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

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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: ABBV-257; Biological: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Site Reference ID/Investigator# 139394

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
American College of Rheumatology (ACR) 20 response rate	ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant.	Up to day 193
American College of Rheumatology (ACR) 50 response rate	ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant.	Up to day 193
American College of Rheumatology (ACR) 70 response rate	ACR criteria measure improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity and acute phase reactant.	Up to day 193
Change in Disease Activity Score 28	Calculated from tender joint, swollen joint and high sensitive C-reactive protein	From day 1 to day 193

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: Heikki Mansikka, PhD, AbbVie

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: July 14, 2015
• First Submitted That Met QC Criteria: August 20, 2015
• First Posted (Estimate): August 24, 2015

Study Record Updates

• Last Update Posted (Estimate): March 3, 2016
• Last Update Submitted That Met QC Criteria: March 1, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: M14-439; 2015-000094-12 (EudraCT Number)