Study to Assess the Injection Site Pain Associated With a New Etanercept Formulation in Adults With Rheumatoid Arthritis or Psoriatic Arthritis

A Multicenter, Randomized, Double-blind, Crossover Study to Assess the Injection Site Pain Associated With a Modified Etanercept Formulation in Adult Subjects With Either Rheumatoid Arthritis or Psoriatic Arthritis

The primary objective was to assess the injection site pain associated with the new formulation of etanercept compared with commercial etanercept in adults with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) as measured by a visual analog scale (VAS).

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid; Arthritis, Psoriatic
• Intervention / Treatment: Drug: Commercial Formulation Etanercept; Drug: New Formulation Etanercept

Detailed Description

This is a phase 3b, multicenter, randomized, double-blind, 2-period, 2-sequence crossover study in adults with RA or PsA who are naive to etanercept. The study will evaluate injection site pain associated with the commercial formulation of etanercept and the new formulation of etanercept immediately after injection of each formulation.The study will consist of a screening period of up to 14 days, a 2 week treatment period with a 30 day post treatment safety follow-up. Each dose will follow the recommended label dosing for adults with RA and PsA: 50 mg weekly (scheduled approximately 7 days apart).

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Research Site
  • California
    • El Cajon, California, United States, 92020
      • Research Site
    • Lomita, California, United States, 90717
      • Research Site
    • Sherman Oaks, California, United States, 91403
      • Research Site
    • Thousand Oaks, California, United States, 91320
      • Research Site
  • Florida
    • Cutler Bay, Florida, United States, 33157
      • Research Site
    • DeLand, Florida, United States, 32720
      • Research Site
    • Doral, Florida, United States, 33126
      • Research Site
    • Largo, Florida, United States, 33770
      • Research Site
    • Miami, Florida, United States, 33165
      • Research Site
    • Winter Haven, Florida, United States, 33880
      • Research Site
  • Illinois
    • Quincy, Illinois, United States, 62301
      • Research Site
    • Skokie, Illinois, United States, 60076
      • Research Site
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Research Site
    • Grand Rapids, Michigan, United States, 49546
      • Research Site
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Research Site
  • New Jersey
    • Freehold, New Jersey, United States, 07728
      • Research Site
  • New York
    • Smithtown, New York, United States, 11787
      • Research Site
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • Research Site
  • Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Research Site
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75231
      • Research Site
    • El Paso, Texas, United States, 79935
      • Research Site
    • Houston, Texas, United States, 77034
      • Research Site
    • Mesquite, Texas, United States, 75150
      • Research Site
    • The Woodlands, Texas, United States, 77382
      • Research Site
  • Washington
    • Bothell, Washington, United States, 98021
      • Research Site
  • West Virginia
    • South Charleston, West Virginia, United States, 25309
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• Subject has provided informed consent prior to initiation of any study specific activities/procedures.
• Male or female subject is 18 years of age or older at time of signing the informed consent form.
• Subject has a diagnosis of RA or PsA and indicated for treatment with etanercept per the current label, based on investigator judgment.
• Subject is naïve to etanercept.
• Subject is able to self-inject etanercept.

Exclusion Criteria

• Subject is diagnosed with Felty's syndrome.
• Subject has active erythrodermic, pustular, guttate psoriasis, or medication induced psoriasis, or other skin conditions.
• Subject has a history of clinically significant skin allergies
• Subject has a history of alcoholic hepatitis, nonalcoholic steatohepatitis or immunodeficiency syndromes.
• Subject has any active infection for which anti-infectives were indicated within 4 weeks prior to screening.
• Subject has had a serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to first dose of investigational product.
• Subject had prosthetic joint infection within 5 years of screening or native joint infection within 1 year of screening.
• Subject has known alcohol addiction or dependency.
• Subject has positive hepatitis B surface antigen, hepatitis B core antibody (confirmed by hepatitis B virus deoxyribonucleic acid (DNA) test) or hepatitis C virus antibody serology at screening, or a positive medical history for hepatitis B or C. (Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enroll).
• Subject has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma.
• Subject has known history of active tuberculosis.
• Subject has used biologic disease modifying agent (DMARD) less than or equal to 3 months prior to screening.
• If subject is receiving continuous treatment with acetaminophen, non-steroidal anti-inflammatory drug or tramadol, hydrocodone, oxycodone, codeine, and/or propoxyphene and the dose is within 4 hours before study visit and dose is not stable for ≥ 2 weeks before first dose of investigational product
• For subjects not on continuous analgesics, subject has taken the following within 4 hours before screening: acetaminophen, non-steroidal anti-inflammatory drugs, hydrocodone, codeine, tramadol, propoxyphene, and/or oxycodone (unless in the form of OxyContin). For subjects not on continuous analgesics, subject has taken OxyContin within 24 hours before screening.
• Subject has received live vaccines less than or equal to 4 weeks prior to first dose of investigational product.
• Subject has laboratory abnormalities during screening.
• Estimated creatinine clearance less than 50 mL/min.
• Subject has any other laboratory abnormality, which, in the opinion of the investigator poses a safety risk, will prevent the subject from completing the study, or will interfere with the interpretation of the study results.
• Subject is currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s).
• Other investigational procedures while participating in this study.
• Women who are pregnant or breastfeeding, or planning to become pregnant or breastfeed during treatment and/or within 4 weeks after the last dose of etanercept.
• Women of child-bearing potential with a positive pregnancy test.
• Women of child-bearing potential who are unwilling to practice true sexual abstinence or unwilling to use 1 of the following effective birth control methods during treatment and for an additional 4 weeks after the last dose of etanercept.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence AB; Participants received a single 50 mg subcutaneous (SC) dose of the commercial formulation etanercept in a prefilled SureClick autoinjector on day 1 (Treatment A) followed by a single 50 mg SC dose of the new formulation of etanercept in a prefilled SureClick autoinjector on day 8 (Treatment B).	Drug: Commercial Formulation Etanercept; Etanercept was supplied in a single-use SureClick autoinjector as a sterile, preservative-free solution for SC injection containing 0.98 mL of 50 mg/mL etanercept in the commercial formulation.; Other Names: Enbrel; Drug: New Formulation Etanercept; Etanercept was supplied in a single-use SureClick autoinjector as a sterile, preservative-free solution for SC injection containing 0.98 mL of 50 mg/mL etanercept in the new formulation.
Experimental: Sequence BA; Participants received a single 50 mg SC dose of the new formulation of etanercept in a prefilled SureClick autoinjector on day 1 (Treatment B) followed by a single 50 mg SC dose of the commercial formulation etanercept in a prefilled SureClick autoinjector on day 8 (Treatment A).	Drug: Commercial Formulation Etanercept; Etanercept was supplied in a single-use SureClick autoinjector as a sterile, preservative-free solution for SC injection containing 0.98 mL of 50 mg/mL etanercept in the commercial formulation.; Other Names: Enbrel; Drug: New Formulation Etanercept; Etanercept was supplied in a single-use SureClick autoinjector as a sterile, preservative-free solution for SC injection containing 0.98 mL of 50 mg/mL etanercept in the new formulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Injection Site Pain	Injection site pain was assessed using a 100 mm visual analog scale (VAS), from 0 mm (No Pain At All) to 100 mm (Worst Pain Imaginable). Participants were asked to indicate the severity of their pain at the injection site by placing a vertical line on the scale.	Immediately following injection of each study drug on day 1 and day 8 of this crossover study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Injection Site Pain by Disease Indication	Injection site pain was assessed using a 100 mm visual analog scale (VAS), from 0 mm (No Pain At All) to 100 mm (Worst Pain Imaginable). Participants were asked to indicate the severity of their pain at the injection site by placing a vertical line on the scale.	Immediately following injection of each study drug on day 1 and day 8 of this crossover study
Number of Participants With Adverse Events	The severity of each adverse event was graded by the investigator using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	From first dose of etanercept to 30 days after the last dose; 38 days.

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Cohen S, Samad A, Karis E, Stolshek BS, Trivedi M, Zhang H, Aras GA, Kricorian G, Chung JB. Decreased Injection Site Pain Associated with Phosphate-Free Etanercept Formulation in Rheumatoid Arthritis or Psoriatic Arthritis Patients: A Randomized Controlled Trial. Rheumatol Ther. 2019 Jun;6(2):245-254. doi: 10.1007/s40744-019-0152-8. Epub 2019 Mar 27.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2016
• Primary Completion (Actual): September 8, 2017
• Study Completion (Actual): October 9, 2017

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: December 5, 2016
• First Posted (Estimate): December 8, 2016

Study Record Updates

• Last Update Posted (Actual): July 18, 2019
• Last Update Submitted That Met QC Criteria: July 8, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Rheumatoid; Arthritis, Psoriatic; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Etanercept
• Other Study ID Numbers: 20140339

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No