Breast DensityPhase 2NCT05068388
Effect of Oral (Z)-Endoxifen in Premenopausal Women With Measurable Breast Density
A Phase 2 study testing Z-Endoxifen in people with Breast Density, run by Atossa Therapeutics, Inc. at 1 site in Sweden.
Trial 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). Read more about this study
- Who is it for?
- Ages 40 to 55 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Density
- What is being tested?
- Z-Endoxifen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 240 participants
- Where
- 1 siteSweden
- Study dates
- 21 Dec 2021to 12 Mar 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 55 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
- Women of childbearing potential using a highly effective method of birth control* throughout the study period and willing to comply with monthly pregnancy testing
- Screening mammogram performed within 3 month of study inclusion
- Mammographic density assessed as BI-RADS® score B, C, or D
- 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
Who cannot join
- Mammographic BI-RADS® malignancy code ≥3 at baseline mammography
- 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)
- A history of breast surgery, e.g., reduction or enlargement, which might affect mammographic density measurements
- Current medical conditions:
- APC (activated protein C) resistance, an inherited coagulation disorder
- Systolic pressure higher than 160 mm Hg or diastolic higher than 100 mm Hg
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- Cataract(s)
- Uncontrolled diabetes (defined as HbA1c >50 mmol/mol)
- Abnormal lab values deemed clinically significant by Investigator
- BMI > 30
- Women who have an increased risk of venous thrombosis due to immobilization, e.g., using wheelchair
- Agents that have the potential to decrease endoxifen levels through increased metabolic clearance:
- Certain anti-epileptic therapies (carbamazepine, fenytoin, fenobarbital, lamotrigine)
- Certain antibiotics (rifamycins)
- St John's wort (in Swedish: johannesört)
- Certain HIV medications (efavirenz, ritonavir)
- Lactating, pregnant, or plan to become pregnant in the next year
- History of thromboembolic disease such as embolus, deep vein thrombosis, stroke, TIA (transient ischemic attack) or myocardial infarction
- Allergy to endoxifen or any of its components
- Previous treatment with an anti-oestrogen, including experimental drug studies (e.g., Karma CREME, Karisma-1 or Karisma-2)
- Prescribed and regular use of anticoagulants (defined as substances included in group B01A in the ATC-system)
- Participation in another investigational clinical trial in the last 6 months
- Not willing or able to understand the study information and/or informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2, Randomized, Double-blinded, Placebo-controlled, Dose-Response Study of Oral (Z)-Endoxifen in Premenopausal Women With Measurable Breast Density
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.
- Conditions
- Breast Density
- Being tested
- Z-Endoxifen, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Z-EndoxifenDrug
Z-Endoxifen
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | oral capsule Receives: Drug: Placebo |
| 1 mg (Z)-endoxifen | Experimental | oral capsule Receives: Drug: Z-Endoxifen |
| 2 mg (Z)-endoxifen | Experimental | oral capsule Receives: Drug: Z-Endoxifen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of mammographic density area (cm2) assessed by iCAD® software
Change from baseline
Measured: 6 months
Secondary outcomes (5)
Change of mammographic density area (cm2) assessed by iCAD® software
Change from baseline
Measured: 3 months
Change of mammographic density area (cm2) assessed by Stratus software
Change from baseline
Measured: 6 months
Change of mammographic density area (cm2) assessed by Stratus software
Change from baseline
Measured: 3 months
Change from baseline responses to the Breast Cancer Prevention Trial Eight Symptom Scale (BESS)
5-point Likert-type scale
Measured: 6 months
Comparison of adverse events
assessment of adverse events
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2021
- Study start21 Dec 2021
- Primary completion14 Jun 2024
- Study completion12 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast DensityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 240 participants (actual)
Sponsor and investigators
- Lead sponsor
- Atossa Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Steven Quay, MD, Study director, Atossa Therapeutics, Inc.Per Hall, MD, Principal investigator, Södersjukhuset, Stockholm, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05068388
- Sponsor's protocol ID
- ATOS-016R
- Status last verified
- May 2026
- First submitted
- 27 Sep 2021
- Last updated
- 20 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hall P, Hammarstrom M, Bergqvist J, Czene K, Eriksson M, Gabrielson M, Tapia J, Quay S, Nash S, Backlund M. Endoxifen for mammographic density reduction-results from the KARISMA endoxifen trial. J Natl Cancer Inst. 2026 Apr 27:djag087. doi: 10.1093/jnci/djag087. Online ahead of print.
PubMed 42070780
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-blinded, Placebo-controlled, Dose-Response Study of Oral (Z)-Endoxifen in Premenopausal Women With Measurable Breast Density
- ClinicalTrials.gov ID
- NCT05068388
- Acronym / sponsor ID
- ATOS-016R
- Conditions
- Breast Density
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 240 participants (actual)
- Lead sponsor
- Atossa Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 21 Dec 2021 (actual)
- Primary completion
- 14 Jun 2024 (actual)
- Study completion
- 12 Mar 2026 (actual)
- First posted
- 5 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebooral capsule |
| 1 mg (Z)-endoxifen | Experimental | Drug: Z-Endoxifenoral capsule |
| 2 mg (Z)-endoxifen | Experimental | Drug: Z-Endoxifenoral capsule |
Who may qualify
- Ages
- 40 to 55 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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)
- Women of childbearing potential using a highly effective method of birth control* throughout the study period and willing to comply with monthly pregnancy testing
- Screening mammogram performed within 3 month of study inclusion
- Mammographic density assessed as BI-RADS® score B, C, or D
- 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
Key exclusion criteria (23 listed)
- Mammographic BI-RADS® malignancy code ≥3 at baseline mammography
- 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)
- A history of breast surgery, e.g., reduction or enlargement, which might affect mammographic density measurements
- Current medical conditions:
- BMI > 30
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Z-EndoxifenZ-Endoxifen | Drug | 1 mg (Z)-endoxifen, 2 mg (Z)-endoxifen |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Change of mammographic density area (cm2) assessed by iCAD® software
Time frame: 6 months
Change from baseline
5 secondary outcomes
Change of mammographic density area (cm2) assessed by iCAD® software
Time frame: 3 months
Change of mammographic density area (cm2) assessed by Stratus software
Time frame: 6 months
Change of mammographic density area (cm2) assessed by Stratus software
Time frame: 3 months
Change from baseline responses to the Breast Cancer Prevention Trial Eight Symptom Scale (BESS)
Time frame: 6 months
Comparison of adverse events
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2026.
- Derived from this study: PubMed 42070780Hall P, Hammarstrom M, Bergqvist J, Czene K, Eriksson M, Gabrielson M, Tapia J, Quay S, Nash S, Backlund M. Endoxifen for mammographic density reduction-results from the KARISMA endoxifen trial. J Natl Cancer Inst. 2026 Apr 27:djag087. doi: 10.1093/jnci/djag087. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Quay, MD study director
Atossa Therapeutics, Inc.
Per Hall, MD principal investigator
Södersjukhuset, Stockholm, Sweden
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Z-Endoxifen in people with Breast Density, run by Atossa Therapeutics, Inc. at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of mammographic density area (cm2) assessed by iCAD® software (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05068388, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2026.