Clinical trial • Phase II/III • Endocrinology|Rare Disease

ATUMELNANT for Classic congenital adrenal hyperplasia|Congenital adrenal hyperplasia

Phase II/III trial of ATUMELNANT for Classic congenital adrenal hyperplasia|Congenital adrenal hyperplasia.

Overview

Trial Therapeutic Area
Endocrinology|Rare Disease
Trial Disease
Classic congenital adrenal hyperplasia|Congenital adrenal hyperplasia
Trial Stage
Phase II/III
Drug Modality
Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
19-08-2025
First CTIS Authorization Date
09-12-2025

Trial design

Randomised, open-label, placebo (tablet) as comparator in part b; active arm: atumelnant (dosed by weight in part b; dosing to be determined in part a). part a cohorts: cohort 1: 40 mg once daily (age 12 to <18 years); cohort 2: 80 mg once daily (age 12 to <18 years); cohort 3: optional cohort, dose to be determined; cohort 4a (age 6-11) and cohort 4b (age 1-5) doses to be determined based on data from ages 12 to <18 years.-controlled, adaptive Phase II/III trial in Netherlands, Poland, Italy and others.

Randomised
Yes
Open Label
Yes
Comparator
Placebo (tablet) as comparator in Part B; Active arm: Atumelnant (dosed by weight in Part B; dosing to be determined in Part A). Part A cohorts: Cohort 1: 40 mg once daily (age 12 to <18 years); Cohort 2: 80 mg once daily (age 12 to <18 years); Cohort 3: optional cohort, dose to be determined; Cohort 4a (age 6-11) and Cohort 4b (age 1-5) doses to be determined based on data from ages 12 to <18 years.
Adaptive
True, Part A is an Open-Label Semi-Sequential Cohorts design with dose escalation/selection (Cohort 1 = 40 mg once daily, Cohort 2 = 80 mg once daily, optional Cohort 3 dose TBD; younger cohorts' doses determined based on older cohort data). Part B dosing is to be determined based on Part A data.
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
95
Trial Duration For Participant
1825

Eligibility

Recruits 95 paediatric patients.

Pregnancy Exclusion
Female participants who are pregnant or lactating.
Vulnerable Population
The trial enrols pediatric participants (ages 1 to <18 years). Participant’s parent(s)/legal representative (if appropriate according to local laws) are required to provide signed informed consent. Age-appropriate assent and information documents are provided (multiple assent forms and pediatric information sheets listed for age groups such as 3-5, 6-11, 12-17); parental/guardian ICFs and country-specific ICFs are available. Multiple country-specific ICFs/assent documents are listed (e.g., Dutch, Polish, Italian, French, German, English).

Inclusion criteria

  • {"criterion_text":"-Part A and B participants are eligible to be included in the study only if all of the following criteria apply: 1. Male or female at birth, between 1 to <18 years of chronological age at the time of signing the ICF.\n-2. Have a medically confirmed diagnosis of classic CAH due to 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.\n-3. Participants must have an elevated morning (before 11:00) serum A4 level >ULN during Screening obtained prior to morning GC administration. Participants who failed Screening based on findings the Investigator believes are temporary and not reflective of the usual state of the participant (eg, normal A4 levels when the participant usually is well above this value) can be considered for rescreening. These cases should be discussed with the Medical Monitor.\n-4. Participants must be on a stable supraphysiologic GC replacement therapy (hydrocortisone, prednisolone, prednisone, methylprednisolone, dexamethasone) for at least one month prior to Screening\n-5. Compliance, as judged per Investigator discretion, with GC replacement and mineralocorticoid replacement (if applicable) regimen documented during the Screening Period.\n-6. Normal TSH and T4 within 3 months of Screening per age-appropriate range. Female participants who have had their first menstrual cycle and engage in heterosexual intercourse must: a) Be of nonchildbearing potential, defined as either surgically sterile. b) 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. Male participants who engage in heterosexual intercourse must: a) 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. b) 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. c)Agree to not donate sperm for the duration of the study and until at least 2 weeks after the last dose of study drug.\n-7. Participant’s parent(s)/legal representative (if appropriate according to local laws) are willing and able to give signed informed consent for participant in the study.\n-8. Willing and able to comply with the study procedures as specified in the protocol and comply with the study treatment. 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

