Idiopathic Pulmonary Fibrosis
Conditions
Keywords
IPF, idiopathic pulmonary fibrosis
Brief summary
This study will assess the safety and tolerability of inhaled LTI-03 in treatment naïve participants with newly diagnosed IPF.
Detailed description
This is a randomized, double-blind, placebo controlled, multi-center, dose escalation, safety and tolerability study of LTI-03 or placebo administered by inhalation in participants recently diagnosed with idiopathic pulmonary fibrosis that have not received prior treatment with anti-fibrotic agents. The study will contain 2 dose cohorts which will run sequentially. Eligible participants will be randomized in a 3:1 ratio to either LTI-03 or placebo. Safety data will be reviewed on an ongoing basis. Enrollment in the second cohort will not begin until the Cohort 1 safety data has been reviewed. The Treatment Period will be 14 days, with subjects self-administering study drug using a provided commercially available dry-powder inhaler.
Interventions
DRUGLTI-03
Caveolin-1-Scaffolding-Protein-Derived Peptide
DRUGPlacebo
Matching placebo
Sponsors
Rein Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The Sponsor, Investigator, and study personnel working on behalf of the Investigator and Sponsor will remain blinded.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subject of age 40 years or older. 2. Willing and able to provide written informed consent. 3. Diagnosis of IPF within 3 years of Screening as confirmed by HRCT of chest or lung biopsy as defined by ATS/ERS/JRS/ALAT guideline. 4. Forced vital capacity (FVC) percent predicted ≥ 40%. 5. Diffusion capacity of the lungs for carbon monoxide (DLCO) percent predicted ≥ 30 and ≤ 80. 6. Forced expiratory volume 1 (FEV1)/FVC ≥ 0.7.
Exclusion criteria
1. Interstitial lung disease other than IPF. 2. Evidence of significant obstructive lung disease. 3. Current diagnosis of asthma. 4. Treatment with an approved or investigational antifibrotic therapy for IPF within 2 months of the Baseline bronchoscopy. 5. Use of N-acetyl cysteine or other supplements within 7 days prior to dosing and throughout the Treatment Period. 6. Inability to use study inhaler device appropriately. 7. Pulmonary exacerbation within 6 months prior to Screening. 8. Febrile illness within 7 days prior to dosing. 9. Participation in a clinical study or treatment with an investigational drug or device within 30 days of the Screening Visit (or 5 half-lives of the investigational agent, whichever is longer). 10. History or evidence at screening of significant renal impairment with eGFR \< 30 mL/min (region specific). 11. History or evidence at screening of significant hepatic impairment with bilirubin \> 3 mg/dL (\> 51.3 µmol/L) and albumin \< 2.8 g/dL (\<28 g/L) and PT prolongation \> 6 sec or INR \> 2.3 (region specific). 12. Serious or active medical or psychiatric condition which, in the opinion of the Investigator, may interfere with treatment, assessment, or compliance with the protocol. 13. Vaccination within 2 weeks of start of dosing (Day 1) and throughout the Treatment Period. 14. Subject has severe progressive or uncontrolled, clinically significant disease that in the judgment of the investigator or designee renders the subject unsuitable for the study. 15. Positive urine pregnancy test in female subjects of childbearing potential as defined below. 16. Female subjects who are lactating. 17. Females of childbearing potential (FOCBP) and men with partners of childbearing potential who do not agree to use an acceptable form of contraception for the duration of study treatment and for at least 90 days after the last dose of study drug. Male subjects who do not agree to refrain from donating sperm during this same period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-emergent Adverse Events (TEAEs) | 21 days (dosing x 14 days; follow up x 7 days) | Incidence of TEAEs by dose |
Countries
Germany, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 2.5 mg LTI-03 BID 2.5 mg LTI-03 BID x 14 days
LTI-03: Caveolin-1-Scaffolding-Protein-Derived Peptide | 9 |
| 5 mg LTI-03 BID 5 mg LTI-03 BID x 14 days
LTI-03: Caveolin-1-Scaffolding-Protein-Derived Peptide | 9 |
| Placebo Matching placebo BID x 14 days
Placebo: Matching placebo | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | 2.5 mg LTI-03 BID | 5 mg LTI-03 BID | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 6 Participants | 5 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 3 Participants | 1 Participants | 8 Participants |
| Age, Continuous | 67.8 years STANDARD_DEVIATION 9.76 | 68.4 years STANDARD_DEVIATION 10.79 | 71.7 years STANDARD_DEVIATION 6.15 | 69.0 years STANDARD_DEVIATION 9.19 |
| BMI | 28.869 kg/m^2 STANDARD_DEVIATION 2.7335 | 29.364 kg/m^2 STANDARD_DEVIATION 6.6335 | 29.330 kg/m^2 STANDARD_DEVIATION 4.9868 | 29.170 kg/m^2 STANDARD_DEVIATION 4.834 |
| Cigarette smoking | 18.25 pack-years STANDARD_DEVIATION 10.327 | 35.99 pack-years STANDARD_DEVIATION 22.861 | 26.88 pack-years STANDARD_DEVIATION 26.772 | 27.06 pack-years STANDARD_DEVIATION 20.331 |
