Phase III randomized, multicenter open label clinical trial to evaluate the efficacy of immunomodulatory therapy in case of psychiatric disorders with proven dysimmunity. TIM-DePisT

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Bordeaux

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

4 Jul 2024 → ongoing

Decision date (initial)

2024-10-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

French Ministry of Health and Solidarity, PHRC-N 2019

External identifiers

EU CT number

2024-518259-49-00

EudraCT number

2021-005078-25

ClinicalTrials.gov

NCT05946486

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the efficacy at 3 months of immunotherapy for patients with psychotic symptoms and proven auto-immunity added to ongoing psychiatric care (with or without standard psychotropic treatment).

Secondary objectives 4

1. To assess the efficacy at 1, 6 and 12 months of immunotherapy added to ongoing psychiatric care (with or without standard psychotropic treatment)
2. To evaluate the prevalence of auto-immune psychosis in France
3. To assess the safety of immunotherapy in case of psychotic symptoms
4. To evaluate the kinetic of auto-Ab at 3 months

Conditions and MedDRA coding

Mental Disorder

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. For step 1 : For Adult and Adolescent (who reached 17 years old): First acute or relapse of psychotic disorders defined by the PANSS scale with or without standard pharmacological treatment.
2. For Step 1 : For Children: Child aged between 6 and 16 years old with a first acute or relapse of psychotic disorders defined by the Kiddie sads-PL scale with or without standard pharmacological treatment.
3. Informed consent concerning the step 1 of the patient or his legal representatives.
4. For step 2 : Patient for whom inclusion criteria for step 1 of the trial are present with or without standard pharmacological treatment.
5. For step 2 : Biological diagnosis of pathogenic CNS autoantibodies in the blood.
6. For step 2 : MDC scale score >3 is required for inclusion in step 2.
7. For step 2, Normal ECG in case of previous heart disease.
8. For step 2, Informed consent concerning the step 2 of the patient or his legal representatives
9. For step 2, Effective contraception for women of childbearing potential during the clinical trial and for at least 12 months after the last rituximab administration.

Exclusion criteria 17

1. For the first step of the clinical trial (diagnostic) : Developmental disorder related to a genetic disease.
2. For the first step :Co-existing disorder of severe neurological disease.
3. For the first step :Chronic psychotic disorders receiving ongoing neuroleptic treatment with efficacy.
4. For the first step: Pregnant or breastfeeding women.
5. For the second step of the clinical trial (Intervention): Hypersensitivity to the active substance (rituximab) or to murine proteins, or to any of the other excipients
6. For the second step : Blood platelets < 75x109/L
7. For the second step: Neutrophils < 1.5x109/L
8. For the second step: Neoplastic pathology
9. For the second step: Hepatitis B or HIV infection
10. For the second step: Contraindication to immunosuppressant treatment (active severe infection, severely immunocompromised state).
11. for the second step: Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
12. for the second step: Pregnant or breastfeeding women at the randomization visit.
13. for the second step: Currently receiving an investigational drug or received an investigational drug or device within 30 days (or 5 half-lives for drugs, whichever is longer) prior to screening.
14. for the second step: Previous treatment with rituximab in the past 12 months.
15. for the second step: Patients with a history of recurring or chronic infections or with underlying conditions which may further predispose them to serious infection (e.g. hypogammaglobulinemia).
16. for the second step: Recent vaccination with live viral vaccine (within 3 months).
17. for the second step: Any other medical illness or disability that, in the opinion of the investigator, would compromise effective trial participation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint outcome is the remission of psychiatric symptoms at 3 months, defined as: For adult and adolescent patients (who reached 17 years old at step 1 inclusion visit) : 20% decrease from baseline of BPRS-E scale. For children patients aged between 6 and 16 years old at step 1 inclusion visit: 25% decrease from baseline of ABC (Aberrant Behavior Checklist) scale.

Secondary endpoints 13

1. for adults and adolescents : general functioning measurement with the GAF scale
2. for adults and adolescents : cognitive assessment thanks to the MOCA scale
3. for adults and adolescents : neurologic evaluation with the 2 scales KREBS and BUSH
4. for adults and adolescents : psychotic disorders measurement with the PANSS scale
5. for adults and adolescents : assessment of the evolution of depressive and manic disorders thanks to the MADRS and YMRS scales.
6. for children (aged between 6 and 16 years old at step 1 inclusion visit) :psychotic disorders measurement with the PANSS scale
7. for children : assessment of the evolution of depressive and manic disorders thanks to the CDRS and YMRS scales
8. for children : neurologic evaluation BUSH scale
9. for all: Persistence rate of autoimmunity in psychiatric disorder at baseline for all participants to the Step 1 of the trial
10. for all: Remission of psychiatric symptoms in each group of participants to the Step 2 of the trial, at M1, M6 and M12
11. for all: Evaluation of severity and improvement with CGI-S and CGI-I
12. for all: Level of autoimmune Abs at 3 months in each group of participants to the Step 2 of the trial
13. for all: Frequency and nature of serious and non-serious adverse events as well as infections in each arm.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Bordeaux

Sponsor organisation

Centre Hospitalier Universitaire De Bordeaux

Address

12 Rue Dubernat, Cs 91286 Cs 91286

City

Talence

Postcode

33400

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Bordeaux

Contact name

Coordinating investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Bordeaux

Contact name

Coordinating investigator

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications