Congenital Adrenal HyperplasiaPhase 2NCT04544410
A Ph2b to Evaluate Tildacerfont in the Reduction of Glucocorticoid Steroid Doses in Adult CAH
A Phase 2 study of Congenital Adrenal Hyperplasia, run by Spruce Biosciences at 43 sites in 16 countries.
Trial summary
An investigation of the ability of Tildacerfont to reduce supraphysiologic glucocorticoid dosing in classic Congenital adrenal hyperplasia (CAH) subjects up to 76 weeks of treatment. Optional open label extension up to 240 weeks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Congenital Adrenal Hyperplasia
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 43 sitesin 16 countries
- Study dates
- 22 Feb 2021to 31 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female subjects ≥18 years old at screening
- Has a known childhood diagnosis of classic CAH due to 21-hydroxylase deficiency based on genetic mutation in CYP21A2 and/or documented (at any time) elevated 17-hydroxyprogesterone (17-OHP) and currently treated with hydrocortisone (HC), HC acetate, prednisone, prednisolone, methylprednisolone, dexamethasone (or a combination of the aforementioned glucocorticoid [GCs])
- Has lower limit of detection ≤ androstenedione (A4) ≤ 2.5x upper limit of normal (ULN) at screening measured before a morning GC dose
- Has been on a stable, supraphysiologic dose of GC replacement (defined as ≥30 mg/day and ≤60 mg/day in HCe) for ≥1 month before screening
- For subjects with the salt-wasting form of CAH, subject has been on a stable dose of mineralocorticoid replacement for ≥1 month before screening
- 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
- 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
Who cannot join
- Has a known or suspected diagnosis of any other known form of classic CAH (not due to 21-hydroxylase deficiency)
- Has a history that includes bilateral adrenalectomy or hypopituitarism
- Has a history of allergy or hypersensitivity to tildacerfont, any of its excipients, or any other CRF1 receptor antagonist
- Shows clinical signs or symptoms of adrenal insufficiency
- 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:
- An ongoing malignancy or <3 years of remission history from any malignancy, other than successfully treated localized skin cancer
Show all 28Show fewer
- eGFR of <45 mL/min/1.73 m2
- Current or history of liver disease (with the exception of Gilbert's syndrome)
- 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
- Active hepatitis B, hepatitis C, or HIV at screening
- Subjects who plan to undergo bariatric surgery during the study are excluded
- Any other condition that would impact subject safety or confound interpretation of study results
- 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. Additionally:
- Increased risk of suicide based on the Investigator's judgment or the results of the C-SSRS conducted at screening and baseline (eg, C-SSRS Type 3, 4, or 5 ideation within the past 6 months or any suicidal behavior within the past 12 months) b. Hospital Anxiety and Depression Scale (HADS) score >12 for either depression or anxiety at screening or baseline
- Has clinically significant abnormal ECG or clinical laboratory results. Abnormal results that must be reviewed and discussed with the Medical Monitor to determine eligibility for this study include but are not limited to:
- Any clinically meaningful abnormal ECG results, including QTcF >450 ms for male participants or >470 ms for female participants
- ALT >2x ULN
- Total bilirubin >1.5x ULN
- Total bile acids >5x ULN
- Routinely works overnight shifts
- 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
- Females who are pregnant or nursing
- Use of any other investigational drug from 30 days or 5 half-lives (whichever is longer) before screening to the end of the study
- Use of the following drugs from 30 days or 5 half-lives (whichever is longer) before the start of the Treatment Period to the end of the study:
- Rosiglitazone, aromatase inhibitors, testosterone, growth hormones, or any other medication or supplement that could impact subject safety or confound interpretation of study results
- The drugs which are:
- Moderate to strong inhibitors and/or inducers of CYP3A4 ii. Sensitive substrates or narrow-therapeutic-range substrates of CYP3A4 (except hormonal contraception containing ≤35 μg ethinyl estradiol) iii. Sensitive substrates or narrow-therapeutic-range substrates of BCRP (except those that can be administered QD in the morning, separated by approximately 10 hours from evening administration of study drug)
- 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
Trial locations and contacts
43 sites in 16 countries.
