Idiopathic Pulmonary Fibrosis (IPF)
Conditions
Keywords
AK3280, IPF, Pirfenidone
Brief summary
This is a phase 3 clinical study conducted in China. The primary objective is to compare the efficacy and safety of AK3280 400 mg versus placebo and active control (pirfenidone) in IPF patients.
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled and open-label active-controlled phase 3 clinical study conducted in China. This study plans to enroll 263 IPF participants. After completing screening assessments and meeting all enrollment criteria, IPF participants will be randomized in a 4:2:1 ratio to: AK3280 400 mg BID group (double-blind); Placebo BID group (double-blind); Pirfenidone 600 mg TID group (open-label). The doctors regularly test participants' lung function. The results of the lung function tests are compared between the groups. The doctors also regularly check participants' health and record any adverse medical events. Participants are in the study for up to one and a half years. Subjects who complete the Week 52 visit of randomized controlled treatment study may be offered the opportunity to enter an open-label extension (OLE) study.
Interventions
DRUGAK3280
Participants will receive AK3280 400 mg twice daily, within 30 minutes after breakfast and dinner, with breakfast and dinner approximately 12 hours apart.
DRUGPlacebo
Participants will receive placebo matching 400 mg twice daily, within 30 minutes after breakfast and dinner, with breakfast and dinner approximately 12 hours apart.
DRUGPirfenidone
Participants will receive pirfenidone three times daily, within 30 minutes after meals. Initial dosing should be titrated gradually under doctor guidance: start with 200 mg each time, increase by 200 mg each time to maintain final dose of 600 mg each time within 2 weeks.
Sponsors
Shanghai Ark Biopharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
During the main study phase, participants, care Provider, and investigators are blinded to AK3280 versus placebo allocation but not to pirfenidone; pulmonary function assessors are blinded to all three groups. The extension study is an open-label phase.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 40 years at enrolment 2. Diagnosis of IPF per ATS/ERS/JRS/ALAT 2022 guidelines 3. HRCT central review completed during screening or within 12 months prior to screening. If participant did not undergo lung surgical biopsy, HRCT imaging must be consistent with usual interstitial pneumonia (UIP) pattern for definitive IPF diagnosis. 4. No prior anti-fibrotic treatment, or discontinued anti-fibrotic therapy for ≥4 weeks or 5 half-lives (whichever is longer) prior to randomization 5. Screening assessments meeting all of the following: 1) Standardized %pFVC ≥ 50% and ≤ 90%；2) Hemoglobin-corrected %pDLco ≥ 30% and ≤ 90%；3) Resting SpO2 ≥ 88%
Exclusion criteria
1. History of hypersensitivity to pirfenidone or AK3280 2. Known intolerance to pirfenidone single dose of 200 mg (total daily dose 600 mg) 3. Hospitalization due to acute IPF exacerbation within 8 weeks prior to screening or during screening 4. Within 4 weeks prior to screening or during screening, local or systemic infection requiring: 1) Hospitalization ≥ 24 hours; or 2) Use of systemic antibiotics (IV, IM, oral, or inhaled) 5. History of active tuberculosis within 12 months prior to screening 6. History of other clinically significant lung diseases besides IPF (e.g., asthma, COPD, interstitial pneumonia of known cause, acute severe pulmonary infection, etc.), or planned lung transplantation within 6 months after signing informed consent 7. Post-bronchodilator FEV1/FVC \< 0.7 or positive bronchodilator response (defined as ≥ 12% relative increase in FEV1 and ≥ 200 mL absolute increase in FEV1 after bronchodilator use) during screening 8. History of heart disease meeting NYHA Class III-IV 9. History of liver cirrhosis, severe hepatic impairment, or end-stage liver disease 10. Screening liver function abnormalities meeting any of the following:1) AST ≥ 2× ULN; 2) ALT ≥ 2× ULN; 3) ALP ≥ 2× ULN; 4) Total bilirubin ≥ 1.5× ULN 11. Screening cystatin C-estimated eGFR \< 60 mL/min/1.73m² 12. Screening coagulation test meeting any of the following: 1) INR \> 2; 2) Both PT and APTT prolonged \> 1.5× ULN 13. History of any clinically diagnosed autoimmune disease, including but not limited to scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis 14. Uncontrolled diabetes during screening (HbA1c \> 10%) 15. History of malignancy or possible malignancy upon evaluation (except treated localized basal cell carcinoma of the skin or cervical carcinoma in situ without recurrence) 16. History of immunodeficiency, including but not limited to HIV infection 17. History of any disease other than IPF with life expectancy \< 18 months; or requiring long-term medical care, or limited self-care ability; or conditions that the investigator believes may affect participant's ability to complete this clinical study, complete study-related assessments, or affect safety or efficacy assessments 18. Use of prohibited medications with potential effects on efficacy endpoints within 4 weeks or 5 half-lives (whichever is longer) prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute change from baseline in FVC at Week 52 | Baseline to Week 52 | The FVC indicates the amount of air a person can forcefully and quickly exhale after taking a deep breath. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute change from baseline in FVC at Week 12, 24, and 42 | Baseline to Week 12, 24, and 42 | The FVC indicates the amount of air a person can forcefully and quickly exhale after taking a deep breath. |
| Proportion of participants with relative decline from baseline in FVC ≥10%, ≥15%, and ≥20% at Week 12, 24, 42, and 52 | At Week 12, 24, 42, and 52 | Relative decline from baseline in FVC ≥10%, ≥15%, and ≥20% indicates varying degrees of disease progression. |
| Absolute change from baseline in standardized %pFVC at Week12, 24, 42, and 52 | Baseline to Week 12, 24, 42, and 52 | Standardized %pFVC is calculated as the ratio of measured FVC to predicted FVC. The predicted FVC is derived using a standardized formula. |
| Proportion of participants with absolute decline from baseline in standardized %pFVC ≥10% at Week 12, 24, 42, and 52 | At Week 12, 24, 42, and 52 | Absolute decline from baseline in standardized %pFVC ≥10% indicates rapid disease progression. |
| Absolute change from baseline in hemoglobin-corrected %pDLco at Week 12, 24, 42, and 52 | At Week 12, 24, 42, and 52 | The hemoglobin-corrected %pDLco measures the ability of oxygen moves from alveoli to blood. |
| Change from baseline in L-PF score at Week 12, 24, 42, and 52 | At Week 12, 24, 42, and 52 | The L-PF is a self-administered, quality of life questionnaire validated for patients with progressive fibrosing interstitial lung disease (ILD), including IPF. |
| Change from baseline in 6MWT distance at Week 12, 24, 42, and 52 | At Week 12, 24, 42, and 52 | — |
| Time to first acute exacerbation of IPF within 52 weeks | Baseline to Week 52 | An exacerbation of IPF is defined as an acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality in HRCT. |
| Progression-free survival (PFS), defined as the time from randomization to disease progression or death, whichever occurs first. | Baseline to Week 52 | IPF disease progression is defined as the occurrence of any of the following events: 1. ≥ 10% absolute decline from baseline in standardized %pFVC 2. ≥ 15% absolute decline from baseline in hemoglobin-corrected %pDLco 3. Unscheduled hospitalization due to respiratory events |
| Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) within 52 weeks | Baseline to Week 52 | TEAEs and SAEs will be assessed via patient-reported symptoms, vital signs, physical examination, 12-lead ECG, HRCT, and laboratory assessments. |
Countries
China
Contacts
CONTACTJayson Zhou
STUDY_DIRECTORZhen Fu, Medical Director
Outcome results
None listed