Arthritis, Rheumatoid; Arthritis, Psoriatic
Conditions
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).
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).
Interventions
DRUGCommercial 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.
DRUGNew 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.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Injection Site Pain | 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
| Measure | Time frame | Description |
|---|---|---|
| Injection Site Pain by Disease Indication | 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. |
| Number of Participants With Adverse Events | 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. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
This study was conducted at 23 centers in the United States. The first participant enrolled on 29 November 2016 and the last participant enrolled on 01 September 2017.
Pre-assignment details
Participants were randomized 1:1 to receive each etanercept formulation in 1 of 2 treatment sequences: AB (treatment A followed by treatment B) or BA (treatment B followed by treatment A).
Participants by arm
| Arm | Count |
|---|---|
| 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). | 56 |
| 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). | 55 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Sponsor Decision | 1 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Sequence BA | Sequence AB |
|---|---|---|---|
| Actual Indication Psoriatic Arthritis | 25 Participants | 10 Participants | 15 Participants |
| Actual Indication Rheumatoid Arthritis | 86 Participants | 45 Participants | 41 Participants |
| Age, Continuous | 55.3 years STANDARD_DEVIATION 13.7 | 55.9 years STANDARD_DEVIATION 13.7 | 54.7 years STANDARD_DEVIATION 13.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 42 Participants | 14 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 69 Participants | 41 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 100 Participants | 50 Participants | 50 Participants |
| Sex: Female, Male Female | 77 Participants | 41 Participants | 36 Participants |
| Sex: Female, Male Male | 34 Participants | 14 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 106 | 0 / 107 |
| other Total, other adverse events | 10 / 106 | 7 / 107 |
| serious Total, serious adverse events | 0 / 106 | 1 / 107 |
Outcome results
Primary
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.
Time frame: Immediately following injection of each study drug on day 1 and day 8 of this crossover study
Population: The primary analysis set included all participants who received both doses of commercial and new etanercept during each study period and who completed the injection site pain score during both study periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept Commercial Formulation | Injection Site Pain | 23.6 mm | Standard Deviation 22.3 |
| Etanercept New Formulation | Injection Site Pain | 19.8 mm | Standard Deviation 22.5 |
Comparison: A mixed effects analysis of variance model was used to assess injection site pain with the new formulation of etanercept as the test treatment and the commercial formulation of etanercept as the reference treatment. Treatment, study period, sequence, and disease indication were evaluated as fixed effect covariates, and subject within sequence was included as a random effect.p-value: 0.04895% CI: [-8, 0]Mixed effects analysis of variance model
Secondary
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.
Time frame: Immediately following injection of each study drug on day 1 and day 8 of this crossover study
Population: Primary analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept Commercial Formulation | Injection Site Pain by Disease Indication | 23.7 mm | Standard Deviation 20.2 |
| Etanercept New Formulation | Injection Site Pain by Disease Indication | 23.3 mm | Standard Deviation 29 |
| Etanercept New Formulation - RA | Injection Site Pain by Disease Indication | 20.5 mm | Standard Deviation 22.6 |
| Etanercept New Formulation - PsA | Injection Site Pain by Disease Indication | 17.2 mm | Standard Deviation 22.3 |
Secondary
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.
Time frame: From first dose of etanercept to 30 days after the last dose; 38 days.
Population: The safety analysis set included all participants who received at least 1 dose of etanercept during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Etanercept Commercial Formulation | Number of Participants With Adverse Events | All adverse events | 10 Participants |
| Etanercept Commercial Formulation | Number of Participants With Adverse Events | Serious adverse events | 0 Participants |
| Etanercept Commercial Formulation | Number of Participants With Adverse Events | AE leading to discontinuation of etanercept | 1 Participants |
| Etanercept Commercial Formulation | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Etanercept New Formulation | Number of Participants With Adverse Events | Fatal adverse events | 0 Participants |
| Etanercept New Formulation | Number of Participants With Adverse Events | All adverse events | 8 Participants |
| Etanercept New Formulation | Number of Participants With Adverse Events | AE leading to discontinuation of etanercept | 3 Participants |
| Etanercept New Formulation | Number of Participants With Adverse Events | Serious adverse events | 1 Participants |