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NCT03823391

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (RA)

Completed Phase 2 Results posted Last updated 19 July 2021
What this trial tests

Phase 2 trial testing ABBV-3373 in Rheumatoid Arthritis (RA) in 48 participants. Completed in 26 August 2020.

Timeline
27 March 2019
Primary endpoint
8 April 2020
26 August 2020

Quick facts

Lead sponsorAbbVie
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment48
Start date27 March 2019
Primary completion8 April 2020
Estimated completion26 August 2020
Sites30 locations across Netherlands, Israel, Germany, Hungary, Poland, Puerto Rico, United States

Drugs / interventions tested

Conditions studied

Sponsor

AbbVie — full company profile →

Who can join

Adults 18 to 75, any sex, with Rheumatoid Arthritis (RA). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

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

Change From Baseline to Week 12 in Disease Activity Score (DAS) 28 (C-reactive Protein [CRP]) Primary · Baseline and Week 12

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 (measured on a visual analog scale \[VAS\] from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0.96 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.

GroupValue95% CI
Adalimumab-2.51± 0.293
ABBV-3373-2.65± 0.215
Change From Baseline to Week 12 in Clinical Disease Activity Index (CDAI) Secondary · Baseline and Week 12

The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient Global Assessment of Disease Activity and Physician Global Assessment of Disease Activity both measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 76 with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity.

GroupValue95% CI
Adalimumab-26.30± 2.656
ABBV-3373-27.99± 1.955
Change From Baseline in Simplified Disease Activity Index (SDAI) Secondary · Baseline and Week 12

The SDAI is the numerical sum of five outcome parameters: tender and swollen joint count (based on a 28-joint assessment), Patient Global Assessment of Disease Activity and Physician Global Assessment of Disease Activity both measured on a VAS from 0-10 cm and level of CRP (in mg/dL; normal \< 1 mg/dL). The SDAI has a range from 0 to 86, with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity.

GroupValue95% CI
Adalimumab-27.42± 2.659
ABBV-3373-28.50± 1.961
Change From Baseline to Week 12 in DAS28 (Erythrocyte Sedimentation Rate [ESR]) Secondary · Baseline and Week 12

The DAS28 (ESR) 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 (measured on a VAS from 0-100 mm), and ESR (in mm/hr). Scores on the DAS28 (ESR) range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline indicates improvement in disease activity.

GroupValue95% CI
Adalimumab-2.55± 0.344
ABBV-3373-2.76± 0.254
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28 (CRP) at Week 12 Secondary · Week 12

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 (measured on a VAS from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0.96 to approximately 10, where higher scores indicate more disease activity. A DAS28 (CRP) score less than or equal to 3.2 indicates low disease activity.

GroupValue95% CI
Adalimumab58.839.2 – 78.5
ABBV-337354.840.1 – 69.5
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 Secondary · Baseline and Week 12

Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria: 1. ≥ 50% improvement in 68-tender joint count; 2. ≥ 50% improvement in 66-swollen joint count; and 3. ≥ 50% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).

GroupValue95% CI
Adalimumab64.745.6 – 83.8
ABBV-337351.636.8 – 66.4

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug up to 70 days after last dose; the treatment duration was 12 weeks in each period.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Period 1: ABBV-3373
Serious: 4/31 (13%)
Deaths: 0/31
Period 1: Adalimumab
Serious: 0/17 (0%)
Deaths: 0/17
Period 2: ABBV-3773 / Placebo
Serious: 0/30 (0%)
Deaths: 0/30
Period 2: Adalimumab / Adalimumab
Serious: 2/16 (13%)
Deaths: 0/16

Serious adverse events (6 terms)

ReactionSystemPeriod 1: ABBV-3373Period 1: AdalimumabPeriod 2: ABBV-3773 / Plac…Period 2: Adalimumab / Ada…
NON-CARDIAC CHEST PAINGeneral disorders
ANAPHYLACTIC SHOCKImmune system disorders
BREAST ABSCESSInfections and infestations
BRONCHITISInfections and infestations
PNEUMONIAInfections and infestations
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations
Other adverse events (33 terms — click to expand)

