This is a randomized, double-blinded, Placebo controlled trial with a 3-part treatment period that will evaluate the efficacy and safety of up to 70 weeks of treatment with tildacerfont in subjects with classic Congenital adrenal hyperplasia (CAH) who have elevated blood hormones at baseline.

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

5 Jan 2021 → 24 Mar 2024

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

2023-503770-21-00

EudraCT number

2019-004764-22

WHO UTN

U1111-1287-6682

ClinicalTrials.gov

NCT04457336

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy, Dose response, Therapy, Pharmacokinetic

To evaluate the effect of tildacerfont in reducing androstenedione in subjects with congenital adrenal hyperplasia over 12 weeks.

Secondary objectives 3

1. 1. To evaluate the effect of tildacerfont on androstenedione levels in subjects with congenital adrenal hyperplasia over 12 weeks.
2. 2. To evaluate the effect of tildacerfont on 17-hydroxyprogesterone levels in subjects with congenital adrenal hyperplasia over 12 weeks.
3. 3. To evaluate the effect of tildacerfonr in reducing testicular adrenal rest tumor(s) in male congenital adrenal hyperplasia subjects with testicular adrenal rest tumor(s) at baseline after 12 weeks on treatment.

Conditions and MedDRA coding

Classic Congenital Adrenal Hyperplasia

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 known childhood diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency based on genetic mutation in CYP21A2 and/or documented (at any time) elevated 17-hydroxyprogesterone and currently treated with hydrocortisone, hydrocortisone acetate, prednisone, prednisolone, methylprednisolone (or a combination of the aforementioned glucocorticoids).
3. 3. Has been on a stable, supraphysiologic dose of glucocorticoid replacement for ≥1 month before screening.
4. 4. Has androstenedione >upper limit of normal at both screening and Week 4 if daily glucocorticoid dose <30 mg OR has androstenedione >2.5x upper limit of normal at both screening and Week 4.
5. 5.For subjects with the salt-wasting form of congenital adrenal hyperplasia, the subject is on a stable dose of mineralocorticoid replacement for ≥1 month 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 26

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. 2.Has a history that includes bilateral adrenalectomy or hypopituitarism.
3. 3.Has a history of allergy or hypersensitivity to tildacerfont, or any of its excipients or any other CRF1 receptor antagonist.
4. 4.Current treatment with dexamethasone as glucocorticoid therapy for congenital adrenal hyperplasia.
5. 5.Is not adherent to glucocorticoid or study drug dosing regimen during the Run-in Period (defined as taking <80% of expected doses based on drug accountability).
6. 6.Shows clinical signs or symptoms of adrenal insufficiency.
7. 7.Has had a clinically significant unstable medical condition, medically significant illness, or chronic disease occurring within 30 days of screening, including but not limited to:
8. 7.a. An ongoing malignancy or <3 years of remission history from any malignancy, other than successfully treated localized skin cancer.
9. 7.b. Estimated glomerular filtration rate of <45 mL/min/1.73 m2.
10. 7.c.Current or history of liver disease (with the exception of Gilbert’s syndrome).
11. 7.d.History of alcohol or substance abuse within the last year, or any significant history of alcohol or substance abuse that would likely prevent the subject from reliably participating in the study, based on the opinion of the Investigator.
12. 7.e.Active hepatitis B, hepatitis C, or human immunodeficiency virus at screening.
13. 7.f. Subjects who plan to undergo bariatric surgery during the study are excluded.
14. 7.g.Any other condition that would impact subject safety or confound interpretation of study results.
15. 8.Psychiatric conditions, including but not limited to depression, bipolar disorder, schizophrenia or schizoaffective disorder that are not effectively controlled on medication and may have an adverse impact on study compliance. Symptoms including hallucinations, delusions and psychosis are exlcusionary.
16. 8.a.Increased risk of suicide based on the Investigator's judgment or the results of the Columbia–Suicide Severity Rating Scale (C-SSRS) conducted at screening and Week 6 (eg, C-SSRS Type 3, 4, or 5 ideation within the past 6 months or any suicidal behavior within the past 12 months)
17. 8.b.Hospital Anxiety and Depression Scale score >12 for either depression or anxiety at screening or Week 6.
18. 9. Has clinically significant abnormal ECG or clinical laboratory results.
19. 10. Routinely works overnight shifts.
20. 11. 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.
21. 12.Females who are pregnant or nursing.
22. 13.Use of any other investigational drug from 30 days or 5 half-lives (whichever is longer) before screening to the end of the study.
23. 14.Use of the following drugs from 30 days or 5 half-lives (whichever is longer) before Day 1 to the end of the study:
24. 14.a.rosiglitazone, aromatase inhibitors, testosterone, or growth hormones or any other medication or supplement that could impact subject safety or confound interpretation of study results.
25. 14.b.drugs listed in the study protocol.
26. 15.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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change from baseline in androstenedione after 12 weeks on treatment (Week 18).

Secondary endpoints 3

1. 1. Proportion of subjects who achieve androstenedione ≤ upper limit of normal after 12 weeks on treatment (Week 18)
2. 2. Proportion of subjects who achieve 17-hydroxyprogesterone ≤ 1200 ng/dL after 12 weeks on treatment (Week 18).
3. 3. Change in the lesion volume of testicular adrenal rest tumor(s) from baseline after 12 weeks on treatment (Week 18)

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Spruce Biosciences Inc.

Sponsor organisation

Spruce Biosciences Inc.

Address

2001 Junipero Serra Boulevard Suite 640

City

Daly City

Postcode

94014-3891

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 · 26 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 14 files

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

Application history

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