RA-P-OCD-01

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Uppsala

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

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

Trial duration

5 Nov 2024 → ongoing

Decision date (initial)

2024-11-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

The Swedish Research Council (vetenskapsrådet)

External identifiers

EU CT number

2024-518391-31-00

EudraCT number

2019-000256-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Is to evaluate whether Rituximab as compared to placebo is a clinically effective treatment for a subgroup of patients suffering from psychosis and/or obsessive-compulsive disorder (OCD) or -behavior (OCB) where there is an indication of immune system involvement.

Secondary objectives 5

1. 1. To assess whether Rituximab treatment (with the doses and timing described in section 8) as compared to placebo is associated with amelioration in psychiatric symptomatology
2. 2. To assess whether Rituximab treatment as compared to placebo is associated with improvement in executive functions
3. 3. To assess whether Rituximab treatment as compared to placebo is associated with amelioration in neurological symptoms
4. 4. To evaluate the longevity of psychiatric, neurological and executive improvements associated with Rituximab treatment for up to 16 months after the first infusion (i.e. 12 months after the last infusion)
5. 5. To evaluate whether Rituximab treatment as described is safe for these patients.

Conditions and MedDRA coding

Psychosis and or Obsessive Compulsive Disorder, with an indication of immune system involvement

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Patients to be included in this study meet the criteria for at least one of the following ICD 10 CM diagnoses: o Obsessive-compulsive disorder ICD F42 or o Obsessive-compulsive behavior ICD R46.81 o Schizophrenia, delusional, and other non-mood psychotic disorders, namely  F20 Schizophrenia  F22 Delusional disorders  F23 Brief psychotic disorder  F25 Schizoaffective disorders  F28 Other psychotic disorder not due to a substance or known physiological condition  F29 Unspecified psychosis not due to a substance or known physiological condition
2. Age: 18-55
3. Severity: Clinical Global impression (CGI): Minimum score of “4 = Moderately ill”
4. Swedish or English proficiency
5. The patient has tried at least 2 standard psychiatric medications at maximal tolerable or maximal recommended dosage for his/her current condition over a period of 6 months, but has not improved significantly
6. Medication has been unchanged for at least one month prior to study start
7. Signed informed consent
8. Use of adequate contraception
9. Radiological evidence of brain atrophy and scarring are absent
10. The clinical picture indicates active inflammatory activity (see specific criteria below), potential for rehabilitation and time from disease and/or episode debut is no longer than 10 years.
11. Acute (<12 weeks) or atypical debut, or episodes of any of the following: a. Symptoms of encephalopathy:  psychotic symptoms, including hallucinations, delusions, paranoia, disorganized speech, disorganized behavior  agitation, confusion  sudden change in personality as perceived by the social environment  drowsiness  loss of functions in daily life  cognitive problems (memory, speech, learning)  emotional dysregulation b. Focal neurological symptoms, e.g.  ataxia, dystonia, myoclonus, sensory losses, paresthesia c. Psychomotor anomaly,  e.g. retardation, catatonic symptoms, parkinsonism d. Loss of drive (sleep, appetite, libido, motivation) e. Obsessions, compulsions (OCD/OCB), f. Hypo- or hypervigilance (for e.g sounds, emotions, other peoples´ or own behavior) g. Sleeping disorders, AND
12. AND At least one of the following criteria: a. Prodromal phase with infection or symptoms of infection (fever, malaise, etc) b. Clinical improvement of psychiatric symptoms after treatment with anti-inflammatory medications other than antibody therapy (such as steroids, NSAIDs IVIG, plasmaphereses), or antibiotics c. Radiological evidence of neuroinflammation (MR) d. EEG pathology or witnessed epileptic seizure e. Biochemical evidence of inflammation, autoimmunity or blood-brain barrier dysfunction in blood or CSF samples, such as one of the following:  presence of oligoclonal bands  elevated CSF cell count  elevated albumin quotient, or elevated albumin in CSF  elevated IgG ratio  elevated levels of neurofilament f. Patient history of autoimmune disorder not associated with neuroinflammation, such as type 1 diabetes, rheumatoid arthritis, Sjögren´s syndrome, inflammatory bowel disease (IBD, comprising Crohn´s disease and ulcerative colitis), celiac disease, Grave´s disease, Hashimoto`s thyroiditis g. Biochemical indication of autoimmunity such as elevated serum anti-TPO, ANA, ANCA, RF or GAD antibodies, PANDAS panel with relationship to symptom development.

Exclusion criteria 15

1. Concomitant malignancies or previous malignancies within the last five years
2. Cannot comply with vaccination recommendations
3. History of severe allergic or anaphylactic reactions in conjunction with prior treatment with monoclonal antibodies
4. Prior antibody therapy including Rituximab (MabThera®/Rituxan®)
5. Patient has been treated with clozapine (which may have immunosuppressant effect), systemic corticosteroids or IVIG within 60 days prior to screening visit
6. Prior treatment with immunosuppressant medications (not including systemic corticosteroids and IVIG) for other medical condition
7. History of or positive screening for HIV, Tuberculosis, Hepatitis B and/or Hepatitis C (ever)
8. Heart disease such as previous heart attack, arrhythmia or heart failure, coronary insufficiency
9. Current drug, alcohol, or chemical abuse
10. Pregnancy at any time during the study
11. Known chronical significant bacterial/viral/fungal infections
12. Diagnosis of well-established neuroinflammatory disease such as MS (ICD codes G00–G09, G35–G37) or SLE (M32)
13. Tested positive for autoantibodies in serum or CSF associated to known and treatable neuroinflammatory disease (such as neuroborreliosis, treatable autoimmune encephalitis). Patients having completed recommended treatment without significant improvement may still be included in this study.
14. History of any illness that in the opinion of the investigator may jeopardize the ability of the patient to participate in the study.
15. Patient is enrolled in another medical trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The clinical efficacy of Rituximab treatment will be evaluated by calculating the average difference between BPRS scores at baseline and main-evaluation (8-month) and comparing it between the treatment-first and the placebo-first group.

Secondary endpoints 5

1. 1. The amelioration in psychiatric symptomatology will be assessed by following the psychiatric rating scales: o CGI o WHODAS, o EQ-VAS, o Y-BOCS o BFCS
2. 2. Improvement in executive functions, will be assessed by following neuropsychiatric tests: o Neuropsychological tests o Mismatch negativity
3. 3. The amelioration of neurological symptoms will be assessed by performing complete, video-recorded neurological exams. This procedure is described in section 11.
4. 4. The longevity of psychiatric, neurological and executive improvements will be examined by the psychiatric ratings scales named in 1. and blood samples every 4 months up to 16 months, and in addition to that a thorough neurological exam, the executive tests named in 2. and CSF samples every 8 months up to 16 months.
5. 5. The safety of Rituximab treatment will be assessed by adverse events monitoring and questionnaires described in detail in section 12.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Uppsala

Sponsor organisation

Region Uppsala

Address

Storgatan 27, Uppsala Domkyrkofors. Uppsala Domkyrkofors.

City

Uppsala

Postcode

753 31

Country

Sweden

Scientific contact point

Organisation

Region Uppsala

Contact name

Janet Cunningham

Public contact point

Organisation

Region Uppsala

Contact name

Janet Cunningham

Locations

1 EU/EEA country · 1 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 4 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