Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2019-003697-70 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VIB4920 1500 mg 4 Times | Experimental | Participants receive intravenous (IV) infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57 |
|
| VIB4920 1500 mg Twice | Experimental | Participants receive IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29. |
|
| VIB4920 3000 mg Twice | Experimental | Participants receive IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29. |
|
| VIB4920 3000 mg Once | Experimental | Participants receive IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57. |
|
| Placebo | Placebo Comparator | Participants receive IV infusion of placebo matched to VIB4920 on Days 1, 15, 29, and 57. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VIB4920 | Drug | liquid for IV infusion following dilution in normal saline |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1 (Baseline), Day 113 |
| 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.) | From first dose of study drug through Day 309 ± 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | |
| PK of VIB4920: Time to Cmax (Tmax) |
Not provided
Principal Inclusion Criteria:
Principal Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Anniston | Alabama | 36207 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37541743 | Derived | Kivitz A, Wang L, Alevizos I, Gunsior M, Falloon J, Illei G, St Clair EW. The MIDORA trial: a phase II, randomised, double-blind, placebo-controlled, mechanistic insight and dosage optimisation study of the efficacy and safety of dazodalibep in patients with rheumatoid arthritis. RMD Open. 2023 Aug;9(3):e003317. doi: 10.1136/rmdopen-2023-003317. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
After a screening period of up to 28 days, eligible participants were randomized in a 1:1:1:1:1 ratio into 5 cohorts.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received intravenous (IV) infusion of placebo matched to VIB4920 on Days 1, 15, 29, and 57. |
| FG001 | VIB4920 3000 mg Once | Participants received IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 2, 2020 | Dec 16, 2022 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Drug | 0.9% saline for IV infusion |
|
| 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 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 |
| 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. | Day 1 (Baseline), Days 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309 |
| 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. | Day 1 (Baseline) to Day 309 Day 1 (Baseline) up to Day 309 (± 7 days) |
| 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. | Day 1 (Baseline), Day 113 |
| 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. | Day 1 (Baseline), Day 113 |
| 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. | Day 113 |
| Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication) | Based on Kaplan-Meier method. | Day 1 (Baseline) up to Day 309 (± 7 days) |
| Sun City |
| Arizona |
| 85704 |
| United States |
| Research Site | Upland | California | 91786 | United States |
| Research Site | Clearwater | Florida | 33765 | United States |
| Research Site | Margate | Florida | 33063 | United States |
| Research Site | Miami Lakes | Florida | 33014 | United States |
| Research Site | Zephyrhills | Florida | 33542 | United States |
| Research Site | Atlanta | Georgia | 30342 | United States |
| Research Site | Lexington | Kentucky | 40504 | United States |
| Research Site | Wheaton | Maryland | 20902 | United States |
| Research Site | Charlotte | North Carolina | 28210 | United States |
| Research Site | Rocky Mount | North Carolina | 27804 | United States |
| Research Site | Salisbury | North Carolina | 28144 | United States |
| Research Site | Vandalia | Ohio | 45377 | United States |
| Research Site | Norman | Oklahoma | 73069 | United States |
| Research Site | Duncansville | Pennsylvania | 16635 | United States |
| Research Site | Baytown | Texas | 77477 | United States |
| Research Site | Dallas | Texas | 75231 | United States |
| Research Site | Poznan | Greater Poland Voivodeship | Poland |
| Research Site | Krakow | Lesser Poland Voivodeship | Poland |
| Research Site | Nadarzyn | Masovian Voivodeship | Poland |
| Research Site | Siedlce | Masovian Voivodeship | Poland |
| Research Site | Bialystok | Podlaskie Voivodeship | Poland |
| Research Site | Elblag | Warmian-Masurian Voivodeship | Poland |
| Research Site | Warsaw | Poland |
| FG002 | VIB4920 1500 mg Twice | Participants received IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29. |
| FG003 | VIB4920 3000 mg Twice | Participants received IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29. |
| FG004 | VIB4920 1500 mg 4 Times | Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Full Analysis Set: all randomized participants who received any dose of study drug, analyzed according to the treatment randomized.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received IV infusion of placebo matched to VIB4920 on Days 1, 15, 29, and 57. |
| BG001 | VIB4920 3000 mg Once | Participants received IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57. |