| Cough Visual Analogue Scale (VAS) Score | 29.6 units on a scale STANDARD_DEVIATION 30.65 | 38.1 units on a scale STANDARD_DEVIATION 21.51 | 35.3 units on a scale STANDARD_DEVIATION 27.2 | 34.2 units on a scale STANDARD_DEVIATION 25.75 |
| Diffusion capacity of the lungs for carbon monoxide (DLCO) | 5.123 mmol/min/kPa STANDARD_DEVIATION 0.7913 | 5.020 mmol/min/kPa STANDARD_DEVIATION 1.5804 | 5.354 mmol/min/kPa STANDARD_DEVIATION 0.6776 | 5.143 mmol/min/kPa STANDARD_DEVIATION 1.1092 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 9 Participants | 6 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Forced Vital Capacity (FVC) | 3.214 L STANDARD_DEVIATION 0.7744 | 3.318 L STANDARD_DEVIATION 0.6421 | 3.085 L STANDARD_DEVIATION 0.2733 | 3.221 L STANDARD_DEVIATION 0.6138 |
| FVC percent predicted | 84.789 percent STANDARD_DEVIATION 10.2189 | 92.111 percent STANDARD_DEVIATION 18.6644 | 75.617 percent STANDARD_DEVIATION 8.941 | 85.242 percent STANDARD_DEVIATION 14.7507 |
| Height | 170.93 cm STANDARD_DEVIATION 9.27 | 169.56 cm STANDARD_DEVIATION 9.53 | 177.17 cm STANDARD_DEVIATION 7.111 | 171.98 cm STANDARD_DEVIATION 9.067 |
| Leicester Cough Questionnaire (LCQ) Total Score | 18.19 units on a scale STANDARD_DEVIATION 3.264 | 16.59 units on a scale STANDARD_DEVIATION 3.236 | 16.12 units on a scale STANDARD_DEVIATION 3.373 | 17.07 units on a scale STANDARD_DEVIATION 3.262 |
| Number of Participants with Past and/or current tobacco use No | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Number of Participants with Past and/or current tobacco use Yes | 8 Participants | 7 Participants | 4 Participants | 19 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 9 Participants | 6 Participants | 24 Participants |
| Region of Enrollment Australia | 1 participants | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Germany | 3 participants | 4 participants | 2 participants | 10 participants |
| Region of Enrollment United Kingdom | 3 participants | 2 participants | 3 participants | 8 participants |
| Region of Enrollment United States | 2 participants | 1 participants | 0 participants | 3 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 6 Participants | 20 Participants |
| Weight | 84.49 kg STANDARD_DEVIATION 11.709 | 85.36 kg STANDARD_DEVIATION 25.108 | 91.45 kg STANDARD_DEVIATION 11.529 | 86.55 kg STANDARD_DEVIATION 17.446 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 | 0 / 6 |
| other Total, other adverse events | 6 / 9 | 7 / 9 | 3 / 6 |
| serious Total, serious adverse events | 0 / 9 | 1 / 9 | 0 / 6 |
Outcome results
Primary
Incidence of Treatment-emergent Adverse Events (TEAEs)
Incidence of TEAEs by dose
Time frame: 21 days (dosing x 14 days; follow up x 7 days)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2.5 mg LTI-03 BID | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 66.7 percentage of participants |
| 2.5 mg LTI-03 BID | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAE with CTCAE severity Grade 3 or higher | 0 percentage of participants |
| 2.5 mg LTI-03 BID | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any study drug-related TEAE | 22.2 percentage of participants |
| 2.5 mg LTI-03 BID | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAE leading to treatment discontinuation | 0 percentage of participants |
| 2.5 mg LTI-03 BID | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any serious TEAE | 0 percentage of participants |
| 2.5 mg LTI-03 BID | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAE leading to death | 0 percentage of participants |
| 5 mg LTI-03 BID | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAE leading to death | 0 percentage of participants |
| 5 mg LTI-03 BID | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 77.8 percentage of participants |
| 5 mg LTI-03 BID | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAE leading to treatment discontinuation | 0 percentage of participants |
| 5 mg LTI-03 BID | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any serious TEAE | 11.1 percentage of participants |
| 5 mg LTI-03 BID | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAE with CTCAE severity Grade 3 or higher | 0 percentage of participants |
| 5 mg LTI-03 BID | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any study drug-related TEAE | 55.6 percentage of participants |
| Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAE with CTCAE severity Grade 3 or higher | 0 percentage of participants |
| Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any study drug-related TEAE | 16.7 percentage of participants |
| Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAE leading to death | 0 percentage of participants |
| Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAE leading to treatment discontinuation | 0 percentage of participants |
| Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 50.0 percentage of participants |
| Placebo | Incidence of Treatment-emergent Adverse Events (TEAEs) | Any serious TEAE | 0 percentage of participants |