Efficacy and Safety of tildacerfont in Reducing Supraphysiologic GC do
Research type
Research Study
Full 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
IRAS ID
278766
Contact name
Heidi Petersen
Contact email
Sponsor organisation
Spruce Biosciences, Inc.
Eudract number
2019-004765-40
Duration of Study in the UK
6 years, 3 months, days
Research summary
Research summary
Congenital adrenal hyperplasia (CAH) is an inherited genetic disorder that affects the adrenal glands, a pair of walnut sized organs above the kidneys.The adrenal glands are responsible for producing three different types of hormones: glucocorticoids (to counteract stress), mineralocorticoids (to control the amount of salt and water in the body) and male sex hormones (also known as androgens). CAH is characterised by deficiency of certain types of enzymes that will impair the production of glucocorticoids. This ultimately results in overproduction of male sex hormones (androgens) in order to compensate for the loss.
CAH is a serious, chronically debilitating and life threatening condition. The current standard of care for CAH is lifelong use of glucocorticoids (GCs) to replace the deficient hormone and suppress androgen overproduction. However, these can have significant side effects and do not always work well in treating CAH. A non-steroidal treatment option that helps control adrenal hormone levels is much warranted and would be beneficial to CAH patients.
Tildacerfont (SPR001) is a small molecule drug being developed by Spruce Biosciences Inc. for the treatment of CAH. The study drug blocks the feedback system in the body which is responsible for increased adrenal androgens in CAH patients.
This is a Phase II study. Approximately 60 participants between 18 and 55 years old are expecting to be enrolled across 55 research sites in the United States of America, Europe and other regions, with an overall participation of around 72 weeks.
The purpose of this study is to evaluate the potential of tildacerfont to reduce the amount of Glucocorticoids (e.g., hydrocortisone) that participants need to take and also to reduce the level of certain hormones in participants bodies.
Lay summary of study results
"This was a study to understand if the research medicine tildacerfont would be helpful and safe as treatment for adults with CAH. CAH is an inherited genetic disorder that affects the adrenal glands, a pair of walnut-sized organs above the kidneys. The disease affects the production of steroid hormones by the adrenal glands. This may lead to production of too little “glucocorticoids” (GCs) such as cortisol (which regulates the body’s response to illness or stress).The current standard of care for CAH is the treatment with GCs. These can have significant side effects and do not always work well in treating CAH.
The purpose of this study was to see if tildacerfont changed the overall amount of GCs (e.g., hydrocortisone) that participants needed to take while in the study, when compared to the amount of GCs needed by participants receiving placebo. A placebo looked like the research medicine but contained no active ingredient. Both tildacerfont and placebo are referred to as study medicines in this document.
This study started in September 2020 and was prematurely ended in January 2025 due to lack of efficacy.
The study took place in the following countries: Australia, Brazil, Canada, Estonia, Germany, Italy, Latvia, Lithuania, Poland, Romania, Spain, South Korea, Sweden, Turkey, United Kingdom and United States.
Participants in the study had to meet the following criteria, among others: Be over the age of 18; Be diagnosed with CAH, and; Be on stable treatment with GCs, in a specific dose range, for at least 1 month before entering the study.
Tildacerfont 200 mg and placebo were both yellow tablets to be taken orally (by mouth) during the evening meal every night.
During a screening period of up to 45 days, participants underwent tests to see if they could receive the study medicine. If needed, participants had an optional “GC conversion period” of 6 or 12 weeks, during which participants changed from dexamethasone to a new GCs dosing regimen determined by the study doctor. Then, they entered a 2-part treatment period: Double-blind phase: 24 weeks of double-blind treatment, meaning that neither the participant nor the research team or the Sponsor knew which study medicine the participant received. Participants were randomly assigned to either tildacerfont 200 mg once a day or placebo, with a 50% (1 in 2) chance of being assigned to each of them; Open-label phase: 52 weeks of treatment with tildacerfont 200 mg once a day.
After completion of the open-label phase, participants could continue receiving tildacerfont in an optional open-label extension period for an additional 240 weeks (about 5 years).
The maximum duration of study participation was up to 6 years and 5 months. Several procedures were done during the study visits, including but not limited to blood and urine tests, electrocardiogram (tests to see how the heart was working), physical examinations, quality of life questionnaires and body images by DXA scan (which uses x-rays to see the body composition), and ultrasound (only in men, to check for testicular adrenal rest tumors). In addition, participants had to complete an electronic diary with the information about the study medicine and GCs taken every day.
Participation ended after the follow-up visit at 30 days after last dose of study medicine.
The main goal of the study was to see if tildacerfont reduced the dose of GCs that participants had to take to manage their CAH. To assess it, the doses of GCs were captured using the electronic diary during the 24 weeks of the double-blind phase. The results showed after the 24 weeks of treatment there were no significant changes from baseline GCs dose in participants taking tildacerfont, when compared to GCs dose taken by participants receiving placebo. In addition, no significant changes were seen in any of the other effectiveness measurements tested after the 24 weeks of treatment.
Tildacerfont was mostly well tolerated. The majority of the medical problems (also called adverse events) seen in participants taking tildacerfont were mild to moderate in severity and were considered by the study doctors as not related to tildacerfont.
The most common adverse events considered related to tildacerfont were increases in the liver enzyme alanine aminotransferase (ALT), nausea, itching, and rash. There were no significant changes in the laboratory tests, vital signs, or electrocardiograms of participants.
No deaths were reported during any part of the study.
A treatment option that helps control steroid hormones when used with GCs may benefit CAH patients. Based on tildacerfont mechanism of action, and on the results from former studies, tildacerfont was proposed and studied as possible treatment for participants with CAH.
However, in the current study no efficacy was seen. The study was prematurely terminated by the Sponsor due to lack of efficacy.
This summary only shows the results from this study, which may be different to the results from other studies.
No further studies with tildacerfont are planned for the moment."
REC name
East of England - Cambridge East Research Ethics Committee
REC reference
20/EE/0271
Date of REC Opinion
27 Jan 2021
REC opinion
Further Information Favourable Opinion