Tamoxifen for Cystic fibrosis

Inclusion criteria

• {"criterion_text":"- Subjects of both sexes, affected by cystic fibrosis, attending the CF Center in Verona\n- Subjects able to perform reliable and reproducible pulmonary function test maneuvers\n- Subjects able to communicate well with the investigator, understand, and comply with the study requirements\n- Female subjects must have a negative serum pregnancy test\n- 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\n- Signed informed consent for participation in the study and for the processing of personal data\n- Patients who do not have mutations currently eligible for therapy with CFTR modulator drugs\n- Age 18 years or older\n- 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\n- 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\n- Clinically stable respiratory disease within 3 weeks before Day 1 (first dose of study drug)"}

Exclusion criteria

• {"criterion_text":"- Patients on any CFTR modulator therapy\n- Hemoglobin levels < 9.0 g/dl\n- 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.\n- History of immunodeficiency diseases\n- History of drug or alcohol abuse\n- History of any disease or condition that, in the investigator’s opinion, could confound the study results.\n- 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\n- Presence at baseline visit of endometrial polyps or vaginal symptoms (e.g., blood discharge, spotting, staining).\n- 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\n- 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.\n- 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.\n- Pulmonary exacerbations within 3 weeks before Day 1 (first dose of study drug)\n- Changes in therapy for lung disease within 3 weeks before Day 1 (first dose of study drug).\n- Family and/or personal history of thromboembolism and thromboembolic conditions up to 1st-degree relatives\n- 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.\n- History of solid organ or hematopoietic transplant\n- History of hypersensitivity to the study drug or drugs of similar chemical classes or any excipients\n- History or presence of prolonged QT interval (QTcB > 450 msec)\n- History of malignancy in any organ system (other than localized basal cell carcinoma of the skin) in the last 5 years"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Evaluation from baseline to week 24 of incidence rates of SAEs, TEAEs and discontinuations due to AEs; frequency counts of specific indication-relevant AEs (examples given) and cumulative AE analyses including number of AEs per patient."}

Secondary endpoints

• {"endpoint_text":"- The secondary endpoints will evaluate the relative change from baseline to week 24 in ppFEV1","definition_or_measurement_approach":"Relative change in percent predicted FEV1 from baseline to week 24."}
• {"endpoint_text":"- The secondary endpoints will evaluate the number of pulmonary exacerbations up to week 24","definition_or_measurement_approach":"Count of pulmonary exacerbations occurring up to week 24."}
• {"endpoint_text":"- The secondary endpoints will evaluate the time to the first pulmonary exacerbation up to week 24","definition_or_measurement_approach":"Time-to-event analysis measuring days from baseline to first pulmonary exacerbation up to week 24."}
• {"endpoint_text":"- The secondary endpoints will evaluate the number of hospitalizations for cystic fibrosis lasting > 24 hours","definition_or_measurement_approach":"Count of hospital admissions for CF lasting more than 24 hours during the study period."}
• {"endpoint_text":"- The secondary endpoints will evaluate the time to the first hospitalization for cystic fibrosis","definition_or_measurement_approach":"Time-to-event analysis measuring days from baseline to first CF-related hospitalization."}
• {"endpoint_text":"- the absolute change in the respiratory domain score of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) from baseline to week 24","definition_or_measurement_approach":"Absolute change in CFQ-R respiratory domain score from baseline to week 24."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Total days on IV antibiotics for sino-pulmonary indications up to week 24."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Total days on oral antibiotics for sino-pulmonary indications up to week 24."}
• {"endpoint_text":"- changes in BMI from baseline to week 24","definition_or_measurement_approach":"Absolute change in body mass index from baseline to week 24."}
• {"endpoint_text":"- changes in sputum microbiology at the beginning and end of the study","definition_or_measurement_approach":"Comparison of sputum microbiology results at baseline and at end of study."}
• {"endpoint_text":"- changes in the amount of chloride measured with the sweat test at the beginning and end of the study","definition_or_measurement_approach":"Change in sweat chloride concentration from baseline to end of study."}

Italy

Earliest CTIS Part Ii Submission Date

19-05-2025

Latest Decision Or Authorization Date

06-10-2025

Processing Time Days

140

Number Of Sites

1

Number Of Participants

35

Primary sponsor

Full Name

Azienda Ospedaliera Universitaria Integrata Verona

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"","full_name":"LEGA ITALIANA FIBROSI CISTICA VENETO - ODV","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"GB Pharma","duties_or_roles":"Source of monetary support","organisation_type":""}