NCT02473289

An Efficacy and Safety Study of Sirukumab in Participants With Major Depressive Disorder

Completed Phase 2 Results posted Last updated 29 April 2025

What this trial tests

Phase 2 trial testing Sirukumab 50 mg in Depressive Disorder, Major in 193 participants. Completed in 22 May 2018.

Timeline

23 July 2015

Primary endpoint
22 May 2018

22 May 2018

Quick facts

Lead sponsor	Janssen Research & Development, LLC
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	193
Start date	23 July 2015
Primary completion	22 May 2018
Estimated completion	22 May 2018
Sites	46 locations across Russia, United Kingdom, Poland, Canada, United States

Drugs / interventions tested

• Sirukumab 50 mg — full drug profile →
• Placebo

Conditions studied

• Depressive Disorder, Major — all drugs for Depressive Disorder, Major →

Sponsor

Janssen Research & Development, LLC — full company profile →

Who can join

Adults 21 to 64, any sex, with Depressive Disorder, Major. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Hamilton Depression Rating Scale (HDRS-17) Total Score at Week 12 Primary · Baseline and Week 12

The HDRS-17 is a clinician-administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. Each of the 17 items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A total score (0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition. Here 'N' (number of p

Group	Value	95% CI
Placebo	-10.6	± 1.43
Sirukumab 50 mg	-11.4	± 1.52

Change From Baseline in HDRS-17 Total Score at Weeks 1, 4 and 8 Secondary · Baseline, Weeks 1, 4 and 8

The HDRS-17 is a clinician-administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. Each of the 17 items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A total score (0 to 52) was calculated by adding the scores of all 17 items. For each item as well as the total score, a higher score represents a more severe condition.

Change at Week 1

Group	Value	95% CI
Placebo	-5.1	± 1.03
Sirukumab 50 mg	-4.6	± 1.15

Change at Week 4

Group	Value	95% CI
Placebo	-7.5	± 1.21
Sirukumab 50 mg	-7.8	± 1.33

Change at Week 8

Group	Value	95% CI
Placebo	-7.9	± 1.29
Sirukumab 50 mg	-11.0	± 1.39

Percentage of Participants With Remission as Assessed by HDRS-17 Total Score at Week 12 Secondary · Week 12

Remission- Percentage of participants with HDRS-17 total score less than or equal to (\<=) 7 were considered as remitters. HDRS-17 defined as clinician-administered rating scale designed to assess severity of symptoms in participants diagnosed with depression with score range of 0 to 52. Each of 17 items is rated by clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A total score (0 to 52) was calculated by adding scores of all 17 items. For eac

Group	Value	95% CI
Placebo	19.0
Sirukumab 50 mg	15.9

Percentage of Participants With Response as Assessed by HDRS-17 Total Score at Week 12 Secondary · Week 12

Response- Percentage of participants with greater than or equal to (\>=) 50 percent (%) improvement on the HDRS-17 total score from baseline at Week 12 were considered as responders. The HDRS-17 defined as clinician-administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. Each of the 17 items is rated by the clinician on either a 3-point (0 to 2) or a 5-point scale (0 to 4). The point scale used a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). A

Group	Value	95% CI
Placebo	33.3
Sirukumab 50 mg	34.1

Change From Baseline in Clinical Global Impression - Severity (CGI-S) Total Score at Weeks 1, 4, 8, 12, 16, and 22 Secondary · Baseline and Weeks 1, 4, 8, 12, 16, and 22

CGI-S defined as clinician-rated scale that assesses the severity of mental illness on a scale of 0 to 7. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating according to:1: normal, not at all ill; 2: borderline mentally ill; 3: mildly ill; 4: moderately ill; 5: markedly ill; 6: severely ill; 7: among the most extremely ill patients. A higher score implies a more severe condition.

Change at Week 1

Group	Value	95% CI
Placebo	-0.6	± 0.14
Sirukumab 50 mg	-0.7	± 0.15

Change at Week 4

Group	Value	95% CI
Placebo	-1.1	± 0.16
Sirukumab 50 mg	-1.0	± 0.17

Change at Week 8

Group	Value	95% CI
Placebo	-1.4	± 0.18
Sirukumab 50 mg	-1.5	± 0.19

Change at Week 12

Group	Value	95% CI
Placebo	-1.5	± 0.21
Sirukumab 50 mg	-1.9	± 0.22

Change at Week 16

Group	Value	95% CI
Placebo	-1.9	± 0.23
Sirukumab 50 mg	-2.1	± 0.24

Change at Week 22

Group	Value	95% CI
Placebo	-2.0	± 0.24
Sirukumab 50 mg	-2.3	± 0.25

Change From Baseline in Patient Health Questionnaire (PHQ-9) Total Score at Weeks 1, 4, 8, 12, 16, and 22 Secondary · Baseline and Weeks 1, 4, 8, 12, 16, and 22

The PHQ-9 used as a participant-reported measure of depressive symptomatology. The PHQ-9 is 9-item scale, where each item is rated on a 4-point scale (0=Not at all, 1=Several Days, 2=More than half the days, and 3=Nearly every day). The participant's item responses were summed to provide a total score range of 0 to 27. Higher scores indicates greater severity of depressive symptoms. The recall period is 2 weeks.

