Exploratory study to evaluate the safety and tolerability of tamoxifen citrate in the treatment of cystic fibrosis in patients without mutations currently eligible for therapy with CFTR modulator drugs

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda Ospedaliera Universitaria Integrata Verona

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Stomatognathic Diseases [C07], Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2025-06-24

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

LEGA ITALIANA FIBROSI CISTICA VENETO - ODV · GB Pharma

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

The study aims to evaluate the safety and tolerability of TMX in patients with cystic fibrosis who do not have mutations currently eligible for therapy with modulator drugs.

Secondary objectives 1

1. The study also aims to evaluate the effects of TMX on: lung function, quality of life, pulmonary exacerbations, hospitalizations for pulmonary exacerbations, antibiotic cycles, BMI, sputum microbiology, sweat test

Conditions and MedDRA coding

cystic fibrosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Subjects of both sexes, affected by cystic fibrosis, attending the CF Center in Verona
2. Female subjects must have a negative serum pregnancy test
3. Sexually active subjects able to follow the contraceptive methods defined within the protocol (non-hormonal contraception) during the study and for 2 months after study discontinuation
4. Signed informed consent for participation in the study and for the processing of personal data
5. Patients who do not have mutations currently eligible for therapy with CFTR modulator drugs
6. Age 18 years or older
7. Predicted forced expiratory volume in 1 second (ppFEV1) ≥ 40% and ≤ 90% (of the predicted value for people of their age, sex, and height) before bronchodilator administration
8. Stable routine CF therapy in terms of dose and medication (inhaled antibiotic cycles, bronchodilator, anti-inflammatory, inhaled corticosteroid, physiotherapy technique/schedule) within 28 days prior to Day 1
9. Clinically stable respiratory disease within 3 weeks before Day 1 (first dose of study drug)
10. Subjects able to perform reliable and reproducible pulmonary function test maneuvers
11. Subjects able to communicate well with the investigator, understand, and comply with the study requirements

Exclusion criteria 19

1. Patients on any CFTR modulator therapy
2. Pulmonary exacerbations within 3 weeks before Day 1 (first dose of study drug)
3. Changes in therapy for lung disease within 3 weeks before Day 1 (first dose of study drug).
4. Family and/or personal history of thromboembolism and thromboembolic conditions up to 1st-degree relatives
5. Documented hereditary thrombophilia (hypercoagulability), e.g., protein C, protein S, and antithrombin deficiency; factor V G169A Leiden, prothrombin G20210A (PT20210A), elevated factor VIII levels, hereditary dysfibrinogenemia.
6. History of solid organ or hematopoietic transplant
7. History of hypersensitivity to the study drug or drugs of similar chemical classes or any excipients
8. History or presence of prolonged QT interval (QTcB > 450 msec)
9. History of malignancy in any organ system (other than localized basal cell carcinoma of the skin) in the last 5 years
10. Hemoglobin levels < 9.0 g/dl
11. Any surgical or medical condition that may significantly alter the absorption, distribution, metabolism, or excretion of drugs, or that may jeopardize the subject in case of participation in the study.
12. History of immunodeficiency diseases
13. History of drug or alcohol abuse
14. History of any disease or condition that, in the investigator’s opinion, could confound the study results.
15. Abnormal liver function, defined as ≥ 3 times the upper limit of normal (ULN) for any of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), total bilirubin
16. Presence at baseline visit of endometrial polyps or vaginal symptoms (e.g., blood discharge, spotting, staining).
17. Participation in a clinical study where an investigational drug was administered within 30 days prior to enrollment in the study or 5 half-lives of the study drug, whichever is longer
18. Female patients who are pregnant or breastfeeding or who wish to become pregnant during the clinical study period and within one month after the end of the study.
19. Female patients of childbearing potential who do not use adequate contraception. A woman is considered of childbearing potential (WOCBP), i.e., fertile, after menarche and until reaching post-menopause, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as the absence of menstruation for 12 months without an alternative medical cause. An elevated follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormone replacement therapy. However, in the absence of 12 months of menstrual cycle, a single FSH measurement is not sufficient.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this study will be evaluated by calculating between baseline and week 24 the incidence of serious adverse events (SAEs), treatment-emergent adverse events (TEAEs) and treatment discontinuation due to AEs. In addition, frequency of specific, indication-relevant adverse events (e.g., thromboembolic events, elevation of liver enzymes, pulmonary exacerbations) and cumulative AE analyses, such as the number of AEs per patient, will be also evaluated.

Secondary endpoints 11

1. The secondary endpoints will evaluate the relative change from baseline to week 24 in ppFEV1
2. The secondary endpoints will evaluate the number of pulmonary exacerbations up to week 24
3. The secondary endpoints will evaluate the time to the first pulmonary exacerbation up to week 24
4. The secondary endpoints will evaluate the number of hospitalizations for cystic fibrosis lasting > 24 hours
5. The secondary endpoints will evaluate the time to the first hospitalization for cystic fibrosis
6. the absolute change in the respiratory domain score of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) from baseline to week 24
7. the use of intravenous antibiotics during the study (total number of days of intravenous antibiotics for sino-pulmonary signs and symptoms up to week 24)
8. the use of oral antibiotics during the study (total number of days of oral antibiotics for sino-pulmonary signs and symptoms up to week 24)
9. changes in BMI from baseline to week 24
10. changes in sputum microbiology at the beginning and end of the study
11. changes in the amount of chloride measured with the sweat test at the beginning and end of the study

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliera Universitaria Integrata Verona

Sponsor organisation

Azienda Ospedaliera Universitaria Integrata Verona

Address

Piazzale Aristide Stefani 1

City

Verona

Postcode

37126

Country

Italy

Scientific contact point

Organisation

Azienda Ospedaliera Universitaria Integrata Verona

Contact name

Marco Cipolli

Public contact point

Organisation

Azienda Ospedaliera Universitaria Integrata Verona

Contact name

Marco Cipolli

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 9 files

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

Application history

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