43 sites in 16 countries
United States18 sites
Spruce Biosciences Clinical Site
Ann Arbor, Michigan, 48109
Spruce Study Site
Baltimore, Maryland, 21287
Spruce Study Site
Birmingham, Alabama, 35294
Spruce Study Site
Canton, Ohio, 44718
Spruce Study Site
Cincinnati, Ohio, 45219
Spruce Study Site
Cleveland, Ohio, 44195
Spruce Study Site
Columbia, South Carolina, 29203
Spruce Study Site
Columbus, Ohio, 43210
Spruce Study Site
Fort Worth, Texas, 76104
Spruce Study Site
Indianapolis, Indiana, 46202
Spruce Study Site
Los Angeles, California, 90027
Spruce Study Site
Minneapolis, Minnesota, 55454
Spruce Study Site
New Brunswick, New Jersey, 08901
Spruce Study Site
Philadelphia, Pennsylvania, 19104
Spruce Study Site
Philadelphia, Pennsylvania, 19107
Spruce Study Site
Philadelphia, Pennsylvania, 19140
Spruce Study Site
Providence, Rhode Island, 02903
Spruce Study Site
San Diego, California, 92123
Australia4 sites
Spruce Study Site
Blacktown
Spruce Study Site
Brisbane, 4029
Spruce Study Site
Elizabeth Vale
Spruce Study Site
Parkville
Spain4 sites
Spruce Study Site
Barcelona
Spruce Study Site
Madrid
Spruce Study Site
Seville
Spruce Study Site
Tarragona
Canada2 sites
Spruce Study Site
Ottawa, Ontario
Spruce Study Site
Sherbrooke, Quebec, J1H 5N4
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of SPR001 (Tildacerfont) in Reducing Supraphysiologic Glucocorticoid Use in Adult Subjects With Classic Congenital Adrenal Hyperplasia
An investigation of the ability of Tildacerfont to reduce supraphysiologic glucocorticoid dosing in classic Congenital adrenal hyperplasia (CAH) subjects up to 76 weeks of treatment. Optional open label extension up to 240 weeks.
Read the detailed description
This is a study that evaluated the ability of tildacerfont to reduce the glucocorticoid steroid dose used by adult subjects with CAH. The first 24-weeks were a double-blind, placebo controlled, comparison of tildacerfont vs placebo. The following 52-weeks allowed all subjects to move to open label tildacerfont to continue to reduce steroid dose where appropriate, and observe long term safety. Subjects were offered a long term open label extension up to 240 weeks.
- Conditions
- Congenital Adrenal Hyperplasia
- Being tested
- Tildacerfont/Placebo
- Keywords
- CAH, Adrenal Disorder, Congenital Adrenal Hyperplasia
- Medical subject headings
- Adrenal Hyperplasia, Congenital, Adrenal Gland Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tildacerfont/PlaceboDrug
Also called SPR001
Tablet, administered daily
| Study group | Role | What they receive |
|---|---|---|
| Tildacerfont Group | Experimental | Tildacerfont administered daily via oral tablet for 24 weeks at dose level 1; followed by open label tildacerfont for 52 weeks Receives: Drug: Tildacerfont/Placebo |
| Placebo | Placebo comparator | Placebo administered daily via oral tablet for 24 weeks; followed by open label tildacerfont for 52 weeks Receives: Drug: Tildacerfont/Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Total Daily GC Dose in Subjects With Classic CAH Over the 24-week, Double Blind, Placebo-Controlled Treatment Period
Absolute change from baseline (Day 1) in GC dose in HCe at Week 24. The analysis of absolute change in total daily GC dose in HCe will include data from Weeks 3, 6, 12, 18 and 24 in a mixed model
Measured: 24 Weeks
Secondary outcomes (3)
Effect of Tildacrfont in Reducing GC Use to Near-physiologic Levels While Maintaining Androgen Control in Subjects With CAH
Proportion of subjects with GC dose ≤11mg/m2/day in HCe and A4 ≤1.2x baseline or A4 ≤ ULN at Week 24
Measured: 24 weeks
Effect of Tildacrfont in Reducing GC Use to Near-physiologic Levels While Maintaining Androgen Control in Subjects With CAH
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
Measured: 24 Weeks
Effectiveness in Reducing Cardiovascular Risk in Subjects With CAH
Proportion of subjects with improvement in at least one cardiovascular risk factor at Week 24
Measured: 24 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2020
- Study start22 Feb 2021
- Primary completion31 Oct 2024
- Study completion31 Jan 2025
Why it stopped: Study did not meet its primary endpoint.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Congenital Adrenal HyperplasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomized in a 1:1 manner to either Tildacerfont or Placebo for 24 weeks followed by 52 weeks open label Tildacerfont
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spruce Biosciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ron Newfield, M.D, Principal investigator, Rady Children's Hospital-San Diego and Professor of clinical pediatrics at UC San Diego School of Medicine.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04544410
- Sponsor's protocol ID
- SPR001-204
- Other IDs
- CAHmelia 204
- Status last verified
- Sep 2025
- First submitted
- 30 Aug 2020
- Last updated
- 1 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of SPR001 (Tildacerfont) in Reducing Supraphysiologic Glucocorticoid Use in Adult Subjects With Classic Congenital Adrenal Hyperplasia
- ClinicalTrials.gov ID
- NCT04544410
- Acronym / sponsor ID
- SPR001-204
- Conditions
- Congenital Adrenal Hyperplasia
- Keywords
- CAH, Adrenal Disorder, Congenital Adrenal Hyperplasia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study did not meet its primary endpoint.
