Efficacy and Safety Evaluation of Buloxibutid in Idiopathic Pulmonary Fibrosis: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

Trial ID: 2023-509069-19-00
Protocol: VP-C21-011
Sponsor: Vicore Pharma AB

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Diseases & Conditions

Idiopathic pulmonary fibrosis

Objectives

The primary objective of this study is to evaluate the **efficacy** of buloxibutid compared to placebo in participants with idiopathic pulmonary fibrosis (IPF), as assessed by forced vital capacity (FVC). This is clinically relevant as FVC is a critical measure of lung function and disease progression in IPF, providing insight into the potential therapeutic benefits of buloxibutid.

Secondary objectives include:

To further evaluate the effects of buloxibutid on disease progression, respiratory-related hospitalization, or death compared to placebo.
To assess the impact of buloxibutid on lung function compared to placebo.
To evaluate the effects on clinical outcomes compared to placebo.
To assess patient-reported health-related quality of life (HRQoL) measures compared to placebo.
To evaluate patient impressions of disease severity and symptoms compared to placebo.
To assess the effects on IPF-associated high resolution computed tomography (HRCT) findings compared to placebo.
To evaluate the effects on survival compared to placebo.
To assess the safety of buloxibutid compared to placebo.
To characterize the pharmacokinetic (PK) profile of buloxibutid in participants with IPF.

Participants

The clinical trial involves a total of **174 participants** diagnosed with **idiopathic pulmonary fibrosis** (IPF). The study population includes both male and female subjects aged 40 years and older, as per the inclusion criteria. Participants were selected based on a confirmed diagnosis of IPF within the last five years, following the ATS/ERS/JRS/ALAT 2022 guidelines, and must have undergone a high-resolution computed tomography (HRCT) scan within 36 months prior to the first visit. The trial includes individuals with a forced vital capacity (FVC) of at least 50% predicted and a diffusing capacity of the lungs for carbon monoxide (DLCO) of at least 35% predicted. Participants are either on a stable dose of licensed IPF therapy or not currently receiving such treatment for various reasons, including prior intolerance or non-responsiveness. The trial population is expected to have a life expectancy of at least 12 months and not require a lung transplant during the trial period. Both male and female participants are required to adhere to specific contraceptive measures. The study does not exclude individuals on a transplant list, and informed consent was obtained from all participants in accordance with ICH-GCP and local laws.

Plans and Procedures

The clinical trial is designed as a **randomized, double-blind, placebo-controlled, parallel-group, multicenter study** to evaluate the efficacy and safety of two doses of **buloxibutid** over a period of 52 weeks in individuals diagnosed with **idiopathic pulmonary fibrosis** (IPF). The primary objective is to assess the efficacy of buloxibutid compared to placebo, with the primary endpoint being the absolute change from baseline in forced vital capacity (FVC) at Week 52. Secondary endpoints include various measures of lung function, quality of life assessments, and safety evaluations.

Participants will be involved in the study for approximately 52 weeks, with the trial expected to conclude by December 31, 2026. The study will commence with a screening visit to confirm eligibility based on criteria such as age, diagnosis of IPF, and lung function parameters. Following successful screening, participants will be randomized to receive either buloxibutid or placebo in a double-blind manner. Study visits will occur at Weeks 4, 12, 24, 36, and 52 to monitor efficacy and safety outcomes, including FVC measurements, quality of life assessments, and adverse event monitoring.

The inclusion criteria require participants to be at least 40 years old, have a confirmed diagnosis of IPF within the last five years, and meet specific lung function criteria. Exclusion criteria are not explicitly detailed in the provided data. Participants are expected to adhere to contraceptive guidelines and provide written informed consent. Conditions that may lead to early termination from the study include significant adverse events or non-compliance with study protocols. The trial is not classified as low intervention and is categorized as a Phase 2b study.

