Clinical trial of statins CAncer preventive and Pleiotropic TherApy IN smokers with chronic obstructive pulmonary disease (COPD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Bialystok

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

19 Jan 2022 → ongoing

Decision date (initial)

2024-12-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Medical Research Agency

External identifiers

EU CT number

2024-516714-37-00

EudraCT number

2020-005641-17

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

The primary objective of clinical part of this study is to compare the effectiveness of atorvastatin with a matched placebo control on the reduction of COPD exacerbations in patients with chronic obstructive pulmonary diseases.

Secondary objectives 2

1. The secondary objective of clinical part of this study is to compare the effectiveness of atorvastatin with a matched placebo control on lung function and health related quality of life changes in patients with chronic obstructive pulmonary diseases.
2. The secondary objective of genomic part is to provide with evidence that atorvastatin exerts direct anti-inflammatory activity regulated on gene level and thus to develop atorvastatin response biomarkers for personalized treatment of COPD.

Conditions and MedDRA coding

Chronic obstructive pulmonary disease (COPD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Subject has signed Informed Consent Form and is able to understand the purpose and procedures required for the study and is willing to participate in the study.
2. Subject [male or female] is aged 40 years and older.
3. Subject is able to understand and comply with the protocol requirements and instructions and is likely to complete the study as planned.
4. Patients with stable COPD with persistent airflow limitation [stable COPD (post-bronchodilator FEV1 < 80% of the predicted normal and post-bronchodilator FEV1/FVC < 0,70 at visit 1) -stage II- IV] and with moderate to very severe airflow limitation according to GOLD guidelines.
5. At least two moderate or severe COPD exacerbations, or at least one leading to hospitalization or ICU admission within 12 months, proceeding screening visit.
6. Current or ex-smokers who have a smoking history of at least 10 pack years [only use of e-cigarettes or IQOS tobacco heating system cannot be use as a equivalent of classic cigarettes smoking].

Exclusion criteria 24

1. Contraindication to statin therapy included but not limited to: known poliomyelitis, motor neuron disease, cranial or temporal arteritis, stroke or myopathy.
2. Statin use within the last 3 months prior to study start.
3. Prior diagnosis of statin induced myopathy or hypersensitivity reaction to another HMG-CoA-reductase inhibitor.
4. CPK levels significantly elevated (> 5 times ULN).
5. Using e-cigarettes or IQOS tobacco heating system.
6. Pregnant or nursing (lactating) women.
7. Women of childbearing potential, unless they are using effective method of contraception during dosing of study treatment.
8. Patient with a clinically significant abnormality at visit 1 in investigator opinion.
9. Patients with a clinically relevant laboratory abnormality at visit 1 in investigator opinion.
10. Subject has known active malignancy of any organ system, i.e., clinical evidence of current malignancy or not in stable remission for at least 5 years since completion of last treatment with exception of non-invasive basal cell carcinoma, squamous cell carcinoma of the skin or cervical intraepithelial neoplasia.
11. Patients unable to perform acceptable spirometry and lung volumes procedures.
12. Patients who had a COPD exacerbations that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the 6 weeks prior to visit 1.
13. Patients who have had a respiratory tract infection within 4 weeks prior to visit 1.
14. Patients requiring oxygen therapy (>15hr/day) on a daily basis for chronic hypoxemia.
15. Patients with a history of asthma or onset of symptoms prior to age 40 years.
16. Patients with concomitant pulmonary disease (e.g. lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, tuberculosis).
17. Patients with primary bronchiectasis.
18. Patients with a diagnosis of α-1 antitrypsin deficiency (AATD).
19. Patients with pulmonary lobectomy or lung volume reduction surgery or lung transplantation.
20. Active abuse of drugs or alcohol, poor compliance anticipated.
21. Use concomitant medications that are known to interact with atorvastatin: warfarin and other coumarin (vitamin K antagonists) anticoagulants, cyclosporin, gemfibrozil or other non or selective nonsteroidal anti-inflammatory drugs, proton pump inhibitors (PPIs) used by last 6 months.
22. Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the study.
23. Use of other investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to screening visit.
24. Those unable in the opinion of the Investigator to comply fully with the study requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Exacerbation rate
2. Time to exacerbation

Secondary endpoints 9

1. Duration of exacerbation
2. Changes in forced expiratory volume in the first second (FEV1)
3. Changes in health-related quality of life (SGRQ score)
4. Changes in inflammatory pathway gene expression in the PBMCs by whole transcriptome RNA-seq analysis.
5. Changes in blood inflammatory markers (Peripheral blood leucocyte count, fibrinogen, Interleukin-6, high sensitivity C – reactive protein)
6. Changes from baseline in pre-dose values of plethysmography (functional residual volume (FRC), inspiratory capacity (IC), transfer factor of the lung for carbon monoxide (DLCO)
7. 6 minute walking distance (6MWD) and the rate of hospitalizations
8. Changes in vital signs (blood pressure, HR), and/or laboratory findings.
9. The rate of hospitalization (pulmonary or MACE)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Bialystok

Sponsor organisation

Medical University Of Bialystok

Address

Ul. Jana Kilinskiego 1

City

Bialystok

Postcode

15-089

Country

Poland

Scientific contact point

Organisation

Medical University Of Bialystok

Contact name

Second Department of Lung Diseases, Lung Cancer and Internal Medicine

Public contact point

Organisation

Medical University Of Bialystok

Contact name

Second Department of Lung Diseases, Lung Cancer and Internal Medicine

Third parties 4

Locations

1 EU/EEA country · 12 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 5 files

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

Application history

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