Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Sirukumab · 9 trials · 4 indications
The Disease Activity Index Score 28 using ESR \[DAS28 (ESR)\] is a derived score combining tender joints (28 joints), swollen joints (28 joints), ESR, and Patient's Global Assessment of Disease Activity. The 28 joints evaluated for swelling and tenderness were shoulder, elbow, wrist, MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of the upper right and upper left extremities as well as the knee joints of the lower right and lower left extremities. The DAS28-ESR is expressed on a score range of "0-10", with the minimum score= 0 (best) to maximum score= 10 (worst).
The ACR 50 Response is defined as greater than or equal to (\>=) 50 percent (%) improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>= 50% improvement in 3 of following 5 assessments: subject's assessment of pain using Visual Analog Scale (VAS) (0-10 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), subject's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS (the scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) (the scale ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP).
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
MACE was defined as a composite of Myocardial Infarction (MI), stroke, death, hospitalization for unstable angina, and hospitalization for Transient Ischemic Attack (TIA). Adjudication of these events by the Endpoint Adjudication Committee (EAC) was performed in a blinded fashion.
Percentage of participants with one or more malignancy was reported.
Percentage of participants with one or more serious infections was reported.
Percentage of participants with one or more GI perforations was reported. GI perforation is a hole that develops through the entire wall of the stomach, small intestine, large bowel, or gallbladder.
Percentage of participants with hepatobiliary abnormalities was reported.
Percentage of participants with serious or moderate/severe systemic hypersensitivity reactions, or serum sickness adverse events (AEs) was reported.
A TEAE was defined as an event that occurred in the treatment period during which it emerged (that is \[i.e.\] started or worsened in severity, relation, or other attribute), and even if the event continued to be present.
ACR 20 response is greater than or equal to (\>=) 20 percent (%) improvement in both tender joint count (68) and swollen joint count (66) and \>= 20% improvement in 3 of following 5 assessments:Participant's assessment of pain using visual analog scale (VAS) (0-10 scale, 0=no pain and 10=worst possible pain),Participant's global assessment of disease activity by using VAS (scale ranges from 0 to 10, \[0 = very well to 10 = very poor\]), Physician's global assessment of disease activity using VAS (scale ranges from 0 to 10, \[0=no arthritis activity to 10=extremely active arthritis\]), Participant's assessment of physical function as measured by Health Assessment Questionnaire-Disability Index (HAQ-DI) (scale ranges from 0= no difficulty to 3= inability to perform a task in that area), and Serum C-reactive protein (CRP). Participants were analyzed according to randomized treatment groups they were assigned, regardless of treatments they actually received. Here, TF= treatment failure.
The van der Heijde-modified Sharpe (vdH-S) score is defined as a measurement of progression in structural damage. It is the sum of joint erosion (32 joints of the hands and 12 joints of the feet) score and joint space narrowing (JSN) (30 joints of the hands and 12 joints of the feet) score. The joint erosion assessment is scored according to the surface area involved, from 0 to 5, with 0 indicating no erosion and 5 indicating complete collapse of bone whereas the JSN assessment including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage. Participants were analyzed according to the randomized treatment groups they were assigned to, regardless of the treatments they actually received. Here, EE= early escape.
The ACR 20 Response is defined as greater than or equal to (\>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS; 0-10 scale, 0 =no pain and 10 =worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, \[0 =no pain to 10 =worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP).
Time to sustained improvement is defined as an improvement of at least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale sustained until Day 28. The 6-point ordinal CRS provides 6 mutually exclusive conditions ordered from best (score 1) to worst (score 6) corresponding to below categories, reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are: not hospitalized, including participants on low level of oxygen (category 1); Hospitalization, not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) (category 5); death (category 6). Higher scores indicated greater worsening.
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 participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Bioavailability will be evaluated by using the formula: AUC from time zero to infinity with extrapolation of the terminal phase of SC injection divided by AUC from time zero to infinity with extrapolation of the terminal phase of IV infusion of sirukumab and multiplied by 100.
The Serum Concentration (Cmax) is defined as maximum observed analyte concentration.
Pharmacokinetic parameters will include the maximum observed plasma concentration (Cmax), time to reach the maximum observed plasma concentration (Tmax), area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast), area under the plasma concentration-time curve from time 0 to 96 hours (AUC0-96h) (S-warfarin only), area under the plasma concentration versus time curve from time 0 to infinity with extrapolation of the terminal phase (AUCinf).
| Arm | Type | Description |
|---|---|---|
| Group 1 (adalimumab 40 mg) | EXPERIMENTAL | Adalimumab 40 mg SC at Weeks 0, 2, and every 2 weeks through Week 52. At Week 16, subjects who have \< 20% improvement from baseline in both swollen and tender joint counts will early escape in a blinded fashion and receive adalimumab 40 mg every week through Week 52. |
| Group 2 (sirukumab 100 mg) | EXPERIMENTAL | Sirukumab 100 mg SC at Weeks 0, 2, and every 2 weeks through Week 52. Subjects may meet the early escape criteria at Week 16 (\< 20% improvement from baseline in both swollen and tender joint counts) but no sirukumab dose adjustments will made for these subjects. However, these subjects will receive placebo injections every 2 weeks between the sirukumab injections (ie, subjects that early escape will receive a weekly injection of alternating sirukumab and placebo, to preserve the blind). |
| Group 3 (sirukumab 50 mg) | EXPERIMENTAL | Sirukumab 50 mg SC at Weeks 0, 4, and every 4 weeks through Week 52. Between sirukumab injections, placebo SC injections will be administered at Weeks 2, 6, and every 4 weeks through Week 50. At Week 16, subjects who have \< 20% improvement from baseline in both swollen and tender joint counts will early escape in a blinded fashion and receive sirukumab 100 mg every 2 weeks through Week 52 and placebo injections every 2 weeks between the sirukumab injections (ie, subjects that early escape will receive a weekly injection of alternating sirukumab and placebo, to preserve the blind). |
| Sirukumab 100 mg | EXPERIMENTAL | - |
| Sirukumab 50 mg / placebo | EXPERIMENTAL | - |
| Sirukumab 50 mg and Placebo | EXPERIMENTAL | - |
| Placebo then Sirukumab 50 mg or Sirukumab 100 mg | EXPERIMENTAL | - |
| Sirukumab 50 mg + Placebo | EXPERIMENTAL | - |
| Group 1 | EXPERIMENTAL | Patients will receive placebo every 2 weeks from Week 0 through Week 22, followed by a subcutaneous (SC) sirukumab dose regimen every 2 weeks through Week 52. |
| Group 2 | EXPERIMENTAL | Patients will receive sirukumab 100 mg SC at Weeks 0, 2, and every 2 weeks through Week 52. |
| Group 3 | EXPERIMENTAL | Patients will receive sirukumab 50 mg SC at Weeks 0, 4, and every 4 weeks through Week 52. Between sirukumab injections, placebo SC administrations will be made at Weeks 2, 6, and every 4 weeks through Week 52. |
| Sirukumab | EXPERIMENTAL | Participants will receive single intravenously (IV) dose infusion of sirukumab on Day 1 along with standard of care treatment. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive IV single dose infusion of placebo on Day 1 along with standard of care treatment. |
| Sirukumab 50 milligram (mg) | EXPERIMENTAL | Participants will receive sirukumab 50 mg as subcutaneous injection on Day 1, 28 and 56. |
| Group 4 | EXPERIMENTAL | 42 participants will receive a single SC injection of 100 mg sirukumab using a PFS-U |
| Group 5 | EXPERIMENTAL | 42 participants will receive a single SC injection of 100 mg sirukumab using a PFS-AI |
| Sirukumab and 5-probe cocktail | EXPERIMENTAL | The 5-probe cocktail will consist of oral doses of midazolam, warfarin/vitamin K, omeprazole, and caffeine. |
| Name | Type | Description |
|---|---|---|
| adalimumab 40 mg | BIOLOGICAL | SC injections |
| sirukumab 100 mg | BIOLOGICAL | SC injections |
| sirukumab 50 mg | BIOLOGICAL | SC injections |
| Placebo | DRUG | SC injections |
| Sirukumab | DRUG | Type=exact, unit=mg, number=50 or 100, form=solution for injection, route=subcutaneous use; every 2 weeks for 100 mg and every 4 weeks for 50 mg, Week 52 through Week 104. |
| Standard of Care (SOC) | OTHER | SOC treatment will be determined by the investigator based on local practice and consists of supportive care. |
| Sirukumab (IV infusion) | DRUG | Participants will receive a single IV infusion of 100 mg sirukumab. |
| Sirukumab (SC injection with PFS-U) | DRUG | Participants will receive a single SC injection of 50 mg sirukumab with PFS-U. |
| Sirukumab (SC injection with PFS-AI) | DRUG | Participants will receive a single SC injection of 50 mg sirukumab with PFS-AI. |
| Midazolam | DRUG | Type=exact number, unit=mg/kg, number 0.03, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50 |
| Warfarin | DRUG | Type=exact number, unit=mg, number= 10, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50 |
| Vitamin K | DRUG | Type=exact number, unit=mg, number =10, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50 |
| Omeprazole | DRUG | Type=exact number, unit=mg, number=20, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50 |
| Caffeine | DRUG | Type=exact number, unit=mg, number=100, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50 |
Inclusion Criteria: * Have a diagnosis of rheumatoid arthritis (RA) for at least 6 months before screening * Have moderately to severely active RA with at least 8 of 68 tender joints and 6 of 66 swollen joints, at screening and at baseline * Have previous or current treatment with methotrexate (MTX...
Sirukumab is an investigational drug being studied for use in major depressive disorder, rheumatoid arthritis, and COVID-19. It is developed by Johnson & Johnson (JNJ) and is in Phase 3 clinical development. Sirukumab is a small molecule immunology therapeutic that has been evaluated in multiple clinical trials.
Sirukumab is a small molecule therapeutic developed by Johnson & Johnson (JNJ) for immunology indications. It is being studied in Phase 3 trials for conditions including major depressive disorder, rheumatoid arthritis, and COVID-19. The drug has been evaluated in six completed clinical trials with a total enrollment of 5,061 participants.
Sirukumab is developed by Johnson & Johnson, which trades under the ticker JNJ. The drug is an investigational small molecule immunology therapeutic currently in Phase 3 clinical development. It has been studied for major depressive disorder, rheumatoid arthritis, and COVID-19 across six completed clinical trials.
Sirukumab is in Phase 3 clinical development. It is an investigational drug, not yet approved, being studied by Johnson & Johnson (JNJ) for major depressive disorder, rheumatoid arthritis, and COVID-19. All six clinical trials for Sirukumab have been completed, with no active trials currently ongoing.
Sirukumab has been studied in six completed clinical trials, including NCT01604343 (Phase 3, rheumatoid arthritis, 1,670 participants), NCT01636557 (Phase 1, rheumatoid arthritis, 12 participants), NCT02079545 (Phase 1, healthy volunteers, 144 participants), and NCT02473289 (Phase 2, major depressive disorder, 193 participants). All trials are completed.
Yes, Sirukumab is also known as CNTO 136. Clinical trials such as NCT01604343 and NCT01636557 refer to the drug as CNTO 136 (Sirukumab). This investigational drug is being developed by Johnson & Johnson (JNJ) for conditions including rheumatoid arthritis, major depressive disorder, and COVID-19.