Congenital Adrenal HyperplasiaPhase 2NCT04457336
A Ph2b to Evaluate Clinical Efficacy and Safety of Tildacerfont in Adult CAH
A Phase 2 study of Congenital Adrenal Hyperplasia, run by Spruce Biosciences at 65 sites in 20 countries.
Trial summary
An investigation of the efficacy and safety of up to 70 weeks of treatment with Tildacerfont in subjects with classic CAH who have elevated biomarkers at baseline on their current GC regimen. Optional open label treatment extension period up to 240 weeks with 200mg Tildacerfont QD. 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
- 96 participants
- Where
- 65 sitesin 20 countries
- Study dates
- 26 Aug 2020to 23 May 2024
- 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-OHP and currently treated with HC, HC acetate, prednisone, prednisolone, methylprednisolone (or a combination of the aforementioned GCs)
- Has been on a stable, supraphysiologic dose of GC replacement (defined as ≥15 mg/day and ≤60 mg/day in HCe) for ≥1 month before screening
- Has A4 >ULN at both screening and Week 4 (measured before any AM GC dose) if daily GC dose <30 mg OR has A4 >2.5x ULN at both screening and Week 4 (measured before any AM GC dose)
- 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
- Current treatment with dexamethasone as GC therapy for CAH
- Prior treatment with dexamethasone is allowed as long as the transition to an alternative GC regimen (eg, HC, prednisone, or prednisolone) has resulted in a stable dose of GC replacement for ≥1 month before screening.
- Is not adherent to GC or study drug dosing regimen during the Run-in Period (defined as taking <80% of expected doses based on drug accountability)
Show all 32Show fewer
- 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
- 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 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)
- HADS score >12 for either depression or anxiety at screening or Week 6
- 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 Day 1 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 following drugs:
- 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
65 sites in 20 countries.
65 sites in 20 countries
United States28 sites
Spruce Study Site
Austin, Texas, 78731
Spruce Study Site
Baltimore, Maryland, 21287
Spruce Clinical Site
Bend, Oregon, 97702
Spruce Study Site
Birmingham, Alabama, 35294
Spruce Study Site
Canton, Ohio, 44718
Spruce Study Site
Chicago, Illinois, 60611
Spruce Study Site
Cincinnati, Ohio, 45219
Spruce Study Site
Cleveland, Ohio, 44195
Spruce Study Site
Columbia, South Carolina, 28203
Spruce Study Site
Columbus, Ohio, 43210
Spruce Study Site
Dallas, Texas, 75093
Spruce Clinical Site
Edinburg, Texas, 78539
Spruce Study Site
Englewood, Colorado, 80113
Spruce Clinical Site
Fort Worth, Texas, 76104
Spruce Study Site
Hickory, North Carolina, 28601
Spruce Clinical Site
Indianapolis, Indiana, 46202
Spruce Clinical Site
Las Vegas, Nevada, 89148
Spruce Study Site
Los Angeles, California, 90027
Spruce Clinical Site
Memphis, Tennessee, 38163
Spruce Clinical Site
Minneapolis, Minnesota, 55454
Spruce Clinical Site
Orange, California, 92868
Spruce Study Site
Philadelphia, Pennsylvania, 19104
Spruce Study Site
Philadelphia, Pennsylvania, 19107
Spruce Study Site
Providence, Rhode Island, 02903
Spruce Study Site
Rochester, Minnesota, 55905
Spruce Study Site
Sacramento, California, 95817
Spruce Clinical Site
Tampa, Florida, 33612
Spruce Study Site
West Palm Beach, Florida, 33401
Australia4 sites
Spruce study site
Brisbane
Spruce Study Site
Elizabeth Vale
Spruce Study Site
Melbourne
Spruce Study Site
Nedlands, Western Australia, 6009
Canada4 sites
Spruce Study Site
London, Ontario
Spruce Study Site
Ottawa, K1H7W9
Spruce Study Site
Sherbrooke, J1H 5N4
Spruce Study Site
St. John's, Newfoundland and Labrador
Italy4 sites
Spruce Study Site
Milan
Spruce Study Site
Naples
Spruce Study Site
Rome
Spruce Study Site
Torino
Spain4 sites
Spruce Study Site
Barcelona
Spruce Study Site
Madrid
Spruce Study Site
Seville
Spruce Study Site
Tarragona
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of SPR001 (Tildacerfont) in Adult Subjects With Classic Congenital Adrenal Hyperplasia
An investigation of the efficacy and safety of up to 70 weeks of treatment with Tildacerfont in subjects with classic CAH who have elevated biomarkers at baseline on their current GC regimen. Optional open label treatment extension period up to 240 weeks with 200mg Tildacerfont QD.
Read the detailed description
This is a study that will test the efficacy and safety of Tildacerfont. The first 12-weeks will be a double-blind, placebo controlled, dose ranging study. The following 58-weeks will assess the long term safety of Tildacerfont. Optional open label treatment extension period up to 240 weeks with 200mg Tildacerfont QD.
- 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 1 | Experimental | Tildacerfont administered daily via oral tablet for 12 weeks at dose level 1 Receives: Drug: Tildacerfont/Placebo |
| Tildacerfont Group 2 | Experimental | Tildacerfont administered daily via oral tablet for 12 weeks at dose level 2 Receives: Drug: Tildacerfont/Placebo |
| Tildacerfont Group 3 | Experimental | Tildacerfont administered daily via oral tablet for 70 weeks at dose level 3 Receives: Drug: Tildacerfont/Placebo |
| Placebo | Placebo comparator | Placebo administered daily via oral tablet for 12 weeks. Receives: Drug: Tildacerfont/Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic Congenital Adrenal Hyperplasia (CAH) Over 12 Weeks
Assessment of dose response for change from baseline in log A4 after 12 weeks on double-blind placebo-controlled treatment (Week 18)
Measured: Baseline and 12 weeks of treatment (Week 18)
Secondary outcomes (4)
To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic CAH Over 12 Weeks
Absolute change from baseline in A4 as determined via application of the delta theorem to the log scale analysis results after 12 weeks on double-blind, placebo-controlled treatment (Week 18). Results show mean Treatment Effect of Dose vs Placebo. A negative value represents a reduction in absolute concentration compared to baseline.
Measured: 12 weeks
To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic CAH Over 12 Weeks
Change from baseline in A4 as assessed on the log scale after 12 weeks on double-blind, placebo-controlled treatment (Week 18). Results show mean % of Treatment Effect of Dose vs Placebo. A negative value represents a % reduction from baseline.
Measured: 12 weeks
To Evaluate the Effect of Tildacerfont in Reducing 17-OHP in Participants With Classic CAH Over 12 Weeks
Change from baseline in 17-OHP as assessed on the log scale after 12 weeks on double-blind, placebo-controlled treatment (Week 18). A negative value represents a % reduction from baseline.
Measured: 12 weeks
To Evaluate the Effect of Tildacerfont in Reducing 17-OHP in Participants With Classic CAH Over 12 Weeks
Absolute change from baseline in 17-OHP as determined via application of the delta theorem to the log scale analysis results after 12 weeks on double-blind, placebo-controlled treatment (Week 18). Results show mean Treatment Effect of Dose vs Placebo. A negative value represents a reduction in absolute concentration compared to baseline.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2020
- Study start26 Aug 2020
- Primary completion9 Feb 2024
- Study completion23 May 2024
Why it stopped: Study SPR001-203 did not meet its primary and secondary endpoints therefore Spruce Biosciences has decided to terminate the study
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 1:1:1:1 manner to one of three doses of Tildacerfont or Placebo.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spruce Biosciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kyriakie Sarafoglou, M.D, Principal investigator, Dept. of Pediatrics, Divisions of Endocrinology and Genetics & Metabolism, Univ. of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04457336
- Sponsor's protocol ID
- SPR001-203
- Other IDs
- CAHmelia 203
- Status last verified
- Jun 2025
- First submitted
- 25 Jun 2020
- Last updated
- 8 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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 8 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of SPR001 (Tildacerfont) in Adult Subjects With Classic Congenital Adrenal Hyperplasia
- ClinicalTrials.gov ID
- NCT04457336
- Acronym / sponsor ID
- SPR001-203
- Conditions
- Congenital Adrenal Hyperplasia
- Keywords
- CAH, Adrenal Disorder, Congenital Adrenal Hyperplasia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study SPR001-203 did not meet its primary and secondary endpoints therefore Spruce Biosciences has decided to terminate the study
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Spruce BiosciencesIndustry (pharma, biotech, devices)
- Study start
- 26 Aug 2020 (actual)
- Primary completion
- 9 Feb 2024 (actual)
- Study completion
- 23 May 2024 (actual)
- First posted
- 7 Jul 2020 (actual)
- Results
- Posted 8 Jul 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 efficacy and safety of up to 70 weeks of treatment with Tildacerfont in subjects with classic CAH who have elevated biomarkers at baseline on their current GC regimen. Optional open label treatment extension period up to 240 weeks with 200mg Tildacerfont QD.