ReactionSystemPeriod 1: ABBV-3373Period 1: AdalimumabPeriod 2: ABBV-3773 / Plac…Period 2: Adalimumab / Ada…
NASOPHARYNGITISInfections and infestations
RHEUMATOID ARTHRITISMusculoskeletal and connective tissue disorders
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations
URINARY TRACT INFECTIONInfections and infestations
HEADACHENervous system disorders
LEUKOPENIABlood and lymphatic system disorders
PERIORBITAL SWELLINGEye disorders
ABDOMINAL DISCOMFORTGastrointestinal disorders
MOUTH SWELLINGGastrointestinal disorders
NAUSEAGastrointestinal disorders
INFUSION SITE BRUISINGGeneral disorders
INJECTION SITE PRURITUSGeneral disorders
OEDEMA PERIPHERALGeneral disorders
PYREXIAGeneral disorders
DRUG HYPERSENSITIVITYImmune system disorders
TYPE I HYPERSENSITIVITYImmune system disorders
BRONCHITISInfections and infestations
GASTROENTERITIS VIRALInfections and infestations
ORAL HERPESInfections and infestations
SINUSITISInfections and infestations
BLOOD PRESSURE INCREASEDInvestigations
LIVER FUNCTION TEST ABNORMALInvestigations
MYCOPLASMA TEST POSITIVEInvestigations
ARTHRALGIAMusculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAINMusculoskeletal and connective tissue disorders
MYALGIAMusculoskeletal and connective tissue disorders
OSTEOARTHRITISMusculoskeletal and connective tissue disorders
HYPOAESTHESIANervous system disorders
SCIATICANervous system disorders
BRONCHIAL HYPERREACTIVITYRespiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAINRespiratory, thoracic and mediastinal disorders
PRURITUSSkin and subcutaneous tissue disorders
HYPERTENSIONVascular disorders

Most-reported serious reactions: NON-CARDIAC CHEST PAIN, ANAPHYLACTIC SHOCK, BREAST ABSCESS, BRONCHITIS, PNEUMONIA, UPPER RESPIRATORY TRACT INFECTION.

Data from ClinicalTrials.gov NCT03823391 adverse events section.

Sponsor's own description

This study will assess the safety, tolerability, and efficacy of ABBV-3373 in participants with moderately to severely active rheumatoid arthritis (RA) on background methotrexate (MTX) compared with adalimumab.

Publications & conference data

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

  1. Payload diversification: a key step in the development of antibody-drug conjugates.
    Conilh L, Sadilkova L, Viricel W, Dumontet C. · · 2023 · cited 152× · PMID 36650546 · DOI 10.1186/s13045-022-01397-y
  2. The role of inflammation in autoimmune disease: a therapeutic target.
    Xiang Y, Zhang M, Jiang D, Su Q, et al · · 2023 · cited 104× · PMID 37859999 · DOI 10.3389/fimmu.2023.1267091
  3. Antibody-Drug Conjugates: Functional Principles and Applications in Oncology and Beyond.
    Theocharopoulos C, Lialios PP, Samarkos M, Gogas H, et al · · 2021 · cited 34× · PMID 34696218 · DOI 10.3390/vaccines9101111
  4. Efficacy and Safety of ABBV-3373, a Novel Anti-Tumor Necrosis Factor Glucocorticoid Receptor Modulator Antibody-Drug Conjugate, in Adults with Moderate-to-Severe Rheumatoid Arthritis Despite Methotrexate Therapy: A Randomized, Double-Blind, Active-Controlled Proof-of-Concept Phas
    Buttgereit F, Aelion J, Rojkovich B, Zubrzycka-Sienkiewicz A, et al · · 2023 · cited 33× · PMID 36512671 · DOI 10.1002/art.42415
  5. Targeting TNF/TNFR superfamilies in immune-mediated inflammatory diseases.
    Veerasubramanian PK, Wynn TA, Quan J, Karlsson FJ. · · 2024 · cited 26× · PMID 39297883 · DOI 10.1084/jem.20240806
  6. Therapeutic Advances in Diabetes, Autoimmune, and Neurological Diseases.
    Liu J, Ting JP, Al-Azzam S, Ding Y, et al · · 2021 · cited 15× · PMID 33802091 · DOI 10.3390/ijms22062805
  7. The next frontier in antibody-drug conjugates: challenges and opportunities in cancer and autoimmune therapy.
    Zhou M, Huang Z, Ma Z, Chen J, et al · · 2025 · cited 8× · PMID 40843358 · DOI 10.20517/cdr.2025.49
  8. Glucocorticoids-based prodrug design: Current strategies and research progress.
    Liu H, Ji M, Xiao P, Gou J, et al · · 2024 · cited 8× · PMID 38966286 · DOI 10.1016/j.ajps.2024.100922

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