Antidepressant Trial With P2X7 Antagonist JNJ-54175446

NCT04116606 | Unknown Phase 2 DMC

• 2 other identifiers: CCTU02512018-001884-21
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Depressive Disorder, Major; Inflammation

Keywords

P2X7; Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Change from baseline in total score on the MADRS scale at week 8

  The Montgomery Asberg Depression Rating Scale (MADRS), a researcher-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. (Visit 4)

  At baseline and at 8 weeks of treatment

Secondary Outcomes (12)

• Change from baseline in total score on the MADRS scale

  At baseline, 2 and 5 weeks of treatment

• Change in scores on Perceived Stress Scale

  At baseline, 2, 5 and 8 weeks of treatment

• Change in scores on SHAPS

  At baseline, 2, 5 and 8 weeks of treatment

• Change in scores on CFQ

  At baseline, 2, 5 and 8 weeks of treatment

• Change in scores on QIDS-SR16

  At baseline, 2, 5 and 8 weeks of treatment

Other Outcomes (3)

• Change in Salivary cortisol levels as a measure of biological stress

  Samples collected within 7 days prior to Baseline visit and within 7 days prior to visit 4

• Measurement of peripheral blood peripheral cytokine and chemokine levels

  Baseline and at 8 weeks fo treatment

• Measurement of peripheral blood immunophenotypes

  Baseline and at 8 weeks fo treatment

Study Arms (2)

Active JNJ-54175446

ACTIVE COMPARATOR

JNJ-54175446 is an unlicensed drug currently being developed by Janssen Pharmaceuticals. The drug is presented in oral capsules, each capsule containing 50 mg of JNJ-54175446. Participants will be asked to self-administer one capsule daily for 8 weeks.

Drug: Active JNJ-54175446

Matching placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Active JNJ-54175446 DRUG

JNJ-54175446 is a novel, potent, selective, and brain-penetrant antagonist of the adenosine triphosphate (ATP)-gated P2X7 channel.

Active JNJ-54175446

Placebo DRUG

Matching placebo containing the same excipients

Matching placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Provided written informed consent
• Between the age of 18 to 60 years inclusive
• 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.
• Has PHQ-9 score of ≥10.
• BMI between 18.0 and 36.0 kg/m2 inclusive.
• Currently being treated with one antidepressant monoaminergic drug (e.g. SSRI, SNRI, TCA) at an adequate dose, and for at least 6 weeks.
• Must be medically stable based on clinical laboratory tests, medical history, vital signs, and 12-lead ECG performed.
• Agree to practice highly effective method of birth control as stated in the protocol.
• A woman of childbearing potential must have a negative serum pregnancy test at screening.
• 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.

You may not qualify if:

• Has a primary DSM-5 diagnosis of posttraumatic stress disorder.
• Has failed to respond to more than 3 antidepressant treatments despite an adequate dose and duration, in the last 24 months.
• 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.
• Has a current or recent history of clinically significant suicidality.
• 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.
• Has positive test result(s) for alcohol or drugs of abuse (including methadone, opiates, cocaine, cannabinoids, amphetamine/methamphetamine and ecstasy).
• 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)
• 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.
• Is currently treated with antipsychotic drugs (D2-antagonists; except for low-dose quetiapine), lithium, other mood stabilizers or opiates.
• Unable to complete MRI scans.
• 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.
• Is a woman who is pregnant or breast feeding.
• Plans to conceive a child while enrolled in this study or within 3 months after the last dose of IMP.

Sponsors & Collaborators

• CCTU-Core: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (5)

Addenbroooke's Hospital

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Cardiff University Brain Research Imaging Centre

Cardiff, CF24 4HQ, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, G3 8SW, United Kingdom

Location

The Maurice Wohl Clinical Neuroscience Institute

London, SE5 9RT, United Kingdom

Location

Warneford Hospital

Oxford, OX3 7JX, United Kingdom

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Inflammation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Edward Bullmore

  Cambridgeshire and Peterborough NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Investigator

Study Record Dates

• First Submitted: September 19, 2019
• First Posted: October 4, 2019
• Study Start: September 12, 2019
• Primary Completion: December 31, 2023
• Study Completion: June 30, 2024
• Last Updated: June 22, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: After declaration of end of trial to authorities and submission of end of trial report.
• Access Criteria: Data will be made available free of charge to anyone interested in the research.

Locations

GB (5)