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

• ClinicalTrials.gov Identifier: NCT05068388
• Recruitment Status: Active, not recruiting
• First Posted: October 5, 2021
• Last Update Posted: April 26, 2024
• Sponsor: Atossa Therapeutics, Inc.
• Information provided by (Responsible Party): Atossa Therapeutics, Inc.

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 (Clinical Trial)
• Actual 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: December 21, 2021
• Estimated Primary Completion Date: August 28, 2024
• Estimated Study Completion Date: December 31, 2025

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 [ Time Frame: 6 months ]
   Change from baseline

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 55 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: having at least one menstruation during the prior 12 months; women with an intrauterine device are considered premenopausal if <52 years
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Sweden

Karma Study Centre

Stockholm, Sweden

Sponsors and Collaborators

Atossa Therapeutics, Inc.

Investigators

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

More Information

• Responsible Party: Atossa Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05068388
• Other Study ID Numbers: ATOS-016R
• First Posted: October 5, 2021
• Last Update Posted: April 26, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No