Evaluate the Safety, Efficacy, and Pharmacokinetics of CRN04894 in Participants with Congenital Adrenal Hyperplasia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Crinetics Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

27 Nov 2023 → 22 Aug 2025

Decision date (initial)

2023-09-26

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Crinetics Pharmaceuticals, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

Safety Objective: To evaluate the safety and tolerability of CRN04894
Primary Efficacy Objective: To evaluate efficacy of CRN04894, measured by change from Baseline in serum androstenedione (A4)

Secondary objectives 1

1. Secondary Efficacy Objective: To evaluate efficacy of CRN04894, measured by change from Baseline in serum 17-hydroxyprogesterone (17-OHP)

Conditions and MedDRA coding

CONGENITAL ADRENAL HYPERPLASIA

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female participants ≥18 to 75 years of age at the time of signing the Informed Consent Form (ICF). Participants ≥16 years of age may be included in sites located in the United States (US)
2. Classic 21-hydroxylase deficiency confirmed by the Investigator and approved by the Medical Monitor.
3. On a stable (defined as no dose change of >5 mg/day hydrocortisone equivalent (see Section 12.5) within 6 months prior to Screening) regimen of glucocorticoid replacement (eg, hydrocortisone, prednisolone, prednisone, methylprednisolone).
4. Compliance, as judged per investigator discretion, with glucocorticoid replacement and mineralocorticoid replacement (if applicable) regimen documented during the Screening Period
5. Minimum total daily dose of ≥15 mg hydrocortisone (or equivalent)
6. If on estrogen therapy (any route), dose must be stable for at least 3 months prior to Screening.

Exclusion criteria 16

1. Diagnosis of any other form of CAH other than classic 21-hydroxylase deficiency
2. Dexamethasone or oral betamethasone use within 30 days of Screening
3. History of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic glucocorticoid therapy
4. Night shift workers or any other reason for abnormal sleep/wake cycles
5. Clinically significant medical condition or abnormal laboratory tests, as judged by the Investigator, other than CAH
6. History of major surgery/surgical therapy for any cause within 4 weeks prior to Screening
7. Diabetes mellitus treated with insulin for less than 6 weeks prior to Screening, or with change in total daily insulin dose by >15% within 6 weeks prior to Screening
8. Poorly controlled diabetes mellitus defined as having a hemoglobin A1c (HbA1c) ≥8.5%(≥69 mmol/mL), or estimated HbA1c based on fructosamine if HbA1c is not evaluable (eg, due to hemoglobinopathies)
9. 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
10. 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
11. 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
12. History of cancer excluding cured/treated dermal squamous or basal cell carcinoma or cervical carcinoma in situ
13. 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.
14. Known history of illicit drug or alcohol abuse within the last year
15. Use of antiandrogen therapy in the past 3 months (eg, spironolactone, finasteride, cyproterone acetate, flutamide)
16. Use of testosterone, androgen-containing supplements, aromatase inhibitors, or growth hormone

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Primary Safety Endpoints: Incidence of treatment-emergent adverse events (TEAEs), including treatment-emergent serious adverse events (SAEs) and any adverse events (AEs) leading to discontinuation
2. Primary Efficacy Endpoint: Change from Baseline in morning (before 11:00) serum A4 at Week 12

Secondary endpoints 1

1. Secondary Efficacy Endpoint: Change from Baseline in morning (before 11:00) serum 17-OHP at Week 12

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Crinetics Pharmaceuticals Inc.

Sponsor organisation

Crinetics Pharmaceuticals Inc.

Address

10222 Barnes Canyon Road Building 2

City

San Diego

Postcode

92121-2711

Country

United States

Scientific contact point

Organisation

Crinetics Pharmaceuticals Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Crinetics Pharmaceuticals Inc.

Contact name

Clinical Medical Lead

Third parties 12

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications