Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, RA, VIB4920, MEDI4920
Brief summary
The purpose of the study is to evaluate the efficacy, safety, and pharmacokinetics (PK) of VIB4920 (formerly MEDI4920) in adult participants with rheumatoid arthritis (RA).
Detailed description
The overall study period will be approximately 337 days. After a screening period of up to 28 days, the participants will be randomized in a 1:1:1:1:1 ratio to receive intravenous dose of VIB4920 and/or placebo in 5 cohorts. Participants are to be followed on their stable background anti-RA therapy at least through 12 weeks (Day 85), at which time rescue therapy may be instituted. All participants will be followed at least through the primary (interim) analysis (Day 113), and those who have not instituted rescue therapy will be followed through Day 309 to determine the duration of clinical response. The primary analysis will be after all participants have completed Day 113, and the final analysis will be after all participants have completed follow-up. Study with completed results acquired from Horizon in 2024.
Interventions
DRUGVIB4920
liquid for IV infusion following dilution in normal saline
DRUGPlacebo
0.9% saline for IV infusion
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
Principal Inclusion Criteria: 1. Male or female adults, \>= 18 years of age at time of informed consent. 2. Diagnosed with RA according to the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2010 criteria \>= 6 months prior to screening. 3. Disease Activity Score in 28 Joints (DAS 28) using C-reactive Protein (DAS28-CRP) \> 3.2 at screening with \>= 4 tender joint count (TJC) and \>= 4 swollen joint count (SJC) out of the 28 joints assessed for DAS28 present at screening and confirmed present at visit 2 prior to randomization. 4. Positive for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA) at screening, in accordance with criteria at the central laboratory. 5. Treated with methotrexate (MTX), with or without a concomitant conventional disease-modifying anti-rheumatic drug (cDMARD). 6. Agreeing to use of protocol defined contraception methods. Principal
Exclusion criteria
1. Prior or current inflammatory joint disease other than RA. 2. Severe interstitial lung disease. 3. Prior receipt of any biologic B-cell-depleting therapy. 4. Receipt of any anti - tumor necrosis factor alpha (TNF-α) biologic agent \< 8 weeks prior to screening. 5. Receipt of any biologic disease-modifying anti-rheumatic drug (bDMARD) with a mechanism of action other than direct TNF-α blockade, \< 12 weeks or \< 5 half-lives of the drug prior to screening. 6. Injectable corticosteroids or treatment with \> 10 mg/day dose of oral prednisolone or equivalent within 4 weeks prior to screening. 7. Previous treatment with anti-cluster of differentiation 40 ligand (CD40L) compounds at any time before randomization. 8. Hepatitis B, hepatitis C, or human immunodeficiency virus infection. 9. Pregnant or lactating or planning to get pregnant during the duration of the study. 10. Evidence of active tuberculosis (TB) or being at high risk for TB. 11. History of more than one episode of herpes zoster in the 12 months prior to screening or any opportunistic infection in the 12 months prior to screening, excluding localized mucocutaneous candidiasis. 12. Receipt of live vaccine or live therapeutic infectious agent within the 4 weeks prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 113 in DAS28-CRP | Day 1 (Baseline), Day 113 | The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline indicates improvement in disease activity. Results are from a mixed-effect model for repeated measures (MMRM) analysis with treatment, visit, visit by treatment interaction, and baseline DAS28-CRP score included in the model. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | From first dose of study drug through Day 309 ± 7 days | Adverse event (AE): any untoward medical occurrence associated with the use of an intervention in humans, whether or not it is considered intervention-related. Serious adverse event (SAE): an AE that results in any of the following outcomes: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity; congenital anomaly/birth defect; other important medical event jeopardizing the participant's well-being. AEs of special interest (AESIs) include: thrombotic and embolic events; anaphylaxis and clinically significant (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 3 or higher) hypersensitivity reactions; severe infusion-related reactions (CTCAE Grade 3 or higher); immune complex disease; severe (CTCAE Grade 3 or higher) and/or opportunistic infections; hepatic function abnormality meeting the definition of Hy's Law; malignant neoplasm. (CTCAE Grade 3=Severe; Grade 4=Life-threatening; Grade 5=Fatal.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) | Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d | — |
| PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D) | Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), Day 56 | — |
| PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4 | Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d | — |
