A Trial to Evaluate Efficacy and Safety of Buloxibutid in People With Idiopathic Pulmonary Fibrosis. (ASPIRE)

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Trial Evaluating the Efficacy and Safety of 2 Doses of Buloxibutid Over 52 Weeks in People With Idiopathic Pulmonary Fibrosis.

The ASPIRE trial is a 52 week randomized, double-blind, placebo-controlled, parallel-group, multicenter trial in which the efficacy, safety, and pharmacokinetics of orally administered buloxibutid, either on top of stable IPF therapy or as monotherapy, are assessed in participants with IPF.

Trial website: www.aspire-ipf.com

Study Overview

• Status: Active, not recruiting
• Conditions: Idiopathic Pulmonary Fibrosis (IPF)
• Intervention / Treatment: Drug: Placebo; Drug: Buloxibutid

Detailed Description

Buloxibutid is an oral angiotensin II type 2 (AT2) receptor agonist and has been shown to improve lung function in IPF over 36 weeks.

Buloxibutid agonizes the AT2 receptor on alveolar epithelial type 2 cells (AEC2s), which are believed to play a central role in the disease. Buloxibutid has been demonstrated preclinically to improve AEC2 viability, alveolar integrity via surfactant secretion and epithelial repair via replenishment of gas exchange alveolar epithelial type 1 cells (AEC1s). This leads to decreasing downstream profibrotic signaling, enhancing resolution of existing fibrotic tissue via upregulation of collagenase matrix metalloproteinases, and addressing vascular disfunction associated with the disease.

The trial will include participants who are on stable licensed IPF therapy or who are currently not treated with a licensed IPF therapy. The latter group will include participants intolerant or not responsive to licensed IPF therapies, participants ineligible to receive these therapies, and participants who have voluntarily declined to receive a licensed IPF therapy after being fully informed of the potential benefits and risks of such therapy. Due to the potential risk of drug-drug interactions (DDIs), concomitant treatment with pirfenidone is not allowed in this trial. Participants who are not on antifibrotic therapy at study start may initiate such treatment during the study.

The trial is planned to enroll 360 participants, 120 participants on oral buloxibutid 100 mg BID, 120 participants on oral buloxibutid 50 mg BID, and 120 participants on oral placebo BID for 52 weeks. The treatment will be blinded and treatment allocation will be randomized.

The primary measurement will be based on spirometry, measuring the forced vital capacity (FVC).

The trial consists of 3 consecutive periods: a screening period of up to 6 weeks, a 52-week treatment period, and a follow-up period of 2-4 weeks after the 52-week visit. The study procedures have been planned with focus on optimizing patient convenience while allowing a safe conduct and strict scientific rigor.