Detailed description
This is a study that will test the efficacy and safety of Tildacerfont. The first 12-weeks will be a double-blind, placebo controlled, dose ranging study. The following 58-weeks will assess the long term safety of Tildacerfont. Optional open label treatment extension period up to 240 weeks with 200mg Tildacerfont QD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- Model description
- Subjects will be randomized in a 1:1:1:1 manner to one of three doses of Tildacerfont or Placebo.
| Arm | Type | Receives |
|---|---|---|
| Tildacerfont Group 1 | Experimental | Drug: Tildacerfont/PlaceboTildacerfont administered daily via oral tablet for 12 weeks at dose level 1 |
| Tildacerfont Group 2 | Experimental | Drug: Tildacerfont/PlaceboTildacerfont administered daily via oral tablet for 12 weeks at dose level 2 |
| Tildacerfont Group 3 | Experimental | Drug: Tildacerfont/PlaceboTildacerfont administered daily via oral tablet for 70 weeks at dose level 3 |
| Placebo | Placebo comparator | Drug: Tildacerfont/PlaceboPlacebo administered daily via oral tablet for 12 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-OHP and currently treated with HC, HC acetate, prednisone, prednisolone, methylprednisolone (or a combination of the aforementioned GCs)
- Has been on a stable, supraphysiologic dose of GC replacement (defined as ≥15 mg/day and ≤60 mg/day in HCe) for ≥1 month before screening
- Has A4 >ULN at both screening and Week 4 (measured before any AM GC dose) if daily GC dose <30 mg OR has A4 >2.5x ULN at both screening and Week 4 (measured before any AM GC dose)
- 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 (32 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
- Current treatment with dexamethasone as GC therapy for CAH
- Is not adherent to GC or study drug dosing regimen during the Run-in Period (defined as taking <80% of expected doses based on drug accountability)
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 1, Tildacerfont Group 2, Tildacerfont Group 3 |
Primary outcome
To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic Congenital Adrenal Hyperplasia (CAH) Over 12 Weeks
Time frame: Baseline and 12 weeks of treatment (Week 18)
Assessment of dose response for change from baseline in log A4 after 12 weeks on double-blind placebo-controlled treatment (Week 18)
4 secondary outcomes
To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic CAH Over 12 Weeks
Time frame: 12 weeks
To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic CAH Over 12 Weeks
Time frame: 12 weeks
To Evaluate the Effect of Tildacerfont in Reducing 17-OHP in Participants With Classic CAH Over 12 Weeks
Time frame: 12 weeks
To Evaluate the Effect of Tildacerfont in Reducing 17-OHP in Participants With Classic CAH Over 12 Weeks
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 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.
Kyriakie Sarafoglou, M.D principal investigator
Dept. of Pediatrics, Divisions of Endocrinology and Genetics & Metabolism, Univ. of Minnesota
65 sites in 20 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 65 sites in 20 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 32 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 8 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 65 sites in United States, Australia, Canada, Italy, Spain and 15 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 8 Jul 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?
To Evaluate the Effect of Tildacerfont in Reducing A4 in Participants With Classic Congenital Adrenal Hyperplasia (CAH) Over 12 Weeks (time frame: Baseline and 12 weeks of treatment (Week 18)). 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 8 Jul 2025.