Change at Week 1

Group	Value	95% CI
Placebo	-2.5	± 0.58
Sirukumab 50 mg	-3.1	± 0.61

Change at Week 4

Group	Value	95% CI
Placebo	-4.4	± 0.75
Sirukumab 50 mg	-5.3	± 0.79

Change at Week 8

Group	Value	95% CI
Placebo	-5.6	± 0.86
Sirukumab 50 mg	-7.6	± 0.87

Change at Week 12

Group	Value	95% CI
Placebo	-7.5	± 0.98
Sirukumab 50 mg	-8.9	± 1.00

Change at Week 16

Group	Value	95% CI
Placebo	-8.2	± 0.98
Sirukumab 50 mg	-9.6	± 1.00

Change at Week 22

Group	Value	95% CI
Placebo	-9.1	± 1.04
Sirukumab 50 mg	-10.7	± 1.05

Change From Baseline in Snaith Hamilton Pleasure Scale (SHAPS) Total Score (Definition 1) at Weeks 1, 4, 8, 12, 16, and 22 Secondary · Baseline and Weeks 1, 4, 8, 12, 16, and 22

The Snaith-Hamilton Pleasure Scale (SHAPS) is short, 14-item instrument to measure anhedonia. Each of the 14 items has a set of four response categories (Definition 1): Definitely Agree (=1), Agree (= 2), Disagree (= 3), and Definitely Disagree (= 4). A SHAPS total score was calculated as the sum of the 14 item scores with a total score range from 14 to 56. A higher total score indicates higher levels of state anhedonia.

Change at Week 1

Group	Value	95% CI
Placebo	-1.4	± 0.72
Sirukumab 50 mg	-3.3	± 0.74

Change at Week 4

Group	Value	95% CI
Placebo	-3.9	± 0.75
Sirukumab 50 mg	-5.1	± 0.78

Change at Week 8

Group	Value	95% CI
Placebo	-5.8	± 0.87
Sirukumab 50 mg	-7.0	± 0.88

Change at Week 12

Group	Value	95% CI
Placebo	-5.9	± 1.00
Sirukumab 50 mg	-8.9	± 1.02

Change at Week 16

Group	Value	95% CI
Placebo	-7.0	± 1.11
Sirukumab 50 mg	-8.8	± 1.12

Change at Week 22

Group	Value	95% CI
Placebo	-7.8	± 1.11
Sirukumab 50 mg	-10.6	± 1.12

Change From Baseline in Snaith Hamilton Pleasure Scale (SHAPS) Total Score (Definition 2) at Weeks 1, 4, 8, 12, 16, and 22 Secondary · Baseline and Weeks 1, 4, 8, 12, 16, and 22

The Snaith-Hamilton Pleasure Scale (SHAPS) is short, 14-item instrument to measure anhedonia. Each of the 14 items has a set of four response categories (Definition 2): Definitely Agree (= 0), Agree (= 0), Disagree (= 1), and Definitely Disagree (= 1). A SHAPS total score was calculated as the sum of the 14 item scores with a score range from 0 to 14. A higher total score indicates higher levels of state anhedonia.

Change at Week 1

Group	Value	95% CI
Placebo	-1.2	± 0.45
Sirukumab 50 mg	-2.0	± 0.47

Change at Week 4

Group	Value	95% CI
Placebo	-2.2	± 0.49
Sirukumab 50 mg	-3.3	± 0.51

Change at Week 8

Group	Value	95% CI
Placebo	-3.6	± 0.57
Sirukumab 50 mg	-4.4	± 0.57

Change at Week 12

Group	Value	95% CI
Placebo	-3.7	± 0.64
Sirukumab 50 mg	-5.4	± 0.66

Change at Week 16

Group	Value	95% CI
Placebo	-4.1	± 0.69
Sirukumab 50 mg	-5.6	± 0.70

Change at Week 22

Group	Value	95% CI
Placebo	-4.6	± 0.71
Sirukumab 50 mg	-6.8	± 0.72

Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score at Weeks 1, 4, 8, 12, 16, and 22 Secondary · Baseline and Weeks 1, 4, 8, 12, 16, and 22

The FACIT-Fatigue is a questionnaire that assesses self-reported tiredness, weakness, and difficulty conducting usual activities due to fatigue. The subscale consists 13-item instrument to measure fatigue. Each of the 13 items has a set of five response categories: Not at all (=0), A little bit (=1), Somewhat (=2), Quite a bit (=3) and Very much (=4). A total FACIT-Fatigue subscale score was calculated as the sum of the 13 item scores (reserved scores \[4 - score\] for all except for 2 items: "I have energy" and "I am able to do my usual activities"), and ranges from 0 to 52, with a higher sco

