A Study To Evaluate Atumelnant In Adults With Congenital Adrenal Hyperplasia

Overview

About this study

The purpose of this study is to evaluate efficacy of atumelnant, compared with placebo, in reducing daily GC dosage while maintaining adrenal androgen control at the end of the 32-week Treatment Period.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Male or female, between ≥18 to <75 years of age at the time of signing the ICF.

  • Willing and able to understand and adhere to the study procedures as specified in the protocol and comply with the study treatment.

  • Have classic CAH due to 21-OHD confirmed by the Investigator and approved by the Medical Monitor.

  • Participants with levels of morning serum A4 as follows:

    • A4 >ULN and treated with <11 mg/m2 /day (physiologic) GC doses OR

    • normal A4 (above mid-range to ≤ULN) and treated with ≥15 mg/m2 /day GC doses OR

    • A4 >ULN and treated with ≥11 mg/m2 /day GC doses.

    • Participants who fail Screening based on findings the Investigator believes are temporary and not reflective of the usual state of the participant can be considered for rescreening. These cases should be discussed with the Medical Monitor.

  • On a stable (defined as no dose change of >5 mg/day hydrocortisone equivalent within 2 months prior to Screening) regimen of GC replacement (eg, hydrocortisone, prednisolone, prednisone, methylprednisolone, dexamethasone) at the time of informed consent.

  • If treated with mineralocorticoids (fludrocortisone), the dose should be stable for at least 2 months prior to Screening without orthostatic hypotension, and with serum sodium and potassium in the normal range.

  • If on estrogen therapy (any route), the dose must be stable for at least 3 months prior to Screening.

  • Female participants who engage in heterosexual intercourse must:

    • Be of nonchildbearing potential, defined as either surgically sterile (ie, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), OR

    • Agree to use a highly effective or a clinically acceptable method of contraception from the beginning of Screening until at least 2 weeks after the last dose of study drug. Contraceptive use by men and women also should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Periodic abstinence (ie, calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. c.

  • Male participants who engage in heterosexual intercourse must:

    • Agree to use a condom when sexually active with a female partner of childbearing potential from Screening until at least 2 weeks after the last dose of study drug (or be surgically sterile [ie, vasectomy with a confirmed absence of sperm in ejaculate]) OR

    • Agree to remain abstinent on a long-term and persistent basis during the study and until at least 2 weeks after the last dose of study drug.

  • Agree to not donate sperm for the duration of the study and until at least 2 weeks after the last dose of study drug.

Exclusion Criteria:

  • Diagnosis of any form of CAH other than classic 21-OHD.

  • Treated with other GC formulations as defined by the following: unstable doses of inhaled GCs, and/or injectable or oral betamethasone or triamcinolone use within 30 days of first Screening Visit.

  • Stress dose of GC therapy within 1 week of start of Screening, defined as any dose above the normal maintenance dose, including but not limited to IV or IM hydrocortisone.

  • History of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic GC therapy.

  • Clinically significant medical condition or abnormal laboratory tests, as judged by the Investigator, other than CAH.

  • History of major surgery/surgical therapy for any cause within 30 days prior to first Screening Visit.

  • Diabetes mellitus treated with insulin for less than 6 weeks prior to Screening, or with change in total daily insulin dose by >30% within 6 weeks prior to Screening.

  • Poorly controlled diabetes mellitus defined as having an HbA1c ≥8.5% (≥69 mmol/mL) or estimated HbA1c based on fructosamine if HbA1c is not evaluable (eg, due to hemoglobinopathies).

  • Participants with hypothyroidism who are not receiving adequate hormone replacement therapy based on thyroid hormone levels measured at the time of Screening, as determined by the Investigator.

  • History of unstable angina or acute myocardial infarction within 12 weeks prior to Screening or other clinically significant cardiac disease at the time of Screening as judged by the Investigator.

