Idiopathic Pulmonary Fibrosis
Conditions
Keywords
IPF, idiopathic pulmonary fibrosis, pulmonary fibrosis, bexotegrast, Beacon, BEACON-IPF
Brief summary
A randomized, double-blind, dose-ranging, placebo-controlled study to evaluate the efficacy and safety of bexotegrast (PLN-74809) for the treatment of idiopathic pulmonary fibrosis (BEACON-IPF).
Detailed description
This is a randomized, double-blind, dose-ranging, placebo-controlled study to evaluate the efficacy and safety of 2 doses of bexotegrast (PLN-74809) \[160 and 320 mg\] taken for 52 weeks by participants with IPF taking and not taking background therapy (ie, nintedanib or pirfenidone). The study will consist of an up to 35-day Screening Period, a 52-week Treatment Period, and a 14 day Safety Follow-up Period. Of note, participants who are not taking background therapy at study entry will be allowed to initiate it at any time during the study.
Interventions
DRUGPLN-74809
PLN-74809
DRUGPlacebo
Placebo
Sponsors
Pliant Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ≥ 40 years of age prior to screening 2. IPF diagnosis ≤ 7 years prior to screening 3. FVCpp ≥ 45% 4. Diffusing capacity for carbon monoxide percent predicted (hemoglobin-adjusted) ≥ 30% and \< 90% 5. Current treatment for IPF with background therapy is allowed, if at a stable dose for ≥ 12 weeks prior to screening 6. If not currently receiving treatment for IPF (either treatment naïve or discontinued prior treatment), participant must not have taken background therapy for at least 8 weeks prior to screening
Exclusion criteria
1. Receiving pharmacologic therapy for pulmonary hypertension 2. Self-reported smoking of any kind (not limited to tobacco) 3. History of malignancy within the past 5 years or ongoing malignancy other than basal cell carcinoma, resected noninvasive cutaneous squamous cell carcinoma, or treated cervical carcinoma in situ 4. Hepatic impairment or end-stage liver disease 5. Renal impairment or end-stage kidney disease requiring dialysis 6. Pregnant or lactating female participant 7. Uncontrolled systemic arterial hypertension 8. Receiving any unapproved or investigational agent intended for treatment of fibrosis in IPF 9. Prior administration of bexotegrast 10. Likely to have lung transplantation during the study (being on transplantation list is not an exclusion) 11. Forced expiratory volume in the first second (FEV1)/FVC ratio \<0.7 at screening 12. Clinical evidence of active infection, including, but not limited to bronchitis, pneumonia, or sinusitis that can affect FVC measurement during screening or at randomization 13. Known acute IPF exacerbation, or suspicion by the Investigator of such, 6 months prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Vital Capacity at Week 52 | Baseline (Day 1) and Week 52 | The FVC was the total amount of air exhaled from the lungs during the lung function test measured by spirometer. Baseline was defined as data collected prior to and closest to administration of the first dose of study drug (bexotegrast or placebo). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Vital Capacity in Participants on and Not on Background Therapy at Week 52 | Baseline (Day 1) and Week 52 | The FVC was the total amount of air exhaled from the lungs during the lung function test measured by spirometer. Background therapy included nintedanib or pirfenidone. Baseline was defined as data collected prior to and closest to administration of the first dose of study drug (bexotegrast or placebo). Change from baseline in FVC was assessed for participants on background therapy and not on background therapy at Baseline. |
| Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Dyspnea and Cough Domain Scores at Week 52 | Baseline (Day 1) and Week 52 | The L-PF questionnaire was developed to assess symptoms and health-related quality of life in participants with IPF. Questionnaire consisted of 44 items divided into 2 modules: symptoms (23 items) and impacts (21 items). Dyspnea (shortness of breath) symptom domain consisted of 12 items, each item score ranged from 0 to 5 and cough symptom domain consisted of 6 items, each item score ranged from 0 to 4. Total score was calculated based on average of item ratings within each domain, multiplied by 100; ranged from 0 to 100 with higher scores indicated greater impairment of disease. Baseline: data collected prior to and closest to administration of first dose of study drug (bexotegrast or placebo). Change from Baseline in L-PF dyspnea and cough domain scores are presented here. |
