A Study in Pediatric Participants With Congenital Adrenal Hyperplasia (Balance-CAH)

Official title

A Phase 2/3 Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Atumelnant Treatment in Pediatric Participants With Congenital Adrenal Hyperplasia Including a Long-Term Extension

Overview

The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of atumelnant treatment in pediatric participants with classic congenital adrenal hyperplasia (CAH).

Detailed description

This Phase 2/3 plus open-label extension study is designed to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of atumelnant treatment in pediatric participants with classic CAH. Part A is a Phase 2, open-label, semi-sequential cohorts portion of the study. Part B is the Phase 3, double-blind, randomized, placebo controlled confirmatory portion of the study. Part C is the open-label extension (OLE) portion of the study. Participants in Part A and B are eligible to enroll in Part C (OLE).

A total of approximately 153 participants may be enrolled in the study (planned and optional cohorts) ages 1 to \< 18 years old.

The first 3 cohorts in Part A are for ages 12 to \<18 years and will be semi-sequential, and Safety Review Committee (SRC) review of data and approval to proceed is required prior to enrolling each subsequent cohort. The fourth cohort in Part A is for ages 1 to 11 years old and will begin after Cohorts 1 and 2 have been completed, additional requirements are fulfilled, and following SRC review of Cohorts 1 and 2 data.

Interventions

• Drug Atumelnant
  Atumelnant, tablets, once daily by mouth, weight-based dosing
• Drug Placebo
  Placebo, tablets, once daily by mouth, weight-based dosing

Primary outcome measures

• Change from baseline in morning serum androstenedione (A4) (Part A) [Time frame: Week 8]
• Percent change from baseline in glucocorticoid (GC) daily dose while serum early morning A4 ≤Upper Limit of Normal (ULN) (Part B) [Time frame: Week 28]
• Change from baseline in serum early morning A4 over time (Part C) [Time frame: Up to Week 260]

Secondary outcome measures (8)

• Change from baseline in morning serum 17-hydroxyprogesterone (17-OHP) (Part A) [Time frame: Week 8]
• Plasma and/or blood concentrations of atumelnant (Part A) [Time frame: Up to Week 8]
• Change from baseline in serum early morning A4 (Part B) [Time frame: Week 4]
• Change from baseline in serum early morning 17-OHP (Part B) [Time frame: Week 4]
• Proportion of participants with physiologic GC dose while serum early morning A4 ≤ULN (Part B) [Time frame: Week 28]
• Change from baseline in serum early morning 17-OHP over time (Part C) [Time frame: Up to Week 260]
• Percent change from baseline in GC daily dose over time (Part C) [Time frame: Up to Week 260]
• Proportion of participants with physiologic GC dose while serum early morning A4 ≤ULN over time (Part C) [Time frame: Up to Week 260]

Eligibility criteria

Inclusion criteria

Part A and B participants are eligible to be included in the study only if all of the following criteria apply:

• Male or female at birth, between 1 to <18 years of chronological age at the time of signing the Informed Consent Form (ICF).
• Have a medically confirmed diagnosis of classic CAH due to 21-hydroxylase deficiency (21-OHD) based on standard medically accepted criteria such as elevated 17-OHP level, confirmed CYP21A2 genetic testing, positive newborn screening with confirmatory second tier testing, or cosyntropin stimulation.
• Participants must have an elevated morning serum A4 level >ULN during Screening obtained prior to morning glucocorticoid (GC) administration.
• Participants must be on a stable supraphysiologic GC replacement therapy for at least one month prior to Screening.
• Compliance, as judged per Investigator discretion, with GC replacement and mineralocorticoid replacement (if applicable) regimen documented during the Screening Period.
• Biochemical euthyroidism as determined by the Investigator.

Part C inclusion criteria require participants to complete treatment in either Part A or Part B and in the Investigator's opinion it would benefit the participant to continue in Part C, regardless of age.

Exclusion criteria

Part A and Part B: Individuals in Part A and Part B who meet any of the following criteria will be excluded from participation in this study:

• Diagnosis of any form of CAH other than classic 21-OHD.
• Participants treated with other GCs within 30 days of Screening.
• Stress dose of GC therapy within 2 weeks of start of Screening, defined as any dose above the normal maintenance dose, including but not limited to intravenous (IV) or intramuscular (IM) hydrocortisone.
• Use of growth hormones within 1 week of start of Screening for short acting, or within 6 weeks of start of Screening for long acting.
• Use of a corticotropin-releasing factor receptor antagonist within 14 days of Screening.
• History of cancer excluding cured/treated dermal squamous or basal cell carcinoma or cervical carcinoma in situ.
• Abnormal sleep/wake cycles (as determined by the Investigator).
• Female participants who are pregnant or lactating.
• Participants who have been dosed with an investigational drug (including atumelnant) in any prior clinical study within 60 days or 5 half-lives (whichever is longer) prior to the first dose.
• Individuals in Part C who do not meet the Part C Inclusion Criteria.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 9 centers

• UCSF Ron Conway Gateway Medical Building — San Francisco
• Boston's Children's Hospital — Boston
• University of Michigan — Ann Arbor
• University of Minnesota — Minneapolis
• Rutgers Robert Wood Johnson Medical School — New Brunswick
• Icahn School of Medicine at Mount Sinai-Mount Sinai Hospital — New York
• Children's Hospital of Philadelphia — Philadelphia
• Cook Children's Health Care System — Fort Worth
• … and 1 more center

France · 6 centers

• Centre Hospitalier Universitaire (CHU) d'Angers — Angers
• Hopital Kremlin-Bicétre - APHP Paris Saclay — Le Kremlin-Bicêtre
• Hopital Jeanne de Flandre - CHU de Lille — Lille
• APHM -Hopital La Timone Enfants — Marseille
• Hopital Necker - Enfants Malades — Paris
• Hopital Robert Debre — Paris

Argentina · 5 centers

• Instituto de Investigaciones Metabólicas — Buenos Aires
• Hospital de Niños de la Santísima Trinidad — Córdoba
• Hospital Italiano de Buenos Aires — Buenos Aires
• Instituto Médico Especializado (IME) — Buenos Aires
• CEDIE "Centro de Investigaciones Endocrinológicas", CONICET-FEI División de Endocrinología — Buenos Aires

Australia · 4 centers

• Institute of Endocrinology of Diabetes, The Children's Hospital at Westmead — Westmead
• Queensland Children's Hospital — South Brisbane
• Monash Children's Hospital, Monash Health — Clayton
• Perth Children's Hospital — Nedlands

Belgium · 4 centers

• UZA (Antwerp University Hospital) — Edegem
• Cliniques Universitaires Saint-Luc — Brussels
• UZ Gent (University Hospital Ghent) — Ghent
• UZ Leuven (Universitair Ziekenhuis Leuven) — Leuven

Italy · 4 centers

• AOU Federico II — Naples
• IRCCS Istituto Giannina Gaslini — Genoa
• IRCCS Ospedale San Raffaele — Milan
• Azienda Ospedaliera Universitaria Meyer IRCCS — Florence

Brazil · 3 centers

• Nucleo de Pesquisa Clinica do Rio Grande do Sul — Porto Alegre
• Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Pa — Ribeirão Preto
• Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP) — São Paulo

United Kingdom · 3 centers

• Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street Hospit — London
• Manchester University NHS Foundation Trust, Royal Manchester Children's Hospital — Manchester
• Sheffield Children's Hospital NHS Trust, Sheffield Children's Hospital, Western Bank — Sheffield

Germany · 2 centers

• Universitätsklinikum Tübingen Klinik fur Kinder und Jugendmedizin — Tübingen
• Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum Klinik für pädiatrische Endok — Berlin

Poland · 2 centers

• lnstytut Centrum Zdrowia Matki Polki, Klinika Endokrynologii i Chor6b Metabolicznych — Lodz
• Uniwersytecki Szpital Kliniczny Nr 1 im. Prof. Tadeusza Sokotowskiego PUM w Szczecinie, Ce — Szczecin

Netherlands · 1 center

• Radboudumc Amalia Children's Hospital, Department of Pediatrics — Nijmegen

Identifiers

NCT: NCT07159841 · CRN04894-13 · 2024-519578-38-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