Clinical trial NCT06588686: A Trial to Evaluate Efficacy and Safety of Buloxibutid in People With Idiopathic Pulmonary Fibrosis.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis (IPF)
Keywords: Angiotensin, IPF, angiotensin II receptor 2, buloxibutid
Lead sponsor: Vicore Pharma AB
Sponsor class: INDUSTRY
Collaborators: name: Population Services International
First posted: 2024-09-19
Enrollment: 270
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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 270 participants, 90 participants on oral buloxibutid 100 mg BID, 90 participants on oral buloxibutid 50 mg BID, and 90 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

Eligibility criteria: Inclusion Criteria

1. Age ≥ 40 years at the time of signing the informed consent.
2. Diagnosed with IPF within 5 years prior to visit 1, as per ATS/ERS/JRS/ALAT 2022 guidelines (Raghu et al., 2022).
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 and visit 2.
5. DLCO (corrected for hemoglobin) ≥35% 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.
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 or visit 2.
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.
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 spirometry data at least twice at visit 1 or visit 2 meeting the minimum 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

Primary outcomes:
measure: To evaluate the efficacy of buloxibutid compared to placebo in participants with IPF as assessed by FVC
timeFrame: week 52
Secondary outcomes:
measure: To further evaluate the effects of buloxibutid on disease progression, respiratory-related hospitalization or death compared to placebo in participants with IPF
timeFrame: week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Hospital, School of Medicine/Lung Health Center
state: Alabama
city: La Mesa
country: United States
facility: Paradigm Clinical Research
state: California
city: Los Angeles
country: United States
facility: Keck Medicine of University of Southern California
state: California
city: Redding
country: United States
facility: Paradigm Clinical Research Centers, Inc.
state: California
city: Sacramento
country: United States
facility: UC Davis Health System
state: California
city: San Diego
country: United States
facility: UC San Diego Medical Center - Hillcrest
state: California
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Gainesville
country: United States
facility: University of Florida Health (UF Health)
state: Florida
city: Kissimmee
country: United States
facility: Clinical Research Specialists
state: Florida
city: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
city: Evanston
country: United States
facility: Endeavor Health - Evanston Hospital
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak
state: Michigan
city: Stony Brook
country: United States
facility: Stony Brook University
state: New York
city: Winston-Salem
country: United States
facility: Southeastern Research Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic - Cleveland, Department of Pulmonary Medicine
state: Ohio
city: Portland
country: United States
facility: Oregon Clinic, Pulmonary, Critical Care & Sleep Medicine East
state: Oregon
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: North Charleston
country: United States
facility: Low Country Lung and Critical Care
state: South Carolina
city: Dallas
country: United States
facility: Baylor Scott & White Research Institute
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah, Health Sciences Center
state: Utah
city: Madison
country: United States
facility: University of Wisconsin Clinical Science Center
state: Wisconsin
city: Córdoba
country: Argentina
facility: IMER Respiratory Medicine Institute
state: Cordoba
city: San Miguel De Tucumán
country: Argentina
facility: Research Institute of Respiratory Diseases
state: Tucuman
city: Buenos Aires
country: Argentina
facility: CEMER Medical Center for Respiratory Diseases
city: Godoy Cruz
country: Argentina
facility: Breathe Comprehensive Clinical Health
city: Mar Del Plata
country: Argentina
facility: Emphysema Foundation, Pneumology
city: Mendoza
country: Argentina
facility: Vistalba Health Center
city: Adelaide
country: Australia
facility: Flinders Medical Centre
city: Concord
country: Australia
facility: Concord Repatriation General Hospital, Department of Respiratory Medicine
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital, Sydney Ltd.
city: Heidelberg
country: Australia
facility: Austin Hospital
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
city: Linz
country: Austria
facility: Kepler University Hospital GmbH, Department of Pulmonology
city: Salzburg
country: Austria
facility: Salzburg Regional Hospital, Department of Pneumology/Respiratory Medicine
city: Vienna
country: Austria
facility: Hospital Penzing, Department of Respiratory and lung diseases
city: Brussels
country: Belgium
facility: Erasme Hospital
city: Brussels
country: Belgium
facility: University Hospitals Saint-Luc
city: Liège
country: Belgium
facility: University Hospital Center Sart-Tilman
city: Yvoir
country: Belgium
facility: UCL Mont-Godinne University Hospitals
city: Kelowna
country: Canada
facility: Kelowna Respiratory & Allergy Clinic
city: Laval
country: Canada
facility: Laval Hospital
city: Québec
country: Canada
facility: Pierre-Le Gardeur
city: Trois-Rivieres
country: Canada
facility: Diex Research Trois-Riviere Inc.
city: Berlin
country: Germany
facility: Vivantes Hospital Neukoelln
city: Essen
country: Germany
facility: RuhrlandClinic - Lung Center
city: Freiburg
country: Germany
facility: University Hospital Freiburg
city: Hannover
country: Germany
facility: Hannover Medical School, Center for Internal Medicine
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg, Clinic of Thoracic Medicine Heidelberg GmbH
city: Immenhausen
country: Germany
facility: Immenhausen Lung Hospital
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen
city: Athens
country: Greece
facility: "Sotiria" Chest Diseases Hospital of Athens - Site 2
city: Athens
country: Greece
facility: General Hospital of Chest Diseases "Sotiria" 5th Pulmonology Department - Site 1
city: Athens
country: Greece
facility: University General Hospital "Attikon", 2nd Pulmonary Department
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion, Pneumonology Clinic
city: Ioánnina
country: Greece
facility: University General Hospital of Ioannina
city: Patras
country: Greece
facility: University General Hospital of Patras
city: Thessaloníki
country: Greece
facility: General Hospital of Thessaloniki
city: Ancona
country: Italy
facility: University Hospital - Ospedali Riuniti Umberto I - GM Lancisi - G Salesi of Ancona
city: Bergamo
country: Italy
facility: Local Healthcare Company Papa Giovanni XXIII (ASST Papa Giovanni XXIII)
city: Modena
country: Italy
facility: University Polyclinic Hospital of Modena
city: Monza
country: Italy
facility: San Gerardo of Tintori IRCCS Foundation
city: Roma
country: Italy
facility: Foundation PTV - Polyclinic Tor Vergata
city: Turin
country: Italy
facility: University Hospital City of Health and Science of Turin - Hospital Molinette
city: Bucheon
country: Korea, Republic of
facility: Soon Chun Hyang Central Medical Center
city: Bucheon
country: Korea, Republic of
facility: The Catholic University Of Korea Bucheon St. Mary's Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Busan
country: Korea, Republic of
facility: InJe University Haeundae Paik Hospital
city: Goyang-si
country: Korea, Republic of
facility: Hanyang University - Myongji Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Seoul
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Mexico City
country: Mexico
facility: National Institute of Respiratory Diseases Ismael Cosio Villegas (INER)
city: Monterrey
country: Mexico
facility: Dr. Jose Eleuterio Gonzalez Monterrey University Hospital
city: Oaxaca
country: Mexico
facility: Oaxaca Site Management Organization S.C - (Osmo)
city: San Nicolás De Los Garza
country: Mexico
facility: Integral Health Medical Unit
city: Bydgoszcz
country: Poland
facility: MICS Medical Centre Bydgoszcz
city: Bydgoszcz
country: Poland
facility: VITAMED Galaj i Cichomski General Partnership
city: Nowa Sól
country: Poland
facility: Twoja Przychodnia Medical Centre of Nowa Sol
city: Świdnik
country: Poland
facility: Allergology- Pulmunology Outpatient Clinic Alergopneuma, Pulmonology Outpatient Clinic
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Trust
Study officials:
References: