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

• ClinicalTrials.gov Identifier: NCT02986139
• Recruitment Status: Completed
• First Posted: December 8, 2016
• Results First Posted: October 31, 2018
• Last Update Posted: July 18, 2019
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Arthritis, Rheumatoid; Arthritis, Psoriatic	Drug: Commercial Formulation Etanercept; Drug: New Formulation Etanercept	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 111 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: 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
• Actual Study Start Date: November 29, 2016
• Actual Primary Completion Date: September 8, 2017
• Actual Study Completion Date: October 9, 2017

Arms and Interventions

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 Name: 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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Injection Site Pain [ Time Frame: Immediately following injection of each study drug on day 1 and day 8 of this crossover study ]
   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.

Secondary Outcome Measures :

1. Injection Site Pain by Disease Indication [ Time Frame: Immediately following injection of each study drug on day 1 and day 8 of this crossover study ]
   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.
2. Number of Participants With Adverse Events [ Time Frame: From first dose of etanercept to 30 days after the last dose; 38 days. ]
   The severity of each adverse event was graded by the investigator using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

Research Site

Birmingham, Alabama, United States, 35216

United States, California

Research Site

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

United States, Florida

Research Site

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

United States, Illinois

Research Site

Quincy, Illinois, United States, 62301

Research Site

Skokie, Illinois, United States, 60076

United States, Michigan

Research Site

Bay City, Michigan, United States, 48706

Research Site

Grand Rapids, Michigan, United States, 49546

United States, Mississippi

Research Site

Flowood, Mississippi, United States, 39232

United States, Missouri

Research Site

Kansas City, Missouri, United States, 64114

United States, New Jersey

Research Site

Freehold, New Jersey, United States, 07728

United States, New York

Research Site

Smithtown, New York, United States, 11787

United States, Ohio

Research Site

Middleburg Heights, Ohio, United States, 44130

United States, Pennsylvania

Research Site

Wyomissing, Pennsylvania, United States, 19610

United States, South Carolina

Research Site

Orangeburg, South Carolina, United States, 29118

United States, Texas

Research Site

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

United States, Washington

Research Site

Bothell, Washington, United States, 98021

United States, West Virginia

Research Site

South Charleston, West Virginia, United States, 25309

Puerto Rico

Research Site

Ponce, Puerto Rico, 00716

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

  Study Documents (Full-Text)

Documents provided by Amgen:

Study Protocol  [PDF] March 30, 2017

Statistical Analysis Plan  [PDF] May 31, 2017

More Information

Additional Information:

AmgenTrials clinical trials website 

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.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02986139
• Other Study ID Numbers: 20140339
• First Posted: December 8, 2016
• Results First Posted: October 31, 2018
• Last Update Posted: July 18, 2019
• Last Verified: July 2019

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Arthritis, Psoriatic; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Etanercept; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Gastrointestinal Agents; Immunosuppressive Agents; Immunologic Factors