(Z)-Endoxifen in Girls With MAS-Associated Peripheral Precocious Puberty

NCT07869732 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ATOS-204-S
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the safety, tolerability, and blood levels of (Z)-endoxifen in girls with McCune-Albright Syndrome that have peripheral precocious puberty. The main question it aims to answer \[is/are\]: Are there any safety concerns? Is there any evidence of efficacy? There is no comparison group. Participants will:

• take a capsule once a day for 3 months;
• have doctor visits (tele-health and in-person);
• blood samples collected; and
• complete questionnaires

Conditions

Precocious Puberty, Gonadotropin-dependent

Keywords

FD/MAS; MAS; McCune-Albright; McCune Albright

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability

  Incidence, severity, seriousness, and relationship of TEAEs and SAEs; clinically significant changes in laboratory tests, vital signs, ECGs, physical examinations, growth, pubertal development, and other targeted safety parameters.

  3 months

Secondary Outcomes (1)

• Evaluate patient and family impact (Psycho-social impact) of the early onset of puberty in girls

  Prior to and during the study (4 to 5 months)

Study Arms (1)

(Z)-endoxifen arm

EXPERIMENTAL

Drug: (Z)-endoxifen

Interventions

(Z)-endoxifen DRUG

(Z)-endoxifen will be administered once daily via the oral route

(Z)-endoxifen arm

Eligibility Criteria

• Age: 4 Years - 9 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Female child aged ≥ 4 to \< 10 years at the time of informed consent.
• Body weight ≥ 16 kg.
• Clinical or molecular diagnosis of McCune-Albright syndrome (MAS), with peripheral precocious puberty and at least one additional characteristic manifestation of MAS other than café-au-lait skin macules, such as polyostotic fibrous dysplasia or another autonomous endocrine manifestation distinct from the participants PPP.
• Clinical evidence of gonadotropin-independent (peripheral) precocious puberty, including onset of vaginal bleeding before 8 years of age and recurrent vaginal bleeding documented as at least 2 episodes during the prior 6 months.
• Prepubertal or low-normal basal luteinizing hormone (LH) and follicle-stimulating hormone (FSH), consistent with predominantly gonadotropin-independent disease activity.
• Advanced bone age, defined as bone age exceeding chronological age by ≥1 year at screening, determined using the protocol-specified standardized radiographic method and central or qualified local reading procedures.
• Active peripheral estrogen activity at study entry that, in the Investigator's judgment, is the primary driver of current clinical manifestations.
• Ability to swallow small capsules with water. Capsule-swallow training may be provided during screening using non-drug training capsules, or other age-appropriate standard site procedures.
• Adequate hepatic, renal, hematologic, and coagulation function based on protocol-defined laboratory criteria.
• Parent or legal guardian able and willing to provide written informed consent, with age-appropriate participant assent when applicable.
• Participant and parent/caregiver are willing and able to comply with study visits, daily diary completion, study treatment administration, and required procedures.

You may not qualify if:

• Prior bilateral oophorectomy or hysterectomy.
• Central precocious puberty (CPP).
• The need for the use of GnRH agonists during the trial.
• Use of a selective estrogen receptor modulator, aromatase inhibitor, other estrogen-modifying agent, or high-dose progestin within 1 month or 5-half-lives, whichever is longer.
• Use of any bone-directed therapies.
• Dominant central precocious puberty requiring initiation or intensification of gonadotropin-releasing hormone analog therapy at screening.
• Clinically significant uncontrolled endocrinopathy likely to interfere with growth, safety, or interpretation of study outcomes, including uncontrolled hyperthyroidism, growth hormone excess, phosphate-wasting osteomalacia, or Cushing syndrome.
• ALT or AST \>3 × upper limit of normal (ULN), total bilirubin \>2 × ULN, or other clinically significant hepatic impairment at screening (post-letrozole 14 day wash-out), unless the abnormality is explained, stable, and approved by the Sponsor Medical Monitor.
• Clinically significant renal impairment, hematologic abnormality, or coagulation abnormality that may increase risk or confound interpretation.
• History of venous thromboembolism or known hereditary thrombophilia.
• Significant ophthalmic conditions, including cataracts
• Known hypersensitivity to endoxifen, tamoxifen, or any formulation excipient.
• Pregnancy or breastfeeding. Pregnancy testing applies only to post-menarche or otherwise at-risk participants as medically and ethically appropriate.
• Participation in another interventional clinical study or receipt of another investigational product within 30 days or 5 half-lives, whichever is longer, before first dose, unless approved by the Sponsor.
• Planned major surgery during the 3-month treatment period that could materially affect safety or endpoint assessment.

Sponsors & Collaborators

• Atossa Therapeutics, Inc.: lead
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator

Study Sites (1)

NIH

Bethesda, Maryland, 20817, United States

Location

MeSH Terms

Conditions

Puberty, Precocious

Interventions

4-hydroxy-N-desmethyltamoxifen

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases

Study Officials

• Alison Boyce, MD

  Lasker Clinical Research Scholar Chief, Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial Research National Institutes of Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-Label, Safety, Tolerability and Exposure Study of (Z)-endoxifen

Study Record Dates

• First Submitted: October 6, 2026
• First Posted: October 9, 2026
• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: October 9, 2026

Record last verified: 2026-10

Locations

US (1)