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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05501574




Registration number
NCT05501574
Ethics application status
Date submitted
11/08/2022
Date registered
15/08/2022

Titles & IDs
Public title
An Open Label Trial Evaluating the Safety, Tolerability, Efficacy and Pharmacokinetic Profile of Tacrolimus Inhalation Powder in Adult Lung Transplant Recipients
Scientific title
An Open Label Trial Evaluating the Safety, Tolerability, Efficacy and Pharmacokinetic Profile of Tacrolimus Inhalation Powder in Adult Lung Transplant Recipients
Secondary ID [1] 0 0
TFF-T2-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung Transplant Rejection 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tacrolimus Inhalation Powder
Treatment: Devices - Plastiape RS00 Dry Powder inhaler device

Experimental: Tacrolimus Inhalation Powder - Single arm open label


Treatment: Drugs: Tacrolimus Inhalation Powder
Tacrolimus powder for inhalation to prevent acute allograft rejection

Treatment: Devices: Plastiape RS00 Dry Powder inhaler device
dry powder inhaler device

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Effect on renal function
Timepoint [1] 0 0
Baseline through 12 weeks
Primary outcome [2] 0 0
Incidence of treatment-emergent AEs, serious adverse events (SAEs), and withdrawals due to AEs.
Timepoint [2] 0 0
baseline through 12 weeks
Primary outcome [3] 0 0
Change in systolic and diastolic blood pressure (mm Hg) over time
Timepoint [3] 0 0
baseline through 12 weeks
Primary outcome [4] 0 0
Changes from baseline in potassium (mEq/L) over time
Timepoint [4] 0 0
baseline through 12 weeks
Primary outcome [5] 0 0
Changes from baseline in forced expiratory volume in one second (FEV-1) in liters
Timepoint [5] 0 0
baseline through 12 weeks
Primary outcome [6] 0 0
Changes from baseline in chest radiography
Timepoint [6] 0 0
baseline through 12 weeks
Primary outcome [7] 0 0
Number of participants with changes from baseline in physical examinations
Timepoint [7] 0 0
baseline through 12 weeks
Primary outcome [8] 0 0
Proportion of patients meeting treatment stopping rules.
Timepoint [8] 0 0
baseline through 12 weeks
Primary outcome [9] 0 0
Incidence of all-cause mortality and allograft-related mortality.
Timepoint [9] 0 0
baseline through 12 weeks
Primary outcome [10] 0 0
Incidence of all-cause hospitalization and allograft-related hospitalization
Timepoint [10] 0 0
baseline through 12 weeks
Primary outcome [11] 0 0
Efficacy of Tacrolimus Inhalation Powder in preventing acute rejection events
Timepoint [11] 0 0
Baseline through 12 weeks
Primary outcome [12] 0 0
Efficacy of Tacrolimus Inhalation Powder in preventing acute rejection events
Timepoint [12] 0 0
Baseline through 12 weeks
Primary outcome [13] 0 0
Tacrolimus maximum concentration (Cmax) by visit
Timepoint [13] 0 0
baseline through 12 weeks
Primary outcome [14] 0 0
Tacrolimus time to maximum concentration (Tmax) by visit
Timepoint [14] 0 0
baseline through 12 weeks
Primary outcome [15] 0 0
Tacrolimus area under the curve from 0 to 6 hours (AUC0-6) by visit.
Timepoint [15] 0 0
baseline through 12 weeks
Primary outcome [16] 0 0
Tacrolimus area under the curve to last measurement (AUClast) by visit.
Timepoint [16] 0 0
baseline through 12 weeks
Primary outcome [17] 0 0
Therapeutic drug monitoring tacrolimus blood levels by visit
Timepoint [17] 0 0
baseline through 12 weeks
Secondary outcome [1] 0 0
Blood and BAL biomarkers
Timepoint [1] 0 0
Baseline through 12 weeks
Secondary outcome [2] 0 0
DSA
Timepoint [2] 0 0
Baseline through 12 weeks
Secondary outcome [3] 0 0
Acute allograft rejection from EBB samples
Timepoint [3] 0 0
Baseline through week 12

Eligibility
Key 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 12 weeks 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 at least six months prior to enrolment and meet all of the following:

1. Receiving oral immediate-release or oral extended-release (not intravenous [IV] 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 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. Stable to enable routine post-treatment bronchoscopy with BAL and EBB. Biopsy is not required in patients with significant increased risk of bleeding after Sponsor Medical Monitor approval.
4. Screening FEV1 and forced vital capacity (FVC) values = 40% predicted (to assure viable graft)
5. Females (women) of child-bearing potential (WOCBP) are defined as those who have experienced menarche and who have not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and who are not post-menopausal. WOCBP must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1 and must agree to practice contraception as defined below if sexually active with males. In addition, no WOCBP may be planning a pregnancy during the study period.

1. Female subjects who are WOCBP must agree to use highly effective contraceptive methods or abstinence for the duration of time on the study and continue to use acceptable contraceptive methods for 3 months after administration of the last dose of study treatment. Highly effective contraception is defined as use of the 2-barrier method (e.g., female diaphragm and male condom), 1 barrier method with spermicide, intrauterine device, or hormonal contraceptives (e.g., implant or oral). If the subject is using a hormonal form of contraception, use must have been stable for at least 4 weeks prior to screening.
2. Abstinence will be acceptable only if it is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation) and withdrawal are not acceptable methods of contraception.
3. Post-menopausal females are eligible if they meet the definition of menopause (at least 12 months of amenorrhea in the absence of other biological causes) and for females < 55 years of age, must also have a documented serum follicle stimulating hormone (FSH) level of > 40mIU/mL at Screening.
6. Male subjects with female partners of childbearing potential must be congenitally sterile or surgically sterile (vasectomy with confirmation of aspermia) or agree to use 2 effective methods of contraception including 1 barrier method (e.g., condom with spermicide and contraception by female partner) for the duration of time on the study and for 3 months after administration of the last dose of study treatment. Use of a condom is required by men during intercourse with a male or female partner to prevent potential delivery of the drug via seminal fluid during the study until the end of treatment visit.
7. If male, must agree not to donate sperm from the first dosing until 90 days after the last dosing.
8. Able to successfully perform spirometry, use the inhalation device, and comply with study restrictions and visit schedule.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.
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 5 times the upper limit of normal (ULN) for ALT and AST.
10. Patients receiving haemodialysis or peritoneal dialysis
11. Active post-transplant lymphoproliferative disorder (PTLD) related to Epstein-Barr Virus (EBV) infection.
12. 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.
13. Demonstrates an inability to operate the inhalation device after training.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St Vincent's Hospital - Darlinghurst
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
TFF Pharmaceuticals, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Zamaneh Mikhak, MD
Address 0 0
TFF Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.