An Open Label Trial Evaluating the Safety and PK Profile of Tacrolimus Inhalation Powder in Adult Lung Transplant Recipients

TFF-T2-001

This is an open label, multicenter, safety and PK study comparing safety, efficacy, and pharmacokinetic (PK) levels of Tacrolimus Inhalation Powder in lung transplant patients that require reduced tacrolimus blood levels due to kidney toxicity. Part A of the study will consist of a 12 week safety, efficacy, and PK study. Part B of the study will be an optional safety extension following successful completion of the 12 week safety, efficacy, and PK study. Patients would have the option to continue Tacrolimus Inhalation Powder for up to 1 year, with a possibility to extend to 2 years depending on the results from Part A.

2023-04-18

2025-01-31

2025-01-31

Recruiting

Early phase I

24

Inclusion Criteria: 1. Provide written informed consent to participate and is willing and able to participate in the study and abide by study restrictions in the judgement of the Investigator. 2. Males or females aged 18 or over, at time of screening. 3. Continuous non-smoker who has not used nicotine-containing products (including e-vaping) for at least 3 months prior to the first dosing and throughout the study, based on patient's self-reporting and urine cotinine levels at screening and Day 1. 4. Have undergone bilateral allograft lung transplantation prior to enrolment and meet all of the following': 1. Receiving oral immediate-release (not intravenous \[IV\], extended release or sublingual) tacrolimus immunosuppression at a stable dose for 3 weeks prior to first dosing according to institutional standards as part of an immunosuppressive regimen along with mycophenolate mofetil (MMF) or azathioprine and corticosteroids- 2. Demonstrating elevated markers of renal dysfunction: blood serum creatinine \> 124 μmol/L (0.14 mg/dL) or estimated glomerular filtration rate (eGFR) \< 45 3. Is able to undergo routine bronchoscopy with BAL and biopsy 4. Screening forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) values ≥ 40% predicted (to assure viable graft) 5. Agree to use acceptable contraception or are not able to bear children. 6. Able to successfully perform spirometry, use the inhalation device, and comply with study restrictions and visit schedule. 7. Body mass index (BMI) ≤ 34.0kg/m2 at screening, and a maximum weight of 120.0kg at screening Exclusion Criteria: 1. Active antibody-mediated rejection (AMR) or any other evidence of acute rejection. 2. Active bacterial, viral or fungal infection not successfully resolved at least 4 weeks prior to study entry. Patients on prophylactic anti-fungal treatment may be enrolled. 3. Presence of uncontrolled gastro-esophageal reflux disease (GERD) 4. History or presence of hypersensitivity or idiosyncratic reaction to tacrolimus or any calcineurin inhibitor. 5. Received a treatment with other investigational drug within 5 times the elimination half-life, if known (e.g., a marketed product) or within 30 days (if the elimination half-life is unknown), whichever is longer, prior to Study Day 1 dosing. 6. Positive for hepatitis B surface antigen (HBsAg) PCR, hepatitis C PCR, and human immunodeficiency virus (HIV) I and II antibodies, tuberculosis (TB), or COVID-19 at Screening. 7. Patients who have taken any of the following prohibited medications within 30 days of the first dose or who are expected to require these medications during the study: 1. Cyclosporin 2. Any form of sirolimus or everolimus 8. Allergy or sensitivity to lactose or milk products 9. Clinically significant hepatic impairment defined as 2.5 times the upper limit of normal (ULN) 10. Active post-transplant lymphoproliferative disorder (PTLD) related to Epstein-Barr Virus (EBV) infection 11. Subjects with significant electrocardiogram (ECG) abnormalities at screening, including a QT interval corrected by the Fridericia correction formula that is ≥ 440 msec in men and ≥ 460 msec in women 12. Demonstrates an inability to operate the inhalation device after training

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 24, 'type': 'ESTIMATED'}}

2023-04-25