A Trial to Evaluate Efficacy and Safety of Buloxibutid in People With Idiopathic Pulmonary Fibrosis.
Purpose
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
Condition
- Idiopathic Pulmonary Fibrosis (IPF)
Eligibility
- Eligible Ages
- Over 40 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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 Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Buloxibutid 100 mg BID |
For 52 weeks. |
|
|
Experimental Buloxibutid 50 mg BID |
For 52 weeks. |
|
|
Placebo Comparator Placebo BID |
For 52 weeks. |
|
Recruiting Locations
Birmingham 4049979, Alabama 4829764 35233
Los Angeles 5368361, California 5332921 90033
Redding 5570160, California 5332921 96001
Sacramento 5389489, California 5332921 95816
San Diego 5391811, California 5332921 92103
San Diego 5391811, California 5332921 92108
Denver 5419384, Colorado 5417618 80206
Gainesville 4156404, Florida 4155751 32610
Kissimmee 4160983, Florida 4155751 34746
Atlanta 4180439, Georgia 4197000 30342
Ria Gripaldo, MD
Evanston 4891382, Illinois 4896861 60201
Shashi Bellam, MD
Kansas City 4273837, Kansas 4273857 66160
Royal Oak 5007804, Michigan 5001836 48073
Reno 5511077, Nevada 5509151 89502
Stony Brook 5139865, New York 5128638 11794
Alpa Desai, MD
Winston-Salem 4499612, North Carolina 4482348 27103
Cleveland 5150529, Ohio 5165418 44195
Bend 5713587, Oregon 5744337 97201
Portland 5746545, Oregon 5744337 97220
Philadelphia 4560349, Pennsylvania 6254927 19140
North Charleston 4589387, South Carolina 4597040 29406
Knoxville 4634946, Tennessee 4662168 37919
Dallas 4684888, Texas 4736286 75246
El Paso 5520993, Texas 4736286 79902
Salt Lake City 5780993, Utah 5549030 84108
Madison 5261457, Wisconsin 5279468 53792
More Details
- NCT ID
- NCT06588686
- Status
- Recruiting
- Sponsor
- Vicore Pharma AB
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