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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05501574




Registration number
NCT05501574
Ethics application status
Date submitted
11/08/2022
Date registered
15/08/2022
Date last updated
25/04/2023

Titles & IDs
Public title
An Open Label Trial Evaluating Tacrolimus Inhalation Powder in Adult Lung Transplant Recipients
Scientific title
An Open Label Trial Evaluating the Safety and PK 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

Experimental: Tacrolimus Inhalation Powder - Single arm open label


Treatment: Drugs: Tacrolimus Inhalation Powder
Tacrolimus powder for inhalation to prevent acute allograft rejection
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants experiencing Adverse Events, Serious Adverse Events, and withdrawals due to Adverse Events
Timepoint [1] 0 0
Baseline through end of study (up to 2 years)
Primary outcome [2] 0 0
Number of participants who experience laboratory test abnormalities
Timepoint [2] 0 0
Baseline through end of study (up to 2 years)
Primary outcome [3] 0 0
Number of participants who experience physical examination abnormalities
Timepoint [3] 0 0
Baseline through end of study (up to 2 years)
Primary outcome [4] 0 0
Number of participants who experience pulse oximetry abnormalities
Timepoint [4] 0 0
Baseline through end of study (up to 2 years)
Primary outcome [5] 0 0
Number of participants who experience vital sign abnormalities
Timepoint [5] 0 0
Baseline through end of study (up to 2 years)
Primary outcome [6] 0 0
Mean change from baseline in chest radiology
Timepoint [6] 0 0
Baseline through end of study (up to 2 years)
Primary outcome [7] 0 0
Mean change from baseline in blood serum creatinine
Timepoint [7] 0 0
Baseline through end of study (up to 2 years)
Primary outcome [8] 0 0
Mean change from baseline in estimated glomerular flow rate (eGFR)
Timepoint [8] 0 0
Baseline through end of study (up to 2 years)
Primary outcome [9] 0 0
Mean change from baseline in forced expiratory volume (FEV1)
Timepoint [9] 0 0
Baseline through end of study (up to 2 years)
Primary outcome [10] 0 0
Mean change from baseline in forced vital capacity (FVC)
Timepoint [10] 0 0
Baseline through end of study (up to 2 years)
Primary outcome [11] 0 0
Mean change from baseline in FEV1/FVC ratio
Timepoint [11] 0 0
Baseline through end of study (up to 2 years)
Primary outcome [12] 0 0
Number of participants meeting treatment stopping rules of acute allograft rejection
Timepoint [12] 0 0
Baseline through end of study (up to 2 years)
Secondary outcome [1] 0 0
Change from baseline in FEV1 percent predicted
Timepoint [1] 0 0
Baseline through end of study (up to 2 years)
Secondary outcome [2] 0 0
PK of tacrolimus in whole blood AUC0-6
Timepoint [2] 0 0
Baseline through week 12
Secondary outcome [3] 0 0
PK of tacrolimus in whole blood AUClast
Timepoint [3] 0 0
Baseline through week 12
Secondary outcome [4] 0 0
PK of tacrolimus in whole blood Cmax
Timepoint [4] 0 0
Baseline through week 12
Secondary outcome [5] 0 0
PK of tacrolimus in whole blood Tmax
Timepoint [5] 0 0
Baseline through week 12
Secondary outcome [6] 0 0
Incidence of all-cause mortality
Timepoint [6] 0 0
Baseline through end of study (up to 2 years)
Secondary outcome [7] 0 0
Incidence of allograft-related mortality
Timepoint [7] 0 0
Baseline through end of study (up to 2 years)
Secondary outcome [8] 0 0
Incidence of all-cause hospitalizations
Timepoint [8] 0 0
Baseline through end of study (up to 2 years)
Secondary outcome [9] 0 0
Incidence of acute allograft-related hospitalizations
Timepoint [9] 0 0
Baseline through end of study (up to 2 years)

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 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
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. 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/04/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/01/2025
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
St Vincent's Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Prince Charles Hospital - Brisbane
Recruitment hospital [3] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
4032 - Brisbane
Recruitment postcode(s) [3] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
TFF Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05501574
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Dale Christensen, PhD
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05501574