A Study to Evaluate the Safety and Effectiveness of Tildacerfont to Reduce Glucocorticoid Use in Classic Congenital Adrenal Hyperplasia

Overview

About this study

The purpose of this study is to evaluate the potential of Tildacerfont to reduce glucocorticoid (GC) burden in adult subjects with classic Classic Congenital Adrenal Hyperplasia (CAH) who have lower limit of detection (LLD) ≤ A4 ≤ 1.5 x upper limit of normal (ULN) and are on supraphysiologic doses of GC therapy.

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 and female subjects ≥ 18 years of age at Screening.
  • Has a documented historical diagnosis of classic CAH due to 21-hydroxylase deficiency based on genetic mutation in CYP21A2 and/or elevated 17-OHP.
  • Has LLD ≤ A4 ≤ 1.5 x ULN both at screening on existing GC regimen and at the end of the Glucocorticoid Conversion Period on a standardized GC regimen (based on Week -8 or Week -2 laboratory assessments, measured before any AM GC dose).
  • Has been on a stable, supraphysiologic dose of GC replacement (defined as ≥ 30 mg/day and ≤ 50 mg/day in HCe) for ≥ 3 months before screening without any evidence of non-adherence to the GC regimen during this period (stress dosing is allowed).
  • For subjects with the salt-wasting form of CAH, subject has been on a stable dose of mineralocorticoid replacement for ≥3 months before screening.
  • Agrees to convert from his/her existing GC regimen to the Sponsor’s standardized GC regimen at the start of the Glucocorticoid Conversion Period.
  • Agrees to follow contraception guidelines.
  • Male subjects must also agree to refrain from donating sperm throughout the Treatment Period and for 90 days after the last dose of study drug.
  • Is able to understand all study procedures and risks involved and provides written informed consent indicating willingness to comply with all aspects of the protocol.

Exclusion Criteria:

  • Has a known or suspected diagnosis of any other known form of classic CAH (not due to 21-hydroxylase deficiency).
  • Has a history that includes bilateral adrenalectomy or hypopituitarism.
  • Has a history of allergy or hypersensitivity to tildacerfont or any other CRF1 receptor antagonist.
  • Is not adherent to GC dosing during the Glucocorticoid Conversion Period (defined as taking 12 for either depression or anxiety at screening or baseline.
  • Shows clinical signs or symptoms of adrenal insufficiency.
  • Has had a clinically significant unstable medical condition, medically significant illness, or chronic disease occurring within 30 days of screening, including but not limited to:
    • An ongoing malignancy or 12 for either depression or anxiety at screening or baseline;
    • Presence of clinically significant renal disease, as evidenced by an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m^2;
    • Current or chronic history of liver disease (including nonalcoholic steatohepatitis and female subjects with a history of intrahepatic cholestasis of pregnancy) or known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones);
    • History of alcohol or substance abuse within the last year, or any significant history of alcohol or substance abuse that would likely prevent the subject from reliably participating in the study, based on the opinion of the Investigator;
    • Active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at screening.
  • Had or has a clinically significant psychiatric disorder, including the following:
    • Evidence of major depressive episode, bipolar disorder, schizophrenia, schizoaffective disorder, major depressive disorder with psychotic features, or any other psychotic disorder within the preceding 6 months;
    • Increased risk of suicide based on the Investigator’s judgment or the results of the Columbia–Suicide Severity Rating Scale (C-SSRS) conducted at screening and baseline (e.g., C-SSRS Type 3, 4, or 5 ideation within the past 6 months or any suicidal behavior within the past 12 months);
    • HADS score > 12 for either depression or anxiety at screening or baseline.
  • Has clinically significant abnormal electrocardiogram (ECG) or clinical laboratory results. Abnormal results that must be reviewed and discussed with the Medical Monitor to determine eligibility for this study include but are not limited to:
    • Any clinically meaningful abnormal ECG results, including Fridericia-corrected QT interval (QTcF) > 450 ms for male participants or > 470 ms for female participants;
    • Alanine aminotransferase (ALT) >2x ULN;
    • Total bilirubin >1.5 x ULN (isolated total bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is 5 x ULN Routinely works overnight shifts;
    • Total bile acids > 5 x ULN.
  • Routinely works overnight shifts
  • Subjects with travel plans/work schedules that result in significant and frequent changes in time zones (> 2 hours) will require Medical Monitor approval for enrollment. 
  • Females who are pregnant or nursing.
  • Use of any other investigational drug from 30 days or 5 half-lives (whichever is longer) before screening to the end of the study.
  • Use of rosiglitazone, aromatase inhibitors, testosterone, or growth hormones from 30 days or 5 half-lives (whichever is longer) before the start of the Glucocorticoid Conversion Period to the end of the study:
    • Use of strong inhibitors and/or inducers of CYP3A4 (with the exception of GCs and birth control) and medications metabolized by Cytochrome P450 (CYP) 3A4, 2B6, 2C8, 2C9, or 2C19, especially those that are sensitive substrates or substrates with narrow therapeutic ranges, should be discussed on a case-by-case basis with the Medical Monitor to determine whether the medication should be discontinued or may be continued with caution. If washout is feasible, then the medication should be withdrawn at least 30 days or 5 half-lives (whichever is longer) before the start of the Glucocorticoid Conversion Period.
  • Use of any anticoagulants or antiplatelet therapies within 30 days before screening.
  • Has a history of an active bleeding disorder.
  • Donation of blood from 60 days before the start of the Glucocorticoid Conversion Period to the end of the study; or donation of platelets, white blood cells, or plasma from 15 days before the start of the Glucocorticoid Conversion Period to the end of the study.

Eligibility last updated 2/1/22. 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, M.D.

Open for enrollment

Contact information:

Vanessa Fell

(507) 266-6068

Fell.Vanessa@mayo.edu

More information

Publications

Publications are currently not available
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CLS-20507411

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