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Spruce BiosciencesIndustry (pharma, biotech, devices)
- Study start
- 22 Feb 2021 (actual)
- Primary completion
- 31 Oct 2024 (actual)
- Study completion
- 31 Jan 2025 (actual)
- First posted
- 10 Sep 2020 (actual)
- Results
- Posted 1 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An investigation of the ability of Tildacerfont to reduce supraphysiologic glucocorticoid dosing in classic Congenital adrenal hyperplasia (CAH) subjects up to 76 weeks of treatment. Optional open label extension up to 240 weeks.
Detailed description
This is a study that evaluated the ability of tildacerfont to reduce the glucocorticoid steroid dose used by adult subjects with CAH. The first 24-weeks were a double-blind, placebo controlled, comparison of tildacerfont vs placebo. The following 52-weeks allowed all subjects to move to open label tildacerfont to continue to reduce steroid dose where appropriate, and observe long term safety. Subjects were offered a long term open label extension up to 240 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Subjects will be randomized in a 1:1 manner to either Tildacerfont or Placebo for 24 weeks followed by 52 weeks open label Tildacerfont
| Arm | Type | Receives |
|---|---|---|
| Tildacerfont Group | Experimental | Drug: Tildacerfont/PlaceboTildacerfont administered daily via oral tablet for 24 weeks at dose level 1; followed by open label tildacerfont for 52 weeks |
| Placebo | Placebo comparator | Drug: Tildacerfont/PlaceboPlacebo administered daily via oral tablet for 24 weeks; followed by open label tildacerfont for 52 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male and female subjects ≥18 years old at screening
- Has a known childhood diagnosis of classic CAH due to 21-hydroxylase deficiency based on genetic mutation in CYP21A2 and/or documented (at any time) elevated 17-hydroxyprogesterone (17-OHP) and currently treated with hydrocortisone (HC), HC acetate, prednisone, prednisolone, methylprednisolone, dexamethasone (or a combination of the aforementioned glucocorticoid [GCs])
- Has lower limit of detection ≤ androstenedione (A4) ≤ 2.5x upper limit of normal (ULN) at screening measured before a morning GC dose
- Has been on a stable, supraphysiologic dose of GC replacement (defined as ≥30 mg/day and ≤60 mg/day in HCe) for ≥1 month before screening
- For subjects with the salt-wasting form of CAH, subject has been on a stable dose of mineralocorticoid replacement for ≥1 month before screening
Key exclusion criteria (28 listed)
- Has a known or suspected diagnosis of any other known form of classic CAH (not due to 21-hydroxylase deficiency)
- Has a history that includes bilateral adrenalectomy or hypopituitarism
- Has a history of allergy or hypersensitivity to tildacerfont, any of its excipients, or any other CRF1 receptor antagonist
- Shows clinical signs or symptoms of adrenal insufficiency
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tildacerfont/PlaceboAlso: SPR001Tablet, administered daily | Drug | Placebo, Tildacerfont Group |
Primary outcome
Change in Total Daily GC Dose in Subjects With Classic CAH Over the 24-week, Double Blind, Placebo-Controlled Treatment Period
Time frame: 24 Weeks
Absolute change from baseline (Day 1) in GC dose in HCe at Week 24. The analysis of absolute change in total daily GC dose in HCe will include data from Weeks 3, 6, 12, 18 and 24 in a mixed model
3 secondary outcomes
Effect of Tildacrfont in Reducing GC Use to Near-physiologic Levels While Maintaining Androgen Control in Subjects With CAH
Time frame: 24 weeks
Effect of Tildacrfont in Reducing GC Use to Near-physiologic Levels While Maintaining Androgen Control in Subjects With CAH
Time frame: 24 Weeks
Effectiveness in Reducing Cardiovascular Risk in Subjects With CAH
Time frame: 24 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ron Newfield, M.D principal investigator
Rady Children's Hospital-San Diego and Professor of clinical pediatrics at UC San Diego School of Medicine.
43 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study of Congenital Adrenal Hyperplasia, run by Spruce Biosciences at 43 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in United States, Australia, Spain, Brazil, Canada and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Total Daily GC Dose in Subjects With Classic CAH Over the 24-week, Double Blind, Placebo-Controlled Treatment Period (time frame: 24 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2025.