RSP-1502 Inhalation for Cystic Fibrosis

Recruiting at 24 trial locations

Overseen By Caralee Forseen, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Respirion Pharmaceuticals Pty Ltd

Must not be taking: Nephrotoxic, Neurotoxic, Ototoxic, others

Disqualifiers: HIV, Active Hepatitis B/C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

A double-blind, active-controlled, multiple-ascending dose, safety study of aerosolized RSP-1502 in subjects with cystic fibrosis Pseudomonas aeruginosa lung infection.

Will I have to stop taking my current medications?

You may need to stop taking certain medications. Specifically, you must stop all inhaled tobramycin from 28 days before the study until 28 days into the study, and all other inhaled antibiotics from 14 days before the study until 28 days into the study. If you are taking medications with known nephrotoxic, neurotoxic, or ototoxic potential, you may need to stop those as well, unless you are on low dose azithromycin with inhaled tobramycin and have no evidence of ototoxicity.

Is RSP-1502 inhalation safe for humans?

Tobramycin inhalation solution, also known as TOBI, has been used safely in cystic fibrosis patients, showing a safety profile comparable to other forms of the drug. Clinical studies indicate it is generally safe for use in humans, with a reduced mortality rate in cystic fibrosis patients compared to those not using it. ^{1 2 3 4 5}

How is the drug RSP-1502 different from other cystic fibrosis treatments?

RSP-1502 is unique because it is an inhalation solution of tobramycin, which is specifically designed to treat lung infections in cystic fibrosis patients by delivering a high dose directly to the lungs, reducing systemic side effects. This approach can improve patient adherence due to its convenient administration and has shown to significantly improve lung function and reduce mortality compared to placebo. ^{1 2 3 6 7}

What evidence supports the effectiveness of the drug RSP-1502 for cystic fibrosis?

Research shows that inhaled tobramycin, a component of RSP-1502, significantly improves lung function and reduces infection in cystic fibrosis patients. It also lowers the need for hospital visits and additional antibiotics, enhancing patients' quality of life. ^{1 2 4 7 8}

Are You a Good Fit for This Trial?

Adults over 18 with cystic fibrosis and chronic lung infection caused by P. aeruginosa, who haven't had significant respiratory symptoms or changes in their CF treatments for the past month. They must be able to avoid other inhaled antibiotics during the study and have a stable organ function as determined by tests. Women of childbearing age should use contraception, men should either be infertile or agree to use condoms.

Inclusion Criteria

I can stop using inhaled tobramycin from Day 28 to Day 28 of the study.

I am a male and will use condoms or am infertile.

Your blood, urine, and other test results must be normal and not interfere with the study assessments.

Exclusion Criteria

You have tested positive for COVID-19 using a rapid test at the screening or on the first day of the trial.

I am currently on medication that could harm my kidneys, nerves, or hearing.

I do not currently have a lung infection with rapidly worsening bacteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive aerosolized RSP-1502 or active control via inhalation for 14 days

2 weeks

Daily visits for dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1-2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• RSP-1502
• Tobramycin inhalation solution

Trial Overview The trial is testing RSP-1502, an aerosolized drug combined with different doses of CaEDTA compared to Tobramycin inhalation solution. Participants will inhale their assigned treatment twice daily for two weeks while being monitored for safety and effectiveness. The best dose will be chosen based on tolerance levels observed across groups.

How Is the Trial Designed?

Group I: RSP-1502 Experimental Treatment 1 Intervention

Cohorts 1-4 will receive RSP-1502 (300 mg tobramycin plus an ascending dose of CaEDTA). Cohort 5 will receive 300 mg tobramycin + CaEDTA at the MTD.

Group II: Active Control Active Control 1 Intervention

• Tobramycin Inhalation Solution 300 mg.

Who Is Running the Clinical Trial?

Respirion Pharmaceuticals Pty Ltd

Lead Sponsor

Trials

1

Recruited

70+

Published Research Related to This Trial

A retrospective cohort study using Cystic Fibrosis Foundation registry data found that patients with cystic fibrosis who used Tobramycin solution for inhalation (TSI) for 4 or more months had a crude risk of death 3.5 times greater than those who did not use TSI, highlighting the challenge of confounding by indication.

After adjusting for factors like age and lung function, the risk ratio decreased to 1.2, suggesting that TSI may actually have a protective effect against mortality, aligning with preliminary randomized trial findings that indicated lower mortality rates in TSI users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mortality of cystic fibrosis patients treated with tobramycin solution for inhalation. Rothman, KJ., Wentworth, CE.[2019]

Both formulations of inhaled tobramycin (Tobi and Bramitob) significantly improve lung function and reduce Pseudomonas aeruginosa density in patients with cystic fibrosis, based on randomized controlled studies.

Inhaled tobramycin is well tolerated, with no evidence of serious side effects like renal or ototoxicity, and it may enhance patient compliance by reducing nebulisation time, which can improve overall quality of life and reduce healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tobramycin for inhalation in cystic fibrosis: Beyond respiratory improvements. Chuchalin, A., Amelina, E., Bianco, F.[2013]

The TOBI Podhaler, a dry powder formulation of tobramycin, is effective for treating chronic Pseudomonas aeruginosa infections in cystic fibrosis patients aged 6 and older, showing a safety and efficacy profile similar to the traditional tobramycin inhaled solution.

The TOBI Podhaler offers a shorter administration time and more convenient usage, which may help reduce the treatment burden for patients compared to previous inhalation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[TOBI Podhaler for treating chronic Pseudomonas aeruginosa infection in cystic fibrosis patients]. Pierart, F.[2020]

High strength tobramycin solution (20% tobramycin sulfate) can be effectively nebulized using various nebulizer systems, with the NE-U22 Omron® and Aeroneb Go® showing the highest efficiency in delivering the medication.

Compared to the standard TOBI® solution, the high strength tobramycin solution resulted in over 73% more respirable inhaled dose, potentially improving treatment outcomes for cystic fibrosis patients with chronic Pseudomonas aeruginosa infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro aerodynamic characterization of the dose emitted during nebulization of tobramycin high strength solution by novel and jet nebulizer delivery systems. Mashat, M., Clark, BJ., Assi, KH., et al.[2018]

Tobramycin solution for inhalation (TSI) significantly improves lung function and reduces Pseudomonas aeruginosa density in cystic fibrosis patients, with a notable effect observed in adolescents, and is more effective than colistin.

TSI is well tolerated with minimal side effects, showing no renal toxicity or hearing loss, and provides a safer alternative to parenteral aminoglycosides while effectively targeting lung infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled tobramycin (TOBI): a review of its use in the management of Pseudomonas aeruginosa infections in patients with cystic fibrosis. Cheer, SM., Waugh, J., Noble, S.[2018]

In a study of 2,534 cystic fibrosis patients, initiating chronic tobramycin inhalation solution (TIS) therapy led to an improvement in forced expiratory volume in 1 second (FEV1) over two years, compared to a comparator group of 17,656 patients who used TIS less than 10% of the time.

While TIS therapy improved the FEV1 levels, it did not change the rate of decline in lung function, indicating that the benefits of TIS were sustained without altering the overall decline trend in lung function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of tobramycin inhalation solution (TOBI®) shows sustained improvement in FEV1 in cystic fibrosis. Konstan, MW., Wagener, JS., Pasta, DJ., et al.[2021]

In a clinical trial involving 41 adults with severe bronchiectasis, tobramycin solution for inhalation (TSI) significantly improved respiratory symptoms and quality of life, as shown by a reduction in symptom severity scores and St. George Respiratory Questionnaire scores.

While TSI was effective for many, some patients experienced adverse events, including cough and wheezing, leading to 10 withdrawals from the study, indicating the need for careful monitoring of patients during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of the safety and efficacy of tobramycin solution for inhalation in patients with severe bronchiectasis. Scheinberg, P., Shore, E.[2022]

A new dry powder inhaler (DPI) for tobramycin, designed to simplify administration, was developed and tested, showing a direct relationship between the amount of drug loaded and the emitted dose, which could enhance treatment for cystic fibrosis patients.

In an in vivo study, healthy volunteers were able to inhale 120 mg of the tobramycin powder in just 3-6 inhalation acts, suggesting that the new inhaler could improve patient adherence to antibiotic therapy by making it more convenient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose administration maneuvers and patient care in tobramycin dry powder inhalation therapy. Buttini, F., Balducci, AG., Colombo, G., et al.[2018]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Mortality of cystic fibrosis patients treated with tobramycin solution for inhalation. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Tobramycin for inhalation in cystic fibrosis: Beyond respiratory improvements. [2013]

3. Belgium pubmed.ncbi.nlm.nih.gov

[TOBI Podhaler for treating chronic Pseudomonas aeruginosa infection in cystic fibrosis patients]. [2020]

4. England pubmed.ncbi.nlm.nih.gov

In vitro aerodynamic characterization of the dose emitted during nebulization of tobramycin high strength solution by novel and jet nebulizer delivery systems. [2018]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Inhaled tobramycin (TOBI): a review of its use in the management of Pseudomonas aeruginosa infections in patients with cystic fibrosis. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Clinical use of tobramycin inhalation solution (TOBI®) shows sustained improvement in FEV1 in cystic fibrosis. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

A pilot study of the safety and efficacy of tobramycin solution for inhalation in patients with severe bronchiectasis. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Dose administration maneuvers and patient care in tobramycin dry powder inhalation therapy. [2018]