Overview
Sponsor-declared trial summary
Phase
Phase II and Phase III (Integrated)
Status
Ongoing, recruiting
Participants planned
30
Countries
1
Sites
3
Autism with Spectrum Disorders and Moderate to Severe Intellectual Disability
The main objective of this study is to assess the feasibility of a protocol for administering OT intranasally as an adjuvant drug treatment to standard psycho-educational interventions in children aged 6 to 12 years with ASD of intensity severe and moderate to profound HI and presenting DC, at three levels: 1. The feas…
Key facts
- Sponsor
- Centre Hospitalier Universitaire De Toulouse
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Psychiatry and Psychology [F] - Behavior and Behavior Mechanisms [F01]
- Trial duration
- 12 Feb 2025 → ongoing
- Decision date (initial)
- 2024-09-10
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-516306-28-00
- EudraCT number
- 2022-000254-28
- ClinicalTrials.gov
- NCT05864508
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
The main objective of this study is to assess the feasibility of a protocol for administering OT intranasally as an adjuvant drug treatment to standard psycho-educational interventions in children aged 6 to 12 years with ASD of intensity severe and moderate to profound HI and presenting DC, at three levels:
1. The feasibility of setting up the pre-therapeutic and monitoring protocol for OT treatment: regular pediatric examination, taking blood samples, carrying out an electrocardiogram;
2. The feasibility of administering a daily OT intranasal spray treatment at the point of care and at home;
3. The safety profile of the medicinal product in this specific population at the two doses (4 IU then 8 IU).
Secondary objectives 1
- The secondary objectives of the study include the evaluation of secondary feasibility criteria, the evaluation of the safety profile of the OT treatment as well as the description of the efficacy of the treatment on a certain number of parameters, at the end of each of the administration periods
Conditions and MedDRA coding
Autism with Spectrum Disorders and Moderate to Severe Intellectual Disability
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | PT | 10063844 | Autism spectrum disorder | 100000004873 |
| 21.1 | PT | 10067989 | Intellectual disability | 100000004852 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 9
- Minor benefiting from a social security scheme
- Diagnosis:autism spectrum disorder according to the Diagnostic and Statistical Manual DSM -5 of severe intensity;
- Age: 6 – 12 years (> 5 years and < 13 years)
- Female or male child
- Comorbidities: Moderate to severe intellectual disability // Presence of challenging behavior objectified by means of clinical examination and the ABC and ABC-I scales
- Psycho-educational and re-educative care within one of the 4 investigative centers
- if prescribed psychotropic treatments (antipsychotics, anxiolytics, hypnotics/sedatives, antidepressants, psychostimulants and antiepileptics), the dosages must be stable for 3 months and must be within the recommended dose limits.
- Understanding of French by both parents (if applicable) and ability for both parents to understand, in particular, the instructions for administering the product and to answer questionnaires
- informed consent signed by the holders of parental authority
Exclusion criteria 14
- The refusal of the holders of parental authority
- Pregnant girls, determined by a positive baseline blood pregnancy test
- Criteria respecting the Syntocinon SPC: Hypersensitivity to Syntocinon /// Hyponatremia < 135 mmol/L /// Hypokalaemia < 3.5 mmol/L /// Hypertension or hypotension
- Behavioral intolerance to the intranasal route
- Hepatic impairment (ALT and/or AST > 3N)
- Kidney failure (creatinine > 3 N)
- History of an ECG considered to be clinically significant abnormal (validated by a cardiologist)
- Type 1 or 2 diabetes
- Prolongation of the QT interval and/or family history of QT prolongation linked to an identified genetic etiology (QTc prolongation threshold > 460 ms). Corrected QTc calculated with Bazett's formula: QTc = QTm/ V RR.
- History of epilepsy or seizures
- Sexually active women of childbearing age without effective contraception (Combined hormonal contraception (containing estrogens and progestins) combined with inhibition of ovulation or progestin-only hormonal contraception combined with inhibition of ovulation)
- Breastfeeding women
- Severe cardiovascular disease (tachycardia, bradycardia, arrhythmias, hypertension, hypotension, myocardial ischemia)
- Latex allergy
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The results will be considered positive if this percentage is greater than or equal to 80%, with a lower limit of the confidence interval of this estimate beyond 61.4%.
