CAHtalyst Adult
Trial question
What is the role of crinecerfont in patients with congenital adrenal hyperplasia?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
49.0% female
51.0% male
N = 182
182 patients (90 female, 92 male).
Inclusion criteria: adult patients with classic 21-hydroxylase deficiency congenital adrenal hyperplasia.
Key exclusion criteria: any condition other than congenital adrenal hyperplasia requiring long-term corticosteroids; evidence of corticosteroid overtreatment.
Interventions
N=122 crinecerfont (at a dose of 100 mg BID for 24 weeks).
N=60 placebo (matching placebo BID for 24 weeks).
Primary outcome
Reduction in daily corticosteroid dose with control of androstenedione at 24 weeks
27.3%
10.3%
27.3 %
20.5 %
13.7 %
6.8 %
0.0 %
Crinecerfont
Placebo
Significant
increase ▲
NNT = 5
Significantly greater reduction in daily corticosteroid dose with control of androstenedione at 24 weeks (27.3% vs. 10.3%; ARD 17, 95% CI 10.2 to 23.8).
Secondary outcomes
Significantly greater reduction in serum androstenedione at 4 weeks (299 ng/dL vs. -45.5 ng/dL; AD 345 ng/dL, 95% CI 232 to 457).
Significant increase in the proportion of patients with physiologic corticosteroid dose with androstenedione control at 24 weeks (63% vs. 18%; RR 3.5, 95% CI 1.42 to 5.58).
No significant difference in reduction in body weight at 24 weeks (1.45% vs. 0.07%; ARD 1.38, 95% CI -0.2 to 2.96).
Safety outcomes
No significant differences in adverse events, adrenal insufficiency, or acute adrenocortical insufficiency.
Conclusion
In adult patients with classic 21-hydroxylase deficiency congenital adrenal hyperplasia, crinecerfont was superior to placebo with respect to reduction in daily corticosteroid dose with control of androstenedione at 24 weeks.
Reference
Richard J Auchus, Oksana Hamidi, Rosario Pivonello et al. Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal Hyperplasia. N Engl J Med. 2024 Aug 8;391(6):504-514.
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