Summary

Eligibility
for people ages 40 years and up (full criteria)
Location
at San Diego, California and other locations
Dates
study started
completion around

Description

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

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.

Details

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

Keywords

Idiopathic Pulmonary Fibrosis (IPF), Angiotensin, IPF, angiotensin II receptor 2, buloxibutid, Pulmonary Fibrosis, Idiopathic Pulmonary Fibrosis, Fibrosis, Buloxibutid, Buloxibutid 100 mg BID, Buloxibutid 50 mg BID

Eligibility

You can join if…

Open to people ages 40 years and up

  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.

You CAN'T join if...

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

Locations

  • UC San Diego Medical Center - Hillcrest not yet accepting patients
    San Diego California 92103 United States
  • Stony Brook University not yet accepting patients
    Stony Brook New York 91942 United States
  • Paradigm Clinical Research not yet accepting patients
    La Mesa California 92942 United States
  • Paradigm Clinical Research Centers, Inc. accepting new patients
    Redding California 96001 United States
  • Oregon Clinic, Pulmonary, Critical Care &amp; Sleep Medicine East not yet accepting patients
    Portland Oregon 96001 United States

Details

Status
accepting new patients at some sites,
but this study is not currently recruiting here
Start Date
Completion Date
(estimated)
Sponsor
Vicore Pharma AB
Links
Trial webpage
ID
NCT06588686
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 270 study participants
Last Updated