This is a randomized, double-blinded, Placebo controlled trial that will evaluate the potential of tildacerfont to reduce glucocorticoid use in adult subjects with classic congenital adrenal hyperplasia who are on supraphysiologic doses of glucocorticoid therapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Spruce Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Genetic Phenomena [G05]

Trial duration

28 Jan 2021 → 31 Jan 2025

Decision date (initial)

2023-04-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Spruce Biosciences, Inc.

External identifiers

EU CT number

2023-503771-13-00

EudraCT number

2019-004765-40

WHO UTN

U1111-1287-6761

ClinicalTrials.gov

NCT04544410

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Therapy, Efficacy, Others

To evaluate the mean absolute glucocorticoid change in subjects with congenital adrenal hyperplasia over the 24-week, Double blind, Placebo-Controlled Treatment period

Secondary objectives 3

1. 1. To evaluate the effect of tildacerfont in reducing glucocorticoid use to near-physiologic levels while maintaining androgen control in subjects with congenital adrenal hyperplasia
2. 2. To evaluate the effect of tildacerfont in reducing GC use to near-physiologic levels while maintaining androgen control in subjects with congenital adrenal hyperplasia
3. 3. To evaluate the effect of tildacerfont in reducing cardiovascular risk in subjects with congenital adrenal hyperplasia.

Conditions and MedDRA coding

Classic Congenital Adrenal Hyperplasia

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board, Food And Drug Administration, Medicines And Healthcare Products Regulatory Agency, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1.Male and female subjects ≥18 years old at screening.
2. 2.Has a documented historical diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency based on genetic mutation in CYP21A2 and/or elevated 17-hydroxyprogesterone and currently treated with hydrocortisone, hydrocortisone acetate, prednisone, prednisolone, methylprednisolone, dexamethasone.
3. 3.Has lower limit of detection ≤ androstenedione ≤ 2.5x upper limit of normal at screening measured before an AM glucocorticoid dose.
4. 4.Has been on a stable, supraphysiologic dose of glucocorticoid replacement for ≥1 month before screening.
5. 5. For subjects with the salt-wasting form of congenital adrenal hyperplasia, subject has been on a stable dose of mineralocorticoid replacement for ≥1 months before screening.
6. 6.Agrees to follow contraception guidelines . Male subjects must also agree to refrain from donating sperm throughout the Treatment Period and for 90 days after the last dose of study drug.
7. 7.Is able to understand all study procedures and risks involved and provides written informed consent indicating willingness to comply with all aspects of the protocol.

Exclusion criteria 15

1. 1.Has a known or suspected diagnosis of any other known form of classic congenital adrenal hyperplasia (not due to 21-hydroxylase deficiency).
2. 6.Psychiatric conditions, including but not limited to bipolar disorder, schizophrenia, or schizoaffective disorders that are not effectively controlled on medication and may have an adverse impact on study compliance. Symptoms including hallucinations, delusions, and psychosis are exclusionary.
3. 7.Has clinically significant abnormal ECG or clinical laboratory results.
4. 8.Routinely works overnight shifts
5. 9.Subjects with travel plans/work schedules that result in significant and frequent changes in time zones (>2 hours) will require Medical Monitor approval for enrollment.
6. 10.Females who are pregnant or nursing.
7. 2.Has a history that includes bilateral adrenalectomy or hypopituitarism.
8. 11.Use of any other investigational drug from 30 days or 5 half-lives (whichever is longer) before screening to the end of the study.
9. 12.Use of the following drugs from 30 days or 5 half-lives (whichever is longer) before the start of the Glucocorticoid Conversion Period to the end of the study.
10. 12.a Rosiglitazone, aromatase inhibitors, testosterone, growth hormones, or any other medication or supplement that could impact subject safety or confound interpretation of study results.
11. 12.b. The drugs listed in protocol.
12. 13. Donation or receipt of blood from 90 days before Screening to the end of the study; donation or receipt of platelets, white blood cells, or plasma from 30 days before Screening to the end of the study.
13. 3.Has a history of allergy or hypersensitivity to tildacerfont, any of its excipients, or any other CRF1 receptor antagonist
14. 4.Shows clinical signs or symptoms of adrenal insufficiency.
15. 5.Has had a clinically significant unstable medical condition, medically significant illness, or chronic disease occurring within 30 days of screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Absolute change from baseline in glucocorticoid dose in hydrocortisone equivalent(s) at Week 24

Secondary endpoints 3

1. 1. 1. Proportion of subjects with baseline GC dose ≤ 35mg HCe who achieve GC dose ≤11 mg/m2/day in HCe and A4 ≤ 1.2x baseline or ≤ ULN at Week 24
2. 2. Proportion of subjects with GC dose ≤11 mg/m2/day in HCe and A4 ≤ 1.2x baseline or A4 ≤ ULN at Week 24
3. 3. Proportion of subjects with improvement in at least one cardiovascular risk factor at Week 24.

Investigational products

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

Test 1

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Spruce Biosciences Inc.

Sponsor organisation

Spruce Biosciences Inc.

Address

611 Gateway Boulevard Suite 740

City

South San Francisco

Postcode

94080-7029

Country

United States

Scientific contact point

Organisation

Spruce Biosciences Inc.

Contact name

Clinical Trials Helpline

Public contact point

Organisation

Spruce Biosciences Inc.

Contact name

Clinical Trials Helpline

Third parties 5

Locations

12 EU/EEA countries · 21 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 79 files

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

Application history

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