| PK of VIB4920: Terminal Elimination Half-Life (t1/2) | Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d | — |
| PK of VIB4920: Volume of Distribution at Steady State (Vss) | Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d | — |
| Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax) | Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d | — |
| Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Day 1 (Baseline) to Day 309 Day 1 (Baseline) up to Day 309 (± 7 days) | ADA positive at any time: observed at least once during the study (baseline included). Treatment-emergent ADA: ADA positive post-baseline only or boosted pre-existing ADA during the study period. Persistent positive: treatment-induced ADA positive at ≥ 2 post-baseline assessments (with ≥ 16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive: treatment-induced ADA post-baseline positive but does not fulfill the criteria of persistent positive. |
| Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs) | Day 1 (Baseline), Day 113 | Excluding data after rescue. Adjusted geometric mean ratio to baseline (90% CI) results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model. Ratios less than 1 indicate a decrease. |
| Change From Baseline to Day 113 in Rheumatoid Factor (RF) | Day 1 (Baseline), Day 113 | Excluding data after rescue. Adjusted geometric mean ratio to baseline (90% CI) results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model. Ratios less than 1 indicate a decrease. |
| Percentage of Participants With Clinical Remission at Day 113 | Day 113 | Clinical remission is defined as DAS28-CRP \< 2.6. The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. |
| Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication) | Day 1 (Baseline) up to Day 309 (± 7 days) | Based on Kaplan-Meier method. |
| Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Day 1 (Baseline), Days 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309 | Total sCD40L (free sCD40L and sCD40L bound to VIB4920) was measured in plasma samples using a modified commercially available kit. |
| PK of VIB4920: Time to Cmax (Tmax) | Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d | — |
Countries
Poland, United States
Participant flow
Pre-assignment details
After a screening period of up to 28 days, eligible participants were randomized in a 1:1:1:1:1 ratio into 5 cohorts.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received IV infusion of placebo matched to VIB4920 on Days 1, 15, 29, and 57. | 16 |
| VIB4920 3000 mg Once Participants received IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57. | 16 |
| VIB4920 1500 mg Twice Participants received IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29. | 16 |
| VIB4920 3000 mg Twice Participants received IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29. | 15 |
| VIB4920 1500 mg 4 Times Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. | 15 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Death | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Other, Not Specified | 0 | 1 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 3 | 1 | 1 |
Baseline characteristics
| Characteristic | VIB4920 1500 mg 4 Times | Total | Placebo | VIB4920 3000 mg Once | VIB4920 1500 mg Twice | VIB4920 3000 mg Twice |
|---|---|---|---|---|---|---|
| Age, Continuous | 56.4 years STANDARD_DEVIATION 15.2 | 56.3 years STANDARD_DEVIATION 12.7 | 56.3 years STANDARD_DEVIATION 14 | 53.2 years STANDARD_DEVIATION 10.7 | 59.0 years STANDARD_DEVIATION 12.2 | 56.5 years STANDARD_DEVIATION 12.2 |
| Disease Activity Score 28 C-reactive Protein (DAS28-CRP) | 5.761 score on a scale STANDARD_DEVIATION 0.711 | 5.615 score on a scale STANDARD_DEVIATION 0.83 | 5.443 score on a scale STANDARD_DEVIATION 1.066 | 5.473 score on a scale STANDARD_DEVIATION 0.883 | 5.945 score on a scale STANDARD_DEVIATION 0.736 | 5.452 score on a scale STANDARD_DEVIATION 0.644 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 75 Participants | 15 Participants | 15 Participants | 15 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 4 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other, Not Specified | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 14 Participants | 73 Participants | 14 Participants | 16 Participants | 15 Participants | 14 Participants |
| Sex: Female, Male Female | 12 Participants | 62 Participants | 12 Participants | 14 Participants | 11 Participants | 13 Participants |
| Sex: Female, Male Male | 3 Participants | 16 Participants | 4 Participants | 2 Participants | 5 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 18 | 1 / 17 | 0 / 13 | 0 / 14 |
| other Total, other adverse events | 10 / 16 | 10 / 18 | 14 / 17 | 11 / 13 | 10 / 14 |
| serious Total, serious adverse events | 0 / 16 | 1 / 18 | 1 / 17 | 0 / 13 | 1 / 14 |
Outcome results
Primary
Change From Baseline to Day 113 in DAS28-CRP
The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline indicates improvement in disease activity. Results are from a mixed-effect model for repeated measures (MMRM) analysis with treatment, visit, visit by treatment interaction, and baseline DAS28-CRP score included in the model.
Time frame: Day 1 (Baseline), Day 113
Population: Full Analysis Set: all randomized participants who received any dose of study drug, analyzed according to the treatment randomized. Participants with an assessment at given time point by group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Day 113 in DAS28-CRP | -1.06 score on a scale | Standard Error 0.26 |
| VIB4920 3000 mg Once | Change From Baseline to Day 113 in DAS28-CRP | -1.90 score on a scale | Standard Error 0.27 |
| VIB4920 1500 mg Twice | Change From Baseline to Day 113 in DAS28-CRP | -1.87 score on a scale | Standard Error 0.27 |
| VIB4920 3000 mg Twice | Change From Baseline to Day 113 in DAS28-CRP | -1.87 score on a scale | Standard Error 0.27 |
| VIB4920 1500 mg 4 Times | Change From Baseline to Day 113 in DAS28-CRP | -1.83 score on a scale | Standard Error 0.28 |
p-value: 0.029690% CI: [-1.47, -0.21]MMRM
p-value: 0.035590% CI: [-1.44, -0.18]MMRM
p-value: 0.036490% CI: [-1.44, -0.18]MMRM
p-value: 0.047890% CI: [-1.41, -0.13]MMRM
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs)
Adverse event (AE): any untoward medical occurrence associated with the use of an intervention in humans, whether or not it is considered intervention-related. Serious adverse event (SAE): an AE that results in any of the following outcomes: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity; congenital anomaly/birth defect; other important medical event jeopardizing the participant's well-being. AEs of special interest (AESIs) include: thrombotic and embolic events; anaphylaxis and clinically significant (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 3 or higher) hypersensitivity reactions; severe infusion-related reactions (CTCAE Grade 3 or higher); immune complex disease; severe (CTCAE Grade 3 or higher) and/or opportunistic infections; hepatic function abnormality meeting the definition of Hy's Law; malignant neoplasm. (CTCAE Grade 3=Severe; Grade 4=Life-threatening; Grade 5=Fatal.)
Time frame: From first dose of study drug through Day 309 ± 7 days
Population: Safety analysis set: all participants who received any dose of study drug, analyzed according to the treatment that they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | Death (Grade 5 severity) | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event of ≥ Grade 3 severity | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event of special interest | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one study drug-related event | 4 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one serious event | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one serious and/or ≥ Grade 3 severity event | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event leading to discontinuation of study drug | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event | 10 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one related serious event | 0 Participants |
| VIB4920 3000 mg Once | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one study drug-related event | 3 Participants |
| VIB4920 3000 mg Once | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one serious and/or ≥ Grade 3 severity event | 1 Participants |
| VIB4920 3000 mg Once | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one related serious event | 0 Participants |
| VIB4920 3000 mg Once | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event of special interest | 1 Participants |
| VIB4920 3000 mg Once | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event | 10 Participants |
| VIB4920 3000 mg Once | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event of ≥ Grade 3 severity | 1 Participants |
| VIB4920 3000 mg Once | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event leading to discontinuation of study drug | 1 Participants |
| VIB4920 3000 mg Once | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | Death (Grade 5 severity) | 0 Participants |
| VIB4920 3000 mg Once | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one serious event | 1 Participants |
| VIB4920 1500 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one related serious event | 0 Participants |
| VIB4920 1500 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event of special interest | 1 Participants |
| VIB4920 1500 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event | 14 Participants |
| VIB4920 1500 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one serious and/or ≥ Grade 3 severity event | 1 Participants |
| VIB4920 1500 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | Death (Grade 5 severity) | 1 Participants |
| VIB4920 1500 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one study drug-related event | 4 Participants |
| VIB4920 1500 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event leading to discontinuation of study drug | 0 Participants |
| VIB4920 1500 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one serious event | 1 Participants |
| VIB4920 1500 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event of ≥ Grade 3 severity | 1 Participants |
| VIB4920 3000 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event of special interest | 0 Participants |
| VIB4920 3000 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event | 11 Participants |
| VIB4920 3000 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event of ≥ Grade 3 severity | 0 Participants |
| VIB4920 3000 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | Death (Grade 5 severity) | 0 Participants |
| VIB4920 3000 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one serious event | 0 Participants |
| VIB4920 3000 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one serious and/or ≥ Grade 3 severity event | 0 Participants |
| VIB4920 3000 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one related serious event | 0 Participants |
| VIB4920 3000 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event leading to discontinuation of study drug | 0 Participants |
| VIB4920 3000 mg Twice | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one study drug-related event | 2 Participants |
| VIB4920 1500 mg 4 Times | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | Death (Grade 5 severity) | 0 Participants |
| VIB4920 1500 mg 4 Times | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event of ≥ Grade 3 severity | 0 Participants |
| VIB4920 1500 mg 4 Times | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one study drug-related event | 2 Participants |
| VIB4920 1500 mg 4 Times | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one serious and/or ≥ Grade 3 severity event | 0 Participants |
| VIB4920 1500 mg 4 Times | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event leading to discontinuation of study drug | 0 Participants |
| VIB4920 1500 mg 4 Times | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event | 11 Participants |
| VIB4920 1500 mg 4 Times | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one serious event | 1 Participants |
| VIB4920 1500 mg 4 Times | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one event of special interest | 0 Participants |
| VIB4920 1500 mg 4 Times | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs) | At least one related serious event | 0 Participants |
Secondary
Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs)
Excluding data after rescue. Adjusted geometric mean ratio to baseline (90% CI) results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model. Ratios less than 1 indicate a decrease.
