2024-511924-15-00招募中3 期
A Randomized, Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Paltusotine in Subjects with Non-pharmacologically Treated Acromegaly (PATHFNDR-2)
适应症
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 61
- 试验地点
- 19
- 主要终点
- Proportion of subjects who achieve biochemical response in IGF-1 (≤ 1.0× the upper limit of normal [ULN]) at the End of the Randomized Control Phase (EOR).
研究概览
简要总结
To evaluate the effect of paltusotine versus placebo on IGF-1 response
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Willing and able to provide written informed consent prior to any study-related procedures.
- •Willing and able to comply with the study procedures as specified in the protocol and comply with the study treatment administration.
- •Subjects ≥18 years of age at the time of Screening who fall into 1 of the following 3 groups are eligible to participate in the study. Medically naïve group (Group 1): Those who have not been previously treated with acromegaly medications (including LA-SRLs) who at Screening have IGF-1 ≥1.3×ULN (the lower limit for eligibility is IGF-1 of 1.25×ULN when rounded to 2 decimal places) confirmed by the central laboratory test at S
- •Group 1 subjects must have had at least 1 pituitary surgery 3 months or more prior to Screening. Previously Treated group (no treatment within previous 4 months) (Group 2): Subjects who have last been treated with acromegaly medications at least 4 months prior to Screening and who have IGF-1 ≥1.3×ULN (the lower limit for eligibility is IGF-1 of 1.25 when rounded to 2 decimal places) confirmed by the central laboratory test at S
- • Washout group (Group 3): Subjects at Screening who are receiving stable treatment (no change in dose for 3 months prior to Screening) with octreotide or lanreotide monotherapy, who have IGF-1 ≤1.0×ULN (the upper limit for eligibility is IGF-1 of 1.04 when rounded to 2 decimal places) at Screening Visit 1 and are willing to washout of their medication during the Screening Period. Any form of pretrial octreotide or lanreotide monotherapy (long- or short-acting [SC, IM, or oral]) can be washed out and will determine the duration of the Screening Period. After informed consent is provided, the subject should not receive further pretrial acromegaly medication. IGF-1 must rise at least 30% from the first Screening Visit to the last Screening Visit and to ≥1.1×ULN (the lower limit for eligibility is IGF-1 of 1.05 when rounded to 2 decimal places) confirmed by the central laboratory test at S2 or S3, if needed) to qualify for enrollment.
- •Previous diagnosis of acromegaly confirmed by the Investigator and approved by the Medical Monitor. This requires evaluable documentation of a pituitary adenoma.
- •If currently using thyroid hormone therapy, the subject should be adequately treated based on clinical status and free thyroxine concentration measured during Screening and on a stable dose of thyroid hormone for at least 8 weeks prior to Screening.
- •Females who engage in heterosexual intercourse must be of nonchildbearing potential, defined as either surgically sterile (ie, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), OR be postmenopausal with at least 1 year of amenorrhea, OR must agree to use either a highly effective or a clinically acceptable method of contraception from the beginning of Screening until at least 30 days after the last dose of study drug.
- •If the subject is male, the subject should agree to use a condom when sexually active with a female partner of childbearing potential from Screening until at least 30 days after the last dose of study drug (or be surgically sterile [ie, vasectomy with documentation]); or remain abstinent (when this is in line with the preferred and usual lifestyle). Male subjects should also agree to not donate sperm for the duration of the study and until at least 30 days after the last dose of study drug.
排除标准
- •History of ineffectiveness or significant intolerance of octreotide or lanreotide treatment, as determined by the Investigator.
- •Known history of, or current alcohol or drug abuse, within the last year
- •Subjects with adrenal insufficiency, diabetes insipidus, or central hypogonadism who are not receiving adequate hormone replacement therapy at the time of Screening, as determined by the Investigator.
- •Concomitant 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.
- •High risk pituitary tumor pattern as defined by: • Compression of the optic chiasm or invasion of adjacent brain structures (other than sphenoid sinus or cavernous sinus) • History of tumor growth within 1 year after surgery or radiation (unless it occurred during a period of medical therapy interruption) • Anticipated requirement for neurosurgical intervention or radiation therapy within the time course of the study. • Pituitary carcinoma currently or at any time in the past.
- •History of major surgery/surgical therapy for any cause within 4 weeks prior to Screening.