| Number of Participants With an Event of Disease Progression | Baseline (Day 1) and up to Week 52 | Number of participants with an event of disease progression was defined as time to first occurrence of ≥10% absolute decline from baseline in forced vital capacity percent predicted (FVCpp), adjudicated respiratory-related hospitalization, adjudicated acute IPF exacerbation, or all-cause mortality. Baseline was defined as data collected prior to and closest to administration of the first dose of study drug (bexotegrast or placebo). The ITT population included all randomized participants, regardless of study drug exposure. |
| Change From Baseline in Quantitative Lung Fibrosis (QLF) Extent at Week 52 | Baseline (Day 1) and Week 52 | High-resolution computerized tomography (HRCT) scans were conducted to assess the extent of QLF in the whole lung. Baseline was defined as data collected prior to and closest to administration of the first dose of study drug (bexotegrast or placebo). The CT protocol population included all participants in the ITT analysis set with evaluable HRCT imaging data per the following criteria: Baseline HRCT scans were \<35 days from randomization, Participant did not experience an exacerbation or progression of IPF AE within approximately 2 weeks prior to a HRCT scan, No identification of HRCT quality issues per the HRCT Imaging Charter. |
| Percentage of Participants With a ≥10% Absolute Decline in Forced Vital Capacity Percent Predicted From Baseline or All-cause Mortality Through Week 52 | Baseline (Day 1) and up to Week 52 | Percentage of participants with a ≥10% absolute decline in FVCpp from baseline or all-cause mortality through Week 52 was planned. Baseline was defined as data collected prior to and closest to administration of the first dose of study drug (bexotegrast or placebo). The ITT population included all randomized participants, regardless of study drug exposure. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | From first dose of study drug (Day 1) up to 14 days post last dose of study drug, up to 378 days | An AE was any event, side-effect, or other untoward medical occurrence that occurred in conjunction with the use of a study drug in humans, whether or not considered to have a causal relationship to the study drug. An SAE was any untoward medical occurrence, that any dose, was life-threatening, resulted in death, required inpatient hospitalization or prolonged existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or an important medical event. TEAEs were AEs that emerged or worsened in severity after the first administration of study drug and 14 days post last dose of study drug. The safety population included all participants who were randomized into the study and received at least 1 dose of study drug. |
| Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Total Score at Week 52 | Baseline (Day 1) and Week 52 | The K-BILD was a brief, self-completed health status measure of ILD which contained 15 items that measured health status in 3 domains (breathlessness and activities \[4 items\], chest symptoms \[3 items\], and psychological \[7 items\]) on a 7-point Likert scale ranging from 0 (severe symptoms) to 6 (no symptoms at all). The K-BILD domain and total score ranges were weighted and transformed; total score ranged from 0 to 100 with higher scores indicated best health status. Baseline was defined as data collected prior to and closest to administration of the first dose of study drug (bexotegrast or placebo). |
| Number of Participants With Disease Progression for Hazard Ratio | Baseline (Day 1) and up to Week 52 | Number of participants with disease progression (defined as adjudicated hospitalization, adjudicated acute IPF exacerbation, or all-cause mortality) for hazard ratio. Baseline was defined as data collected prior to and closest to administration of the first dose of study drug (bexotegrast or placebo). The ITT population included all randomized participants, regardless of study drug exposure. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Czechia, Denmark, France, Germany, Greece, India, Israel, Italy, Japan, Netherlands, New Zealand, Poland, Portugal, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORPliant Therapeutics Medical Monitor
Pliant Therapeutics, Inc.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 71.7 years STANDARD_DEVIATION 7.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 91 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 273 Participants |
| Sex: Female, Male Female | 83 Participants |
| Sex: Female, Male Male | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 106 | 6 / 105 | 4 / 108 |
| other Total, other adverse events | 26 / 106 | 32 / 105 | 40 / 108 |
| serious Total, serious adverse events | 6 / 106 | 17 / 105 | 21 / 108 |
Outcome results
None listed