JCEM: In adults with congenital adrenal hyperplasia with 21-hydroxylase deficiency, Crinecerfont reduces hormonal markers elevated by the disease

Background: Congenital adrenal hyperplasia (CAH) is a group of rare autosomal recessive disorders that cause disturbances in adrenal steroid synthesis, including impaired cortisol synthesis

Congenital adrenal hyperplasia (CAH) is a group of rare autosomal recessive disorders that cause disturbances in adrenal steroid synthesis, including impaired cortisol synthesis

However, supraphysiological GC doses and non-physiological times (eg, evening dosing) are often required to reduce increased ACTH secretion and androgen hypersecretion

CRF1R antagonism reduces ACTH secretion, which in 21OHD reduces downstream androgen production and reduces symptoms of hyperandrogenism, while also potentially allowing GCs to be administered at more physiological doses

Objective: This study aimed to evaluate the safety, tolerability and efficacy of CRF1R selective antagonist CRI-74788 in the treatment of 21OHD

METHODS: This open-label phase 2 study was conducted at 6 centers in the United States using a sequential cohort design (NCT03525886)

Results: Among the 18 subjects, 11 were female, 7 were male, 8 in cohort 1, 7 in cohort 2, 8 in cohort 3, and 8 in cohort 4

Figure 1 Learning Design

Figure 1 Learning Design

Table 1 Effects of estrogen on adrenal androgens and precursors

Table 1 Effects of estrogen on adrenal androgens and precursors

Figure 2 For groups 1 and 2, dosing was performed at 22:00 on day 14; pre-dose sampling time was 21:45

Figure 2 For groups 1 and 2, dosing was performed at 22:00 on day 14; pre-dose sampling time was 21:45

Figure 3

Figure 3

Table 2 Proportion of participants with a 50% or more reduction in morning window hormone values ​​from baseline to day 14, and the proportion reaching normal values

Table 2 Proportion of participants with a 50% or more reduction in morning window hormone values ​​from baseline to day 14, and the proportion reaching normal values

CONCLUSIONS: In adult patients with 21OHD, 14 days of Crinecerfont treatment reduced ACTH and had clinically meaningful reductions in elevated 17OHP, androstenedione, testosterone (women) or androstenedione/testosterone ratio (men)

In adult patients with 21OHD, 14 days of Crinecerfont treatment reduced ACTH and had clinically meaningful reductions in elevated 17OHP, androstenedione, testosterone (women), or androstenedione/testosterone ratio (men)

Crinecerfont Lowers Elevated Hormone Markers in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia.


Leave a Comment here