A Phase 3 Study of Efficacy and Safety of AK3280 in Patients With Idiopathic Pulmonary Fibrosis

Официальное название

A Multicenter, Randomized, Double-Blind, Placebo-Controlled and Open-Label Active-Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of AK3280 in Patients With Idiopathic Pulmonary Fibrosis (IPF)

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат AK3280
  Participants will receive AK3280 400 mg twice daily, within 30 minutes after breakfast and dinner, with breakfast and dinner approximately 12 hours apart.
• Препарат Placebo
  Participants will receive placebo matching 400 mg twice daily, within 30 minutes after breakfast and dinner, with breakfast and dinner approximately 12 hours apart.
• Препарат Pirfenidone
  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.

Первичные конечные точки

• Absolute change from baseline in FVC at Week 52 [Срок оценки: Baseline to Week 52]

Вторичные конечные точки (10)

• Absolute change from baseline in FVC at Week 12, 24, and 42 [Срок оценки: Baseline to Week 12, 24, and 42]
• Proportion of participants with relative decline from baseline in FVC ≥10%, ≥15%, and ≥20% at Week 12, 24, 42, and 52 [Срок оценки: At Week 12, 24, 42, and 52]
• Absolute change from baseline in standardized %pFVC at Week12, 24, 42, and 52 [Срок оценки: Baseline to Week 12, 24, 42, and 52]
• Proportion of participants with absolute decline from baseline in standardized %pFVC ≥10% at Week 12, 24, 42, and 52 [Срок оценки: At Week 12, 24, 42, and 52]
• Absolute change from baseline in hemoglobin-corrected %pDLco at Week 12, 24, 42, and 52 [Срок оценки: At Week 12, 24, 42, and 52]
• Change from baseline in L-PF score at Week 12, 24, 42, and 52 [Срок оценки: At Week 12, 24, 42, and 52]
• Change from baseline in 6MWT distance at Week 12, 24, 42, and 52 [Срок оценки: At Week 12, 24, 42, and 52]
• Time to first acute exacerbation of IPF within 52 weeks [Срок оценки: Baseline to Week 52]
• Progression-free survival (PFS), defined as the time from randomization to disease progression or death, whichever occurs first. [Срок оценки: Baseline to Week 52]
• Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) within 52 weeks [Срок оценки: Baseline to Week 52]

Критерии участия

Критерии включения

• Age ≥ 40 years at enrolment
• Diagnosis of IPF per ATS/ERS/JRS/ALAT 2022 guidelines
• 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.
• No prior anti-fibrotic treatment, or discontinued anti-fibrotic therapy for ≥4 weeks or 5 half-lives (whichever is longer) prior to randomization
• Screening assessments meeting all of the following: 1) Standardized %pFVC ≥ 50% and ≤ 90%；2) Hemoglobin-corrected %pDLco ≥ 30% and ≤ 90%；3) Resting SpO2 ≥ 88%

Критерии исключения

• History of hypersensitivity to pirfenidone or AK3280
• Known intolerance to pirfenidone single dose of 200 mg (total daily dose 600 mg)
• Hospitalization due to acute IPF exacerbation within 8 weeks prior to screening or during screening
• 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)
• History of active tuberculosis within 12 months prior to screening
• 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
• 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
• History of heart disease meeting NYHA Class III-IV
• History of liver cirrhosis, severe hepatic impairment, or end-stage liver disease
• 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
• Screening cystatin C-estimated eGFR < 60 mL/min/1.73m²
• Screening coagulation test meeting any of the following: 1) INR > 2; 2) Both PT and APTT prolonged > 1.5× ULN
• History of any clinically diagnosed autoimmune disease, including but not limited to scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis
• Uncontrolled diabetes during screening (HbA1c > 10%)
• History of malignancy or possible malignancy upon evaluation (except treated localized basal cell carcinoma of the skin or cervical carcinoma in situ without recurrence)
• History of immunodeficiency, including but not limited to HIV infection
• 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
• Use of prohibited medications with potential effects on efficacy endpoints within 4 weeks or 5 half-lives (whichever is longer) prior to randomization

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• China-Japan Friendship Hospital — Пекин

Идентификаторы

NCT: NCT07719023 · AK3280-2005

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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