2024-519578-38-00招募中3 期
A Phase 2/3 Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Atumelnant Treatment in Pediatric Participants with Congenital Adrenal Hyperplasia Including a Long-Term Extension
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 19
- 试验地点
- 6
- 主要终点
- Part A: -Incidence of TEAEs including treatment emergent SAEs and any Aes leading to discontinuation. -Change from baseline in morning A4 at Week 8 Part B: -Percent change from baseline in GC daily dose at Week 28 while serum early morning A4≤ULN Part C: -Change from baseline in morning A4 over time
研究概览
简要总结
Part A: -To evaluate the safety and tolerability of atumelnant in pediatric participants with CAH -To evaluate efficacy of atumelnant, measured by change from baseline in serum A4 Part B: -To evaluate efficacy of atumelnant in reducing daily GC dose while maintaining adrenal androgren normalization Part C: -To evaluate efficacy of atumelnant measured by change from baseline in A4
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Part C
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •Part A and B participants are eligible to be included in the study only if all of the following criteria apply:
- •Male or female at birth, between 1 to <18 years of chronological age at the time of signing the ICF.
- •Have a medically confirmed diagnosis of classic CAH due to 21-OHD based on standard medically accepted criteria such as elevated 17-OHP level, confirmed CYP21A2 genetic testing, positive newborn screening with confirmatory second-tier testing, or cosyntropin stimulation.
- •Participants must have an elevated morning (before 11:00) serum A4 level >ULN during Screening obtained prior to morning GC administration. Participants who failed Screening based on findings the Investigator believes are temporary and not reflective of the usual state of the participant (eg, normal A4 levels when the participant usually is well above this value) can be considered for rescreening. These cases should be discussed with the Medical Monitor.
- •Participants must be on a stable supraphysiologic GC replacement therapy (hydrocortisone, prednisolone, prednisone, methylprednisolone, dexamethasone) for at least one month prior to Screening
- •Compliance, as judged per Investigator discretion, with GC replacement and mineralocorticoid replacement (if applicable) regimen documented during the Screening Period.
- •Normal TSH and T4 within 3 months of Screening per age-appropriate range. Female participants who have had their first menstrual cycle and engage in heterosexual intercourse must: a) Be of nonchildbearing potential, defined as either surgically sterile. b) Agree to use a highly effective method of contraception from the beginning of Screening until at least 2 weeks after the last dose of study drug. Male participants who engage in heterosexual intercourse must: a) Agree to use a condom when sexually active with a female partner of childbearing potential from Screening until at least 2 weeks after the last dose of study drug. b) Agree to remain abstinent on a long-term and persistent basis during the study and until at least 2 weeks after the last dose of study drug. c)Agree to not donate sperm for the duration of the study and until at least 2 weeks after the last dose of study drug.
- •Participant’s parent(s)/legal representative (if appropriate according to local laws) are willing and able to give signed informed consent for participant in the study,
- •Willing and able to comply with the study procedures as specified in the protocol and comply with the study treatment. Part C inclusion criteria require participants to complete treatment in either Part A or Part B and in the Investigator’s opinion it would benefit the participant to continue in Part C, regardless of age.
排除标准
- •Part A and Part B: Individuals in Part A and Part B who meet any of the following criteria will be excluded from participation in this study:
- •Diagnosis of any form of CAH other than classic 21-OHD.
- •Participants treated with other GC formulations within 30 days of Screening.
- •Stress dose of GC therapy within 2 weeks of start of Screening, defined as any dose above the normal maintenance dose, including but not limited to IV or IM hydrocortisone.
- •Use of growth hormones within 1 week of start of Screening for short acting, or within 6 weeks of start of Screening for long acting.
- •Use of a corticotropin-releasing factor receptor antagonist within 14 days of Screening.
