E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment-resistant patients with Obsessive Compulsive Disorder (OCD) |
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E.1.1.1 | Medical condition in easily understood language |
Treatment-resistant patients with Obsessive Compulsive Disorder (OCD) |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate whether markedly ill, treatment resistant psychiatric patients, assumed to have an inflammatory aetiology for their symptoms and diagnosed with obsessive-compulsive disorder are improved after treatment with the immunomodulatory drug rituximab (anti-CD20 antibodies). |
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E.2.2 | Secondary objectives of the trial |
• To examine whether baseline levels of inflammatory markers predict treatment response. • To examine whether changes in inflammatory markers or B-cell depletion correlate with treatment response. • To examine metabolic mediators prior and after treatment and if they correlate with treatment response. • To examine whether there is a change in markers for gut permeability after treatment. • To examine whether there is a change in cognition after treatment. • To investigate the patients’ experiences of the novel treatment with a qualitative content analysis. • To assess safety and tolerability of rituximab during treatment for OCD.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Age: 18 to 40 years 2) Duration of psychiatric illness: exceeding 2 years 3) Rated “Markedly ill”, “Severely ill” or ”Among the most extremely ill patients” on the Clinical Global Impression – Severity scale (CGI-S) 4) Global Assessment of Functioning below 50 5) Current diagnosis according to Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5) of OCD 6) Treatment resistance, i.e. failing to remit despite adequate treatments 7) If female and with any risk for pregnancy: willing to use contraceptives. 8) If psychotropic treatment is prescribed for OCD plasma concentrations of the drug must be identified. 9) Subjects should be judged by the investigator to be lucid and oriented to person, place, time, and situation when giving the informed consent. 10) Immunoglobulin levels within the normal range
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E.4 | Principal exclusion criteria |
1) on-going immunomodulatory treatment 2) pregnancy or breast-feeding 3) weight below 40 kg 4) clinically relevant on-going infection 5) chronic infections 6) positive screening test for hepatitis B, C, HIV or tuberculosis 7) any change of psychotropic medication within the previous 4 weeks 8) much or very much improved already at baseline according to CGI-I, i.e. scores of 1 or 2 by the clinician 9) severe heart failure (NYHA grade IV) or other severe heart disease or history of cardiac arrhythmia or myocardial infarction 10) unable to make an informed decision to consent to the trial 11) in compulsory treatment 12) treatment with clozapine within the last 2 months 13) previous treatments with immunosuppressive agents 14) malignancy currently or within 2 years prior to inclusion
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is change in symptoms measured as change in Y-BOCS score. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Global improvement at week 20, according to a balanced assessment (mean value of three independent assessors: 1) The treating clinician, 2) The patient’s self-assessment and 3) A next-of-kin) using the Clinical Global Impression-Improvement (CGI-I) scale (range 1-7; 1 representing “Very much improved”). • Change in Personal and Social Performance Scale (PCP) measuring overall disability • Change from baseline up to week 20 of illness severity (CGI-S) assessed by the clinician • Difference from baseline up to week 20 in inflammatory markers in blood (gene expression and proteins) in relationship to clinical response (CGI-I) • Proportion of responders to treatment, i.e. rated as Much or very much improved since baseline according to CGI-I assessed by three different informants: 1) The treating clinician, 2) The patient’s self-assessment and 3) A next of kin. If the mean value of these three is below 2.5 then the patient will be regarded as a responder (representing much or very much improved since baseline). • Safety and tolerability of rituximab during treatment for OCD measured with the questionnaire Any Adverse Reactions (AAR). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |