Phase IIb Randomized, Placebo‑Controlled Study of Oral AZD8965 on Forced Vital Capacity in Patients with Idiopathic Pulmonary Fibrosis

The primary objective is to assess the clinical efficacy of AZD8965 compared with placebo on the absolute change from baseline in FVC (mL) at Week 24, a direct measure of disease progression in Idiopathic Pulmonary Fibrosis. Secondary objectives include: – evaluation of the dose‑response relationship of AZD8965 on the absolute change from baseline in FVC (mL); – assessment of the absolute change from baseline in percent predicted FVC; – determination of the rate of decline in FVC (mL per week); – evaluation of safety and tolerability of AZD8965 versus placebo; – characterization of the pharmacokinetic profile of AZD8965.

221 individuals diagnosed with Idiopathic Pulmonary Fibrosis were enrolled. Eligible participants were adults aged 40 years or older, inclusive of both male and female subjects, and could include individuals classified as vulnerable. Enrollment required a confirmed IPF diagnosis, a forced vital capacity (FVC) of at least 45 % of predicted normal, and a diffusing capacity for carbon monoxide (DLCO) corrected for hemoglobin of at least 25 % of predicted. Subjects were either receiving a stable dose of locally approved antifibrotic therapy or were not receiving standard care at the time of enrollment. The trial population was selected based on these clinical criteria, reflecting a generally stable health status aside from the underlying fibrotic lung disease. Lifestyle factors such as diet or physical activity were not specified as enrollment requirements.

The study is a Phase IIb, randomized, double-blind, placebo-controlled parallel‑group trial evaluating the efficacy, safety and tolerability of AZD8965 in adults diagnosed with Idiopathic Pulmonary Fibrosis. Approximately 200 participants meeting the inclusion criteria will be screened, and eligible individuals will be allocated 1:1 to receive either AZD8965 (oral film‑coated tablet) or matching placebo for a treatment period of 24 weeks. Baseline assessments, including forced vital capacity (FVC) measurement, will be performed at the screening/baseline visit, followed by study visits at Weeks 4, 12, 18 and 24 to monitor efficacy endpoints, adverse events, vital signs, laboratory parameters, ECGs and plasma drug concentrations. The end‑of‑study visit at Week 24 will include a final FVC assessment and safety evaluation. Participants are expected to remain in the trial for approximately six months. Early termination may occur if a participant experiences a serious adverse event, fails to meet protocol‑defined safety criteria, withdraws consent, or exhibits disease progression that precludes continued study drug administration.

The investigational product AZD8965 is supplied as a film coated tablet for oral administration. Each tablet contains a dose of 00 mg of the active substance azd8965 and is to be taken by mouth. The dosing regimen specifies once‑daily administration throughout the 24‑week treatment period.

The comparator in the study is a matching placebo tablet, designated “Placebo to AZD8965.” The placebo contains no active pharmaceutical ingredient and is identical in appearance to the active tablet to maintain blinding. It is also administered orally once daily for the same duration as the active treatment.

Both study medications are dispensed in labeled containers with dosing instructions. Participants receive a medication diary and are instructed to record each dose taken. Compliance is assessed at each study visit by tablet count and review of the diary entries. Any missed doses are documented, and participants receive reminders to adhere to the prescribed schedule.

The primary efficacy assessment will be the absolute change from baseline in forced vital capacity (FVC) measured in milliliters at Week 24. Participants will undergo FVC measurement at screening (baseline) and again at the Week 24 visit, and the difference between these two values will constitute the primary endpoint.

Secondary efficacy evaluations will include:

• Change from baseline in FVC (mL) at additional time points
• Change from baseline in % predicted FVC
• Calculation of the slope (rate of decline) in FVC expressed as mL per week