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

• Sponsor: Atossa Genetics, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05068388
• Collaborator: (none)
• Enrollment: 240
• Location: 1
• Arms: 3
• Anticipated Duration (Months): 36.3
• Patients Per Site Per Month: 6.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Density	Drug: Z-Endoxifen; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-blinded, Placebo-controlled, Dose-Response Study of Oral (Z)-Endoxifen in Premenopausal Women With Measurable Breast Density
• Actual Study Start Date: Dec 21, 2021
• Anticipated Primary Completion Date: Jul 28, 2023
• Anticipated Study Completion Date: Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo oral capsule	Drug: Placebo; Placebo
Experimental: 1 mg (Z)-endoxifen oral capsule	Drug: Z-Endoxifen; Z-Endoxifen
Experimental: 2 mg (Z)-endoxifen oral capsule	Drug: Z-Endoxifen; Z-Endoxifen

Outcome Measures

Primary Outcome Measures

1. Change of mammographic density area (cm2) assessed by iCAD® software [6 months]

   Change from baseline

Secondary Outcome Measures

1. Change of mammographic density area (cm2) assessed by iCAD® software [3 months]

   Change from baseline

2. Change of mammographic density area (cm2) assessed by Stratus software [6 months]

   Change from baseline

3. Change of mammographic density area (cm2) assessed by Stratus software [3 months]

   Change from baseline

4. Change from baseline responses to the Breast Cancer Prevention Trial Eight Symptom Scale (BESS) [6 months]

   5-point Likert-type scale

5. Comparison of adverse events [6 months]

   assessment of adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 55 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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:

5. APC (activated protein C) resistance, an inherited coagulation disorder

6. Systolic pressure higher than 160 mm Hg or diastolic higher than 100 mm Hg

7. Cataract(s)

8. Uncontrolled diabetes (defined as HbA1c >50 mmol/mol)

9. Abnormal lab values deemed clinically significant by Investigator

10. BMI > 30

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

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

13. Certain anti-epileptic therapies (carbamazepine, fenytoin, fenobarbital, lamotrigine)

14. Certain antibiotics (rifamycins)

15. St John's wort (in Swedish: johannesört)

16. Certain HIV medications (efavirenz, ritonavir)

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

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

19. Allergy to endoxifen or any of its components

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

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

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Karma Study Centre	Stockholm		Sweden

Sponsors and Collaborators

• Atossa Genetics, Inc.

Investigators

• Study Director: Steven Quay, MD, Atossa Therapeutics, Inc.
• Principal Investigator: Per Hall, MD, Södersjukhuset, Stockholm, Sweden

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Atossa Genetics, Inc.
• ClinicalTrials.gov Identifier: NCT05068388
• Other Study ID Numbers: ATOS-016R
• First Posted: Oct 5, 2021
• Last Update Posted: Jan 5, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Study Results

No Results Posted as of Jan 5, 2022