Inhaled nintedanib powder for idiopathic pulmonary fibrosis

A Randomized, Double-Blind, Placebo-Controlled, Phase 1b Clinical Study of the Safety, Tolerability, and Pharmacokinetics of MNKD-201 (Nintedanib Dry Powder Inhalation) in Patients With Idiopathic Pulmonary Fibrosis

This Phase 1b study will test inhaled nintedanib powder (MNKD-201) versus placebo in adults with idiopathic pulmonary fibrosis to see if it is safe, tolerated, and how the drug is absorbed and processed in the body.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 40 Years to 85 Years
• Sex: All
• Sponsor: Mannkind Corporation (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation, prednisone
• Locations: 9 sites (Fresno, California and 8 other locations)
• Trial ID: NCT07344558 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase 1b study using a multiple ascending dose (MAD) design to characterize the safety, tolerability, and pharmacokinetics of inhaled nintedanib powder (MNKD-201) in patients with IPF. Eligible participants are adults aged 40–85 with confirmed IPF and pulmonary function thresholds (FVC >45% predicted and DLCO ≥40% predicted). Participants may be treatment-naive or on a stable dose of background pirfenidone or nerandomilast for at least three months prior to screening. Dosing cohorts will receive escalating inhaled doses of MNKD-201 or matching placebo with clinical and spirometry monitoring and PK sampling to define systemic exposure and tolerability.

Who should consider this trial

Good fit: Adults aged 40–85 with a confirmed diagnosis of IPF, FVC >45% predicted, DLCO ≥40% predicted, body weight >40 kg, able to perform spirometry, and either treatment-naive or on a stable dose of pirfenidone or nerandomilast are ideal candidates.

Not a fit: Patients with more advanced lung impairment (FVC ≤45% or DLCO <40%), those outside the age or weight limits, pregnant people, or those unable to perform required assessments are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, inhaled nintedanib could deliver the antifibrotic drug directly to the lungs, potentially reducing systemic side effects while preserving local drug activity.

How similar studies have performed: Oral nintedanib is an established antifibrotic therapy for IPF, but inhaled nintedanib is a novel delivery approach with limited prior clinical data to date.

Eligibility criteria

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.

Where this trial is running

Fresno, California and 8 other locations

• Valdi — Fresno, California, United States (Recruiting)
• Palmtree Clinical Research — Palm Springs, California, United States (Recruiting)
• Innova Pharma Research — Doral, Florida, United States (Recruiting)
• New Life Medical Research — Hialeah, Florida, United States (Recruiting)
• New Access Research and Medical Services — Miami, Florida, United States (Recruiting)
• Southeastern Research Center — Winston-Salem, North Carolina, United States (Recruiting)
• Low Country Research — Charleston, South Carolina, United States (Recruiting)
• Metroplex Pulmomary & Sleep Center — McKinney, Texas, United States (Recruiting)
• Pulmonary Medicine Consultants — McKinney, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Donna McKinley

Conditions Idiopathic Pulmonary Fibrosis; Nintedanib; dry powder inhalation