Trial website: www.aspire-ipf.com

• Study Type: Interventional
• Enrollment (Actual): 378
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1602
    • CEMER Medical Center for Respiratory Diseases
  • Buenos Aires, Argentina, C1028AAP
    • Belgrano Clinical Research Center
  • Buenos Aires, Argentina, C1056ABI
    • CINME - Metabolic Research Center
  • Buenos Aires, Argentina, C1426ABP
    • Medical Center Dra. De Salvo
  • Córdoba, Argentina, X5003DCE
    • IMER Respiratory Medicine Institute
  • Godoy Cruz, Argentina, 5501
    • Breathe Comprehensive Clinical Health
  • Mar del Plata, Argentina, 7600
    • Emphysema Foundation, Pneumology
  • Mendoza, Argentina, 5509
    • Vistalba Health Center
  • Rosario, Argentina, S2000
    • InnovaCiencia
  • Santa Fe, Argentina, 3000
    • Ibamedica
  • Tucumán Province
    • San Miguel de Tucumán, Tucumán Province, Argentina, 4000
      • Research Institute of Respiratory Diseases
• Australia
  • Adelaide, Australia, SA 5042
    • Flinders Medical Centre
  • Brisbane, Australia, QLD 4032
    • The Prince Charles Hospital
  • Concord, Australia, NSW 2139
    • Concord Repatriation General Hospital, Department of Respiratory Medicine
  • Darlinghurst, Australia, NSW 2010
    • St Vincent's Hospital, Sydney Ltd.
  • Douglas, Australia, QLD 4814
    • Townsville University Hospital
  • Heidelberg, Australia, VIC 3084
    • Austin Hospital
  • Sydney, Australia, NSW 2050
    • Royal Prince Alfred Hospital
  • Woodville, Australia, SA 5011
    • The Queen Elizabeth Hospital
  • Victoria
    • Footscray, Victoria, Australia, 3011
      • Lung Research Victoria
• Austria
  • Salzburg, Austria, 5020
    • Salzburg Regional Hospital, Department of Pneumology/Respiratory Medicine
  • Vienna, Austria, 1140
    • Hospital Penzing, Department of Respiratory and lung diseases
  • Upper Austria
    • Linz, Upper Austria, Austria, 4021
      • Kepler University Hospital GmbH, Department of Pulmonology
• Belgium
  • Brussels, Belgium, 1070
    • Erasme Hospital
  • Brussels, Belgium, 1200
    • University Hospitals Saint-Luc
  • Liège, Belgium, 4000
    • University Hospital Center Sart-Tilman
  • Yvoir, Belgium, 5530
    • UCL Mont-Godinne University Hospitals
• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1W 1V3
      • Kelowna Respiratory & Allergy Clinic
  • Quebec
    • Trois-Rivières, Quebec, Canada, G9A 4P3
      • Diex Research Trois-Riviere Inc.
• Germany
  • Berlin, Germany, 12351
    • Vivantes Hospital Neukoelln
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79106
      • University Hospital Freiburg
    • Heidelberg, Baden-Wurttemberg, Germany, 69126
      • University Hospital Heidelberg, Clinic of Thoracic Medicine Heidelberg GmbH
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • University Hospital Tuebingen
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60596
      • Clinical Research Centre Respiratory Medicine
    • Immenhausen, Hesse, Germany, 34 376
      • Immenhausen Lung Hospital
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Hannover Medical School, Center for Internal Medicine
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany, 45122
      • RuhrlandClinic - Lung Center
• Greece
  • Athens, Greece, 11527
    • "Sotiria" Chest Diseases Hospital of Athens
  • Athens, Greece, 11527
    • General Hospital of Chest Diseases "Sotiria" 5th Pulmonology Department
  • Athens, Greece, PC 12462
    • University General Hospital "Attikon", 2nd Pulmonary Department
  • Ioannina, Greece, 45500
    • University General Hospital of Ioannina
  • Pátrai, Greece, 26504
    • University General Hospital of Patras
  • Thessaloniki, Greece, PC 57010
    • General Hospital of Thessaloniki "G. Papanikolaou", University Department of Pulmonology
  • Crete
    • Heraklion, Crete, Greece, 715 00
      • University General Hospital of Heraklion, Pneumonology Clinic
• Italy
  • Ancona, Italy, 60126
    • University Hospital - Ospedali Riuniti Umberto I - GM Lancisi - G Salesi of Ancona
  • Bergamo, Italy, 24127
    • Local Healthcare Company Papa Giovanni XXIII (ASST Papa Giovanni XXIII)
  • Monza, Italy, 20900
    • San Gerardo of Tintori IRCCS Foundation
  • Roma, Italy, 00133
    • Foundation PTV - Polyclinic Tor Vergata
  • Turin, Italy, 10126
    • University Hospital City of Health and Science of Turin - Hospital Molinette
  • Liguria
    • Genoa, Liguria, Italy, 16132
      • IRCCS Policlinic Hospital San Martino
• Mexico
  • Oaxaca City, Mexico, 68000
    • Oaxaca Site Management Organization S.C - (Osmo)
  • Mexico City
    • Mexico City, Mexico City, Mexico, 14080
      • National Institute of Respiratory Diseases Ismael Cosio Villegas (INER)
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Dr. Jose Eleuterio Gonzalez Monterrey University Hospital
    • San Nicolás de los Garza, Nuevo León, Mexico, 66465
      • Integral Health Medical Unit
• Poland
  • Bydgoszcz, Poland, 85-065
    • MICS Medical Centre Bydgoszcz
  • Bydgoszcz, Poland, 85-079
    • VITAMED Galaj i Cichomski General Partnership
  • Lodz, Poland, 90-153
    • Norbert Barlicki University Clinical Hospital in Lodz Departament of Pneumology and Allergy
  • Nowa Sól, Poland, 67-100
    • Twoja Przychodnia Medical Centre of Nowa Sol
  • Świdnik, Poland, 21-040
    • Allergology- Pulmunology Outpatient Clinic Alergopneuma, Pulmonology Outpatient Clinic
• South Korea
  • Bucheon-si, South Korea, 14584
    • Soon Chun Hyang Central Medical Center
  • Bucheon-si, South Korea, 14647
    • The Catholic University Of Korea Bucheon St. Mary's Hospital
  • Busan, South Korea, 47392
    • Inje University Busan Paik Hospital
  • Busan, South Korea, 48108
    • Inje University Haeundae Paik Hospital
  • Goyang-si, South Korea, 10475
    • Hanyang University - Myongji Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 02841
    • Korea University Anam Hospital
  • Seoul, South Korea, 04401
    • Soon Chun Hyang University Hospital Seoul
• Taiwan
  • Kaohsiung City, Taiwan, 833401
    • Kaohsiung Chang Gung Memorial Hospital
  • Kaohsiung City, Taiwan, 807377
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • New Taipei City, Taiwan, 220
    • Far Eastern Memorial Hospital
  • Taichung, Taiwan, 404327
    • China Medical University Hospital
  • Tainan, Taiwan, 704302
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100225
    • National Taiwan University Hospital
  • Taipei, Taiwan, 112201
    • Taipei Veterans General Hospital
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital Birmingham
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter Hospital
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
  • London, United Kingdom, E9 6SR
    • Homerton University Hospital
  • Manchester, United Kingdom, M23 9LT
    • Wythenshawe Hospital
  • Oxford, United Kingdom, OX3 9DU
    • Oxford University Hospitals NHS Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • UAB Hospital, School of Medicine/Lung Health Center
  • California
    • Los Angeles, California, United States, 90033
      • Keck Medicine of University of Southern California
    • Redding, California, United States, 96001
      • Paradigm Clinical Research Centers, Inc.
    • Sacramento, California, United States, 95816
      • UC Davis Health System
    • San Diego, California, United States, 92103
      • UC San Diego Medical Center - Hillcrest
    • San Diego, California, United States, 92108
      • Paradigm Clinical Research
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Medical and Research Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Health (UF Health)
    • Kissimmee, Florida, United States, 34746
      • Clinical Research Specialists
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Emory Saint Joseph's Hospital
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Endeavor Health - Evanston Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital, Pulmonary & Critical Care Medicine
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital - Royal Oak
  • Nevada
    • Reno, Nevada, United States, 89502
      • Renown Clinical Research
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook University
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Southeastern Research Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic - Cleveland, Department of Pulmonary Medicine
  • Oregon
    • Bend, Oregon, United States, 97201
      • Summit Health - Bend
    • Portland, Oregon, United States, 97220
      • Oregon Clinic, Pulmonary, Critical Care & Sleep Medicine East
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Low Country Lung and Critical Care
  • Tennessee
    • Knoxville, Tennessee, United States, 37919
      • StatCare - Bearden
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Scott & White Research Institute
    • El Paso, Texas, United States, 79902
      • El Paso Pulmonary Association
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah, Health Sciences Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Clinical Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age ≥ 40 years at the time of signing the informed consent.
2. Diagnosed with IPF within 7 years prior to visit 1, as per applicable ATS/ERS/JRS/ALAT guidelines at the time of diagnosis.

