Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
This is a Phase 2a, single -center, randomized, double-blind, placebo-controlled study to evaluate type 1 collagen deposition in the lungs following once-daily treatment with PLN-74809 for 12-weeks. This study is occurring at Massachusetts General Hospital.
Detailed description
This is a Phase 2a, single-center, randomized, double-blinded, placebo-controlled study to evaluate type 1 collagen deposition in the lungs of participants with Idiopathic Pulmonary Fibrosis (IPF) following once-daily (QD) treatment with 160 mg PLN-74809 for 12 weeks. The study consists of an up to 28-day screening period, a 12-week treatment period, and a 2 week (±3 days) post treatment follow-up period. Approximately 12 eligible participants will be randomized in a 2:1 ratio (160 mg PLN-74809 vs placebo; approximately 8 receiving PLN-74809 and 4 receiving placebo) on Day 1 (Visit 3). Randomization will be stratified by use of standard of care IPF therapy with pirfenidone or nintedanib. PET/MRI scans will be conducted at Baseline and at Week 12.
Interventions
DRUGPLN-74809
160 mg PLN-74809
DRUGPlacebo
Matching placebo
Sponsors
Pliant Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
double-blind
Intervention model description
2:1 randomization PLN-74809:placebo
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants, aged 40 years or older * Diagnosis of IPF, within 8 years prior to Screening * FVC % predicted ≥45%; historical FVC for entry in the study is permitted if within 1 month of screening * Diffusing capacity for carbon monoxide DLco (hemoglobin-adjusted) ≥30%; historical DLco for entry in the study is permitted if within 1 month of Screening * Participants currently receiving treatment for IPF with nintedanib or pirfenidone are permitted, if on a stable dose for at least 3 months
Exclusion criteria
* Currently receiving or planning to initiate treatment for IPF (fibrosis) with agents not approved for that indication by the FDA * Forced expiratory volume during the first seconds of the forced breath (FEV1)/FVC ratio \<0.7 at Screening * Clinical evidence of active infection, including but not limited to bronchitis, pneumonia, sinusitis that can affect FVC measurement or IPF progression * Known acute IPF exacerbation or suspicion by the Investigator of such, within 6 months of Screening * Smoking of any kind within 3 months of Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome | 12 weeks | Change from Baseline in top quartile whole lung PET standardized uptake value (SUV) following 12 weeks of treatment with PLN-74809. The whole lung SUV measures the intensity of the uptake of the radiotracer, 68GA-CBP8: peptide-based collagen binding probe 8 tagged with Gallium-68 radioisotope, in lung tissue. A negative change from baseline is a positive outcome and represents a decrease in the whole lung SUV corresponding to a decrease in collagen deposition in the lung. A positive change from baseline is a negative outcome and represents an increase in the whole lung SUV corresponding to an increase in collagen deposition in the lung. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Safety and Tolerability | From screening period (up to 28 days) to treatment period of 12 weeks, to 2 weeks after last dose | Safety and tolerability of PLN-74809 as measured by the incidence of adverse events. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory 1 | 12 weeks | Change from baseline in Forced vital capacity at 12 weeks. |
| Exploratory 2 | 12 weeks | Change from baseline in Cough Severity Visual Analog Scale at 12 weeks. Cough severity is assessed on a 100-mm linear scale ranging from no cough (0mm) to worst cough (100mm). Higher score means worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PLN-74809 160 mg PLN-74809
PLN-74809: 160 mg PLN-74809 | 7 |
| Placebo Placebo
Placebo: Matching placebo | 3 |
| Total | 10 |
Baseline characteristics
| Characteristic | PLN-74809 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 3 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 3 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 3 |
| other Total, other adverse events | 6 / 7 | 1 / 3 |
| serious Total, serious adverse events | 0 / 7 | 0 / 3 |
Outcome results
Primary
Primary Outcome
Change from Baseline in top quartile whole lung PET standardized uptake value (SUV) following 12 weeks of treatment with PLN-74809. The whole lung SUV measures the intensity of the uptake of the radiotracer, 68GA-CBP8: peptide-based collagen binding probe 8 tagged with Gallium-68 radioisotope, in lung tissue. A negative change from baseline is a positive outcome and represents a decrease in the whole lung SUV corresponding to a decrease in collagen deposition in the lung. A positive change from baseline is a negative outcome and represents an increase in the whole lung SUV corresponding to an increase in collagen deposition in the lung.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PLN-74809 | Primary Outcome | -0.0147 Unitless | Standard Deviation 0.10145 |
| Placebo | Primary Outcome | 0.0740 Unitless | Standard Deviation 0.11839 |
Secondary
Secondary Safety and Tolerability
Safety and tolerability of PLN-74809 as measured by the incidence of adverse events.
Time frame: From screening period (up to 28 days) to treatment period of 12 weeks, to 2 weeks after last dose
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PLN-74809 | Secondary Safety and Tolerability | 6 Participants |
| Placebo | Secondary Safety and Tolerability | 1 Participants |
Other Pre-specified
Exploratory 1
Change from baseline in Forced vital capacity at 12 weeks.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PLN-74809 | Exploratory 1 | 21.4 mL | Standard Deviation 86.49 |
| Placebo | Exploratory 1 | -120.0 mL | Standard Deviation 84.85 |
Other Pre-specified
Exploratory 2
Change from baseline in Cough Severity Visual Analog Scale at 12 weeks. Cough severity is assessed on a 100-mm linear scale ranging from no cough (0mm) to worst cough (100mm). Higher score means worse outcome.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PLN-74809 | Exploratory 2 | -25.1 Mm | Standard Deviation 29.11 |
| Placebo | Exploratory 2 | 40.3 Mm | Standard Deviation 34.65 |