  • {"criterion_text":"-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: 1. Diagnosis of any form of CAH other than classic 21-OHD.\n-2. Participants treated with other GC formulations within 30 days of Screening.\n-3. 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 IV or IM hydrocortisone.\n-4. 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.\n-5. Use of a corticotropin-releasing factor receptor antagonist within 14 days of Screening.\n-6. 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 <60 mL/min/1.73 m2 using CKD-EPI formula) at Screening; or Significant liver disease or ALT and/or AST >3×ULN, and/or TBil >1.5×ULN during Screening. TBil >1.5×ULN (Participants with Gilbert’s syndrome can be included with TBil >1.5×ULN as long as direct bilirubin is ≤1.5×ULN AND <35% of TBil)\n-7. History of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic GC therapy.\n-8. 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 (defined as any condition that affects the heart’s structure, function, or electrical system, regardless of stage of disease); moderate or severe renal insufficiency (estimated glomerular filtration rate <60 mL/min/1.73 m2 using the Bedside Schwartz Equation)) at Screening; or Significant liver disease or ALT and/or AST >3×ULN, and/or TBil >1.5×ULN during Screening. TBil >1.5×ULN (Participants with Gilbert’s syndrome can be included with TBil >1.5×ULN as long as direct bilirubin is ≤1.5×ULN AND <35% of TBil)..\n-9. Poorly controlled diabetes mellitus as judged by the Investigator.\n-10. 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.\n-11. History of cancer excluding cured/treated dermal squamous or basal cell carcinoma or cervical carcinoma in situ.\n-12. ECG: a. Ages 12 to <18: QTcF interval >450 msec (males) or >470 msec (females), PR interval >220 msec, QRS interval >120 msec, second- or third-degree atrioventricular block, left bundle branch block, or hemiblock at Screening. b. Ages 1 to 11: Anything abnormal, even if not clinically significant, is an exclusion. A cardiologist can override a machine reading.\n-13. Abnormal sleep/wake cycles (as determined by the Investigator).\n-14. Participants with known history of (that is within the past 12 months) or current alcohol or drug abuse. Participants that are abusing, in the opinion of the Investigator, cannabis, tobacco, and/or the use of e-cigarettes (vaping).\n-15. Participants with 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.\n-16. Participants with 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.\n-17. Female participants who are pregnant or lactating.\n-18. An employee or immediate family member of an employee of Crinetics.\n-19. 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 the first dose.\n-20. Part C: 20. Individuals in Part C who do not meet the Part C Inclusion Criteria"}

Endpoints

Primary endpoints

  • {"endpoint_text":"-Incidence of TEAEs including treatment emergent SAEs and any Aes leading to discontinuation.","definition_or_measurement_approach":""}
  • {"endpoint_text":"-Change from baseline in morning A4 at Week 8","definition_or_measurement_approach":""}
  • {"endpoint_text":"-Percent change from baseline in GC daily dose at Week 28 while serum early morning A4≤ULN","definition_or_measurement_approach":""}
  • {"endpoint_text":"-Change from baseline in morning A4 over time","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"-Change from baseline in morning serum 17-OHP at Week 8","definition_or_measurement_approach":""}
  • {"endpoint_text":"-Plasma and blood concentrations of atumelnant","definition_or_measurement_approach":""}
  • {"endpoint_text":"-Change from baseline in morning A4 at Week 4","definition_or_measurement_approach":""}
  • {"endpoint_text":"-Change from baseline in morning 17 OHP at Week 4","definition_or_measurement_approach":""}
  • {"endpoint_text":"-Proportion of participants with physiologic GC dose while morning A4 ","definition_or_measurement_approach":""}
  • {"endpoint_text":"-Change from baseline in morning 17-OHP over time","definition_or_measurement_approach":""}
  • {"endpoint_text":"-Percent change from baseline in GC daily dose over time","definition_or_measurement_approach":""}
  • {"endpoint_text":"-Proportion of participants with physiologic GC dose while morning A4 ","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
95
Recruitment Window Months
51
Consent Approach
Informed consent must be provided by the parent(s)/legal representative (if appropriate according to local laws) for pediatric participants. Age-appropriate assent forms and participant information sheets are provided for pediatric age groups (documents listed for ages including 3-5, 6-11, 12-17). Country-specific ICFs and assent forms are available (documents in Dutch, Polish, Italian, French, German, English are listed). Additional parental/guardian, pregnant-partner and newborn consent/ICF documents are provided where applicable.

Geography

Total Number Of Sites
28
Total Number Of Participants
61

Netherlands

Earliest CTIS Part Ii Submission Date
19-11-2025
Latest Decision Or Authorization Date
09-12-2025
Processing Time Days
20
Number Of Sites
1
Number Of Participants
4

Sites

Site Name
Radboud universitair medisch centrum Stichting
Department Name
Department of Pediatrics
Contact Person Name
Hedi Claahsen
Contact Person Email
hedi.claahsen@radboudumc.nl

Poland

Earliest CTIS Part Ii Submission Date
21-11-2025
Latest Decision Or Authorization Date
14-12-2025
Processing Time Days
23
Number Of Sites
6
Number Of Participants
15

Sites

Site Name
Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego
Department Name
Odział Kliniczny Endokrynologii i Pediatrii
Contact Person Name
Anna Kucharska
Contact Person Email
anna.kucharska1@wum.edu.pl
Site Name
Uniwersytecki Szpital Kliniczny Nr 1 Im. Prof. Tadeusza Sokolowskiego Pum W Szczecinie
Department Name
Centrum Wsparcia Badań Klinicznych Pomorskiego Uniwersytetu Medycznego w Szczecinie
Contact Person Name
Elżbieta Petriczko
Contact Person Email
cwbk@pum.edu.pl
Site Name
Instytut Centrum Zdrowia Matki Polki
Department Name
Klinika Endokrynologii i Chorób Metabolicznych
Contact Person Name
Renata Stawerska
Contact Person Email
renata.stawerska@iczmp.edu.pl
Site Name
SP SK Nr 1 Im Prof. S. Szyszko Śląskiego Uniwersytetu Medycznego w Katowicach
Department Name
Oddział Endokrynologii Dziecięcej
Contact Person Name
Agnieszka Zachurzok
Contact Person Email
azachurzok@sum.edu.pl
Site Name
Uniwersytecki Dzieciecy Szpital Kliniczny Im. L. Zamenhofa W Bialymstoku
Department Name
Klinika Pediatrii, Endokrynologii, Diabetologii z Pododdziałem Kardiologii
Contact Person Name
Artur Bossowski
Contact Person Email
artur.bossowski@udsk.pl
Site Name
Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
Department Name
Klinika Pediatrii, Endokrynologii, Diabetologii i Chorób Metabolicznych
Contact Person Name
Beata Wikiera
Contact Person Email
beata.wikiera@umw.edu.pl

Italy

Earliest CTIS Part Ii Submission Date
14-11-2025
Latest Decision Or Authorization Date
09-12-2025
Processing Time Days
25
Number Of Sites
6
Number Of Participants
15

Sites

Site Name
IRCCS Istituto Giannina Gaslini
Department Name
Pediatric Endocrine Unit
Contact Person Name
Natascia Di Iorgi
Contact Person Email
natasciadiiorgi@gaslini.org
Site Name
Ospedale Pediatrico Bambino Gesu
Department Name
Unità di Endocrinologia e Diabetologia
Contact Person Name
Stefano Cianfarani
Contact Person Email
stefano.cianfarani@uniroma2.it
Site Name
Ospedale San Raffaele S.r.l.
Department Name
Department of Pediatrics
Contact Person Name
Gianni Russo
Contact Person Email
russo.gianni@hsr.it
Site Name
Azienda Ospedaliera Universitaria Meyer IRCCS
Department Name
SOC Diabetologia e Endocrinologia - SS Auxoendocrinologia
Contact Person Name
Stefano Stagi
Contact Person Email
stefano.stagi@unifi.it
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
Child and Mother
Contact Person Name
Mariacarolina Salerno
Contact Person Email
sarleno@unina.it
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
Child and Mother
Contact Person Name
Mariacarolina Salerno
Contact Person Email
sarleno@unina.it

Belgium

Earliest CTIS Part Ii Submission Date
20-11-2025
Latest Decision Or Authorization Date
10-12-2025
Processing Time Days
20
Number Of Sites
4
Number Of Participants
9

Sites

Site Name
Cliniques Universitaires Saint-Luc
Department Name
Department of Pediatrics
Contact Person Name
Philippe Lysy
Site Name
Universitair Ziekenhuis Gent
Department Name
Department of Pediatrics
Contact Person Name
Martine Cools
Contact Person Email
martine.cools@uzgent.be
Site Name
Universitair Ziekenhuis Antwerpen
Department Name
Department of Pediatrics
Contact Person Name
Marieke den Brinker
Contact Person Email
marieke.denbrinker@uza.be
Site Name
UZ Leuven
Department Name
Pediatric endocrinology and diabetes department
Contact Person Name
An Jacobs
Contact Person Email
an.jacobs@uzleuven.be

Germany

Earliest CTIS Part Ii Submission Date
08-09-2025
Latest Decision Or Authorization Date
12-12-2025
Processing Time Days
95
Number Of Sites
5
Number Of Participants
11

Sites

Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Klinik für pädiatrische Endokrinologie und Diabetologie
Contact Person Name
Uta Neumann
Contact Person Email
uta.neumann@charite.de
Site Name
Medical Center - University Of Freiburg
Department Name
Kinder- und Jugendklinik
Contact Person Name
Clemens Kamrath
Site Name
Universitaetsklinikum des Saarlandes AöR
Department Name
Klinik für Allgemeine Pädiatrie und Neonatologie
Contact Person Name
Tilman Rohrer
Contact Person Email
tilman.rohrer@uks.eu
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Klinik für Kinder- und Jugendmedizin
Contact Person Name
Gerhard Binder
Site Name
University Hospital Cologne AöR
Department Name
Klinik und Poliklinik für Kinder- und Jugendmedizin
Contact Person Name
Heike-Katharina Hoyer-Kuhn

France

Earliest CTIS Part Ii Submission Date
24-11-2025
Latest Decision Or Authorization Date
15-12-2025
Processing Time Days
21
Number Of Sites
6
Number Of Participants
7

Sites

Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Centre Hospitalier Universitaire de Lille
Contact Person Name
Christine LEFEVRE
Contact Person Email
christine.lefevre@chu-lille.fr
Site Name
Centre Hospitalier Universitaire D'Angers
Department Name
Département Endocrinologie Pédiatrique
Contact Person Name
Regis COUTANT
Contact Person Email
ReCoutant@chu-angers.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Département Pédiatrie Multidisciplinaire
Contact Person Name
Rachel REYNAUD
Contact Person Email
Rachel-reynaud@ap-hm.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Service d’Endocrinologie Pédiatrique
Contact Person Name
Laetitia MARTINERIE
Contact Person Email
Laetitia.martinerie@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Endocrinologie, Diabétologie et Gynécologie Pédiatrique
Contact Person Name
Dulanjalee KARIYAWASAM
Contact Person Email
dulanjalee.kariyawasam@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Département Endocrinologie Pédiatrique
Contact Person Name
Claire BOUVATTIER
Contact Person Email
claire.bouvattier@aphp.fr

Sponsor

Primary sponsor

Full Name
Crinetics Pharmaceuticals Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
PPD Development LP
Responsibilities
1,11,12,13,2,5,8
Name
Altasciences Compagnie Inc.
Responsibilities
PK Lab; 3
Name
Everest Clinical Research Corporation
Responsibilities
6;7
Name
Pharmaron (Germantown) Lab Services Inc.
Responsibilities
4

Third parties

  • {"country":"United States","full_name":"Edetek Inc.","duties_or_roles":"ePRO","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"LabConnect GmbH","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United Kingdom","full_name":"Illingworth Research Group Limited","duties_or_roles":"13","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Advarra Inc.","duties_or_roles":"Optional training platform","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"LabConnect Europe B.V.","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Mayo Collaborative Services LLC","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Atreo Inc.","duties_or_roles":"3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Canada","full_name":"Altasciences Compagnie Inc.","duties_or_roles":"PK Lab; 3","organisation_type":"Pharmaceutical company"}
  • {"country":"Canada","full_name":"Everest Clinical Research Corporation","duties_or_roles":"6;7","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Pharmaron (Germantown) Lab Services Inc.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"1,11,12,13,2,5,8","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Labor Berlin Charite Vivantes GmbH","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Qualitymetric Incorporated LLC","duties_or_roles":"In trial optional interview","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"SGS Analytics Germany GmbH","duties_or_roles":"Safety-related labs (urine) - sample storage; 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Cardiac Safety","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Atumelnant 40 mg tablet
Active Substance
ATUMELNANT
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised
Starting Dose
40 mg once daily (Cohort 1, Part A, age 12 to <18 years)
Dose Levels
40 mg; 80 mg; dose to be determined (optional cohorts and younger ages)
Frequency
once daily
Maximum Dose
80 mg
Dose Escalation Increase
40 mg -> 80 mg
Investigational Product Name
Atumelnant 20 mg tablets
Active Substance
ATUMELNANT
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised
Dose Levels
20 mg
Maximum Dose
80 mg
Investigational Product Name
Atumelnant 80 mg tablets
Active Substance
ATUMELNANT
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Authorised
Starting Dose
80 mg once daily (Cohort 2, Part A, age 12 to <18 years)
Dose Levels
80 mg; 40 mg; dose to be determined (optional cohorts and younger ages)
Frequency
once daily
Maximum Dose
80 mg
Dose Escalation Increase
40 mg -> 80 mg
Investigational Product Name
Tablet
Modality
Other

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