3. HRCT scan within 36 months prior to visit 1 with central reading confirming either a or b, and c

   1. A pattern consistent with usual interstitial pneumonia (UIP) according to ATS/ERS/JRS/ALAT 2022 guideline (Raghu et al., 2022) UIP or probable UIP.
   2. A pattern indeterminate for UIP according to ATS/ERS/JRS/ALAT 2022 guidelines (Raghu et al., 2022) and a historical biopsy (surgical lung biopsy or transbronchial lung cryobiopsy) consistent with IPF.
   3. Extent of fibrosis > extent of emphysema.
4. FVC ≥50% predicted at visit 1.
5. DLCO (corrected for hemoglobin) ≥30% predicted at visit 1.

6. Either:

   1. On a stable dose of licensed IPF therapy for at least 8 weeks prior to visit 1 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.
   2. 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 visit 1.
7. Anticipated life expectancy of at least 12 months at visit 1 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).

8. 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.

   For UK and countries within the EU: 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 trial drug.

9. Written informed consent, consistent with ICH-GCP and local laws, obtained before the initiation of any trial-related procedure.

Exclusion Criteria

Participants are excluded from the trial if any of the following criteria apply:

1. Concurrent serious medical condition that in the opinion of the investigator constitutes a risk or a contraindication for 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 visit 1, 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.
2. Airways obstruction with a pre-bronchodilator forced expiratory volume in one second (FEV1)/FVC ratio <0.7 at visit 1.
3. Lower respiratory tract infection requiring antibiotics and not fully recovered according to investigator judgement within 4 weeks prior to visit 2.
4. Confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requiring hospitalization and not fully recovered according to investigator judgement within 4 weeks prior to visit 2.
5. 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 visit 1.
6. Severe renal impairment (i.e., estimated glomerular filtration rate (eGFR) ≤35 ml/min/1.73 m2 at visit 1 according to Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula).
7. 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 visit 1, 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.
8. Heart failure NYHA Class IV, acutely decompensated right heart failure, PH with syncopal episode, confirmed myocardial infarction, unstable angina or uncontrolled hypertension, within 6 months prior to visit 1.
9. Known hypersensitivity or intolerance to buloxibutid or to any other components of the test product, including excipients.
10. Pregnant or breast-feeding female participants.

11. Acute IPF exacerbation within 3 months prior to visit 1 and/or during the screening period, as defined by Collard et al., 2016:

    1. Acute worsening or development of dyspnea typically <1 month duration.
    2. 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).
    3. Deterioration not fully explained by cardiac failure or fluid overload.
12. Inability to generate a spirometry test at visit 1 meeting the standards of the ATS/ERS 2019 guideline (Graham et al., 2019).
13. Treatment with pirfenidone within 8 weeks prior to visit 1 or anticipated need for pirfenidone during participation in the trial.

More exclusion criteria may apply.

Trial website: www.aspire-ipf.com

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Buloxibutid 100 mg BID; For 52 weeks.	Drug: Buloxibutid; Buloxibutid; Other Names: C21
Experimental: Buloxibutid 50 mg BID; For 52 weeks.	Drug: Buloxibutid; Buloxibutid; Other Names: C21
Placebo Comparator: Placebo BID; For 52 weeks.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy of buloxibutid compared to placebo in participants with IPF as assessed by FVC	• Absolute change from baseline in FVC (mL) at week 52	week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To further evaluate the effects of buloxibutid on disease progression, respiratory-related hospitalization or death compared to placebo in participants with IPF	• A composite of the proportion of patients with an absolute FVC percent predicted (FVCpp) decrease from baseline of ≥10%; a respiratory-related hospitalization, or death, up to week 52	week 52

Collaborators and Investigators

• Sponsor: Vicore Pharma AB
• Collaborators: Population Services International
• Investigators: Study Director: Cecilia Ganslandt, MD, Vicore Pharma AB

Publications and helpful links

Helpful Links

• Trial webpage

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: September 6, 2024
• First Submitted That Met QC Criteria: September 6, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Angiotensin, IPF, angiotensin II receptor 2, buloxibutid
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Substandard Drugs; Pharmaceutical Preparations; compound 21
• Other Study ID Numbers: VP-C21-011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No