A Trial of TTA-121 on Autism Spectrum Disorder

An Early Phase II Trial for Efficacy and Safety of TTA-121 on Autism Spectrum Disorder

To test efficacy and safety of a novel nasal spray of oxytocin on social deifies in autism spectrum disorder, and To compare effect sizes of different doses

Study Overview

• Status: Unknown
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: TTA-121

• Study Type: Interventional
• Enrollment (Anticipated): 144
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 431-3192
      • Hamamatsu University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 54 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Diagnosis of autism spectrum disorder based on Diagnostic and Statistical Manual of Mental Disorders-V with score exceeding the cut-off value of 10 for qualitative abnormalities in social reciprocity on Autism Diagnostic Interview Revised (ADIR)
2. Full scale Intelligent quotient above 80 as measured using the Wechsler Adult Intelligent Scale-III
3. Written informed consent for participating the trial

Exclusion Criteria:

1. Diagnosis of bipolar disorder or schizophrenia spectrum disorder
2. Primary diagnosis of depressive disorders, obsessive-compulsive and related disorders, anxiety disorders, trauma- and stressor-related disorders, dissociative disorders, somatic symptom and related disorders, or neurodevelopmental disorders other than autism spectr um disorder
3. Instability in symptoms of comorbid mental disorders such as depressive disorders or anxiety disorders
4. History of changes in medication or doses of psychotropics within one month before registration
5. Current treatment with more than one psychotropics
6. History of hyper-sensitivity to oxytocin
7. History of seizures or traumatic brain injury with loss of consciousness for longer than 5 minutes
8. History of alcohol-related disorders, substance abuse, or addiction
9. Family history of male breast cancer
10. Subject who has severe complications
11. Known hypersensitivity to some drugs and foods
12. Subject who is not able to consent contraception during study period
13. Participation in another registration clinical trial and administration of investigational drug during 120 days before informed consent
14. Other Subjects whom a lead investigator or the patient's primary physician deems are not appropriate for this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Low dose once per day and placebo; Four weeks administrations of TTA-121 3U once per day in morning and placebo once per day in evening. After four weeks washout, four weeks administrations of placebo twice per day in morning and evening.	Drug: TTA-121; A nove intranasal spray of oxytocin and placebo
Other: Low dose twice per day and placebo; Four weeks administrations of TTA-121 3U twice per day in morning and evening. After four weeks washout, four weeks administrations of placebo twice per day in morning and evening.	Drug: TTA-121; A nove intranasal spray of oxytocin and placebo
Other: High dose once per day and placebo; Four weeks administrations of TTA-121 10U once per day in morning and placebo once per day in evening. After four weeks washout, four weeks administrations of placebo twice per day in morning and evening.	Drug: TTA-121; A nove intranasal spray of oxytocin and placebo
Other: High dose twice per day and placebo; Four weeks administrations of TTA-121 10U twice per day in morning and evening. After four weeks washout, four weeks administrations of placebo twice per day in morning and evening.	Drug: TTA-121; A nove intranasal spray of oxytocin and placebo
Other: Placebo and low dose once per day; Four weeks administrations of placebo twice per day in morning and evening. After four weeks washout, four weeks administrations of TTA-121 3U once per day in morning and placebo once per day in evening.	Drug: TTA-121; A nove intranasal spray of oxytocin and placebo
Other: Placebo and low dose twice per day; Four weeks administrations of placebo twice per day in morning and evening. After four weeks washout, four weeks administrations of TTA-121 3U twice per day in morning and evening.	Drug: TTA-121; A nove intranasal spray of oxytocin and placebo
Other: Placebo and high dose once per day; Four weeks administrations of placebo twice per day in morning and evening. After four weeks washout, four weeks administrations of TTA-121 10U once per day in morning and placebo once per day in evening.	Drug: TTA-121; A nove intranasal spray of oxytocin and placebo
Other: Placebo and high dose twice per day; Four weeks administrations of placebo twice per day in morning and evening. After four weeks washout, four weeks administrations of TTA-121 10U twice per day in morning and evening.	Drug: TTA-121; A nove intranasal spray of oxytocin and placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy on autism spectrum social core symptom assessed by social reciprocity score on the Autism Diagnostic Observation Schedule module 4	Changes in social reciprocity score (range: 0-14, Higher value represent a worth outcome) on Autism Diagnostic Observation Schedule module 4 between baseline and endpoint of each administration period	At baseline, which was before and on the same day as the first administration, and at endpoint, which was started approximately 15 min after the last drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy on autism spectrum core symptom assessed by communication score on the Autism Diagnostic Observation Schedule module 4	Changes in communication score (range: 0-8, Higher value represent a worth outcome) on Autism Diagnostic Observation Schedule module 4 between baseline and endpoint of each administration period	At baseline, which was before and on the same day as the first administration, and at endpoint, which was started approximately 15 min after the last drug administration
Efficacy on autism spectrum core symptom assessed by repetitive and restricted behavior score on the Autism Diagnostic Observation Schedule module 4	Changes in repetitive and restricted behavior score (range: 0-10, Higher value represent a worth outcome) on Autism Diagnostic Observation Schedule module 4 between baseline and endpoint of each administration period	At baseline, which was before and on the same day as the first administration, and at endpoint, which was started approximately 15 min after the last drug administration
Efficacy on autism spectrum core symptom assessed by revised algorithm score of social affect on the Autism Diagnostic Observation Schedule module 4	Changes in revised algorithm score of social affect (range: 0-20, Higher value represent a worth outcome) on Autism Diagnostic Observation Schedule module 4 between baseline and endpoint of each administration period	At baseline, which was before and on the same day as the first administration, and at endpoint, which was started approximately 15 min after the last drug administration
Efficacy on autism spectrum core symptom assessed by revised algorithm of repetitive and restricted behavior score on the Autism Diagnostic Observation Schedule module 4	Changes in revised algorithm of repetitive and restricted behavior score (range: 0-10, Higher value represent a worth outcome) on Autism Diagnostic Observation Schedule module 4 between baseline and endpoint of each administration period	At baseline, which was before and on the same day as the first administration, and at endpoint, which was started approximately 15 min after the last drug administration
Efficacy assessed by Clinical Global Impression-Improvement	Changes in Clinical Global Impression-Improvement (range: 1-7, Higher value represent a worse outcome) between baseline and endpoint of each administration period	At baseline, which was before and on the same day as the first administration, and at endpoint, which was assessed within 100 min after the last drug administration
Efficacy assessed by Clinical Global Impression-Severity	Changes in Clinical Global Impression-Severity (range: 1-7, Higher value represent a worse outcome) between baseline and endpoint of each administration period	At baseline, which was before and on the same day as the first administration, and at endpoint, which was assessed within 100 min after the last drug administration
Efficacy assessed by Global Assessment of Functioning	Changes in Global Assessment of Functioning (range: 1-100, Higher value represent a better outcome) between baseline and endpoint of each administration period	At baseline, which was before and on the same day as the first administration, and at endpoint, which was assessed within 100 min after the last drug administration
Efficacy assessed by gaze fixation time on social region	Changes in gaze fixation time on social region during being talked between baseline and endpoint of each administration period	At baseline, which was before and on the same day as the first administration, and at endpoint, which was started approximately 60 min after the last drug administration
Efficacy assessed by quantitative analysis of facial expression	Changes in quantitative measure of facial expression on videos recorded during ADOS administration between baseline and endpoint of each administration period	At baseline, which was before and on the same day as the first administration, and at endpoint, which was started approximately 15 min after the last drug administration

