This is a multi-center, randomized, double-blind, multiple dose levels, parallal group, placebo-controlled study, to evaluate the safety, PK profiles and preliminary efficacy of TTYP01 tablets in adolescents and children with ASD.
This is a multi-center, randomized, double-blind, multiple dose levels, parallal group, placebo-controlled study, to evaluate the safety, PK profiles and preliminary efficacy of TTYP01 tablets in adolescents and children with ASD. The trial will be conducted in 3 stages. It plans to firstly enroll 24 adolescent participants (≥12 to \< 16 years) with ASD. After all the 24 adolescent participants have completed the 4-week follow-up and observation, the Data and Safety Monitoring Board (DSMB) will review the data obtained from these adolescent participants, and then make a recommendation on whether to enroll pediatric participants (≥6 to \< 12 years) with ASD and continue the adolescent participants' enrollment, whether it is necessary to adjust the protocol, or whether to terminate the trial for safety considerations, etc. If pediatric participants can be enrolled, it plans to first enroll 24 pediatric participants, and the DSMB will review all data after all these participants have completed the 4-week follow-up and observation, and then make a recommendation on whether to continue enrollment of adolescent and pediatric participants, whether to adjust the protocol, or whether to terminate the trial for safety considerations, etc. If the enrollment of adolescent and pediatric participants can be continued, the trial will proceed to Stage 3 until 150 adolescent and pediatric participants with ASD are enrolled. In addition, throughout the trial, the DSMB may conduct irregular reviews of safety, tolerability, PK, and efficacy data, and give recommendations based on the results of the review, including but not limited to adjusting the trial protocol and early termination of the trial for safety considerations. A DSMB review is triggered if a neurotoxicity AE occurs. The composition, responsibilities, etc. of the DSMB are described in Section 4.2 of the protocol. Eligible participants will be randomized in a 1:1:1 ratio to receive TTYP01 low-dose, TTYP01 high-dose and placebo treatment. Randomization is stratified by age group (≥12 vs \< 12 years of age). Participants will be given the corresponding dose of the investigational product for 12 weeks based on their weight and groups as listed in the table in the protocol. The dosing regimen can be adjusted based on the safety, tolerability, PK and other data accumulated in the previous period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
150
Taken with a moderate amount of warm water or after disperse in a moderate amount of warm water, at least 60 minutes before breakfast and dinner.
Taken with a moderate amount of warm water or after disperse in a moderate amount of warm water, at least 60 minutes before breakfast and dinner.
Peking University Sixth Hospital
Beijing, China
RECRUITINGThe Second Xiangya Hospital of Central South University
Changsha, China
NOT_YET_RECRUITINGWest China Hospital of Sichuan University
Chengdu, China
Change from baseline in ABC-SW（Aberrant Behavioral Checklist - Social Withdrawal） scores at Week 12.
The ABC (Aberrant Behavioral Checklist) scale has 58 items. The scale is broken down into five subscales including ABC-SW（Aberrant Behavioral Checklist - Social Withdrawal）, ABC-I, A, C （Aberrant Behavioral Checklist - Irritability, Agitation, Crying）, ABC-SB （Aberrant Behavioral Checklist - Stereotypic Behavior）, ABC-H, N (Aberrant Behavioral Checklist - Hyperactivity, Noncompliance ), and ABC-IS (Aberrant Behavioral Checklist - Inappropriate Speech ). Scale ratings can be completed by parents, special educators, psychologists, direct caregivers, nurses, and others with knowledge of the person being assessed. The rater has to answer each of the 58 questions using a 4-point Likert scale. A score of a "0" means the behavior is not a problem, a score of a "1" means slight problem, a score of a "2" means a serious problem, and a "3" means a severe problem.
Time frame: At baseline and week 12
Incidence and severity of treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), serious adverse events (SAEs), and TEAEs that lead to treatment discontinuation.
To evaluate the safety and tolerability of TTYP01 tablets in adolescent and pediatric participants with ASD.
Time frame: Throughout the trial period
Plasma concentrations and population PK profiles of edaravone and its metabolites in adolescent and pediatric ASD participants.
Concentrations of edaravone and its metabolites are assayed in the plasma of adolescent and pediatric participants with ASD. They will be analyzed with descriptive statistics according to planned sampling points.
Time frame: Visit 2 (Day 1): 30 minutes (±5 minutes) and 3 hours (±10 minutes) after the first dose; Visit 8 (Week 12 ±2 Days)or Early withdrawal: before the first dose (0 hour), and 30 minutes (±5 minutes) after the first dose on the day of the visit.
Changes from baseline in ABC-SW scores at Weeks 4 and 8.
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Nanjing Brain Hospital, The Affiliated Brain Hospital of Nanjing Medical University
Nanjing, China
NOT_YET_RECRUITINGTianjin Mental Health Center
Tianjin, China
NOT_YET_RECRUITINGThe ABC (Aberrant Behavioral Checklist) scale has 58 items. The scale is broken down into five subscales including ABC-SW（Aberrant Behavioral Checklist - Social Withdrawal）, ABC-I, A, C （Aberrant Behavioral Checklist - Irritability, Agitation, Crying）, ABC-SB （Aberrant Behavioral Checklist - Stereotypic Behavior）, ABC-H, N (Aberrant Behavioral Checklist - Hyperactivity, Noncompliance ), and ABC-IS (Aberrant Behavioral Checklist - Inappropriate Speech ). Scale ratings can be completed by parents, special educators, psychologists, direct caregivers, nurses, and others with knowledge of the person being assessed. The rater has to answer each of the 58 questions using a 4-point Likert scale. A score of a "0" means the behavior is not a problem, a score of a "1" means slight problem, a score of a "2" means a serious problem, and a "3" means a severe problem.
Time frame: At baseline, Weeks 4 and 8
Changes from baseline in other ABC subscale scores at Weeks 4, 8 and 12.
The ABC (Aberrant Behavioral Checklist) scale has 58 items. The scale is broken down into five subscales including ABC-SW（Aberrant Behavioral Checklist - Social Withdrawal）, ABC-I, A, C （Aberrant Behavioral Checklist - Irritability, Agitation, Crying）, ABC-SB （Aberrant Behavioral Checklist - Stereotypic Behavior）, ABC-H, N (Aberrant Behavioral Checklist - Hyperactivity, Noncompliance ), and ABC-IS (Aberrant Behavioral Checklist - Inappropriate Speech ). Scale ratings can be completed by parents, special educators, psychologists, direct caregivers, nurses, and others with knowledge of the person being assessed. The rater has to answer each of the 58 questions using a 4-point Likert scale. A score of a "0" means the behavior is not a problem, a score of a "1" means slight problem, a score of a "2" means a serious problem, and a "3" means a severe problem.
Time frame: At baseline, Weeks 4, 8 and 12
Clinical Global Impressions-Improvement (CGI-I) scores at Weeks 4, 8, and 12.
The CGI includes the CGI-S and CGI-I. The CGI rating scale allows for an overall assessment of participant improvement over time. At baseline, the CGI-S assessment is performed and the rating investigator rates the severity of the participant's condition based on a 7-point scale ranging from 1 (no symptoms) to 7 (very severe symptoms). At the follow-up visit, the scoring investigator assessed the degree of improvement in the participant's symptoms relative to baseline based on the CGI-I items on a 7-point scale ranging from 1 (very marked improvement) to 7 (very marked deterioration).
Time frame: At Weeks 4, 8, and 12.
Changes from baseline in Clinical Global Impressions-Severity (CGI-S) scores at Weeks 4, 8, and 12.
The CGI includes the CGI-S and CGI-I. The CGI rating scale allows for an overall assessment of participant improvement over time. At baseline, the CGI-S assessment is performed and the rating investigator rates the severity of the participant's condition based on a 7-point scale ranging from 1 (no symptoms) to 7 (very severe symptoms). At the follow-up visit, the scoring investigator assessed the degree of improvement in the participant's symptoms relative to baseline based on the CGI-I items on a 7-point scale ranging from 1 (very marked improvement) to 7 (very marked deterioration).
Time frame: At baseline, Weeks 4, 8 and 12
Changes from baseline in Social Responsiveness Scale 2 (SRS-2) total scores at Weeks 4, 8, and 12.
The SRS-2 assesses participants' social communication, social awareness, social motivation, and self-regulation. Scales can be completed by parents and teachers.Both the SRS-2 total score and the five subscale scores can be used to assess the severity of ASD symptoms. The SRS-2-School Age was used in this study. The SRS-2 contains 65 items, each of which is rated by the assessor on a scale of 1 (not true), 2 (sometimes true), 3 (often true), and 4 (almost always true) based on the behavioral performance of the person being assessed. Scores range from 65-260, where higher scores indicate more severe social problems.
Time frame: At baseline, Weeks 4, 8 and 12
Changes from baseline in Autism Treatment Evaluation Checklist (ATEC) total scores at Weeks 4, 8, and 12.
The ATEC contains four subscales: language/communication, social, sensory/cognitive awareness, and health/physical/behavioral, and scale ratings can be completed by parents, special educators, psychologists, direct caregivers, nurses, and others who know the person being assessed. Scores from each subscale are combined to calculate a total score, which ranges from 0 to 179. Higher scores indicate more severe autism symptoms and behavioral problems, and lower scores indicate improvement in symptoms.
Time frame: At baseline, Weeks 4, 8 and 12
Changes from baseline in the total score of the Attention-Deficit Hyperactivity Disorder Rating Scale-IV - Home version (ADHD-RS-IV [Home version]) at Weeks 4, 8, and 12.
The ADHD-RS assesses the child's attention deficit and hyperactive/impulsive behaviors over the past six months. Scale ratings can be completed by parents and teachers. The ADHD-RS consists of 18 items that cover various aspects of attention and hyperactivity symptoms. Participants assess the extent of each item based on their performance using a four-point scale:0 (Never or Rarely), 1 (Sometimes), 2 (Often), and 3 (Very Often). By combining these items, a composite score can be derived that measures the severity of attention deficit and hyperactivity symptoms. Higher scores indicate more severe symptoms.
Time frame: At baseline, Weeks 4, 8 and 12
Changes from baseline in Behavior Rating Inventory of Executive Function (BRIEF) (Parent Version) scores at Weeks 4, 8, and 12.
The Children's BRIEF (Parent Version) assesses executive functioning in children and adolescents, including aspects of working memory, planning/organization, and task monitoring, and the scale can be completed by a parent or guardian. The first version of the Children's BRIEF (Parent Version) was used in this study. The parent version of the BRIEF for school-age children assesses the executive functioning of children aged 6 to 18 years old, and contains 86 items divided into 2 latitudes: behavioral regulation index (BRI, including 3 factors of inhibition, switching and emotional control) and metacognition index (MI, including 5 factors of task initiation, working memory, planning, organizing and monitoring). Each item was rated on a scale of 1 to 3 (1=never; 2=sometimes; 3=often), with higher ratings reflecting more severe impairment of executive function.
Time frame: At baseline, Weeks 4, 8 and 12
Proportion of participants with ≥25% reduction in ABC-SW score relative to baseline at Week 12.
The ABC (Aberrant Behavioral Checklist) scale has 58 items. The scale is broken down into five subscales including ABC-SW（Aberrant Behavioral Checklist - Social Withdrawal）, ABC-I, A, C （Aberrant Behavioral Checklist - Irritability, Agitation, Crying）, ABC-SB （Aberrant Behavioral Checklist - Stereotypic Behavior）, ABC-H, N (Aberrant Behavioral Checklist - Hyperactivity, Noncompliance ), and ABC-IS (Aberrant Behavioral Checklist - Inappropriate Speech ). Scale ratings can be completed by parents, special educators, psychologists, direct caregivers, nurses, and others with knowledge of the person being assessed. The rater has to answer each of the 58 questions using a 4-point Likert scale. A score of a "0" means the behavior is not a problem, a score of a "1" means slight problem, a score of a "2" means a serious problem, and a "3" means a severe problem.
Time frame: At baseline and week 12
Proportion of participants with a CGI-I score ≤ 2 at Week 12.
The CGI includes the CGI-S and CGI-I. The CGI rating scale allows for an overall assessment of participant improvement over time. At baseline, the CGI-S assessment is performed and the rating investigator rates the severity of the participant's condition based on a 7-point scale ranging from 1 (no symptoms) to 7 (very severe symptoms). At the follow-up visit, the scoring investigator assessed the degree of improvement in the participant's symptoms relative to baseline based on the CGI-I items on a 7-point scale ranging from 1 (very marked improvement) to 7 (very marked deterioration).
Time frame: At Week 12