Evaluate the Efficacy and Safety of TTYP01 Tablets in Adolescents and Children With ASD

Shanghai Auzone Biological Technology Co., Ltd.

Status and phase: Enrolling; Phase 2

Conditions: Autism Spectrum Disorder (ASD)

Treatments: Drug: TTYP01 Tablets (12mg or 18mg); Drug: Placebo (Simulant TTYP01 Tablets)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06757504

TTYP01-Ⅱ-ASD

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 150 estimated patients

Sex: All

Ages: 6 to 16 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Participants are eligible for the study only if all of the following inclusion criteria are met:

1. Aged ≥ 6 to <16 years at the time of signing the ICF (age <16 years after 12-week treatment), including adolescents aged ≥ 12 to<16 years at the time of signing the ICF (age <16 years after 12-week treatment), and children aged ≥ 6 to<12 years at the time of signing the ICF;
2. Male or female;
3. Participants diagnosed with ASD according to the ASD diagnostic criteria in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and confirmed by the Schedule for Affective Disorders and Schizophrenia for School Aged Children Present and Lifetime version (K-SADS-PL), DSM-5 ASD module;
4. Child Autism Rating Scale 2-ST (CARS 2-ST) raw score ≥36;
5. CGI-S score ≥4;
6. Participants and their legal guardians understand and are willing to participate in this trial, with ICF signed by the legal guardian and participants aged ≥ 8 years; for participants who, at the discretion of the investigator, have cognitive deficits that prevent them from signing the ICF, their legal guardians sign the ICF on behalf of them;
7. Females of childbearing potential (as defined in Appendix 15.1) agree to remain abstinent or use a reliable method of contraception for the duration of the trial and until 3 months after the last dose of the investigational product.

Exclusion criteria

Any participant who meets any of the following criteria will be excluded:

1. Weight <20.0 kg or >70.0 kg, or BMI ≥35.0 kg/m^2;
2. Pregnant or lactating women;
3. Presence of a serious mental disorder as assessed by the investigator, e.g., schizophrenia, bipolar disorder, depressive disorder, etc.; the presence of significant anxiety, tension, agitation, fear, depression, or the presence of suicidal risk, significant risk of self-injury, impulsivity, aggression, or behaviors based on the medical history and the routine mental status examination;
4. History of epileptic seizures within 3 months prior to screening, or presence of a history of severe physical or neurological disease, history of severe head trauma;
5. Participants with a history or symptoms of other mental illness that, at the discretion of the investigator, may affect the results of the study;
6. Participants with a history of any unstable physical or neurological condition or currently suffering from a physical or neurological condition that, at the discretion of the investigator, may put them at risk of a significant adverse event or interfere with the assessment of safety and efficacy during the course of the trial;
7. Pre-existing educational training and/or behavioral treatments fail to be stabilized prior to screening and consistent throughout the trial;
8. Participants who are unable to discontinue or may use other treatments during the screening period and throughout the trial due to their condition, including: antipsychotic medications (except those that may be used in combination during the trial as specified in the protocol), medications that may have a therapeutic effect on ASD, nootropic drugs, medications for ADHD, intestinal flora modification, and other intestinal flora modification supplementation alternatives;
9. Participants who have used treatment modalities such as transcranial magnetic stimulation therapy, direct current stimulation therapy, electroencephalographic biofeedback therapy, auditory integration training, executive function training, acupuncture therapy, etc., within 2 months prior to randomization, or may use such treatments during the treatment period;
10. 12-ECG and laboratory results as outlined below: (1)QTc is outside the normal range of the site; (2)Platelets are below the lower limit of normal for the site; (3)Haemoglobin is below the lower limit of normal for the site; (4)Neutrophil count is below the lower limit of normal for the site; (5)ALT or AST ≥ 2 × upper limit of normal, or total bilirubin > upper limit of normal for the site; (6)Urea nitrogen or creatinine is above the upper limit of normal for the site; (7)Any other abnormal laboratory, vital sign, or 12-ECG findings that, at the discretion of the investigator, are abnormal and clinically significant and will affect the safety of the participant or the interpretation of the study results;
11. Participation in any clinical trial of a drug or non-drug intervention within the last 1 month;
12. Concomitant medications/therapies that are prohibited in the protocol may be required during the trial;
13. Participants expected to undergo elective surgery during the trial;
14. Participants whose parents/guardians are unable to understand and/or complete the scale assessments in this trial.
15. Hypersensitivity to edaravone and excipients (Soluplus, sodium bisulphite, microcrystalline cellulose, magnesium stearate, polyvinylpolypyrrolidone) in TTYP01 tablets;
16. Participants who are judged by the investigator to be ineligible for other reasons.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

150 participants in 3 patient groups, including a placebo group

TTYP01 low-dose group

Experimental group

Description:

TTYP01 Tablets (12mg or 18mg), Twice daily for 12 weeks. Dosage is determined based on body weight and group assignment, with the low-dose group receiving 12mg-30mg BID, the dosing regimen is detailed in the trial protocol.

Treatment:

Drug: Placebo (Simulant TTYP01 Tablets)

Drug: TTYP01 Tablets (12mg or 18mg)

TTYP01 high-dose group

Experimental group

Description:

TTYP01 Tablets (12mg or 18mg), Twice daily for 12 weeks. Dosage is determined based on body weight and group assignment, with the high-dose group receiving 24mg-60mg BID, the dosing regimen is detailed in the trial protocol.

Treatment:

Drug: Placebo (Simulant TTYP01 Tablets)

Drug: TTYP01 Tablets (12mg or 18mg)

Placebo group

Placebo Comparator group

Description:

Simulant TTYP01 Tablets, Twice daily for 12 weeks.

Treatment:

Drug: Placebo (Simulant TTYP01 Tablets)