Time frame: Day 1 (Baseline), Day 113
Population: Full Analysis Set: all randomized participants who received any dose of study drug, analyzed according to the treatment randomized. Participants with an assessment at given time point by group.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs) | 1.08 ratio |
| VIB4920 3000 mg Once | Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs) | 0.69 ratio |
| VIB4920 1500 mg Twice | Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs) | 0.82 ratio |
| VIB4920 3000 mg Twice | Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs) | 0.84 ratio |
| VIB4920 1500 mg 4 Times | Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs) | 0.62 ratio |
p-value: 0.058490% CI: [0.43, 0.94]MMRM
p-value: 0.227490% CI: [0.51, 1.11]MMRM
p-value: 0.279490% CI: [0.52, 1.14]MMRM
p-value: 0.019990% CI: [0.39, 0.85]MMRM
Secondary
Change From Baseline to Day 113 in Rheumatoid Factor (RF)
Excluding data after rescue. Adjusted geometric mean ratio to baseline (90% CI) results are from MMRM analysis on log(ratio to baseline) with treatment, visit, visit by treatment interaction, and log(baseline) included in the model. Ratios less than 1 indicate a decrease.
Time frame: Day 1 (Baseline), Day 113
Population: Full Analysis Set: all randomized participants who received any dose of study drug, analyzed according to the treatment randomized. Participants with an assessment at given time point by group.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to Day 113 in Rheumatoid Factor (RF) | 1.20 ratio |
| VIB4920 3000 mg Once | Change From Baseline to Day 113 in Rheumatoid Factor (RF) | 0.77 ratio |
| VIB4920 1500 mg Twice | Change From Baseline to Day 113 in Rheumatoid Factor (RF) | 0.74 ratio |
| VIB4920 3000 mg Twice | Change From Baseline to Day 113 in Rheumatoid Factor (RF) | 0.72 ratio |
| VIB4920 1500 mg 4 Times | Change From Baseline to Day 113 in Rheumatoid Factor (RF) | 0.57 ratio |
p-value: 0.000790% CI: [0.52, 0.79]MMRM
p-value: 0.000390% CI: [0.5, 0.76]MMRM
p-value: 0.000190% CI: [0.48, 0.74]MMRM
p-value: <0.000190% CI: [0.38, 0.59]MMRM
Secondary
Percentage of Participants With Clinical Remission at Day 113
Clinical remission is defined as DAS28-CRP \< 2.6. The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity.
Time frame: Day 113
Population: Full Analysis Set: all randomized participants who received any dose of study drug, analyzed according to the treatment randomized. Participants with an assessment at given time point by group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Clinical Remission at Day 113 | 18.8 percentage of participants |
| VIB4920 3000 mg Once | Percentage of Participants With Clinical Remission at Day 113 | 18.8 percentage of participants |
| VIB4920 1500 mg Twice | Percentage of Participants With Clinical Remission at Day 113 | 6.3 percentage of participants |
| VIB4920 3000 mg Twice | Percentage of Participants With Clinical Remission at Day 113 | 13.3 percentage of participants |
| VIB4920 1500 mg 4 Times | Percentage of Participants With Clinical Remission at Day 113 | 13.3 percentage of participants |
p-value: 0.77590% CI: [0.2, 8]Regression, Logistic
p-value: 0.697490% CI: [0.1, 5.5]Regression, Logistic
p-value: 0.931890% CI: [0.1, 5.7]Regression, Logistic
p-value: 0.910890% CI: [0.2, 5.1]Regression, Logistic
Secondary
Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920
ADA positive at any time: observed at least once during the study (baseline included). Treatment-emergent ADA: ADA positive post-baseline only or boosted pre-existing ADA during the study period. Persistent positive: treatment-induced ADA positive at ≥ 2 post-baseline assessments (with ≥ 16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive: treatment-induced ADA post-baseline positive but does not fulfill the criteria of persistent positive.
