Clinical trial NCT02338609: Long-term Monitoring of Growth and Development of Pediatric Patients Previously Treated With Everolimus
Official title: Long-term Follow-up Study to Monitor the Growth and Development of Pediatric Patients Previously Treated With Everolimus in Study CRAD001M2301 (EXIST-LT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Growth and Development
Keywords: TSC-associated SEGA,
height,
weight,
Tanner Stage,
growth development,
everolimus,
RAD001
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-01-14
Enrollment: 15
Sex: ALL
Minimum age (years): 0
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants Who Achieved Tanner Stage V at or Before Age 16 (Females) or 17 (Males)
timeFrame: Annually, up to 14 years from the first visit in parent study CRAD001M2301 (including up to 9 years of follow-up in study CRAD001M2305)
measure: Number of Participants With Notably Low and Notably High Height and Body Mass Index (BMI) Standard Deviation Score (SDS)
timeFrame: 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)
measure: Endocrine Laboratory Values LH and FSH in Male Participants
timeFrame: Annually, starting at 10-year age until 16-year age (in both studies CRAD001M2301 and CRAD001M2305)
measure: Endocrine Laboratory Values LH and FSH in Female Participants
timeFrame: Annually, starting at 10-year age until 16-year age (in both studies CRAD001M2301 and CRAD001M2305)
measure: Endocrine Laboratory Values of Testosterone in Male Participants
timeFrame: Annually, starting at 10-year age until 16-year age (in both studies CRAD001M2301 and CRAD001M2305)
measure: Endocrine Laboratory Values of Estrogen in Female Participants
timeFrame: Annually, starting at 10-year age until 16-year age (in both studies CRAD001M2301 and CRAD001M2305)
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
measure: Participants Age at Menarche/Thelarche (Females) or Adrenarche (Males)
timeFrame: 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)
measure: Participants Age at Tanner Stage II, III, IV, V
timeFrame: 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)
measure: TAND Checklist: Number of Participants Achieved Basic Developmental Milestones and the Age at Which Participants Achieved the Basic Developmental Milestones
timeFrame: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
measure: TAND Checklist: Number of Participants With Behavioral Disorders
timeFrame: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
measure: TAND Checklist - Number of Participants With Psychiatric Disorders
timeFrame: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
measure: TAND Checklist - Number of Participants With Scholastic Issues
timeFrame: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
measure: TAND Checklist: Number of Participants With Difficulty in Specific Brain Skills
timeFrame: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
measure: TAND Checklist - Number of Participants With Psychological Issues
timeFrame: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
measure: TAND Checklist - Number of Participants With Varied Levels of Language Skills
timeFrame: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
measure: TAND Checklist - Number of Participants With Different Levels of Physical Dependency
timeFrame: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
measure: TAND Checklist: Number of Participants With Different Levels of Mobility
timeFrame: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
measure: TAND Checklist: Number of Participants With Different Levels of Intelligence Quotient
timeFrame: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
measure: TAND Checklist: Number of Participants With Different Levels of Intellectual Ability
timeFrame: From enrollment in study CRAD001M2305 until end of study, up to approximately 9 years.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University Of California LA SC
state: California
city: Saint Paul
country: United States
facility: Minnesota Epilepsy Group
state: Minnesota
city: Cincinnati
country: United States
facility: Cinn Children Hosp Medical Center SC
state: Ohio
city: Dallas
country: United States
facility: Texas Scottish Rite Hos for Child SC
state: Texas
city: Brussel
country: Belgium
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: