A trial to evaluate efficacy and safety of buloxibutid in people with idiopathic pulmonary fibrosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vicore Pharma AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

12 Dec 2024 → ongoing

Decision date (initial)

2024-11-18

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Vicore Pharma AB

External identifiers

EU CT number

2023-509069-19-00

WHO UTN

U1111-1298-8720

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

To evaluate the efficacy of buloxibutid compared to placebo in participants with IPF as assessed by FVC

Secondary objectives 9

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

Conditions and MedDRA coding

idiopathic pulmonary fibrosis

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Medicines And Healthcare Products Regulatory Agency, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Age ≥ 40 years at the time of signing the informed consent
2. 2. Diagnosed of IPF within 7 years prior to V1, as per applicable ATS/ERS/JRS/ALAT at the time of diagnosis.
3. 3. 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.
4. 4. FVC ≥50% predicted at V1.
5. 5. DLCO (corrected for hemoglobin) ≥30% predicted at V1
6. 6. 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.
7. 7. 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).
8. 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. 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.
9. 9. Written informed consent, consistent with ICH-GCP and local laws, obtained before the initiation of any trial-related procedure.

Exclusion criteria 21

1. 1. 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.
2. 10. Pregnant or breast-feeding female participants
3. 11. 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.
4. 12. Inability to generate a spirometry test at V1 meeting the standards of the ATS/ERS 2019 guideline.
5. 13. Treatment with pirfenidone (substrate of CYP1A2) within 8 weeks prior to V1 or anticipated need for pirfenidone during the participation in the trial.
6. 14. 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.
7. 15. 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.
8. 16. Previous participation in a clinical trial with buloxibutid and received at least one dose of buloxibutid.
9. 17. 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.
10. 18. Inability to refrain from smoking (including e-cigarettes and cannabis) on days of site visits until completion of trial procedures.
11. 19. 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.
12. 2. Airways obstruction with a pre-bronchodilator forced expiratory volume in one second (FEV1)/FVC ratio <0.7 at V1.
13. 20. The investigator considers the participant unlikely to comply with trial procedures, restrictions and requirements.
14. 3. Lower respiratory tract infection requiring antibiotics and not fully recovered according to investigator judgement within 4 weeks prior to V2.
15. 4. 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.
16. 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 V1. Retesting is allowed once.
17. 6. 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.
18. 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 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.
19. 8. 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.
20. 9. Know hypersensitivity or intolerance to buloxibutid or to any other components of the test product, including excipients.
21. 21. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Absolute change from baseline in FVC (mL) at Week 52

Secondary endpoints 9

1. 1. Proportion of participants with an absolute FVC percent predicted (FVCpp) decrease from baseline ≥10%, a respiratory-related hospitalization or death, up to Week 52
2. 2. Annual rate of decline in FVC at Week 52 FVC analyses at Weeks 4, 12, 24, 36 and 52: • Absolute change from baseline in FVC (mL) • Absolute change from baseline in FVCpp • Proportion of participants with an absolute FVCpp increase of ≥5% from baseline • Proportion of participants with an absolute FVCpp increase of ≥10% from baseline
3. 3. Proportion of participants with an acute IPF exacerbation up to Week 52 • Time to first acute IPF exacerbation up to Week 52 • Proportion of participants with a respiratory-related hospitalization up to Week 52 • Number of respiratory-related hospitalizations up to Week 52 • Time to first respiratory-related hospitalizations up to Week 52
4. 4. Change from baseline in Living with Pulmonary Fibrosis (L-PF) total score, symptoms total score, impacts total score, and individual symptom domain scores (cough, dyspnea, and fatigue) at Weeks 4, 12, 24, 36 and 52 • Change from baseline in EuroQoL-5D 5 levels (EQ-5D-5L) health index value and visual analogue scale (VAS) score at Weeks 24 and 52
5. 5. Change from baseline in cough severity VAS score at Weeks 4, 12, 24, 36 and 52 • Change from baseline in PGI-S and PI-S of cough, shortness of breath and fatigue at Weeks 4, 12, 24, 36 and 52 • Proportion of participants with an improvement from baseline of at least 1 step on PGI-S and PI-S of cough, shortness of breath and fatigue at Weeks 4, 12, 24, 36 and 52 • PGI-C at Week 52
6. 6. Change from baseline in quantitative HRCT analysis parameters at Week 52 including lung volume, airway volume, fibrosis quantification and vascular quantification.
7. 7. All-cause mortality up to Week 52
8. 8. The incidence, severity, outcome, and relationship to investigational medicinal product (IMP) for treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), and adverse events of special interest (AESIs) • Change from baseline in safety laboratory assessments, vital signs, and electrocardiograms (ECGs)
9. 9. Plasma concentration of buloxibutid

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vicore Pharma AB

Sponsor organisation

Vicore Pharma AB

Address

Kornhamnstorg 53

City

Stockholm

Postcode

111 27

Country

Sweden

Scientific contact point

Organisation

Vicore Pharma AB

Contact name

Global Medical Director

Public contact point

Organisation

Vicore Pharma AB

Contact name

Global Medical Director

Third parties 14

Locations

6 EU/EEA countries · 34 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 92 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

15 submissions — initial application plus substantial / non-substantial modifications