  • Participants with polycythemia and prior thrombotic events as judged by the Investigator.

  • Concomitant mental condition rendering him/her unable to understand the nature, scope, and possible consequences of the study, and/or evidence of poor compliance with medical instructions.

  • History of cancer excluding cured/treated dermal squamous or basal cell carcinoma or cervical carcinoma in situ.

  • Women who are pregnant or lactating or, if of childbearing potential, who are unwilling to use highly effective contraception as described in this study. Male participants who are unwilling to use highly effective contraception as described in this study.

  • Known history of illicit drug or alcohol abuse within the last year.

  • Chronic use of antiandrogen therapy in the past 3 months (eg, spironolactone, finasteride, cyproterone acetate, flutamide) prior to Day 1.

  • Use of testosterone, androgen-containing supplements, aromatase inhibitors, or growth hormone.

  • Use of medications that are strong or moderate inducers of CYP3A4 within 30 days prior to Day 1 of the study. These include but are not limited to apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, or St. John’s wort.

  • Use of medications (all routes of administration; ie, oral, topical, and inhaled) or ingestion of food (eg, grapefruit juice) that are strong or moderate inhibitors of CYP3A4 within 7 days prior to Day 1 of the study. Examples include but are not limited to protease inhibitors and NNRTIs for HIV or HCV, antifungals (eg, ketoconazole), some antibiotics (eg, ciprofloxacin) and calcium channel blockers (eg, diltiazem), and antidepressants (eg, fluvoxamine).

  • Use of medications that are strong or moderate inducers of P-gp within 30 days prior to Day 1 of the study. These include but are not limited to apalutamide, carbamazepine, fosphenytoin, lorlatinib, phenytoin, rifampicin, or St. John's wort.

  • Use of medications that are strong or moderate inhibitors of P-gp within 14 days prior to Day 1 of the study. These include but are not limited to amiodarone, carvedilol, clarithromycin, dronedarone, itraconazole, lapatinib, protease inhibitors and NNRTIs for HIV or HCV (lopinavir and ritonavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir and ritonavir, telaprevir, tipranavir and ritonavir), or verapamil, propafenone, quinidine, or ranolazine.

  • Use of P-gp substrates, such as digoxin, edoxaban, fexofenadine, and dabigatran extexilate, as they may be subject to enhanced absorption and increased exposure when given concomitantly with atumelnant.

  • Use of any investigational drug within the past 60 days or 5 half-lives (whichever is longer) prior to the first dose; or plan to use an investigational drug in another study.

  • Average (of 3 ECGs) QTcF interval >450 msec (men) or >470 msec (women), PR interval >220 msec, QRS interval >120 msec, second- or third-degree atrioventricular block, left bundle branch block, or hemiblock at Screening.

  • Renal insufficiency as measured by eGFR rate using the CKD-EPI formula <40 mL/min/1.73m2 .

  • Significant liver disease or ALT and/or AST >3×ULN, and/or TBil >1.5×ULN during Screening. Participants with previously diagnosed Gilbert’s syndrome not accompanied by other hepatobiliary disorders and associated with TBil <3.5 mg/dL (<51.3 μmol/L) will be permitted.

  • Known history of, or concern for, risk of hypersensitivity reaction to atumelnant or any of its excipients.

  • Participants who are committed to an institution by virtue of an order issued either by the judicial or administrative authorities.

  • Participants with an increased risk of developing adrenal insufficiency as judged by the Investigator.

  • Use of oral betamethasone or budesonide within 30 days of Screening.

  • Severe erythrocytosis as judged by the Investigator.

  • Use of a corticotropin-releasing factor receptor antagonist within 14 days of Screening.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

 

Eligibility last updated 08/26/2025. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Irina Bancos

Contact us for the latest status

Contact information:

Vanessa Fell

(507) 266-6068

Fell.Vanessa@mayo.edu

More information

Publications

Publications are currently not available
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CLS-20597461

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