An Extension Study to Evaluate Safety and Efficacy of Atumelnant in Participants With Congenital Adrenal Hyperplasia

Official title

An Open-label, Long-term Extension Study to Evaluate Safety and Efficacy of Atumelnant in Participants With Congenital Adrenal Hyperplasia (CALM2-CAH)

Overview

The purpose of this study is to evaluate the long-term safety, tolerability, and efficacy of atumelnant (CRN04894).

Detailed description

This single-arm, long-term, open-label, study is designed to evaluate the safety, tolerability, and efficacy of atumelnant (CRN04894) in participants with congenital adrenal hyperplasia (CAH). Enrollment will be limited to individuals who completed a parent Crinetics atumelnant CAH study, and in the opinion of the Investigator had an acceptable benefit-risk assessment in the completed study and would benefit from continued dosing in this Open-Label Extension (OLE) study.

A total of approximately 150 - 200 participants may be enrolled in the study.

Interventions

• Drug atumelnant (CRN04894)
  Atumelnant is an orally active nonpeptide melanocortin 2 receptor (MC2R) or adrenocorticotropic hormone (ACTH) receptor antagonist.

Primary outcome measures

• Incidence of treatment-emergent adverse events (TEAEs), including treatment-emergent serious adverse events (SAEs), adverse events of special interest (AESI [adrenal insufficiency]) and any adverse events (AEs) leading to discontinuation [Time frame: Week 108]
• Incidence of glucocorticoid (GC) deficiency / adrenal insufficiency and adrenal crisis [Time frame: Week 108]
• Incidence of hospitalizations related to congenital adrenal hyperplasia (CAH) [Time frame: Week 108]
• Change from baseline in morning (before 11:00 AM) serum androstenedione (A4) over time [Time frame: Week 108]

Secondary outcome measures (2)

• Change from baseline in morning (before 11:00 AM) serum 17-hydroxyprogesterone (17-OHP) over time [Time frame: Week 108]
• Change from baseline in daily glucocorticoid (GC) dose (hydrocortisone [HC] mg equivalents body surface area [BSA] adjusted) over time [Time frame: Week 108]

Eligibility criteria

Inclusion criteria

Participants are eligible to be included in the study only if all the following criteria apply:

• Participants with CAH who have completed the Treatment Period in a Crinetics parent atumelnant CAH study, and in the opinion of the Investigator had an acceptable benefit-risk assessment in the completed study and would benefit from continued dosing in this extension study.

• Group 1: Participants meeting the above criteria and did not have study drug administration interrupted between End of Trial (EOT) of the parent study and the commencement of the OLE study.
• Group 2: Participants meeting the above criteria but had study drug administration interrupted between EOT of the parent study and the commencement of the OLE study.
• Female participants who engage in heterosexual intercourse must:

• Be of nonchildbearing potential, defined as either surgically sterile (ie, hysterectomy, bilateral salpingectomy for at least 3 months, or bilateral oophorectomy), OR
• Be postmenopausal with at least 1 year of amenorrhea. In participants with less than 1 year of amenorrhea, confirmation is required with 2 follicle-stimulating hormone (FSH) measurements. A documented, historical test result measured prior to Screening may be used as 1 of the 2 measurements. The FSH value should be ≥30 IU/L to confirm menopausal status, OR
• Agree to use a highly effective 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.
• Male participants 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). Male participants should also agree to not donate sperm for the duration of the study and until at least 2 weeks after the last dose of study drug.
• Participants are willing and able to give signed informed consent, including compliance with the requirements and restrictions listed in the Informed Consent Form (ICF).
• Participants are willing and able to comply with the study procedures as specified in the protocol and comply with the study treatment.

Exclusion criteria

Participants are excluded from the study if any of the following criteria apply:

• Any medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardize the participant's safety or ability to complete the study.
• Participants have known history of (that is within the past 12 months), or current alcohol or drug abuse.
• Participants have any 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.
• Participants have a known allergy or hypersensitivity to any of the test materials or related compounds, including being at high risk of adrenal insufficiency as judged by the Investigator.
• 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.
• Participant is an employee or immediate family member of an employee of Crinetics.
• Participants who have been dosed with an investigational drug (other than atumelnant) in any prior clinical study within 60 days or 5 half-lives (whichever is longer) prior to informed consent or plan to use an investigational drug in another study.
• Participants who have had an active malignant disease within the last 5 years prior to Screening excluding dermal squamous or basal cell carcinoma of the skin with complete local excision or resected cervical carcinoma in situ.
• Participants who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.

Specific for Participants Not Currently Receiving Atumelnant

• Participants with any clinically significant abnormal laboratory test during Screening or clinically significant concomitant disease other than CAH including but not limited to cardiovascular disease; moderate or severe renal insufficiency (estimated glomerular filtration rate <30 mL/min/1.73 m2 using Chronic Kidney Epidemiology Collaboration \[CKD-EPI\] formula) at Screening; or Significant liver disease or alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >3× upper limit of normal (ULN), and/or total bilirubin >1.5×ULN during Screening. Participants with previously diagnosed Gilbert's syndrome not accompanied by other hepatobiliary disorders and associated with total bilirubin <3.5 mg/dL (<51.3 μmol/L) will be permitted.
• Participants with a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic glucocorticoid therapy.
• Participants with a history of major surgery/surgical therapy for any cause within 4 weeks prior to Screening.
• Participants with poorly controlled diabetes mellitus defined as having a hemoglobin A1c (HbA1c) ≥8.5% (≥69 mmol/mL).
• 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.
• Participant has an average (of 3 electrocardiograms \[ECGs\]) Fridericia's corrected QT (QTcF) interval >450 milliseconds (msec) (men) or >470 msec (women), time interval between P and R waves (PR interval) >220 msec, time interval of the QRS complex (QRS) interval >120 msec, second- or third-degree atrioventricular block, left bundle branch block, or hemiblock at Screening.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Brazil · 5 centers

• Crinetics Study Site — Curitiba
• Crinetics Study Site — Porto Alegre
• Crinetics Study Site — Botucatu
• Crinetics Study Site — Rio de Janeiro
• Crinetics Study Site — São Paulo

United States · 3 centers

• Crinetics Study Site, Minneapolis, Minnesota 55454 — Minneapolis
• Crinetics Study Site — Morehead City
• Crinetics Study Site — Philadelphia

United Kingdom · 2 centers

• Crinetics Study Site — Birmingham
• Crinetics Study Site — London

Argentina · 1 center

• Crinetics Study Site — Córdoba

Germany · 1 center

• Crinetics Study Site — Munich

Italy · 1 center

• Crinetics Study Site — Roma

Identifiers

NCT: NCT06712823 · CRN04894-09 · 2024-514846-35-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