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Lung Transplant RejectionPhase 2NCT05501574

An Open Label Trial Evaluating the Safety, Tolerability, Efficacy and Pharmacokinetic Profile of Tacrolimus Inhalation Powder in Adult Lung Transplant Recipients

A Phase 2 study testing Tacrolimus Inhalation Powder and Plastiape RS00 Dry Powder inhaler device in people with Lung Transplant Rejection, run by TFF Pharmaceuticals, Inc. at 2 sites in Australia.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Part A: This is an open label, single-arm study that will evaluate the safety, tolerability, efficacy and PK of Tacrolimus Inhalation Powder over 12 weeks in lung transplant patients who require reduced blood levels of tacrolimus due to kidney toxicity. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Transplant Rejection
What is being tested?
Tacrolimus Inhalation Powder and Plastiape RS00 Dry Powder inhaler device
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
2 sitesAustralia
Study dates
18 Apr 2023to 23 Dec 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Males or females aged 18 or over at time of screening.
  • 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.
  • Have undergone bilateral allograft lung transplantation at least six months prior to enrolment and meet all of the following:
  • 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
  • Demonstrating elevated markers of renal dysfunction: blood serum creatinine > 124 μmol/L (0.14 mg/dL) or estimated glomerular filtration rate (eGFR) < 45
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  • 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.
  • Screening FEV1 and forced vital capacity (FVC) values ≥ 40% predicted (to assure viable graft)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • If male, must agree not to donate sperm from the first dosing until 90 days after the last dosing.
  • Able to successfully perform spirometry, use the inhalation device, and comply with study restrictions and visit schedule.

Who cannot join

  • Active antibody-mediated rejection (AMR) or any other evidence of acute rejection
  • Active bacterial, viral or fungal infection not successfully resolved at least 4 weeks prior to study entry.
  • Presence of uncontrolled gastro-esophageal reflux disease (GERD)
  • History or presence of hypersensitivity or idiosyncratic reaction to tacrolimus or any calcineurin inhibitor.
  • 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.
  • 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.
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  • 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:
  • Cyclosporin
  • Any form of sirolimus or everolimus
  • Allergy or sensitivity to lactose or milk products.
  • Clinically significant hepatic impairment defined as 5 times the upper limit of normal (ULN) for ALT and AST.
  • Patients receiving haemodialysis or peritoneal dialysis
  • Active post-transplant lymphoproliferative disorder (PTLD) related to Epstein-Barr Virus (EBV) infection.
  • 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.
  • Demonstrates an inability to operate the inhalation device after training.

Trial locations and contacts

2 sites in 1 country.

Australia2 sites

  • St Vincent's Hospital

    Darlinghurst, New South Wales, 2010

  • The Alfred Hospital

    Melbourne, Victoria, 3004

Other trials in Australia

About this study

Part A: This is an open label, single-arm study that will evaluate the safety, tolerability, efficacy and PK of Tacrolimus Inhalation Powder over 12 weeks in lung transplant patients who require reduced blood levels of tacrolimus due to kidney toxicity. Tacrolimus Inhalation Powder is being developed as an alternative to oral tacrolimus for prevention of rejection in adult lung transplant recipients.

Part B of this study is an optional safety extension following successful completion of Part A. Patients would have the option to continue Tacrolimus Inhalation Powder for up to 1 year, with a possibility to extend to 2 years pending analysis of Part A data. Participants would return to clinic every 12 weeks for safety assessments, dose adjustments, and to receive more Tacrolimus Inhalation Powder. After 2 years, if the drug is still under development, the subject will be invited to continue receiving Tacrolimus Inhalation Powder under a special access program.

Being tested
Tacrolimus Inhalation Powder, Plastiape RS00 Dry Powder inhaler device

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tacrolimus Inhalation PowderDrug

    Also called Tacrolimus

    Tacrolimus powder for inhalation to prevent acute allograft rejection

  • Plastiape RS00 Dry Powder inhaler deviceDevice

    dry powder inhaler device

Study groups in NCT05501574
Study groupRoleWhat they receive
Tacrolimus Inhalation PowderExperimentalSingle arm open label
Receives: Drug: Tacrolimus Inhalation Powder; Device: Plastiape RS00 Dry Powder inhaler device

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Effect on renal function

    Mean change from baseline in renal function (glomerular filtration rate and creatinine) over time.

    Measured: Baseline through 12 weeks

  2. Incidence of treatment-emergent AEs, serious adverse events (SAEs), and withdrawals due to AEs.

    safety and tolerability

    Measured: baseline through 12 weeks

  3. Change in systolic and diastolic blood pressure (mm Hg) over time

    safety and tolerability

    Measured: baseline through 12 weeks

  4. Changes from baseline in potassium (mEq/L) over time

    safety and tolerability

    Measured: baseline through 12 weeks

  5. Changes from baseline in forced expiratory volume in one second (FEV-1) in liters

    safety and tolerability

    Measured: baseline through 12 weeks

  6. Changes from baseline in chest radiography

    safety and tolerability

    Measured: baseline through 12 weeks

  7. Number of participants with changes from baseline in physical examinations

    safety and tolerability

    Measured: baseline through 12 weeks

  8. Proportion of patients meeting treatment stopping rules.

    safety and tolerability

    Measured: baseline through 12 weeks

  9. Incidence of all-cause mortality and allograft-related mortality.

    safety and tolerability

    Measured: baseline through 12 weeks

  10. Incidence of all-cause hospitalization and allograft-related hospitalization

    safety and tolerability

    Measured: baseline through 12 weeks

  11. Efficacy of Tacrolimus Inhalation Powder in preventing acute rejection events

    Proportion of patients with no evidence of allograft rejection.

    Measured: Baseline through 12 weeks

  12. Efficacy of Tacrolimus Inhalation Powder in preventing acute rejection events

    Median time to first evidence of rejection.

    Measured: Baseline through 12 weeks

  13. Tacrolimus maximum concentration (Cmax) by visit

    Pharmacokinetics

    Measured: baseline through 12 weeks

  14. Tacrolimus time to maximum concentration (Tmax) by visit

    Pharmacokinetics

    Measured: baseline through 12 weeks

  15. Tacrolimus area under the curve from 0 to 6 hours (AUC0-6) by visit.

    Pharmacokinetics

    Measured: baseline through 12 weeks

  16. Tacrolimus area under the curve to last measurement (AUClast) by visit.

    pharmacokinetics

    Measured: baseline through 12 weeks

  17. Therapeutic drug monitoring tacrolimus blood levels by visit

    Pharmacokinetics

    Measured: baseline through 12 weeks

Secondary outcomes (3)

  1. Blood and BAL biomarkers

    Ratio of BAL:Blood tacrolimus trough levels at Visit 1b and Visit 9b after oral and inhaled administration, respectively, and change in ratio.

    Measured: Baseline through 12 weeks

  2. DSA

    Donor-specific antibody levels (DSA) at baseline on oral tacrolimus and after treatment with Tacrolimus Inhalation Powder.

    Measured: Baseline through 12 weeks

  3. Acute allograft rejection from EBB samples

    To determine if Tacrolimus Inhalation Powder reduces (if elevated) or maintains (if already low) signs of acute allograft rejection from endobronchial biopsy (EBB) samples compared with baseline oral tacrolimus therapy.

    Measured: Baseline through week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2022
  2. Study start18 Apr 2023
  3. Primary completion29 Oct 2024
  4. Study completion23 Dec 2024

Why it stopped: Study was terminated due to funding constraints

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05501574
Sponsor's protocol ID
TFF-T2-001
Status last verified
Dec 2024
First submitted
11 Aug 2022
Last updated
6 Jan 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tacrolimus Inhalation Powder and Plastiape RS00 Dry Powder inhaler device in people with Lung Transplant Rejection, run by TFF Pharmaceuticals, Inc. at 2 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study was terminated due to funding constraints). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect on renal function (time frame: Baseline through 12 weeks). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05501574.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2025.

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Clinical Trial NCT05501574 | AzTrials