- •Diabetes mellitus treated with insulin for less than 6 weeks prior to the study entry, or with change in total daily insulin dose by >15% within 6 weeks prior to Screening.
- •History of unstable angina or acute myocardial infarction within the 12 weeks preceding the Screening Visit or other clinically significant cardiac disease at the time of screening as judged by the Investigator.
- •Known history of hepatitis B or human immunodeficiency virus, or active hepatitis C infection.
- •Active malignant disease within the last 5 years with exception of basal and squamous cell carcinoma of the skin with complete local excision and resected carcinoma in situ of cervix.
- •Use of the following medications as outlined: Any history of acromegaly medication use (Group 1 only) Lanreotide depot or octreotide LAR (within 16 weeks before Screening) (Group 2 only) Pasireotide LAR (within 24 weeks prior to Screening) Pegvisomant (within 16 weeks before Screening) Dopamine agonists (within 16 weeks before Screening) Any combination of 2 or more acromegaly medications at Screening Proton pump inhibitors (from start of Screening) until the end of the study Note: Withdrawal of these medications should be part of the subject’s medical care plan prior to Screening; entry into the study should not be the sole reason for withdrawal of a prior medication.
- •Clinically significant abnormal findings during the Screening Period or any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardize the subject’s safety or ability to complete the study.
- •Current use of oral estrogen replacement therapy for <12 weeks prior to Screening.
- •Current use of medications that are strong inducers of CYP3A4 within 2 weeks prior to Screening
- •Known allergy or hypersensitivity to any of the test materials or related compounds.
- •Active COVID-19 confirmed or suspected based on clinical symptoms
- •Symptomatic cholelithiasis
- •Clinically significant concomitant disease including but not limited to cardiovascular disease, severe renal insufficiency (estimated glomerular filtration rate <30 mL/min/1.73 m2), or significant liver disease (including cirrhosis).
- •An employee or immediate family member of an employee of Crinetics or investigator and clinical site staff.
- •Participation in any previous clinical study with paltusotine.
- •Subjects who have received an investigational drug (either approved or not approved) in any prior clinical study within 30 days or 5 half-lives (whichever is longer) prior to Screening.
- •Systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg during Screening. If the initial measurement is out of range, it may be repeated 2 more times after 15 minutes and the last assessment should be used to determine subject’s eligibility.
- •History of pituitary radiation therapy within 3 years of Screening.
- •Resting (at least 10 minutes) palpated pulse rate <45 bpm or >105 bpm during Screening. If either of these criteria is met, the assessment should be repeated 2 more times and the last assessment should be used to determine the subject’s eligibility.
- •QT interval corrected using Fridericia’s formula (QTcF) >480 msec (or corrected QT [QTc] interval >500 msec in the presence of complete bundle branch block) or PR interval >240 msec during Screening based on a central reading of an average of 3 ECGs each separated in time by approximately 1 minute after the subject has rested quietly in the supine position for at least 10 minutes without significant stimulation (noise, television, etc.).
- •Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >3×ULN, and/or total bilirubin >1.5×ULN during Screening. Subjects with previously diagnosed Gilbert’s syndrome not accompanied by other hepatobiliary disorders and associated with total bilirubin <3.5 mg/dL (<51.3 µmol/L) will be permitted.
- •Poorly controlled diabetes mellitus defined as having a hemoglobin A1c (HbA1c) ≥8.5% (≥69 mmol/mol), or estimated HbA1c based on fructosamine if HbA1c is not evaluable (eg, due to hemoglobinopathies).
- •Female subjects who are pregnant or lactating. Subjects must have a negative pregnancy test during Screening and prior to the first dose of study drug
结局指标
主要结局
Proportion of subjects who achieve biochemical response in IGF-1 (≤ 1.0× the upper limit of normal [ULN]) at the End of the Randomized Control Phase (EOR).
Proportion of subjects who achieve biochemical response in IGF-1 (≤ 1.0× the upper limit of normal [ULN]) at the End of the Randomized Control Phase (EOR).
次要结局
- Change from baseline in IGF-1, in units of ULN, to EOR.
- Proportion of subjects who achieve IGF-1 <1.3×ULN at EOR.
- Proportion of subjects with GH <1 ng/mL at Week 22.
- Change from baseline in Total Acromegaly Symptoms Diary (ASD) score to EOR.
研究者
Clinical Medical Lead
Scientific
Crinetics Pharmaceuticals Inc.
研究点 (19)
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