Treatment

The clinical trial involves the administration of **Buloxibutid**, a chemical compound, in the form of hard capsules. The active substance in these capsules is Buloxibutid, also known by synonyms such as Oxybutidan, Compound 21, and VP01. The pharmaceutical form is a hard capsule, and the route of administration is oral. Participants will receive a maximum daily dose of 200 mg, with a total maximum dose of 72.8 grams over the course of the 52-week treatment period. The trial aims to evaluate the efficacy of Buloxibutid in individuals with idiopathic pulmonary fibrosis, with the primary assessment based on forced vital capacity (FVC).

In addition to the experimental treatment, a **placebo** is used as a comparator in this double-blind, placebo-controlled study. The placebo is designed to match the Buloxibutid oral capsules in appearance and is administered orally. The use of a placebo allows for the assessment of the true efficacy of Buloxibutid by providing a baseline for comparison. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment regimen.

Efficacy

The efficacy of buloxibutid in the treatment of **idiopathic pulmonary fibrosis** (IPF) will be assessed through a series of primary and secondary endpoints over a 52-week period. The primary endpoint is the absolute change from baseline in forced vital capacity (FVC) measured in milliliters at Week 52. This will provide a direct measure of lung function improvement or decline in participants receiving buloxibutid compared to those receiving a placebo.

Secondary endpoints include a variety of measures to further evaluate the efficacy of the treatment. These include the proportion of participants experiencing a decrease in FVC percent predicted (FVCpp) by 10% or more, respiratory-related hospitalizations, or death up to Week 52. The annual rate of decline in FVC will also be analyzed at multiple timepoints: Weeks 4, 12, 24, 36, and 52. Additional assessments will include changes in the Living with Pulmonary Fibrosis (L-PF) total score, EuroQoL-5D 5 levels (EQ-5D-5L) health index value, and visual analogue scale (VAS) scores for symptoms such as cough, dyspnea, and fatigue.

Further secondary endpoints involve the incidence of acute IPF exacerbations, respiratory-related hospitalizations, and all-cause mortality up to Week 52. The study will also monitor treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs), alongside changes in safety laboratory assessments, vital signs, and electrocardiograms (ECGs). Plasma concentration of buloxibutid will be measured to assess pharmacokinetics.

These efficacy parameters will be collected and analyzed using validated scales and laboratory tests at specified intervals throughout the trial duration, ensuring a comprehensive evaluation of buloxibutid's impact on IPF.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Age ≥ 40 years at the time of signing the informed consent
Diagnosed of IPF within 7 years prior to V1, as per applicable ATS/ERS/JRS/ALAT at the time of diagnosis.
HRCT scan within 36 months prior to V1 with central reading confirming either a or b, and c: a. A pattern consistent with usual interstitial pneumonia (UIP) according to ATS/ERS/JRS/ALAT 2022 guideline: UIP or probable UIP. b. A pattern indeterminate for UIP according to ATS/ERS/JRS/ALAT 2022 guideline and a historical biopsy (surgical lung biopsy or transbronchial lung cryobiopsy) consistent with IPF. c. Extent of fibrosis > extent of emphysema.
FVC ≥50% predicted at V1.
DLCO (corrected for hemoglobin) ≥30% predicted at V1
Either: a. On a stable dose of licensed IPF therapy for at least 8 weeks prior to V1 and expected to remain on this background treatment after randomization. Due to the risk of DDIs, concomitant treatment with pirfenidone is not allowed in this trial. b. Not currently receiving treatment for IPF with a licensed therapy for any reason, including prior intolerance, non-responsiveness, ineligibility, lack of access or voluntarily decline. Any such previous treatment must have been discontinued >8 weeks prior to V1.
Anticipated life expectancy of at least 12 months at V1 and not anticipated to require a lung transplant during the trial period (being on a transplant list does not exclude a participant from the trial).
Contraceptive use by women of childbearing potential (WOCBP) which is highly effective and consistent with local regulations regarding the methods of contraception for those participating in clinical trials. Male participants, if heterosexually active with a female partner of childbearing potential, or a pregnant or breastfeeding partner, must agree to use barrier contraception (male condom) and abstain from sperm donation for the duration of the treatment period and for at least 2 weeks after the last dose of the study drug.
Written informed consent, consistent with ICH-GCP and local laws, obtained before the initiation of any trial-related procedure.