Time frame: Day 1 (Baseline) to Day 309 Day 1 (Baseline) up to Day 309 (± 7 days)
Population: Safety analysis set: all participants who received any dose of study drug, analyzed according to the treatment that they actually received. Participants who received active study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Transient positive | 33.3 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Baseline ADA positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | ADA positive at any time | 44.4 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Treatment-emergent ADA | 44.4 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Post-baseline ADA positive | 44.4 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Baseline only ADA positive | 0 percentage of participants |
| Placebo | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Persistent positive | 11.1 percentage of participants |
| VIB4920 3000 mg Once | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Baseline only ADA positive | 0 percentage of participants |
| VIB4920 3000 mg Once | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Treatment-emergent ADA | 11.8 percentage of participants |
| VIB4920 3000 mg Once | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | ADA positive at any time | 11.8 percentage of participants |
| VIB4920 3000 mg Once | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Transient positive | 11.8 percentage of participants |
| VIB4920 3000 mg Once | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Baseline ADA positive | 0 percentage of participants |
| VIB4920 3000 mg Once | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Persistent positive | 0 percentage of participants |
| VIB4920 3000 mg Once | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Post-baseline ADA positive | 11.8 percentage of participants |
| VIB4920 1500 mg Twice | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Baseline only ADA positive | 0 percentage of participants |
| VIB4920 1500 mg Twice | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Post-baseline ADA positive | 38.5 percentage of participants |
| VIB4920 1500 mg Twice | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | ADA positive at any time | 38.5 percentage of participants |
| VIB4920 1500 mg Twice | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Baseline ADA positive | 0 percentage of participants |
| VIB4920 1500 mg Twice | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Treatment-emergent ADA | 38.5 percentage of participants |
| VIB4920 1500 mg Twice | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Persistent positive | 0 percentage of participants |
| VIB4920 1500 mg Twice | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Transient positive | 38.5 percentage of participants |
| VIB4920 3000 mg Twice | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Baseline ADA positive | 0 percentage of participants |
| VIB4920 3000 mg Twice | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Transient positive | 28.6 percentage of participants |
| VIB4920 3000 mg Twice | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Persistent positive | 0 percentage of participants |
| VIB4920 3000 mg Twice | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | ADA positive at any time | 28.6 percentage of participants |
| VIB4920 3000 mg Twice | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Post-baseline ADA positive | 28.6 percentage of participants |
| VIB4920 3000 mg Twice | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Treatment-emergent ADA | 28.6 percentage of participants |
| VIB4920 3000 mg Twice | Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920 | Baseline only ADA positive | 0 percentage of participants |
Secondary
Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax)
Time frame: Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d
Population: PK Analysis Set: Participants who received active study drug and had at least one quantifiable plasma PK observation post-first dose. Participants were analyzed according to the treatment that they actually received. Participants with an assessment at given dose time points by group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax) | Dose 1 | 877 μg/mL | Standard Deviation 204 |
| VIB4920 3000 mg Once | Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax) | Dose 1 | 476 μg/mL | Standard Deviation 127 |
| VIB4920 3000 mg Once | Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax) | Dose 2 | 504 μg/mL | Standard Deviation 162 |
| VIB4920 1500 mg Twice | Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax) | Dose 1 | 860 μg/mL | Standard Deviation 275 |
| VIB4920 1500 mg Twice | Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax) | Dose 2 | 1050 μg/mL | Standard Deviation 349 |
| VIB4920 3000 mg Twice | Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax) | Dose 1 | 421 μg/mL | Standard Deviation 102 |
| VIB4920 3000 mg Twice | Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax) | Dose 2 | 564 μg/mL | Standard Deviation 163 |
| VIB4920 3000 mg Twice | Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax) | Dose 3 | 601 μg/mL | Standard Deviation 181 |
| VIB4920 3000 mg Twice | Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax) | Dose 4 | 568 μg/mL | Standard Deviation 140 |
Secondary
PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D)
Time frame: Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), Day 56
