A Crossover Study of the Safety and Tolerability of Two Formulations of Adalimumab

A Multicenter, Randomized, Single-Blind Crossover Study of the Safety and Tolerability of Two Adalimumab Formulations in Adult Subjects With Rheumatoid Arthritis

This study will compare injection site pain levels between current Humira® formulation versus a new formulation of Humira in patients with Rheumatoid Arthritis (RA), who are either currently on a stable dose (minimum six consecutive doses) of on-label Humira or biological naïve who will be prescribed on-label Humira as treatment for their Rheumatoid Arthritis. The study is being conducted in three countries, Australia (3 sites), Canada (2 sites), and Germany (2 sites).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: Adalimumab

Detailed Description

61 participants were randomized, and 60 received at least one dose of the study drug. One participant, who was randomized to the New formulation of adalimumab/Current formulation adalimumab arm of the study, discontinued from the study and never received study drug.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Malvern East, Australia, 3145
    • Site Reference ID/Investigator# 63354
  • Maroochydore, Australia, 4558
    • Site Reference ID/Investigator# 63355
  • Shenton Park, Australia, 6008
    • Site Reference ID/Investigator# 63353
• Canada
  • Hamilton, Canada, L8N 2B6
    • Site Reference ID/Investigator# 67105
  • Winnipeg, Canada, R3A 1M3
    • Site Reference ID/Investigator# 64122
• Germany
  • Munich, Germany, 80336
    • Site Reference ID/Investigator# 63356
  • Ostseebad Damp, Germany, 24351
    • Site Reference ID/Investigator# 69242

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:

• Male or female subject age 18 years or older, who requires Humira 40 mg SC every other week (eow) or every week (ew) for the treatment of rheumatoid arthritis, in accordance with the local Humira label.
• Subject must be a current, on-label user of Humira who rates his/her average Humira injection site related pain as at least 3 cm on a pain Visual Analogue Scale and has had at least 6 consecutive doses of Humira prior to Screening, or a biologic naïve subject who requires initiation of on-label treatment with Humira.
• Subject has diagnosis of rheumatoid arthritis (RA) as defined by the 1987 revised ACR classification criteria or the ACR/EULAR 2010 criteria,
• Female subjects are either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy and/or hysterectomy), or are practicing at least one method of birth control throughout the study and for at least 70 days after the last dose of study drug.
• All female subjects of childbearing potential must have a negative test for pregnancy on a serum sample at Screening and prior to study drug dosing on a urine sample obtained at Visit 1.

Exclusion Criteria:

• Subject has been treated with any investigational drug of a chemical or biologic nature within a minimum of 30 days or 5 half-lives (whichever is longer) of the drug prior to Visit 1.
• Any infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to Visit 1 or oral anti-infectives within 14 days prior to Visit 1.
• Prior exposure to natalizumab (Tysabri®) or efalizumab (Raptiva®).
• Known hypersensitivity to adalimumab or its excipients.
• History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of demyelinating disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Current formulation adalimumab; One dose with 40 mg of current formulation of adalimumab in a pre-filled syringe	Biological: Adalimumab; Subcutaneously 40 mg every other week (eow) or every week (ew) (as dosing requires); Other Names: ABT-D2E7; Humira
Experimental: New formulation of adalimumab; One dose with 40 mg of new formulation of adalimumab in a pre-filled syringe	Biological: Adalimumab; Subcutaneously 40 mg every other week (eow) or every week (ew) (as dosing requires); Other Names: ABT-D2E7; Humira

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Injection Site Pain on a Visual Analogue Scale (VAS)	The primary response variable is participant's immediate pain of injection on a visual analogue scale (VAS) of 0 to 10 (cm), with 0 representing no pain and 10 representing the worst possible pain.	Immediately after injection.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With no Hemorrhage/Petechiae in the Draize Scale	Hemorrhage/petechiae (bleeding/spots of bleeding underneath the skin) was assessed.	10 minutes and 30 minutes after injection
Percentage of Participants With no Erythema in the Draize Scale	Erythema (redness) was assessed.	10 minutes and 30 minutes after injection
Percentage of Participants With no Edema in the Draize Scale	Edema (swelling) was assessed.	10 minutes and 30 minutes after injection
Percentage of Participants With no Pruritus in the Draize Scale	Pruritus (itching) was assessed.	10 minutes and 30 minutes after injection
Mean Injection Site Pain on a Visual Analogue Scale (VAS)	The secondary response variable is participant's pain of injection on a visual analogue scale (VAS) of 0 to 10 (cm) recorded 15 minutes after the injection.	15 minutes post injection
Number of Participants With Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment.	Adverse events were collected from the time of study drug administration until 70 days following discontinuation of study drug. Serious adverse events were collected from the time that participant signed the informed consent.

Collaborators and Investigators

• Sponsor: AbbVie (prior sponsor, Abbott)

Publications and helpful links

General Publications

• Nash P, Vanhoof J, Hall S, Arulmani U, Tarzynski-Potempa R, Unnebrink K, Payne AN, Cividino A. Randomized Crossover Comparison of Injection Site Pain with 40 mg/0.4 or 0.8 mL Formulations of Adalimumab in Patients with Rheumatoid Arthritis. Rheumatol Ther. 2016 Dec;3(2):257-270. doi: 10.1007/s40744-016-0041-3. Epub 2016 Aug 18.

Helpful Links

• This clinical study may be evaluating a usage that is not currently FDA-approved. Please see US Prescribing Information for approved uses.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: December 1, 2011
• First Submitted That Met QC Criteria: December 29, 2011
• First Posted (Estimate): December 30, 2011

Study Record Updates

• Last Update Posted (Estimate): February 20, 2014
• Last Update Submitted That Met QC Criteria: January 23, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Pain; Rheumatoid Arthritis; On label Humira users
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: M11-964; 2011-003953-25 (EudraCT Number)