Secondary endpoints 3
- Precise statement of the reasons for a possible interruption of the protocol
- Qualitative assessment by caregivers and parents of the heaviness of implementing the protocol through semi-directive qualitative and quantitative interviews
- - Results of the questionnaires
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SUB09580MIG · Substance
- Active substance
- Oxytocin
- Pharmaceutical form
- NASAL SPRAY
- Route of administration
- NASAL SPRAY
- Max daily dose
- 8 IU international unit(s)
- Max total dose
- 8 IU international unit(s)
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
SUB12581MIG · Substance
- Active substance
- Sodium Chloride
- Pharmaceutical form
- INJECTABLE SOLUTION
- Route of administration
- NASAL SPRAY
- Max daily dose
- 0.4 ml millilitre(s)
- Max total dose
- 0.4 ml millilitre(s)
- Max treatment duration
- 1 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Centre Hospitalier Universitaire De Toulouse
- Sponsor organisation
- Centre Hospitalier Universitaire De Toulouse
- Address
- 2 Rue Viguerie
- City
- Toulouse
- Postcode
- 31300
- Country
- France
Scientific contact point
- Organisation
- Centre Hospitalier Universitaire De Toulouse
- Contact name
- Dr Julie ANDANSON
Public contact point
- Organisation
- Centre Hospitalier Universitaire De Toulouse
- Contact name
- Florine LEGAY
Locations
1 EU/EEA country · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 30 | 3 |
| Rest of world | — | 0 | — |
Investigational sites
APHP - Hôpital Universitaire Pitié-Salpêtrière
Psychiatrie de l’Enfant et de l’Adolescent, 47-83 Boulevard de l'hôpital, 75013, PARIS
Centre Hospitalier Universitaire De Montpellier
Psychiatrie de l’Enfant et de l’Adolescent, 39 Avenue Charles Flahault, Pavillon 32, Montpellier Cedex 5
Centre Hospitalier Universitaire De Toulouse
Service Universitaire de Psychiatrie de l’Enfant et de l’Adolescent,, 1 Place Du Docteur Joseph Baylac, 31300, Toulouse
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2025-02-12 | 2025-02-12 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Serious breaches 1 · Art. 52 CTR
Serious breach SB-85003
- Sponsor became aware
- 2025-05-27
- Date of breach
- 2025-04-19
- Submission date
- 2025-06-02
- Member states concerned
- France
- Categories
- Protocol
- Areas impacted
- Subject safety, Data reliability or robustness
- Benefit-risk balance changed
- No
- Description
- Le produit arrive à péremption un mois après ou-verture. La famille n’a pas réalisé le changement de flacons au 30ème jour de traitement : l’enfant a pris le traitement périmé pendant 11 jours.
- Sponsor actions
- Mesures correctives :
- Modification du circuit PUI : modification de l’ordonnance pour préciser à nouveau la péremption des produits.
- Appel téléphonique aux titulaires de l’autorité parentale : ré-information de la nécessité de changer le flacons, informa-tion sur la prise de produit périmé
- Instructions de changement de flacon don-nées à nouveau lors de la visite 2
- Ajout d’une mention à la main sur le carnet patient au bout d’un mois (le patient rece-vant une dose de 8UI le flacon devrait être terminé avant la date de péremption si la compliance est bonne).
- Rappel du changement de flacon lors de l’appel téléphonique S9 et S11
- L’évènement est déclaré en tant que situa-tion spéciale dans le CRF de l’étude.
Mesures préventives :
- Information par mail des centres ouverts et modification des diapositives de MEP pour les centres à ouvrir
- Modification du carnet patient pour ajout d’une mention sur les pages de suivi de compliance pour la péremption des pro-duits tous les 30 jours (+/- quelques jours).
- Flacon à pré-compléter avec la date d’ouverture/fin d’utilisation par le pharma-cien pour les dispensations à venir
- Information sera faite par le médecin à chaque appel téléphonique.
| Organisation | City | Country | Type |
|---|---|---|---|
| Centre Hospitalier Universitaire De Toulouse | Toulouse | France | Other |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 17 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-516306-28-00 | 8 |
| Protocol (for publication) | D4_ANNEXE 10 _ Vineland II | 1.0 |
| Protocol (for publication) | D4_Carnet suivi_ ocytocine (4UI) | 1.0 |
| Protocol (for publication) | D4_Carnet suivi_ ocytocine (8UI) | 1.0 |
| Protocol (for publication) | D4_Carnet suivi_ placebo | 2.0 |
| Protocol (for publication) | D4_Carnet suivi_ocytocine | 2 |
| Protocol (for publication) | D4_Fiche patient_Suivi grossesse | 2.0 |
| Protocol (for publication) | D4_Illustration _ inhalation nasale | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1.0 |
| Recruitment arrangements (for publication) | M1_Document not required | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Titulaires autorite | 7 |
| Subject information and informed consent form (for publication) | L2_Carte patient | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_Resume des donnees cliniques | 1.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_ OXYTOCIN ALLEMAND | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_ OXYTOCIN Traduit | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC Syntocinon | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2024-516306-28-00 | 8 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-30 | France | Acceptable 2024-08-09
|
2024-09-10 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-01-15 | France | Acceptable 2025-02-28
|
2025-03-05 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-07-18 | France | Acceptable 2025-08-14
|
2025-08-19 |