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Exclusion Criteria

Concurrent serious medical condition which in the opinion of the investigator constitutes a risk or a contraindication for the participation in the trial or that could interfere with the trial objectives, conduct or evaluation, including active or suspected malignancy or history of malignancy within 5 years prior to V1, except appropriately treated basal cell carcinoma of the skin, fully resected and cured squamous cell carcinoma of the skin, “under surveillance” prostate cancer or in situ carcinoma of uterine cervix.
Pregnant or breast-feeding female participants
Acute IPF exacerbation within 3 months prior to V1 and/or during the screening period, as defined by Collard et al, 2016: a. Acute worsening or development of dyspnoea typically <1 month duration. b. Computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with usual interstitial pneumonia pattern (if no previous computed tomography is available, the qualifier "new" can be dropped). c. Deterioration not fully explained by cardiac failure or fluid overload.
Inability to generate a spirometry test at V1 meeting the standards of the ATS/ERS 2019 guideline.
Treatment with pirfenidone (substrate of CYP1A2) within 8 weeks prior to V1 or anticipated need for pirfenidone during the participation in the trial.
Treatment with the specific medications listed as per protocol within 2 weeks prior to V2 or anticipated need for such medication during the participation in this trial.
Current or previous participation in any other clinical trial where the participant has received a dose of IMP within 4 weeks or 5 half-lives of the IMP, whichever is longest, prior to V1.
Previous participation in a clinical trial with buloxibutid and received at least one dose of buloxibutid.
Abnormal laboratory value at V1 indicating a potential risk for the participant if enrolled in the trial as evaluated by the investigator. Retesting is allowed once.
Inability to refrain from smoking (including e-cigarettes and cannabis) on days of site visits until completion of trial procedures.
Where applicable per country regulation, the participant must not currently be committed to an institution by virtue of an order issued either by judicial or administrative authorities.
Airways obstruction with a pre-bronchodilator forced expiratory volume in one second (FEV1)/FVC ratio <0.7 at V1.
The investigator considers the participant unlikely to comply with trial procedures, restrictions and requirements.
Lower respiratory tract infection requiring antibiotics and not fully recovered according to investigator judgement within 4 weeks prior to V2.
Confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requiring hospitalization not fully recovered according to investigator judgement within 4 weeks prior to V2.
Known impaired hepatic function or clinically significant liver disease (Child-Pugh B or C hepatic impairment), or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 times upper limit of normal (ULN) or total bilirubin >1.5 times ULN at V1. Retesting is allowed once.
Severe renal impairment (i.e., estimated glomerular filtration rate (eGFR) ≤35 ml/min/1.73 m2 at V 1 according to Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula). Retesting is allowed once.
Prolonged QTcF (QT interval with Fridericia’s correction) (>450 ms), AV-block II or III, uncontrolled arrhythmia or other clinically significant abnormality in the resting ECG at V1, as judged by the investigator. Patients with implantable cardiovascular devices (e.g. pacemaker) affecting the QT interval time may be enrolled in the trial based upon investigator judgement, following cardiologist consultation if deemed necessary, and only after discussion with the medical monitor.
Heart failure NYHA Class IV, acutely decompensated right heart failure, pulmonary hypertension with syncopal episode, confirmed myocardial infarction, unstable angina or uncontrolled hypertension, within 6 months prior to V1.
Know hypersensitivity or intolerance to buloxibutid or to any other components of the test product, including excipients.
Resting oxygen saturation of < 89% using up to 4 L/min of supplemental oxygen at sea level and up to 6 L/min at altitude (≥ 5000 feet [1524 meters] above sea level) during screening.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Austria	Not Recruiting	28 Nov 2024	13
Belgium	Not Recruiting	28 Nov 2024	12
Germany	Not Recruiting	28 Nov 2024	23
Greece	Not Recruiting	28 Nov 2024	17
Italy	Not Recruiting	28 Nov 2024	17
Poland	Not Recruiting	28 Nov 2024	12