- •Participants with any clinically significant abnormal laboratory test during Screening or clinically significant concomitant disease other than CAH including but not limited to cardiovascular disease; moderate or severe renal insufficiency (estimated glomerular filtration rate <60 mL/min/1.73 m2 using CKD-EPI formula) at Screening; or Significant liver disease or ALT and/or AST >3×ULN, and/or TBil >1.5×ULN during Screening. TBil >1.5×ULN (Participants with Gilbert’s syndrome can be included with TBil >1.5×ULN as long as direct bilirubin is ≤1.5×ULN AND <35% of TBil)
- •History of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic GC therapy.
- •Participants with any clinically significant abnormal laboratory test during Screening or clinically significant concomitant disease other than CAH including but not limited to cardiovascular disease (defined as any condition that affects the heart’s structure, function, or electrical system, regardless of stage of disease); moderate or severe renal insufficiency (estimated glomerular filtration rate <60 mL/min/1.73 m2 using the Bedside Schwartz Equation)) at Screening; or Significant liver disease or ALT and/or AST >3×ULN, and/or TBil >1.5×ULN during Screening. TBil >1.5×ULN (Participants with Gilbert’s syndrome can be included with TBil >1.5×ULN as long as direct bilirubin is ≤1.5×ULN AND <35% of TBil)..
- •Poorly controlled diabetes mellitus as judged by the Investigator.
- •Participants with hypothyroidism who are not receiving adequate hormone replacement therapy based on thyroid hormone levels measured at the time of Screening, as determined by the Investigator.
- •History of cancer excluding cured/treated dermal squamous or basal cell carcinoma or cervical carcinoma in situ.
- •ECG: a. Ages 12 to <18: QTcF interval >450 msec (males) or >470 msec (females), PR interval >220 msec, QRS interval >120 msec, second- or third-degree atrioventricular block, left bundle branch block, or hemiblock at Screening. b. Ages 1 to 11: Anything abnormal, even if not clinically significant, is an exclusion. A cardiologist can override a machine reading.
- •Abnormal sleep/wake cycles (as determined by the Investigator).
- •Participants with known history of (that is within the past 12 months) or current alcohol or drug abuse. Participants that are abusing, in the opinion of the Investigator, cannabis, tobacco, and/or the use of e-cigarettes (vaping).
- •Participants with any mental condition rendering him/her unable to understand the nature, scope, and possible consequences of the study, and/or evidence of poor compliance with medical instructions.
- •Participants with a known allergy or hypersensitivity to any of the test materials or related compounds, including being at high risk of adrenal insufficiency as judged by the Investigator.
- •Female participants who are pregnant or lactating.
- •An employee or immediate family member of an employee of Crinetics.
- •Participants who have been dosed with an investigational drug (other than atumelnant) in any prior clinical study within 60 days or 5 half-lives (whichever is longer) prior to the first dose. Part C:
- •Individuals in Part C who do not meet the Part C Inclusion Criteria
结局指标
主要结局
Part A: -Incidence of TEAEs including treatment emergent SAEs and any Aes leading to discontinuation. -Change from baseline in morning A4 at Week 8 Part B: -Percent change from baseline in GC daily dose at Week 28 while serum early morning A4≤ULN Part C: -Change from baseline in morning A4 over time
Part A: -Incidence of TEAEs including treatment emergent SAEs and any Aes leading to discontinuation. -Change from baseline in morning A4 at Week 8 Part B: -Percent change from baseline in GC daily dose at Week 28 while serum early morning A4≤ULN Part C: -Change from baseline in morning A4 over time
次要结局
- Part A: -Change from baseline in morning serum 17-OHP at Week 8 -Plasma and blood concentrations of atumelnant
- Part B: -Change from baseline in morning A4 at Week 4 -Change from baseline in morning 17 OHP at Week 4 -Proportion of participants with physiologic GC dose while morning A4
- Part C: -Change from baseline in morning 17-OHP over time -Percent change from baseline in GC daily dose over time -Proportion of participants with physiologic GC dose while morning A4
研究者
Clinical Medical Lead
Scientific
Crinetics Pharmaceuticals Inc.
研究点 (6)
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