Change at Week 1

Group	Value	95% CI
Placebo	1.75	± 4.671
Sirukumab 50 mg	4.91	± 10.097

Change at Week 4

Group	Value	95% CI
Placebo	6.87	± 10.119
Sirukumab 50 mg	6.44	± 9.633

Change at Week 8

Group	Value	95% CI
Placebo	8.93	± 9.913
Sirukumab 50 mg	10.09	± 10.346

Change at Week 12

Group	Value	95% CI
Placebo	11.65	± 13.476
Sirukumab 50 mg	13.82	± 11.486

Change at Week 16

Group	Value	95% CI
Placebo	13.55	± 12.029
Sirukumab 50 mg	13.95	± 12.066

Change at Week 22

Group	Value	95% CI
Placebo	14.54	± 13.585
Sirukumab 50 mg	17.23	± 12.051

Adverse events — posted to ClinicalTrials.gov

Time frame: Approximately 26 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 2/99 (2%)

Deaths: 0/99

Sirukumab 50 mg

Serious: 3/94 (3%)

Deaths: 0/94

Serious adverse events (5 terms)

Reaction	System	Placebo	Sirukumab 50 mg
Acute Myocardial Infarction	Cardiac disorders	—	—
Cellulitis	Infections and infestations	—	—
Transaminases Increased	Investigations	—	—
Depression Suicidal	Psychiatric disorders	—	—
Suicide Attempt	Psychiatric disorders	—	—

Other adverse events (3 terms — click to expand)

Reaction	System	Placebo	Sirukumab 50 mg
Headache	Nervous system disorders	—	—
Injection Site Erythema	General disorders	—	—
Injection Site Pain	General disorders	—	—

Most-reported serious reactions: Acute Myocardial Infarction, Cellulitis, Transaminases Increased, Depression Suicidal, Suicide Attempt.

Data from ClinicalTrials.gov NCT02473289 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the efficacy of sirukumab as adjunctive treatment to antidepressant therapy (monoaminergic antidepressant) where sirukumab (administered as a 50 milligram (mg) subcutaneous (SC) injection at Day 1, Day 28 and Day 56 during the 12- week double-blind treatment period) is compared to adjunctive placebo based on the change from baseline to 12-week endpoint in depressive symptoms as measured by the total score on the Hamilton Depression Rating Scale (HDRS), in participants diagnosed with Major Depressive Disorder (MDD) who have had a suboptimal response to the current standard oral antidepressant therapy and have a screening high sensitivity C-Reactive Protein (hsCRP) \>=0.300 milligram per deciliters (mg/dL) (International System of Units (SI) 3.00 mg/L). A cohort of subjects with hsCRP \<0.300 milligram per deciliter will also be enrolled to allow a better understanding of the relationship between CRP and clinical changes.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls.
   Osimo EF, Pillinger T, Rodriguez IM, Khandaker GM, et al · · 2020 · cited 577× · PMID 32113908 · DOI 10.1016/j.bbi.2020.02.010
2. Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels.
   Osimo EF, Baxter LJ, Lewis G, Jones PB, et al · · 2019 · cited 534× · PMID 31258105 · DOI 10.1017/s0033291719001454
3. Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions.
   Kappelmann N, Lewis G, Dantzer R, Jones PB, et al · · 2018 · cited 460× · PMID 27752078 · DOI 10.1038/mp.2016.167
4. Immune and Neuroendocrine Mechanisms of Stress Vulnerability and Resilience.
   Ménard C, Pfau ML, Hodes GE, Russo SJ. · · 2017 · cited 252× · PMID 27291462 · DOI 10.1038/npp.2016.90
5. Associations of immunological proteins/traits with schizophrenia, major depression and bipolar disorder: A bi-directional two-sample mendelian randomization study.
   Perry BI, Upthegrove R, Kappelmann N, Jones PB, et al · · 2021 · cited 160× · PMID 34280516 · DOI 10.1016/j.bbi.2021.07.009
6. Effects of immunomodulatory drugs on depressive symptoms: A mega-analysis of randomized, placebo-controlled clinical trials in inflammatory disorders.
   Wittenberg GM, Stylianou A, Zhang Y, Sun Y, et al · · 2020 · cited 140× · PMID 31427751 · DOI 10.1038/s41380-019-0471-8
7. The Two-Faced Cytokine IL-6 in Host Defense and Diseases.
   Narazaki M, Kishimoto T. · · 2018 · cited 139× · PMID 30423923 · DOI 10.3390/ijms19113528
8. Therapeutic Implications of Brain-Immune Interactions: Treatment in Translation.
   Miller AH, Haroon E, Felger JC. · · 2017 · cited 117× · PMID 27555382 · DOI 10.1038/npp.2016.167