A randomized controlled trial with Rituximab for Psychotic disorder in adults

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Oerebro Laen

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

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

Trial duration

27 Aug 2024 → ongoing

Decision date (initial)

2024-08-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512408-20-00

EudraCT number

2022-000220-37

ClinicalTrials.gov

NCT05622201

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To investigate whether psychiatric patients diagnosed with schizophrenia spectrum disorder (SSD) are improved after an intravenous treatment with the immunomodulatory drug rituximab (anti- CD20 antibodies) in comparison with patients receiving NaCl (placebo).
Treatment response in this study is defined as ≥ 30 % improvement in PANSS combined with a clinician rated CGI-I score of 1 or 2, corresponding to very much improved or much improved at week 12.

Secondary objectives 10

1. Change in Personal and Social Performance Scale (PSP) measuring overall disability from baseline up to week 12 and 24.
2. Proportion of responders to treatment, i.e. rated as much or very much improved since baseline according to CGI-I up to week 12 and 24.
3. Improvement since baseline (CGI-I) up to week 12 and 24.
4. Severity according to CGI-S compared to baseline at week 12 and week 24.
5. Improvement in PANSS up to week 24 compared to baseline.
6. Differences in patient self-rated health (VAS-health) and PGE since baseline at week 12 and 24.
7. Baseline levels of inflammatory markers in relation to treatment response.
8. Safety and tolerability of rituximab during treatment for SSD
9. Change in brain morphology and/or activity in fMRI.
10. Mental health symptom domains (Level 1 Cross-cutting symptom measure of global symptom severity) in relationship to response.

Conditions and MedDRA coding

Schizophrenia spectrum disorder (SSD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age: 18 to 55 years
2. Duration of psychiatric illness: exceeding 1 year
3. Diagnosed with Schizophrenia spectrum disorder (SSD) according to Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5)
4. If female and with any risk for pregnancy: willing to use contraceptives* or abstinence if normal and preferred lifestyle
5. Subjects should be judged by the investigator to be lucid and oriented to person, place, time, and situation when giving the informed consent
6. Insufficiently recovered from previous antipsychotic treatments
7. A minimum score of 4 in CGI-Severity at baseline

Exclusion criteria 12

1. pregnancy or breast-feeding
2. weight below 40 kg
3. clinically relevant ongoing infection at the discretion of the physician
4. chronic infections
5. positive test for hepatitis B, hepatitis C, HIV, or TB prior to treatment
6. malignancy currently or within 2 years prior to inclusion
7. current severe heart failure (NYHA grade IV) or any other severe heart disease (e.g. or history of cardiac arrhythmia or myocardial infarction)
8. any change of antipsychotic medication within the previous 4 weeks
9. unable to make an informed decision to consent to the trial
10. ongoing clozapine treatment
11. ongoing immunomodulatory treatment
12. treatments with monoclonal antibodies within 1 year prior to the inclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Positive and Negative Syndrome Scale (PANSS) is a measure for severity in patients with schizophrenia (Kay et al. 1987). It is widely used in the study of antipsychotic therapy and is known as the “gold standard” for the assessment of schizophrenia. To assess a patient using PANSS, an approximately 45-minute clinical interview is conducted. The patient is rated from 1 to 7 on 30 different symptoms based on the interview as well as reports from family members or caretaking healthcare workers...
2. ... The time span considered is the week before the rating. Seven items measure “positive” symptoms, 7 items “negative” symptoms, and 16 items general psychopathology. Each item is graded between 1 and 7 resulting in a total score between 30 which correspond to no symptoms and a maximum of 210 points. We will evaluate the item A6 for depression separately at baseline and endpoints in order to assess depressive symptoms.

Secondary endpoints 10

1. Personal and Social Performance Scale (PSP) (Morosini et al., 2000) is a 100-point single-item rating scale, subdivided into 10 equal intervals. The ratings are based on the assessment of patient’s functioning in four main areas: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behaviors. In responders, we expect a 25 % reduction or more in the PSP score.
2. Clinical Global Impression-Improvement scale (CGI-I) measures change of symptoms on a 7-point Likert scale. CGI-I will also be administered to the next-of-kin. In both the clinical and next-of-kin assessment, clinical response in this study is regarded as a score of 1 or 2 corresponding to very much improved or much improved. Investigators may score CGI-I into half points, but those will be transformed into whole numbers in the analyses of the data.
3. Clinical Global Impression-Severity scale (CGI-S) is a clinician rated measure of overall clinical severity in the context of the diagnostic group. A person with no clinical complaints or problems will get a score of 1. The score 7, which indicates the highest level of severity is phrased as “Among the most extremely ill patients”.
4. Positive and Negative Syndrome Scale (PANSS) is a measure for severity in patients with schizophrenia. Improvements will be calculated by reducing the baseline scores with 30 points (which equals no symptoms) to reach a PANSS 0 score.
5. VAS-health is a patient self-evaluated health measure using a horizontal visual analogue scale ranging from 0 (= worst imaginable health) to 100 (= best imaginable health) the day of the visit. A 25 % reduction from baseline will be regarded as a self-reported treatment response measure.
6. Patient’s Global Evaluation (PGE) provides a self-administered global measure of improvement on a 7-point Likert scale identical to the CGI-I scoring system. In this study minimal improvement, i.e. a score of 3 (or below) is regarded as treatment response as individuals with SSD frequently tend to lack ability to observe improvements.
7. Baseline levels of inflammatory markers in relation to treatment response (i.e. a PANSS reduction of 30% or more) will be examined at both endpoints. Change in inflammatory markers in relation to response will also be investigated. Severity and frequencies of adverse events according to Any Adverse Reactions-Revised (AAR-R).
8. Severity and frequencies of adverse events according to Any Adverse Reactions-Revised (AAR-R).
9. Change in brain activity (e.g. blood flow and Default mode network) and morphology before and after treatment and in relation to response.
10. Level 1 Cross-cutting symptom measure of global symptom severity (APA, 2013) is a patient rated measure included in the DSM-5, which assesses mental health domains that are important across psychiatric diagnoses. It includes 13 domains and each of the items are rated 0-4 on a Likert scale. We will investigate if each endorsed domain is associated with response.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Oerebro Laen

Sponsor organisation

Region Oerebro Laen

Address

Sodra Grev Rosengatan

City

Orebro

Postcode

701 85

Country

Sweden

Scientific contact point

Organisation

Region Oerebro Laen

Contact name

Susanne Bejerot

Public contact point

Organisation

Region Oerebro Laen

Contact name

Susanne Bejerot

Locations

1 EU/EEA country · 8 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 9 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