Antidepressant Trial With P2X7 Antagonist JNJ-54175446

• Status: Recruiting
• Trial end date: 2022-06-30
• Target enrollment: 0
• Participant gender: All

Summary

Depression is one of the most important causes of disability in the world today, with major personal, social and economic costs. Although some moderately effective drug treatments are already available, about a third of patients with major depressive disorder (MDD) remain depressed despite current treatment.

There is growing evidence that inflammation - the response of the body's immune system to physical and social stresses - can cause depressive symptoms in some patients. It is therefore predicted that anti-inflammatory drugs could have anti-depressant effects and the research team aims to test this using a new drug, JNJ-54175446, which blocks the activity of a receptor called P2X7. P2X7 is present on many immune cells and plays a key role in the release of inflammatory molecules during stress, which may be linked to stress-related depression.

The research team will recruit approximately up to 142 participants with MDD to this clinical trial. Patients will have moderate-severe depressive symptoms despite ongoing treatment with a conventional anti-depressant drug, and they will have blood test results at screening that indicate they are likely to have active P2X7 signalling in the brain. Eligible participants will be randomly allocated to receive either 50mg/day JNJ-54175446 or placebo for 8 weeks. Participants will be assessed at weeks 2, 5 and 8 using a standard clinical depression scale and the scores compared between those treated with placebo and those treated with JNJ-54175446. To understand more about the effects of JNJ-54175446 on the immune system and the brain, patients will also complete additional blood tests, questionnaires and magnetic resonance imaging (MRI) brain scans at different visits throughout the trial. The trial will be carried out across 5 centres in the UK.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: CCTU-Core
• Collaborator: Janssen Pharmaceuticals
• Treatments: Antidepressive Agents

Criteria

The key eligibility criteria are listed below, to obtain the full list please contact the trial team.

Inclusion Criteria:

1. Provided written informed consent

2. Between the age of 18 to 60 years inclusive

3. Meets the Diagnostic and statistical manual - 5 (DSM-5) diagnostic criteria for MDD without psychotic features (past or present), as confirmed by the M.I.N.I v7.0.

4. Has PHQ-9 score of ≥10.

5. BMI between 18.0 and 36.0 kg/m2 inclusive.

6. Currently being treated with one antidepressant monoaminergic drug (e.g. SSRI, SNRI, TCA) at an adequate dose, and for at least 6 weeks.

7. Must be medically stable based on clinical laboratory tests, medical history, vital signs, and 12-lead ECG performed.

8. Agree to practice highly effective method of birth control as stated in the protocol.

9. A woman of childbearing potential must have a negative serum pregnancy test at screening.

10. Agree not to donate eggs or sperm from start of dosing and for at least 3 months after receiving the last dose of study drug.

Exclusion Criteria:

1. Has a primary DSM-5 diagnosis of posttraumatic stress disorder.

2. Has failed to respond to more than 3 antidepressant treatments despite an adequate dose and duration, in the last 24 months.

3. Presence of two copies of the loss-of-function C allele at rs3751143, and/or has one copy of the loss-of-function A allele at rs1653624 in the P2RX7 gene.

4. Has a current or recent history of clinically significant suicidality.

5. Has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 12 months before screening.

6. Has positive test result(s) for alcohol or drugs of abuse (including methadone, opiates, cocaine, cannabinoids, amphetamine/methamphetamine and ecstasy).

7. Has a current diagnosis of a psychotic disorder (e.g. schizophrenia, bipolar disorder), an eating disorder (e.g. anorexia, bulimia), or learning disability or a personality disorder that is considered by the investigator to interfere with the ability of the subject to adhere to the protocol (e.g. narcissistic personality, borderline personality disorder)

8. Has used:

• Monoamine oxidase inhibitors (MAOIs) within 12 weeks before screening

• Within 6 weeks prior to enrolment use of other antidepressant drugs not belonging to the allowed classes of SSRI, SNRI, or TCA.

9. Is currently treated with antipsychotic drugs (D2-antagonists; except for low-dose quetiapine), lithium, other mood stabilizers or opiates.

10. Unable to complete MRI scans.

11. Has current signs/symptoms of liver or renal insufficiency, diabetes mellitus (type I and II), hypothyroidism or hyperthyroidism without stable treatment, or other significant and uncontrolled medical conditions.

12. Is a woman who is pregnant or breast feeding.

13. Plans to conceive a child while enrolled in this study or within 3 months after the last dose of IMP.

14. Has a history of malignancy within 5 years before screening.

15. Has received an investigational drug/vaccines, used an invasive investigational medical device within 60 days before the planned first dose of IMP, or has participated in 2 or more interventional clinical studies in the previous 1 year, or is currently enrolled in any drug or non-drug interventional study.

16. Venous blood concentration of C-reactive protein, measured by high sensitivity assay (hs-CRP) less than 1 mg/L.

17. Has had major surgery, (i.e. requiring general anaesthesia) within 12 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time they are expected to participate in the study.