| BG002 | VIB4920 1500 mg Twice | Participants received IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29. |
| BG003 | VIB4920 3000 mg Twice | Participants received IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29. |
| BG004 | VIB4920 1500 mg 4 Times | Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants | No |
| |||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
| |||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
| |||||||||||||||
| Disease Activity Score 28 C-reactive Protein (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. | Mean | Standard Deviation | score on a scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Least Squares Mean | Standard Error | score on a scale | Day 1 (Baseline), Day 113 |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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.) | Safety analysis set: all participants who received any dose of study drug, analyzed according to the treatment that they actually received. | Posted | Count of Participants | Participants | From first dose of study drug through Day 309 ± 7 days |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax) | 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. | Posted | Mean | Standard Deviation | μg/mL | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | PK of VIB4920: Time to Cmax (Tmax) | 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. | Posted | Median | Full Range | day | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) | 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. | Posted | Mean | Standard Deviation | μg·day/mL | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D) | 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. | Posted | Mean | Standard Deviation | μg·day/mL | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4 | 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. | Posted | Mean | Standard Deviation | mL/day | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | PK of VIB4920: Terminal Elimination Half-Life (t1/2) | 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. | Posted | Mean | Standard Deviation | day | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | PK of VIB4920: Volume of Distribution at Steady State (Vss) | 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. | Posted | Mean | Standard Deviation | mL | 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 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Mean | Standard Deviation | ng/mL | Day 1 (Baseline), Days 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Number | percentage of participants | Day 1 (Baseline) to Day 309 Day 1 (Baseline) up to Day 309 (± 7 days) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Geometric Mean | 90% Confidence Interval | ratio | Day 1 (Baseline), Day 113 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Geometric Mean | 90% Confidence Interval | ratio | Day 1 (Baseline), Day 113 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Number | percentage of participants | Day 113 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication) | Based on Kaplan-Meier method. | Full Analysis Set: all randomized participants who received any dose of study drug, analyzed according to the treatment randomized. Participants who received rescue medication. | Posted | Median | 90% Confidence Interval | days | Day 1 (Baseline) up to Day 309 (± 7 days) |
|
From screening (all cause mortality) or first dose of study drug (adverse events) through through Day 309 ± 7 days.
Safety analysis set: all participants who received any dose of study drug, analyzed according to the treatment that they actually received.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received IV infusion of placebo matched to VIB4920 on Days 1, 15, 29, and 57. | 0 | 16 | 0 | 16 | 10 | 16 |
| EG001 | VIB4920 3000 mg Once | Participants received IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57. | 0 | 18 | 1 | 18 | 10 | 18 |
| EG002 | VIB4920 1500 mg Twice | Participants received IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29. | 1 | 17 | 1 | 17 | 14 | 17 |
| EG003 | VIB4920 3000 mg Twice | Participants received IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29. | 0 | 13 | 0 | 13 | 11 | 13 |
| EG004 | VIB4920 1500 mg 4 Times | Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. | 0 | 14 | 1 | 14 | 10 | 14 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | General disorders | MedDRA 24.1 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 24.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Supraventricular extrasystoles | Cardiac disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Ventricular extrasystoles | Cardiac disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Hiatus hernia | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Reflux gastritis | Gastrointestinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Nasal herpes | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA 24.1 | Systematic Assessment |
| |
| Chest injury | Injury, poisoning and procedural complications | MedDRA 24.1 | Systematic Assessment |
| |
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 24.1 | Systematic Assessment |
| |
| Post vaccination syndrome | Injury, poisoning and procedural complications | MedDRA 24.1 | Systematic Assessment |
| |
| Synovial rupture | Injury, poisoning and procedural complications | MedDRA 24.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Blood glucose abnormal | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Body temperature increased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Heart sounds abnormal | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Respiratory rate increased | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| SARS-CoV-2 antibody test positive | Investigations | MedDRA 24.1 | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Impaired fasting glucose | Metabolism and nutrition disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Osteoporosis postmenopausal | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Sacroiliac joint dysfunction | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Tenosynovitis stenosans | Musculoskeletal and connective tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Parkinsonian rest tremor | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Leukocyturia | Renal and urinary disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Paranasal sinus inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Rosacea | Skin and subcutaneous tissue disorders | MedDRA 24.1 | Systematic Assessment |
| |
| Haemorrhoid operation | Surgical and medical procedures | MedDRA 24.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 24.1 | Systematic Assessment |
|
Horizon requests that any investigator/institution that plans on presenting/publishing results provide written notification of their request 60 days prior to their presentation/publication. Horizon requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Horizon needs to secure patent or proprietary protection.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ilias Alevizos, PhD, DMD | Horizon Therapeutics USA, Inc. | 866-479-6742 | clinicaltrials@horizontherapeutics.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 7, 2021 | Dec 16, 2022 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| White |
|
| Other, Not Specified |
|
| MMRM |
| 0.0355 |
Results are from MMRM analysis with treatment, visit, visit by treatment interaction, and baseline DAS28-CRP score included in the model. |
| LS Mean Difference |
| -0.81 |
| Standard Error of the Mean |
| 0.38 |
| 2-Sided |
| 90 |
| -1.44 |
| -0.18 |
LS Mean difference is VIB4920 minus placebo. Differences less than 0 favor VIB4920. |
| Superiority |
| MMRM | 0.0364 | Results are from MMRM analysis with treatment, visit, visit by treatment interaction, and baseline DAS28-CRP score included in the model. | LS Mean Difference | -0.81 | Standard Error of the Mean | 0.38 | 2-Sided | 90 | -1.44 | -0.18 | LS Mean difference is VIB4920 minus placebo. Differences less than 0 favor VIB4920. | Superiority |
| MMRM | 0.0478 | Results are from MMRM analysis with treatment, visit, visit by treatment interaction, and baseline DAS28-CRP score included in the model. | LS Mean Difference | -0.77 | Standard Error of the Mean | 0.38 | 2-Sided | 90 | -1.41 | -0.13 | LS Mean difference is VIB4920 minus placebo. Differences less than 0 favor VIB4920. | Superiority |
| VIB4920 3000 mg Once |
Participants received IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57. |
| OG002 | VIB4920 1500 mg Twice | Participants received IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29. |
| OG003 | VIB4920 3000 mg Twice | Participants received IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29. |
| OG004 | VIB4920 1500 mg 4 Times | Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
|
|
Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
|
|
Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57.
|
|
Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
|
|
| VIB4920 1500 mg 4 Times |
Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
|
|
| OG003 | VIB4920 1500 mg 4 Times | Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
|
|
| OG003 |
| VIB4920 1500 mg 4 Times |
Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
|
|
| OG003 |
| VIB4920 1500 mg 4 Times |
Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
|
|
Participants received IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29.
| OG004 | VIB4920 1500 mg 4 Times | Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
|
|
| OG003 | VIB4920 1500 mg 4 Times | Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
|
|
Participants received IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29. |
| OG004 | VIB4920 1500 mg 4 Times | Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
|
|
|
Participants received IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29. |
| OG004 | VIB4920 1500 mg 4 Times | Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
|
|
|
| OG003 | VIB4920 3000 mg Twice | Participants received IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29. |
| OG004 | VIB4920 1500 mg 4 Times | Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
|
|
|
| OG004 | VIB4920 1500 mg 4 Times | Participants received IV infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57. |
|
|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
|
|
|
|
|
|
|
|
|
|
|