This is a randomized, double-blind, placebo-controlled study with a three-part treatment period evaluating the efficacy and safety of up to 52 weeks of treatment with Tildacerfont in patients with classic congenital adrenal hyperplasia (CAH) with elevated hormone levels in the blood as a baseline.
Zusammenfassung der Studie
Congenital adrenal hyperplasia (CAH) is a severe, chronically debilitating, and life-threatening genetic disorder characterized by impaired adrenal synthesis of cortisol and a subsequent overproduction of adrenal androgens. Cortisol deficiency leads to hypersecretion or overproduction of certain hormones, ultimately resulting in an excess of androgens. An excess of androgens can lead to irregular menstruation, absence of menstrual periods (amenorrhea), hirsutism, and virilization in women; testicular adrenal rest tumors (TARTs) in men; and increased sebum production, acne, altered blood pressure profiles in the afternoon, and impaired fertility in both sexes. The current standard of care for CAH is long-term use of glucocorticoids (GCs) at supraphysiological levels to replace the missing cortisol and suppress androgen overproduction. This is a problematic therapy with significant side effects, and a non-steroidal treatment option would be preferable. Tildacerfont may allow a CAH patient to have normal androgen levels while taking GC in the normal replacement range. Currently, Tildacerfont has shown an acceptable safety profile at effective doses in nonclinical toxicology studies, clinical phase 1 studies in healthy volunteers, and phase 2 studies in adult patients with classic CAH. SPR001-203 is a dose-finding study examining the efficacy and safety of treatment for up to 70 weeks. Neither the patients nor their investigator know which treatment the patients are receiving, and patients are selected, e.g., by coin toss, to receive either the study drug or the placebo. An optional open-label extension period provides additional unblinded treatment with Tildacerfont at 200 mg QD for up to 240 weeks.
(BASEC)
Untersuchte Intervention
The main purpose of this study is to investigate the drug SPR001 (Tildacerfont) for patients with classic congenital adrenal hyperplasia (CAH). SPR001 is an investigational drug, i.e., a drug that is being tested. The efficacy and safety of SPR001 will be evaluated up to a treatment duration of 70 weeks in patients with classic CAH who have elevated biomarkers at study entry. The study consists of a three-part treatment phase. During the first 12 weeks, subjects will be randomized in a 1:1:1:1 ratio to receive either placebo or Tildacerfont at a dose of 50 mg once daily, 100 mg once daily, or 200 mg once daily. During the second 12 weeks, all subjects will receive the active ingredient (Tildacerfont) at varying doses with possible dose escalation. During the final 46 weeks, all subjects will receive 200 mg of Tildacerfont.
(BASEC)
Untersuchte Krankheit(en)
Congenital adrenal hyperplasia (CAH) is a group of rare diseases. There is a deficiency of one of the enzymes needed to produce certain hormones. CAH affects the adrenal glands, which are located on top of each kidney.
(BASEC)
Men and women ≥ 18 years old at screening (or: at the pre-examination) Have a known childhood diagnosis of classic CAH based on a genetic CYP21A2 mutation and/or elevated 17-OHP (17α-hydroxyprogesterone) and are currently being treated with GCs (glucocorticoids) listed in Section 5.1.1 of the protocol. Have received a stable supraphysiological dose of GC for ≥ 1 month prior to screening. (BASEC)
Ausschlusskriterien
Have a known/suspected diagnosis of another form of CAH History of bilateral adrenalectomy/pituitary insufficiency or allergy/hypersensitivity to the study drug Current treatment with dexamethasone as GC therapy for CAH. (BASEC)
Studienstandort
St Gallen, Zürich
(BASEC)
Sponsor
Medpace Switzerland AG
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Pamela Wedel
+1 415 655 4169
pwedel@cluttersprucebiosciences.comSponsor
(BASEC)
Allgemeine Auskünfte
Dept. of Pediatrics, Divisions of Endocrinology and Genetics & Metabolism, Univ. of Minnesota
(ICTRP)
Wissenschaftliche Auskünfte
Dept. of Pediatrics, Divisions of Endocrinology and Genetics & Metabolism, Univ. of Minnesota
(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Zürich
(BASEC)
Datum der Bewilligung durch die Ethikkommission
19.10.2022
(BASEC)
ICTRP Studien-ID
NCT04457336 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
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 (BASEC)
Wissenschaftlicher Titel
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 (ICTRP)
Öffentlicher Titel
A Ph2b to Evaluate Clinical Efficacy and Safety of Tildacerfont in Adult CAH (ICTRP)
Untersuchte Krankheit(en)
Congenital Adrenal Hyperplasia (ICTRP)
Untersuchte Intervention
Drug: Tildacerfont/Placebo (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator). (ICTRP)
Ein-/Ausschlusskriterien
Gender: All
Maximum age: N/A
Minimum age: 18 Years
Inclusion Criteria:
- Male and female subjects over 18 years old, inclusive
- Has a known childhood diagnosis of classic CAH due to 21-hydroxylase deficiency
based on genetic mutation in CYP21A2 and/or documented 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 =15 mg/day and =60
mg/day in HC equivalents
- For subjects with the salt-wasting form of CAH, subject has been on a stable dose of
mineralocorticoid replacement for =1 month before screening
Exclusion Criteria:
- 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.
- Shows clinical signs or symptoms of adrenal insufficiency (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Change in androstenedione (ICTRP)
Proportion of subjects who achieve reduction A4 levels;Proportion of subjects who achieve reduction in 17-OHP;Effectiveness in reducing TART(s) in Male CAH subjects (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Kyriakie Sarafoglou, M.D, Dept. of Pediatrics, Divisions of Endocrinology and Genetics & Metabolism, Univ. of Minnesota (ICTRP)
Sekundäre IDs
CAHmelia 203, SPR001-203 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT04457336 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
52-lay-person-summary-of-results-en-2023-503770-21-00-spruce-de.pdfLink zu den Ergebnissen im Primärregister
nicht verfügbar