A Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple Subcutaneous Injections of ABBV-257 in Subjects With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This is a Phase 1, randomized, double-blind, placebo-controlled, multiple dose study designed to assess the safety, tolerability, pharmacokinetics, and immunogenicity of different dose levels of ABBV-257 given with methotrexate. ABBV-257 or placebo will be administered once every other week (EOW) for a total of 4 doses. Subjects will continue on their stable dose of methotrexate weekly throughout participation in the study. This study will be conducted in approximately 24 subjects in 3 dose groups, with 8 subjects per group. Within each group, 6 subjects will be randomized to receive ABBV-257 and 2 subjects will receive placebo. Subjects participating in one dose group will be ineligible to participate in another dose group in the study.

Detailed Description
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Multiple dose study designed to assess the safety, tolerability, pharmacokinetics, and immunogenicity of different dose levels of ABBV-257 given with methotrexate.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study in Subjects With Rheumatoid Arthritis to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Doses of ABBV-257

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: ABBV-257
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Rheumatoid Arthritis based on the 2010 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria, or ACR 1987 for patients with diagnosis prior 2011 ≥ 3 months. Except for methotrexate (MTX), the subject must have discontinued all disease modifying anti-rheumatic drugs (DMARD) for at least 5 half-lives before the first dose of study drug, and undergone cholestyramine washout if received Leflunomide within the past 3 months. Subject must have been on MTX therapy > 3 months and on a stable dose (7.5 - 25 mg/week), for at least 4 weeks prior to the first dose of study drug. Subject must be able to continue on stable dose of MTX for the duration of study participation. Body Mass Index (BMI) is 19 to 35, inclusive. (BMI is calculated as weight [kg] divided by height [m2].) Judged to be in good general health as determined by the Investigator based upon the results of medical history, laboratory profile, physical examination and 12-lead electrocardiogram (ECG) performed at screening Exclusion Criteria: Evidence of anti-ABBV-257 antibody results in a pre-study serum sample. History of significant allergic reaction or significant sensitivity to any constituents of the study drug; or history of anaphylactic reaction to any agent (e.g., food products and bee sting); or history of a major reaction to any Immunoglobulin G (IgG) containing product. History of persistent chronic or active infection(s) requiring hospitalization or treatment with intravenous or oral antimicrobials/antibiotics within 30 days prior to initial study drug administration. History or evidence of active tuberculosis (TB) or the subject has evidence of risk factor for latent TB. Clinically significant abnormal screening laboratory results as evaluated by the Investigator, including serum values of Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) greater than 2.25 × the upper limit of normal, or creatinine greater than 1.5 × the upper limit of normal, or absolute neutrophil count < 1500 μ/L. Subject has any medical condition or illness other than RA that is not well controlled with treatment that would, in the opinion of the investigator, preclude study participation or interfere with other symptoms of Rheumatoid Arthritis (RA).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low dose ABBV-257<br>Low dose every other week (eow), Weeks 0-8 | Biological: ABBV-257<br>* subcutaneous injection<br>Biological: Placebo<br>* Placebo for ABBV-257<br>|
| Experimental: Medium dose of ABBV-257<br>Medium dose every other week (eow), Weeks 0-8 | Biological: ABBV-257<br>* subcutaneous injection<br>Biological: Placebo<br>* Placebo for ABBV-257<br>|
| Experimental: high dose of ABBV-257<br>high dose every other week (eow), Weeks 0-8 | Biological: ABBV-257<br>* subcutaneous injection<br>Biological: Placebo<br>* Placebo for ABBV-257<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with adverse events | This will be collected through out the study | Up to day 193 | 
| Change in Vital signs | Vital signs including blood pressure and heart rate will be assessed | From day 1 to day 193 | 
| Change in Physical examination | Changes in any physical exam assessed by the physician will be assessed. | From day 1 to day 193 | 
| Changes in Electrocardiogram (ECG) | ECG measurements will be assessed | From day 1 to day 193 | 
| Maximum observed serum concentration (Cmax) | This will be assessed using non-compartmental methods. | Up to day 50 | 
| Time to maximum observed serum concentration (Tmax) | This will be assessed using non-compartmental methods. | Up to day 50 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity by measurement of Anti-drug antibody | Immunogenicity will be measured to see if the body has produced an immune response to ABBV-257 | Up to day 193 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis