(Z)-endoxifen for early puberty in girls with McCune-Albright Syndrome

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 can't join 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.
• Any serious concomitant medical, developmental, behavioral, or psychiatric condition that, in the Investigator's judgment, would make participation unsafe, prevent reliable completion of study procedures, or compromise study integrity.