Population: PK Analysis Set: Participants who received active study drug and had at least one quantifiable plasma PK observation post-first dose. Participants were analyzed according to the treatment that they actually received. Participants with an assessment at given dose time points by group. Per protocol, due to the nature of the dosing and sampling for the VIB4920 1500 mg 4 Times arm, this analysis was not done.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D) | Dose 1 | 7280 μg·day/mL | Standard Deviation 1370 |
| VIB4920 3000 mg Once | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D) | Dose 1 | 4280 μg·day/mL | Standard Deviation 1280 |
| VIB4920 3000 mg Once | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D) | Dose 2 | 5310 μg·day/mL | Standard Deviation 2000 |
| VIB4920 1500 mg Twice | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D) | Dose 2 | 9910 μg·day/mL | Standard Deviation 3250 |
| VIB4920 1500 mg Twice | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D) | Dose 1 | 7870 μg·day/mL | Standard Deviation 2570 |
Secondary
PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast)
Time frame: Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d
Population: PK Analysis Set: Participants who received active study drug and had at least one quantifiable plasma PK observation post-first dose. Participants were analyzed according to the treatment that they actually received. Participants with an assessment at given dose time points by group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 1 | 7350 μg·day/mL | Standard Deviation 1380 |
| VIB4920 3000 mg Once | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 1 | 3980 μg·day/mL | Standard Deviation 1580 |
| VIB4920 3000 mg Once | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 2 | 5280 μg·day/mL | Standard Deviation 2000 |
| VIB4920 1500 mg Twice | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 2 | 10000 μg·day/mL | Standard Deviation 3320 |
| VIB4920 1500 mg Twice | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 1 | 7870 μg·day/mL | Standard Deviation 2570 |
| VIB4920 3000 mg Twice | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 4 | 5770 μg·day/mL | Standard Deviation 1110 |
| VIB4920 3000 mg Twice | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 1 | 2960 μg·day/mL | Standard Deviation 604 |
| VIB4920 3000 mg Twice | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 2 | 4060 μg·day/mL | Standard Deviation 1290 |
| VIB4920 3000 mg Twice | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) | Dose 3 | 6350 μg·day/mL | Standard Deviation 1840 |
Secondary
PK of VIB4920: Terminal Elimination Half-Life (t1/2)
Time frame: Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d
Population: PK Analysis Set: Participants who received active study drug and had at least one quantifiable plasma PK observation post-first dose. Participants were analyzed according to the treatment that they actually received. Participants with an assessment at given dose time points by group. Per protocol, due to the nature of the dosing and sampling for the VIB4920 1500 mg 4 Times arm, this analysis was done for Dose 4 only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PK of VIB4920: Terminal Elimination Half-Life (t1/2) | Dose 1 | 9.27 day | Standard Deviation 1.61 |
| VIB4920 3000 mg Once | PK of VIB4920: Terminal Elimination Half-Life (t1/2) | Dose 1 | 9.06 day | Standard Deviation 1.98 |
| VIB4920 3000 mg Once | PK of VIB4920: Terminal Elimination Half-Life (t1/2) | Dose 2 | 9.55 day | Standard Deviation 1.51 |
| VIB4920 1500 mg Twice | PK of VIB4920: Terminal Elimination Half-Life (t1/2) | Dose 1 | 9.02 day | Standard Deviation 1.06 |
| VIB4920 1500 mg Twice | PK of VIB4920: Terminal Elimination Half-Life (t1/2) | Dose 2 | 9.88 day | Standard Deviation 1.41 |
| VIB4920 3000 mg Twice | PK of VIB4920: Terminal Elimination Half-Life (t1/2) | Dose 4 | 10.5 day | Standard Deviation 2.06 |
Secondary
PK of VIB4920: Time to Cmax (Tmax)
Time frame: Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d
Population: PK Analysis Set: Participants who received active study drug and had at least one quantifiable plasma PK observation post-first dose. Participants were analyzed according to the treatment that they actually received. Participants with an assessment at given dose time points by group.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | PK of VIB4920: Time to Cmax (Tmax) | Dose 1 | 0.0899 day |
| VIB4920 3000 mg Once | PK of VIB4920: Time to Cmax (Tmax) | Dose 1 | 0.0875 day |
| VIB4920 3000 mg Once | PK of VIB4920: Time to Cmax (Tmax) | Dose 2 | 0.0681 day |
| VIB4920 1500 mg Twice | PK of VIB4920: Time to Cmax (Tmax) | Dose 1 | 0.0875 day |
| VIB4920 1500 mg Twice | PK of VIB4920: Time to Cmax (Tmax) | Dose 2 | 0.0667 day |
| VIB4920 3000 mg Twice | PK of VIB4920: Time to Cmax (Tmax) | Dose 1 | 0.0903 day |
| VIB4920 3000 mg Twice | PK of VIB4920: Time to Cmax (Tmax) | Dose 2 | 0.0486 day |
| VIB4920 3000 mg Twice | PK of VIB4920: Time to Cmax (Tmax) | Dose 3 | 0.0472 day |
| VIB4920 3000 mg Twice | PK of VIB4920: Time to Cmax (Tmax) | Dose 4 | 0.0667 day |
Secondary
PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4
Time frame: Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d
Population: PK Analysis Set: Participants who received active study drug and had at least one quantifiable plasma PK observation post-first dose. Participants were analyzed according to the treatment that they actually received. Participants with an assessment at given dose time points by group. Per protocol, due to the nature of the dosing and sampling for the VIB4920 1500 mg 4 Times arm, this analysis was done for Dose 4 only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4 | Dose 1 (CL) | 430 mL/day | Standard Deviation 91.9 |
| VIB4920 3000 mg Once | PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4 | Dose 1 (CL) | 371 mL/day | Standard Deviation 92.5 |
| VIB4920 3000 mg Once | PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4 | Dose 2 (CLss) | 314 mL/day | Standard Deviation 104 |
| VIB4920 1500 mg Twice | PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4 | Dose 1 (CL) | 417 mL/day | Standard Deviation 144 |
| VIB4920 1500 mg Twice | PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4 | Dose 2 (CLss) | 340 mL/day | Standard Deviation 140 |
| VIB4920 3000 mg Twice | PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4 | Dose 4 (CLss) | 294 mL/day | Standard Deviation 49.8 |
Secondary
PK of VIB4920: Volume of Distribution at Steady State (Vss)
Time frame: Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d
Population: PK Analysis Set: Participants who received active study drug and had at least one quantifiable plasma PK observation post-first dose. Participants were analyzed according to the treatment that they actually received. Participants with an assessment at given dose time points by group. Per protocol, due to the nature of the dosing and sampling for the VIB4920 1500 mg 4 Times arm, this analysis was done for Dose 4 only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PK of VIB4920: Volume of Distribution at Steady State (Vss) | Dose 1 | 4350 mL | Standard Deviation 1300 |
| VIB4920 3000 mg Once | PK of VIB4920: Volume of Distribution at Steady State (Vss) | Dose 1 | 3750 mL | Standard Deviation 601 |
| VIB4920 3000 mg Once | PK of VIB4920: Volume of Distribution at Steady State (Vss) | Dose 2 | 3490 mL | Standard Deviation 926 |
| VIB4920 1500 mg Twice | PK of VIB4920: Volume of Distribution at Steady State (Vss) | Dose 1 | 4540 mL | Standard Deviation 1470 |
| VIB4920 1500 mg Twice | PK of VIB4920: Volume of Distribution at Steady State (Vss) | Dose 2 | 3600 mL | Standard Deviation 1720 |
| VIB4920 3000 mg Twice | PK of VIB4920: Volume of Distribution at Steady State (Vss) | Dose 4 | 3210 mL | Standard Deviation 865 |
Secondary
Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication)
Based on Kaplan-Meier method.
Time frame: Day 1 (Baseline) up to Day 309 (± 7 days)
Population: Full Analysis Set: all randomized participants who received any dose of study drug, analyzed according to the treatment randomized. Participants who received rescue medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication) | NA days |
| VIB4920 3000 mg Once | Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication) | NA days |
| VIB4920 1500 mg Twice | Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication) | NA days |
| VIB4920 3000 mg Twice | Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication) | NA days |
| VIB4920 1500 mg 4 Times | Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication) | NA days |
p-value: 0.980590% CI: [0.1, 10.6]Regression, Cox
p-value: 0.980590% CI: [0.1, 10.6]Regression, Cox
p-value: 0.340790% CI: [0.45, 20.09]Regression, Cox
p-value: 0.980590% CI: [0.1, 10.6]Regression, Cox
Secondary
Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time
Total sCD40L (free sCD40L and sCD40L bound to VIB4920) was measured in plasma samples using a modified commercially available kit.
Time frame: Day 1 (Baseline), Days 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309
Population: Full Analysis Set: all randomized participants who received any dose of study drug, analyzed according to the treatment randomized. Participants with an assessment at given time point by group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 169 | 0.3114 ng/mL | Standard Deviation 1.1653 |
| Placebo | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 29 | 4.8431 ng/mL | Standard Deviation 3.377 |
| Placebo | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 141 | 0.2547 ng/mL | Standard Deviation 0.9863 |
| Placebo | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 15 | 4.6759 ng/mL | Standard Deviation 3.6596 |
| Placebo | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 253 | 0.3436 ng/mL | Standard Deviation 1.2855 |
| Placebo | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 309 | -0.5654 ng/mL | Standard Deviation 2.1154 |
| Placebo | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 225 | 0.2450 ng/mL | Standard Deviation 0.9167 |
| Placebo | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 197 | 0.2757 ng/mL | Standard Deviation 1.0316 |
| Placebo | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 281 | -0.0343 ng/mL | Standard Deviation 0.1283 |
| Placebo | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 57 | 0.8150 ng/mL | Standard Deviation 1.6053 |
| Placebo | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 113 | 0.3420 ng/mL | Standard Deviation 1.3246 |
| Placebo | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 85 | 0.4483 ng/mL | Standard Deviation 1.1842 |
| VIB4920 3000 mg Once | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 253 | 3.1418 ng/mL | Standard Deviation 11.7555 |
| VIB4920 3000 mg Once | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 197 | 0 ng/mL | Standard Deviation 0 |
| VIB4920 3000 mg Once | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 225 | 0 ng/mL | Standard Deviation 0 |
