Inhalation therapy in adult bronchiectasis patients with new asymptomatic Pseudomonas aeruginosa infection– an open-label, proof of concept - randomized controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Philipps-Universitaet Marburg

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

22 Jun 2022 → ongoing

Decision date (initial)

2024-09-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

PARI Pharma GmbH · Deutsches Zentrum für Lungenforschung (DZL)

External identifiers

EU CT number

2023-509277-22-00

EudraCT number

2021-002335-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To evaluate the effect of ColiFin® therapy compared to SOC sputum/airway culture negativity for PA 28 weeks after randomization.

Secondary objectives 10

1. To evaluate the effect of ColiFin® therapy compared to SOC on change in PA bacterial density (semi-quatitative analysis) in sputum from randomization to end of treatment
2. To evaluate the effect of ColiFin® therapy compared to SOC on the frequency of (mild to moderate) pulmonary exacerbations (requiring antibiotic treatment) in 28 weeks after randomization
3. To evaluate the effect of ColiFin® therapy compared to SOC on the frequency of severe exacerbations (hospitalizations)in 28 weeks after randomization
4. To evaluate the effect of ColiFin® therapy compared to SOC on time to first pulmonary exacerbation (requiring antibiotic treatment) after start of treatment til week 28
5. To evaluate the effect of ColiFin® therapy compared to SOC on quality of life (QoL) measured by the St. George’s Respiatory Quenstionnaire (SGRQ) from randomization til week 28
6. To evaluate the effect of ColiFin® therapy compared to SOC on Respiratory Symptom Score (RSS) measured by the Quality of Life Questionnaire Bronchiectasis (QoL-B) from randomization til week 28
7. To evaluate the effect of ColiFin® therapy compared to SOC on overall QoL measured by the Quality of Life Questionnaire Bronchiectasis (QoL-B) from randomization til week 28
8. To evaluate the effect of ColiFin® therapy compared to SOC on change in ppFEV1 from randomization til week 28
9. To evaluate the change in antibiotic susceptibility in isolated sputum PA from randomization til week 28
10. To evaluate the safety of ColiFin® therapy during the course of the study

Conditions and MedDRA coding

Bronchiectasis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age ≥ 18 years at screening
2. Bronchiectasis verified by chest CT scan
3. New positive sputum culture for PA (not older than 12 weeks at screening)
4. No recent onset of new respiratory symptoms or worsening of pre-existing respiratory symptoms (e.g. cough, sputum amount, sputum colour, sputum viscosity, haemoptysis, decreased exercise capacity, malaise, fatigue etc.) over the last 2 months before new positive PA sputum culture, as per investigator judgement
5. Written informed consent
6. Negative serum/urine pregnancy test in women of childbearing potential (WOCBP) at screening
7. WOCBP must agree to maintain a highly effective method of contraception during study treatment and at least 4 weeks thereafter
8. Male subjects have to use condom during treatment and until the end of relevant systemic exposure in the male subject, plus a further 90-day period and non-pregnant WOCBP partner have to use any contraception method additionally

Exclusion criteria 13

1. Bronchiectasis due to cystic fibrosis
2. Known prior infection with PA in the past 5 years before the new positive PA culture
3. Treatment with pseudomonas-active antibiotics in the period between new PA positive sputum culture and baseline visit
4. Planned pseudomonas-active antibiotic treatment during the time of study participation
5. Any treatment with inhaled antibiotics or long-term pseudomonas-active treatment (≥3 months) in the past 5 years before screening
6. Known intolerance to ColiFin® in prior medical history
7. Hypersensitivity/Known intolerance to Colistimethate sodium, Colistin, polymyxin B or to other polymyxins
8. Known diagnosis of myasthenia gravis or porphyria
9. ppFEV1 < 30% (post-bronchodilator)
10. Pregnant women
11. Breast feeding women
12. strongly impaired renal function, GFR ≤ 30 ml/min
13. Participation in any other interventional clinical trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of sputum/airway culture negativity (=3 consecutively negative sputum/airway cultures) for PA 28 weeks after randomisation

Secondary endpoints 9

1. Change in PA (semi-quantitative) in sputum from baseline to Day 29 of treatment
2. Rate of pulmonary exacerbations in 28 weeks after randomisation
3. Rate of severe exacerbations (hospitalizations) in 28 weeks after randomisation
4. Time to first pulmonary exacerbation after start of treatment
5. Change from baseline in respiratory symptom domain of the SGRQ ountil 28 weeks after randomization
6. Change from baseline in quality of life measured by SGRQ until 28 weeks after randomization
7. Change from baseline in quality of life measured by QOL-B until 28 weeks after randomization
8. Change from baseline on change in ppFEV1
9. Change in antibiotic susceptibility in isolated sputum PA until 28 weeks after randomization

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Philipps-Universitaet Marburg

Sponsor organisation

Philipps-Universitaet Marburg

Address

Karl-Von-Frisch-Strasse 4

City

Marburg

Postcode

35043

Country

Germany

Scientific contact point

Organisation

Philipps-Universitaet Marburg

Contact name

Dr. Constanze C. Maresch

Public contact point

Organisation

Philipps-Universitaet Marburg

Contact name

Dr. Constanze C. Maresch

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications