A study of safety and efficacy of NBI-74788 in Classic Congenital Adrenal Hyperplasia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Neurocrine Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

Trial duration

23 Nov 2020 → ongoing

Decision date (initial)

2024-07-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Neurocrine Biosciences, Inc.

External identifiers

EU CT number

2023-509171-16-00

EudraCT number

2019-004873-17

ClinicalTrials.gov

NCT04490915

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Pharmacogenetic, Pharmacokinetic, Efficacy

• To evaluate the efficacy of Crinecerfont (100 mg twice daily [bid]), compared with placebo, in reducing daily glucocorticoid dosage while maintaining adrenal androgen control.
• To evaluate the efficacy of Crinecerfont, compared with placebo, in reducing adrenal steroid levels following an initial 4-week treatment period.
• To evaluate the effect of Crinecerfont, compared with placebo, on clinical endpoints associated with supraphysiologic glucocorticoid dosing.
• To evaluate plasma concentrations of Crinecerfont and metabolites.
• To assess the safety and tolerability of Crinecerfont.
• To evaluate an alternate dosing regimen of crinecerfont in subjects who have not reduced their glucocorticoid dose by Month 12

Conditions and MedDRA coding

Classic Congenital Adrenal Hyperplasia (CAH)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Subjects must provide written informed consent.
2. Be a female or male at least 18 years of age.
3. Have a medically confirmed diagnosis of classic 21-hydroxylase deficiency.
4. Be on a stable, supraphysiologic glucocorticoid dose regimen that has been stable for at least 1 month prior to screening.
5. If treated with fludrocortisone, dose should be stable for at least 1 month prior to screening with an upright plasma renin activity (PRA) during screening that is not greater than ULN on the subject's usual sodium intake. If PRA is >ULN, the subject must have systolic blood pressure >100 mmHg, without orthostatic hypotension, and with serum sodium and potassium in the normal range.
6. Female subjects of childbearing potential with fertile male partners must agree to use contraception consistently from screening until the final study visit or 30 days after the last dose of study drug, whichever is longer. A female who is not of childbearing potential must meet one of the following:

Exclusion criteria 9

1. Have a known or suspected diagnosis of any of the other forms of classic CAH including 11-β-hydroxylase deficiency, 17-α-hydroxylase deficiency, 3-β-hydroxysteroid dehydrogenase deficiency, P450 sidechain cleavage deficiency, or P450 oxidoreductase deficiency.
2. Have a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic therapy with oral glucocorticoids, or requiring chronic therapy with inhaled glucocorticoids that based on dose and hormone profile the investigator deems would yield significant systemic exposure interfering with study endpoints.
3. Have a clinically significant medical condition or chronic disease (including history of neurological, hepatic, renal, cardiovascular, gastrointestinal, significant malabsorption, hematologic, pulmonary, psychiatric, or endocrine disease [excluding CAH]) that in the opinion of the investigator would preclude the subject from participating in and completing the study or that could confound interpretation of study outcome.
4. History of malignancy, unless successfully treated with curative intent and considered to be cured.
5. Have a known history of clinically concerning cardiac arrhythmia (including long QT syndrome) or prolongation of screening (pretreatment) QT interval corrected for heart rate using Fridericia's correction (QTcF) of >450 msec (males) or >470 msec (females).
6. Known sensitivity (ie, hypersensitivity) or allergy to any corticotropinreleasing hormone (CRH) receptor antagonist.
7. Have evidence of chronic renal or liver disease Used any active investigational drug within 30 days or 5 half-lives (whichever is longer) before screening, or plans to use an investigational drug (other than the study drug) during the study.
8. Females who are pregnant or lactating.
9. Are using any excluded concomitant medication and cannot discontinue use of these medications for the duration of the study (also refer to Section 9.9.1): • Orally administered glucocorticoids for indications other than CAH. • Strong inducers of CYP3A4 or CYP2B6 except topically administered medications. • Medications that affect cortisol or glucocorticoid metabolism (eg, phenytoin, mitotane, phenobarbital, strong CYP3A4 inhibitors such as ketoconazole, clarithromycin, cholestyramine, certain antivirals) except topically administered medications. • Aromatase inhibitors (eg, anastrozole, letrozole, testolactone).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change from baseline in glucocorticoid daily dose (in hydrocortisone equivalents adjusted for BSA [mg/m2/day]) at Week 24.

Secondary endpoints 3

1. Change from baseline in serum androstenedione at Week 4.
2. Achievement of a reduction in glucocorticoid daily dose to physiologic levels Week 24.
3. Changes from baseline in HOMA-IR, weight, and fat mass at Week 24

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Neurocrine Biosciences Inc.

Sponsor organisation

Neurocrine Biosciences Inc.

Address

6027 Edgewood Bend Court

City

San Diego

Postcode

92130-8235

Country

United States

Scientific contact point

Organisation

Neurocrine Biosciences Inc.

Contact name

Neurocrine Medical Information Call Center

Public contact point

Organisation

Neurocrine Biosciences Inc.

Contact name

Neurocrine Medical Information Call Center

Third parties 16

Locations

12 EU/EEA countries · 31 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 186 files

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

Application history

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