Idiopathic Pulmonary Fibrosis (IPF)
Conditions
Keywords
Nintedanib, dry powder inhalation
Brief summary
MKC-NI-002 is a Phase 1b, randomized, double-blind, placebo-controlled study of nintedanib inhalation powder (MNKD-201) in patients with Idiopathic Pulmonary Fibrosis (IPF). The trial consists of Multiple Ascending Doses (MAD) with the primary objective to evaluate safety, tolerability and pharmacokinetics (PK) of MNKD-201 compared to placebo in patients with IPF.
Interventions
DRUGMNKD-201(Nintedanib DPI)
MNKD-201 is a dry powder nintedanib formulation for oral inhalation.
DRUGPlacebo
The placebo control in this study is an empty cartridge without any powder.
Sponsors
Mannkind Corporation
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Is ≥40 to ≤85 years of age at the time of signing the informed consent form. 2. Diagnosis of IPF 3. Either treatment-naive or is currently on background pirfenidone or nerandomilast on a stable dose for at least 3 months prior to Screening. 4. Has FVC \>45% of predicted of normal, as determined by the central spirometry reader, during Screening. 5. DLCO corrected for hemoglobin \[Visit 1\] ≥40% of predicted of normal, within 12 months of Screening. If no historical DLCO is available prior to Screening, this is to be done during Screening and read locally. 6. Has a body weight \>40 kg (\>88 lbs.) at Screening. 7. For female participants of childbearing potential, agreement to use acceptable birth control 8. For male participants who can father a child and are having intercourse with females of childbearing potential, agreement to use a protocol-recommended method of contraception 9. Is capable of performing spirometry, as required by the study procedures and ATS guidelines. 10. CT chest within 2 years of Screening, consistent with an IPF diagnosis, per investigator assessment.
Exclusion criteria
1. Known explanation for interstitial lung disease, including but not limited to radiation, sarcoidosis, hypersensitivity pneumonitis, and bronchiolitis obliterans organizing pneumonia. 2. Diagnosis of any connective tissue disease, including but not limited to scleroderma/systemic sclerosis, polymyositis/dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis, regardless of whether or not it is presumed to be related to their pulmonary fibrosis diagnosis. 3. Major extrapulmonary physiological restriction (e.g., chest wall abnormality, large pleural effusion), as determined by the investigator. 4. Significant Cardiovascular diseases 5. Recent systemic infection within 4 weeks before the Screening visit or symptomatic viral or bacterial infection at time of Screening. 6. Prior hospitalization for confirmed coronavirus disease 2019 (COVID-19), acute exacerbation of IPF or any lower respiratory tract infection within 3 months of Screening. 7. Has a history of asthma, with the exception of resolved childhood asthma. 8. Has known obstructive lung disease 9. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin \>1.5 times the upper limit of normal (ULN) during Screening. 10. Advanced liver and kidney function. 11. Current or recent (within 30 days of Screening) use of nintedanib. 12. Use of prednisone \>10 mg/day within 1 month prior to Screening, or other significant immunosuppression 13. Active lung cancer (primary or metastatic) or any cancer requiring chemotherapy or radiation therapy within 3 years, except appropriately treated non-melanoma skin cancer, localized non-malignant prostate cancer, or in situ carcinoma of uterine cervix. 14. Has participated in another clinical study of a new chemical entity, new device, or a prescription medicine within the 1 month before Screening 15. Current alcohol, medication, or illicit drug abuse 16. Has lost more than 400 mL blood, e.g., as a blood donor, or donor of blood products, during the 3 months prior to Screening. 17. Has received a live vaccine within the 3 months prior to the first dose of study drug. 18. Smokes (any substance including electronic cigarettes and marijuana) within 3 months prior to Screening or is an ex-cigarette smoker who gave up \<1 year ago. 19. Has oxygen requirement of \> 6 liters/min at rest.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| (Cohort 1) Events of Bronchospasm | Up to Day 7 | The within-treatment number and proportion of participants with events of bronchospasm (e.g., treatment emergent adverse events \[TEAE\] immediately after inhalation of wheezing or chest tightness) |
| (Cohort 2) Events of Bronchospasm | Up to Day 7 | The within-treatment number and proportion of participants with events of bronchospasm (e.g., treatment emergent adverse events \[TEAE\] immediately after inhalation of wheezing or chest tightness) |
| (Cohort 1) Changes in FEV1 (mL) from pre-dose to post-dose | Up to Day 7 | The within-treatment number and proportion of participants with changes in FEV1 from pre-dose to any time post-dose |
| (Cohort 2) Changes in FEV1 (mL) from pre-dose to post-dose | Up to Day 7 | The within-treatment number and proportion of participants with changes in FEV1 from pre-dose to any time post-dose |
| (Cohort 1) Changes in FEV1 / FVC ratio from pre-dose to post-dose | Up to Day 7 | The within-treatment number and proportion of participants with changes in FEV1/FVC ratio from pre-dose to any time post-dose |
| (Cohort 2) Changes in FEV1 / FVC ratio from pre-dose to post-dose | Up to Day 7 | The within-treatment number and proportion of participants with changes in FEV1/FVC ratio from pre-dose to any time post-dose |
| (Cohort 1) Rate of Study Drug Discontinuations | Up to Day 7 | The within-treatment number and proportion of participants with study drug dose discontinuations |
| (Cohort 2) Rate of Study Drug Discontinuations | Up to Day 7 | The within-treatment number and proportion of participants with study drug dose discontinuations |
| (Cohort 1) Rate of Study Drug Dose Reductions | Up to Day 7 | The within-treatment number and proportion of participants with study drug dose reductions |
| (Cohort 2) Rate of Study Drug Dose Reductions | Up to Day 7 | The within-treatment number and proportion of participants with study drug dose reductions |
| (Cohort 1) Rate of Treatment Emergent Adverse Events (TEAEs) | Up to Day 7 | The within-treatment number and proportion of participants with TEAEs overall and by severity, relationship to study drug, and outcome |
| (Cohort 2) Rate of Treatment Emergent Adverse Events (TEAEs) | Up to Day 7 | The within-treatment number and proportion of participants with TEAEs overall and by severity, relationship to study drug, and outcome |
| (Cohort 1) Rate of Treatment Related Adverse Events (TRAEs) | Up to Day 7 | The within-treatment number and proportion of participants with TRAEs overall and by severity and outcome |
| (Cohort 2) Rate of Treatment Related Adverse Events (TRAEs) | Up to Day 7 | The within-treatment number and proportion of participants with TRAEs overall and by severity and outcome |
| (Cohort 1) Rate of Serious Adverse Events (SAEs) | Up to Day 7 | The within-treatment number and proportion of participants with SAEs overall and by severity, relationship to study drug, and outcome |
| (Cohort 2) Rate of Serious Adverse Events (SAEs) | Up to Day 7 | The within-treatment number and proportion of participants with SAEs overall and by severity, relationship to study drug, and outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine the maximum tolerated dose (MTD) of MKND-201 in patients with IPF | Up to Day 7 | MTD within the tested MNKD-201 dose range |
Countries
United States
Contacts
STUDY_DIRECTORWassim Fares, MD, MSc, FCCP
Mannkind Corporation
Outcome results
None listed