Long-term Follow-up Study to Monitor the Growth and Development of Pediatric Patients Previously Treated With Everolimus in Study CRAD001M2301 (EXIST-LT)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 5
- 主要终点
- Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
研究概览
简要总结
The primary objective of CRAD001M2305 was to report the long-term effects of everolimus treatment on height, weight and sexual development (using Tanner Stages) in children and adolescents with Tuberous Sclerosis Complex (TSC)-associated with Subependymal Giant Cell Astrocytoma (SEGA). The study monitored the growth and development of pediatric patients with TSC-associated SEGA, previously enrolled in CRAD001M2301 (NCT00789828) until they reach Tanner Stage V, or until age 16 for females or 17 for males whichever occurred first.
详细描述
CRAD001M2305 was a prospective, multi-center phase IIIb/IV study. This study investigated if the physical and sexual development of pediatric patients was affected by previous or ongoing treatment with everolimus. The study monitored the growth and development of pediatric patients with TSC-associated SEGA, previously enrolled in CRAD001M2301(NCT00789828) until they reached Tanner Stage V, or until age 16 for females or 17 for males whichever occurred first. Continued treatment with everolimus was at investigator discretion and was not required for participation in CRAD001M2305. Growth (height, weight), and sexual development (Tanner Stages, sex hormone levels, age at menarche, thelarche (females) and adrenarche (males)), and brain development (assessed by TAND Checklist, dates of brain MRI) of patients participating in this long-term follow-up study was followed at annual visits to the site until patients achieve Tanner Stage V or age 16 (females), age 17 (males) whichever occurred first. Adverse events, concomitant medication, appearance of menarche, were monitored and data collected every 3 months ("3-monthly"). Unless clinically indicated these 3-monthly visits were performed per telephone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pediatric female patients who were on study treatment in study [CRAD001M2301] within the past 6 months and have not reached Tanner Stage V or age 16 at the time of completion of [CRAD001M2301] or
- •Pediatric male patients who were on study treatment in study [CRAD001M2301] within the past 6 months and have not reached Tanner Stage V or age 17 at the time of completion of [CRAD001M2301]
- •Written informed consent according to local guidelines
排除标准
- •Pediatric female patients who were on study treatment in CRAD001M2301 and have not reached Tanner Stage V but are within 3 month of turning age 16 or
- •Pediatric male patients who were on study treatment in CRAD001M2301 and have not reached Tanner Stage V but are within 3 months of turning age 17
- •Any patient who was pregnant prior to start of CRAD001M2305
研究组 & 干预措施
Everolimus
All patients will have been previously treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study.
干预措施: Everolimus (Drug)
结局指标
主要结局
Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
时间窗: Baseline, annually up to Year 10 of treatment since the start of everolimus in parent study CRAD001M2301 (including a median of 5 years of exposure to everolimus in study CRAD001M2305)
Height and body weight (with minimal clothing, without shoes) were measured annually. The height standard deviation score (SDS) and BMI SDS were calculated based on height/BMI data collected during the study and published reference height/BMI information (De Onis M, et al. Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ. 2007 Sep;85(9):660-7). The number of participants with height and BMI SDS values lower than the 5th percentile (notably low) or higher than the 95th percentile (notably high) are reported. The baseline corresponds to the last available assessment on or before the start of everolimus in the parent study CRAD001M2301. The assessment is performed up to age of 12 years.
Endocrine Laboratory Values LH and FSH in Female Participants
时间窗: Annually, starting at 10-year age until 16-year age (in both studies CRAD001M2301 and CRAD001M2305)
Luteinizing hormone (LH) is a glycoprotein hormone that is co-secreted along with follicle-stimulating hormone by the gonadotrophin cells in the adenohypophysis (anterior pituitary). Untreated LH deficiency results in infertility, and if it occurs before puberty, the patient fails to develop puberty and secondary sexual characteristics. Follicle-stimulating hormone (FSH) is a hormone produced by the anterior pituitary in response to gonadotropin-releasing hormone (GnRH) from the hypothalamus. FSH plays a role in sexual development and reproduction in both males and females.
Endocrine Laboratory Values LH and FSH in Male Participants
时间窗: Annually, starting at 10-year age until 16-year age (in both studies CRAD001M2301 and CRAD001M2305)
Luteinizing hormone (LH) is a glycoprotein hormone that is co-secreted along with follicle-stimulating hormone by the gonadotrophin cells in the adenohypophysis (anterior pituitary). Untreated LH deficiency results in infertility, and if it occurs before puberty, the patient fails to develop puberty and secondary sexual characteristics. Follicle-stimulating hormone (FSH) is a hormone produced by the anterior pituitary in response to gonadotropin-releasing hormone (GnRH) from the hypothalamus. FSH plays a role in sexual development and reproduction in both males and females.
Endocrine Laboratory Values of Testosterone in Male Participants
时间窗: Annually, starting at 10-year age until 16-year age (in both studies CRAD001M2301 and CRAD001M2305)
Testosterone is the primary male hormone responsible for regulating sex differentiation, producing male sex characteristics, spermatogenesis, and fertility.
Number of Participants Who Achieved Tanner Stage V at or Before Age 16 (Females) or 17 (Males)
时间窗: Annually, up to 14 years from the first visit in parent study CRAD001M2301 (including up to 9 years of follow-up in study CRAD001M2305)
Tanner Staging, also known as Sexual Maturity Rating (SMR), is an objective classification system that providers use to document and track the development and sequence of secondary sex characteristics of children during puberty. Tanner Stage included two components for boys (testis and pubic hair) and two components for girls (breast development and pubic hair). Tanner Stage V: Males and females: Terminal hair that extends beyond the inguinal crease onto the thigh. Female Breast Development Scale: Areolar mound recedes into single breast contour with areolar hyperpigmentation, papillae development, and nipple protrusion. Male External Genitalia Scale: \> 20 ml (or \> 4.5 cm long)
Endocrine Laboratory Values of Estrogen in Female Participants
时间窗: Annually, starting at 10-year age until 16-year age (in both studies CRAD001M2301 and CRAD001M2305)
Estrogen is a steroid hormone associated with the female reproductive organs and is responsible for developing female sexual characteristics.
次要结局
- TAND Checklist - Number of Participants With Scholastic Issues(From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.)
- Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.)
- Participants Age at Menarche/Thelarche (Females) or Adrenarche (Males)(Up to approximately 14.4 years from the first dose of everolimus in parent study CRAD001M2301 (including up to 9 years of follow-up in study CRAD001M2305))
- TAND Checklist: Number of Participants With Difficulty in Specific Brain Skills(From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.)
- TAND Checklist: Number of Participants With Behavioral Disorders(From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.)
- TAND Checklist - Number of Participants With Psychological Issues(From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.)
- TAND Checklist: Number of Participants With Different Levels of Intelligence Quotient(From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.)
- Participants Age at Tanner Stage II, III, IV, V(Up to approximately 14.4 years from the first dose of everolimus in parent study CRAD001M2301 (including up to 9 years of follow-up in study CRAD001M2305))
- TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones(From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.)
- TAND Checklist - Number of Participants With Psychiatric Disorders(From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.)
- TAND Checklist - Number of Participants With Varied Levels of Language Skills(From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.)
- TAND Checklist - Number of Participants With Different Levels of Physical Dependency(From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.)
- TAND Checklist: Number of Participants With Different Levels of Mobility(From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.)
- TAND Checklist: Number of Participants With Different Levels of Intellectual Ability(From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.)