Clinical Trials/NCT05424887

NCT05424887

Not yet recruiting

Phase 2

A Randomized, Double-blind, Multi-center Phase II Clinical Study to Evaluate the Efficacy and Safety of Two Different Dose Groups of AK3280 in Patients With Idiopathic Pulmonary Fibrosis (IPF) Compared to the Placebo Control Group

Shanghai Ark Biopharmaceutical Co., Ltd.1 site in 1 country105 target enrollmentJuly 2022

ConditionsIdiopathic Pulmonary Fibrosis

InterventionsAK3280 Placebo

DrugsAK3280 Placebo

Overview

Phase: Phase 2
Intervention: AK3280
Conditions: Idiopathic Pulmonary Fibrosis
Sponsor: Shanghai Ark Biopharmaceutical Co., Ltd.
Enrollment: 105
Locations: 1
Primary Endpoint: 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.
Status: Not yet recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Detailed Description

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.

Registry

clinicaltrials.gov

Start Date

July 2022

End Date

October 2024

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Shanghai Ark Biopharmaceutical Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients who sign the informed consent form before participating in the study.
•Patients who understand the importance of complying with the study medication regulations and completing all assessments on time during the entire study process, and agree to strictly abide by the protocol regulations, including the restrictions on concomitant medication during the study process.
•Patients aged ≥40 years and ≤80 years at the time of enrollment.
•Patients diagnosed with IPF within five years before screening (but at least 6 months before the first medication) who meet the standards of the latest American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) 2018 guidelines. The diagnosis of IPF needs to be reconfirmed during the screening assessment.
•Patients who have completed the HRCT central review assessment during the screening period or completed the HRCT central assessment within 12 months before screening to confirm the diagnosis of IPF. If the patient is unable to provide pulmonary surgical biopsy pathology, the HRCT image must conform to usual interstitial pneumonia to confirm the diagnosis of IPF. Patients who have undergone pulmonary surgical biopsy as part of the initial diagnosis must submit their pathological slices for central review and assessment.
•Patients who cannot tolerate pirfenidone or nintedanib and have received no more than 8 consecutive weeks of regular nintedanib or pirfenidone treatment, or patients who, the investigator considers, are not suitable to receive pirfenidone or nintedanib treatment, or patients who refuse to receive pirfenidone or nintedanib treatment.
•Patients with %FVC between 50% and 90% (inclusive) at screening, and hemoglobin-corrected %DLco between 30% and 90% (inclusive).
•Patients with relatively stable basic lung function, manifested by a \<10% relative difference in FVC values at the screening day and the day before administration. The calculation formula is: (FVC value (L) at screening - FVC value (L) one day before administration) )/(FVC value (L) at screening )× 100% And patients who have no other clinically significant acute exacerbations of IPF determined by the investigators at the screening day and the day before administration.
•Patients whose 6MWT distance is ≥100 m without auxiliary support.

Exclusion Criteria

•Patients suffering from interstitial pneumonia of other known causes.
•Patients who plan to undergo lung transplantation within 6 months after screening.
•Patients suffering from other clinically significant lung diseases (such as asthma, chronic obstructive pulmonary disease, etc.) in addition to IPF.
•Patients suffering from any disease whose life expectancy is less than 12 months other than IPF; or patients requiring long-term medical care, or with limited self-care ability, or the investigator believes that it may affect the patient's participation in the completion of this clinical study, or completion of study-related examinations, or affect safety assessments or efficacy assessments.
•Patients who have any evidence or clinically significant adverse physical conditions or abnormal examinations (physical examination, vital signs, ECG or laboratory test abnormalities, etc.) that the investigator believes may affect patient safety or the study endpoint assessments.
•Patients with forced expiratory volume in the first second (FEV1)/FVC ratio \<0.7 after the use of bronchodilators at screening.
•Patients with a positive bronchodilation test, manifested as a ≥ 12% increase in FEV1 and an absolute increase≥200 mL in FEV1 after the use of bronchodilators.
•Patients with peripheral capillary blood oxygen saturation (SpO2) at rest \<88%.
•Patients suffering from any clinically diagnosed connective tissue disease, including but not limited to scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis.
•Patients with New York Heart Association (NYHA) heart function classification of Class III-IV.

Arms & Interventions

100 mg AK3280

After the 4-week screening period, Eligible subjects will be administered daily 100 mg AK3280 b.i.d. for 24weeks

Intervention: AK3280

200 mg AK3280

After the 4-week screening period, Eligible subjects will be administered daily 200 mg AK3280 b.i.d. for 24weeks

Intervention: AK3280

placebo

There are placebo controls in each dose cohort to assess the safety profile of the study medication. Subjects will be randomized to receive a placebo simultaneously as those subjects randomized to AK3280.

Intervention: Placebo

Extension Study Cohort

The extension study includes a 24-week medication observation period and a 4-week safety follow-up period. Subjects who meet the requirements will enter the extension study after 24 weeks of treatment in the main study. Subjects entering the extension study will continue to orally take AK3280 200 mg for 24 weeks.

Intervention: AK3280

Outcomes

Primary Outcomes

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.

Time Frame: Up to 24 weeks

Change in percentage of the predicted FVC from baseline

Secondary Outcomes

The proportion of patients with a percentage of decrease≥ 10%, ≥ 15% or ≥ 20% in FVC from baseline in each group(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(Main study: Up to 24 weeks; Extended study: Up to 48 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.(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(Main study: Up to 24 weeks; Extended study: Up to 48 weeks)
Number of participants with abnormal Physical examination findings(Main study: Up to 24 weeks; Extended study: Up to 48 weeks)
Pharmacokinetic endpoint：Time to peak (Tmax) of AK3280 and AK3280 M2(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(Day 1 and Day 7)
Pharmacokinetic endpoint：Accumulation coefficient of AK3280 and AK3280 M2(Day 1 and Day 7)
The changes from baseline in %DLco， in the AK3280 treatment group compared to the placebo control group(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(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(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(Main study: Up to 24 weeks; Extended study: Up to 48 weeks)
Number of participants with abnormal vital signs(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(Day 1 and Day 7)
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(Main study: Up to 24 weeks; Extended study: Up to 48 weeks)
Number of participants with abnormal 12-lead ECG readings(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(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(Main study: Up to 24 weeks; Extended study: Up to 48 weeks)
Assessment of adverse events(Main study: Up to 24 weeks; Extended study: Up to 48 weeks)
Assessment of serious adverse events (SAEs)(Main study: Up to 24 weeks; Extended study: Up to 48 weeks)
Pharmacokinetic endpoint：Area under the plasma drug concentration-time curve from 0 hour to 12 hours (AUC0-12h) of AK3280 and AK3280 M2(Day 1 and Day 7)
Pharmacokinetic endpoint：Oral clearance (CL/F) of AK3280 and AK3280 M2(Day 1 and Day 7)
Pharmacokinetic endpoint：Terminal half-life (t1/2) of AK3280 and AK3280 M2(Day 1 and Day 7)
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(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(Main study: Up to 24 weeks; Extended study: Up to 48 weeks)
Number of participants with abnormal laboratory test results(Main study: Up to 24 weeks; Extended study: Up to 48 weeks)
Pharmacokinetic endpoint：Oral volume of distribution (Vd/F) of AK3280 and AK3280 M2(Day 1 and Day 7)