decrease in %DLco * DLco will be measured at 4 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks after the first administration on D1 respectively.
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
The proportion of subjects with a ≥15% absolute decrease in %DLco,in the AK3280 treatment group compared to the placebo control group
\- After hemoglobin correction, the proportion of subjects with a ≥15% absolute decrease in %DLco * DLco will be measured at 4 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks after the first administration on D1 respectively.
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
The absolute decrease in forced vital capacity (FVC) from baseline , in the AK3280 treatment group compared to the placebo control group
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FVC will be measured at 4 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks after the first administration on D1 respectively.
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
The proportion of patients with a percentage of decrease≥ 10%, ≥ 15% or ≥ 20% in FVC from baseline in each group
FVC will be measured at 4 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks after the first administration on D1 respectively.
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
The time to the percentage of decrease in FVC reaching 10% from baseline
FVC will be measured at 4 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks after the first administration on D1 respectively.
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
Within 24 and 48 weeks of medication, the changes from baseline in the 6MWT(six-minute walk test) distance in the AK3280 treatment group compared to the placebo control group
The 6MWT distance will be measured at 4 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks after the first administration on D1 respectively.
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
Within 24 and 48 weeks of medication, the acute exacerbation of IPF subjects - The time from randomization to the first acute exacerbation - The proportion of subjects who experience at least one acute exacerbation
A subject needs to meet all 3 criteria below to be judged to have acute exacerbation of IPF: * Acute worsening or progression of dyspnea occurs within 1 month (manifested as rapid decline in lung function, worsening of hypoxemia, worsening of irritating dry cough, and worsening of wheezing after exercise, etc.) * Chest HRCT(high-resolution computed tomography) shows new diffuse ground glass opacities (GGO) and/or consolidation opacities in both lungs on the background of the original mesh opacities, honeycomb opacities and other manifestations of usual interstitial pneumonia (UIP) * Heart failure or fluid overload is ruled out
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
Within 24 and 48 weeks of medication, the IPF-related mortality, all-cause mortality in IPF subjects
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
The changes from baseline in the SGRQ(Saint George's Respiratory Questionnaire) total score in the AK3280 treatment group compared to the placebo control group
Saint George's Respiratory Questionnaire Part 1 : Symptoms component (frequency \& severity) with a 1, 3 or 12-month recall (best performance with 3- and 12-month recall); Part 2: Activities that cause or are limited by breathlessness; Impact components (social functioning, psychological disturbances resulting from airways disease) refer to current state as the recall. Scores range from 0 to 100, with higher scores indicating more limitations.
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
The proportion of subjects with changes from baseline in the SGRQ ≥4 points from baseline
Scores range from 0 to 100, with higher scores indicating more limitations.
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
Within 24 and 48 weeks of medication, the proportion of patients who have dose adjustments due to AEs in the AK3280 treatment group and the placebo control group
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
Within 24 and 48 weeks of medication, the proportion of subjects who discontinue the medication due to adverse events (AE) in the AK3280 treatment group and the placebo control group
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
Assessment of adverse events
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
Assessment of serious adverse events (SAEs)
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
Number of participants with abnormal vital signs
Vital signs: include pulse, respiration, body temperature and blood pressure
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
Number of participants with abnormal Physical examination findings
Physical examination : include height, weight, skin, head and neck, mouth, chest, abdomen, lymph nodes, nerves and mind, limbs and other sites
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
Number of participants with abnormal 12-lead ECG readings
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
Number of participants with abnormal laboratory test results
Laboratory tests:include blood routine examination, blood biochemistry ,urine routine test
Time frame: Main study: Up to 24 weeks; Extended study: Up to 48 weeks
Pharmacokinetic endpoint:The maximum plasma drug concentration (Cmax) of AK3280 and AK3280 M2
Time frame: Day 1 and Day 7
Pharmacokinetic endpoint:Time to peak (Tmax) of AK3280 and AK3280 M2
Time frame: Day 1 and Day 7
Pharmacokinetic endpoint:Area under the plasma drug concentration-time curve from 0 hour to 12 hours (AUC0-12h) of AK3280 and AK3280 M2
Time frame: Day 1 and Day 7
Pharmacokinetic endpoint:Area under the plasma drug concentration-time curve extrapolated from 0 hour to infinity (AUC0-∞) of AK3280 and AK3280 M2
Time frame: Day 1 and Day 7
Pharmacokinetic endpoint:Oral clearance (CL/F) of AK3280 and AK3280 M2
Time frame: Day 1 and Day 7
Pharmacokinetic endpoint:Oral volume of distribution (Vd/F) of AK3280 and AK3280 M2
Time frame: Day 1 and Day 7
Pharmacokinetic endpoint:Terminal half-life (t1/2) of AK3280 and AK3280 M2
Time frame: Day 1 and Day 7
Pharmacokinetic endpoint:Accumulation coefficient of AK3280 and AK3280 M2
Time frame: Day 1 and Day 7