Collaborators and Investigators

• Sponsor: Hamamatsu University
• Collaborators: Japan Agency for Medical Research and Development
• Investigators: Principal Investigator: Hidenori Yamasue, MD, PhD, Department of Psychiatry, Hamamatsu University School of Medicine

Publications and helpful links

General Publications

• Yamasue H, Kojima M, Kuwabara H, Kuroda M, Matsumoto K, Kanai C, Inada N, Owada K, Ochi K, Ono N, Benner S, Wakuda T, Kameno Y, Inoue J, Harada T, Tsuchiya K, Umemura K, Yamauchi A, Ogawa N, Kushima I, Ozaki N, Suyama S, Saito T, Uemura Y, Hamada J, Kano Y, Honda N, Kikuchi S, Seto M, Tomita H, Miyoshi N, Matsumoto M, Kawaguchi Y, Kanai K, Ikeda M, Nakamura I, Isomura S, Hirano Y, Onitsuka T, Kosaka H, Okada T. Effect of a novel nasal oxytocin spray with enhanced bioavailability on autism: a randomized trial. Brain. 2022 Apr 18;145(2):490-499. doi: 10.1093/brain/awab291.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2018
• Primary Completion (Anticipated): March 16, 2020
• Study Completion (Anticipated): March 30, 2020

Study Registration Dates

• First Submitted: February 28, 2018
• First Submitted That Met QC Criteria: March 13, 2018
• First Posted (Actual): March 15, 2018

Study Record Updates

• Last Update Posted (Actual): December 20, 2019
• Last Update Submitted That Met QC Criteria: December 18, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
• Other Study ID Numbers: UMIN000031412

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No