| VIB4920 3000 mg Once | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 169 | 0 ng/mL | Standard Deviation 0 |
| VIB4920 3000 mg Once | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 57 | 64.4177 ng/mL | Standard Deviation 16.4322 |
| VIB4920 3000 mg Once | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 15 | 30.7744 ng/mL | Standard Deviation 7.4954 |
| VIB4920 3000 mg Once | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 29 | 67.5427 ng/mL | Standard Deviation 16.4322 |
| VIB4920 3000 mg Once | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 141 | 1.6517 ng/mL | Standard Deviation 3.7565 |
| VIB4920 3000 mg Once | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 281 | 0 ng/mL | Standard Deviation 0 |
| VIB4920 3000 mg Once | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 85 | 53.1583 ng/mL | Standard Deviation 20.6513 |
| VIB4920 3000 mg Once | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 113 | 21.4686 ng/mL | Standard Deviation 19.3705 |
| VIB4920 3000 mg Once | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 309 | 0 ng/mL | Standard Deviation 0 |
| VIB4920 1500 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 141 | 55.4204 ng/mL | Standard Deviation 28.947 |
| VIB4920 1500 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 253 | -0.5946 ng/mL | Standard Deviation 2.1439 |
| VIB4920 1500 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 169 | 21.1296 ng/mL | Standard Deviation 27.1973 |
| VIB4920 1500 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 113 | 75.4407 ng/mL | Standard Deviation 18.2921 |
| VIB4920 1500 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 85 | 77.5360 ng/mL | Standard Deviation 18.744 |
| VIB4920 1500 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 15 | 36.0088 ng/mL | Standard Deviation 14.4324 |
| VIB4920 1500 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 309 | -0.5720 ng/mL | Standard Deviation 1.8088 |
| VIB4920 1500 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 225 | -0.4043 ng/mL | Standard Deviation 1.5127 |
| VIB4920 1500 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 29 | 66.7047 ng/mL | Standard Deviation 15.3708 |
| VIB4920 1500 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 197 | 4.4354 ng/mL | Standard Deviation 9.9146 |
| VIB4920 1500 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 281 | -0.5640 ng/mL | Standard Deviation 1.7835 |
| VIB4920 1500 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 57 | 62.5560 ng/mL | Standard Deviation 14.4445 |
| VIB4920 3000 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 225 | -0.0137 ng/mL | Standard Deviation 1.194 |
| VIB4920 3000 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 15 | 28.2492 ng/mL | Standard Deviation 10.4252 |
| VIB4920 3000 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 141 | 53.2827 ng/mL | Standard Deviation 31.6165 |
| VIB4920 3000 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 169 | 18.3170 ng/mL | Standard Deviation 20.2842 |
| VIB4920 3000 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 309 | -0.7833 ng/mL | Standard Deviation 2.7135 |
| VIB4920 3000 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 29 | 68.0636 ng/mL | Standard Deviation 28.6523 |
| VIB4920 3000 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 57 | 63.6939 ng/mL | Standard Deviation 25.55 |
| VIB4920 3000 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 85 | 57.2587 ng/mL | Standard Deviation 20.0742 |
| VIB4920 3000 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 113 | 53.4514 ng/mL | Standard Deviation 26.2712 |
| VIB4920 3000 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 197 | 2.5057 ng/mL | Standard Deviation 4.488 |
| VIB4920 3000 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 253 | -0.5292 ng/mL | Standard Deviation 1.9082 |
| VIB4920 3000 mg Twice | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 281 | -0.4729 ng/mL | Standard Deviation 1.7693 |
| VIB4920 1500 mg 4 Times | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 169 | 23.5727 ng/mL | Standard Deviation 26.051 |
| VIB4920 1500 mg 4 Times | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 113 | 68.5636 ng/mL | Standard Deviation 19.3458 |
| VIB4920 1500 mg 4 Times | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 141 | 52.3943 ng/mL | Standard Deviation 29.4422 |
| VIB4920 1500 mg 4 Times | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 253 | -0.9485 ng/mL | Standard Deviation 2.3281 |
| VIB4920 1500 mg 4 Times | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 85 | 69.8821 ng/mL | Standard Deviation 19.2623 |
| VIB4920 1500 mg 4 Times | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 57 | 64.1329 ng/mL | Standard Deviation 12.4842 |
| VIB4920 1500 mg 4 Times | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 29 | 68.1386 ng/mL | Standard Deviation 12.1314 |
| VIB4920 1500 mg 4 Times | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 309 | -0.9485 ng/mL | Standard Deviation 2.3281 |
| VIB4920 1500 mg 4 Times | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 281 | -0.9485 ng/mL | Standard Deviation 2.3281 |
| VIB4920 1500 mg 4 Times | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 15 | 33.9007 ng/mL | Standard Deviation 8.7777 |
| VIB4920 1500 mg 4 Times | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 225 | -0.2971 ng/mL | Standard Deviation 0.8718 |
| VIB4920 1500 mg 4 Times | Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time | Change at Day 197 | 4.6343 ng/mL | Standard Deviation 5.3603 |