Effect of Oral (Z)-Endoxifen in Premenopausal Women With Measurable Breast Density

Phase 2

Active, not recruiting

• Conditions: Breast Density
• Interventions: Drug: Z-Endoxifen; Drug: Placebo

• Registration Number: NCT05068388
• Lead Sponsor: Atossa Therapeutics, Inc.

Brief Summary

This is a randomized, double-blinded, placebo-controlled dose-response efficacy study of oral (Z)-endoxifen in premenopausal women with measurable breast density. There will be 5 in-clinic visits (Screening, Day 1, Months 1, 3 and 6) and 3 self-report visits (Months 2, 4 and 5). Standard of care mammograms will be used for the screening mammogram as well as the 24-month follow up visit.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-09-27
• Study First Submitted QC: 2021-09-27
• Study First Posted: 2021-10-05
• Study Start: 2021-12-21
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-25
• Last Update Posted: 2024-04-26
• Primary Completion: 2024-08-28
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 240

Inclusion Criteria

1. Premenopausal women (defined as having at least one menstruation during the prior 12 months; women with an intrauterine device are considered premenopausal if <52 years)
2. Women of childbearing potential using a highly effective method of birth control* throughout the study period and willing to comply with monthly pregnancy testing
3. Screening mammogram performed within 3 month of study inclusion
4. Mammographic density assessed as BI-RADS® score B, C, or D
5. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects

Exclusion Criteria

1. Mammographic BI-RADS® malignancy code ≥3 at baseline mammography

2. Any previous diagnosis of breast cancer, including carcinoma in situ, or any other cancer (non-melanoma skin cancer and in situ cancer of the cervix are not exclusion criteria)

3. A history of breast surgery, e.g., reduction or enlargement, which might affect mammographic density measurements

4. Current medical conditions:

   1. APC (activated protein C) resistance, an inherited coagulation disorder
   2. Systolic pressure higher than 160 mm Hg or diastolic higher than 100 mm Hg
   3. Cataract(s)
   4. Uncontrolled diabetes (defined as HbA1c >50 mmol/mol)
   5. Abnormal lab values deemed clinically significant by Investigator

5. BMI > 30

6. Women who have an increased risk of venous thrombosis due to immobilization, e.g., using wheelchair

7. Agents that have the potential to decrease endoxifen levels through increased metabolic clearance:

   1. Certain anti-epileptic therapies (carbamazepine, fenytoin, fenobarbital, lamotrigine)
   2. Certain antibiotics (rifamycins)
   3. St John's wort (in Swedish: johannesört)
   4. Certain HIV medications (efavirenz, ritonavir)

8. Lactating, pregnant, or plan to become pregnant in the next year

9. History of thromboembolic disease such as embolus, deep vein thrombosis, stroke, TIA (transient ischemic attack) or myocardial infarction

10. Allergy to endoxifen or any of its components

11. Previous treatment with an anti-oestrogen, including experimental drug studies (e.g., Karma CREME, Karisma-1 or Karisma-2)

12. Prescribed and regular use of anticoagulants (defined as substances included in group B01A in the ATC-system)

13. Participation in another investigational clinical trial in the last 6 months

14. Not willing or able to understand the study information and/or informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2 mg (Z)-endoxifen	Z-Endoxifen	oral capsule
Placebo	Placebo	oral capsule
1 mg (Z)-endoxifen	Z-Endoxifen	oral capsule

Primary Outcome Measures

Name	Time	Method
Change of mammographic density area (cm2) assessed by iCAD® software	6 months	Change from baseline

Secondary Outcome Measures

Name	Time	Method
Change of mammographic density area (cm2) assessed by iCAD® software	3 months	Change from baseline
Change of mammographic density area (cm2) assessed by Stratus software	3 months	Change from baseline
Change from baseline responses to the Breast Cancer Prevention Trial Eight Symptom Scale (BESS)	6 months	5-point Likert-type scale
Comparison of adverse events	6 months	assessment of adverse events

Trial Locations

Locations (1)

Karma Study Centre; 🇸🇪 Stockholm, Sweden