Chronic Stable Plaque Psoriasis
Conditions
Brief summary
The purpose of this study is to demonstrate equivalent efficacy of GP2015 and Enbrel® in patients with moderate to severe chronic plaque-type psoriasis with respect to PASI 75 response rate at Week 12.
Detailed description
The purpose of this confirmatory safety and efficacy study (GP15-302) was to demonstrate equivalence in efficacy and similarity in safety and immunogenicity of GP2015 and Enbrel (EU-authorized) in patients with moderate to severe chronic plaque-type psoriasis and to evaluate the effects of repeated switching between GP2015 and Enbrel on efficacy, overall safety, and immunogenicity. Since only EU-authorized Enbrel was utilized in this study, the use of the term Enbrel throughout this report describes EU-authorized Enbrel only.
Interventions
DRUGGP2015 Etanercept
Sandoz has developed GP2015 Etanercept (Sandoz's code for the drug product containing the active ingredient etanercept) to be biosimilar to Enbrel.
DRUGEnbrel
Enbrel is used as reference product to GP2015.
Sponsors
Hexal AG
Sandoz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women at least 18 years of age at time of screening * Chronic plaque-type psoriasis diagnosed for at least 6 months before baseline * Moderate to severe psoriasis as defined at baseline by: * PASI score of 10 or greater and, * Investigator´s Global Assessment score of 3 or greater (based on a scale of 0 - 4) and, * Body Surface Area affected by plaque-type psoriasis of 10% or greater * Chronic plaque-type psoriasis patients who have previously received phototherapy or systemic psoriasis therapy at least once or who are candidates for such therapies in the opinion of the investigator.
Exclusion criteria
* Forms of psoriasis other than chronic plaque-type * Drug-induced psoriasis * Ongoing use of prohibited treatments * Previous exposure to etanercept * Active ongoing inflammatory diseases other than psoriasis that might confound the evaluation of the benefit of treatment with etanercept Other In-/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PASI 75 Response Rate at Week 12 - GP2015 Etanercept vs. Enbrel ® Etanercept | Week 12 | The 95% CI for the Psoriasis Area and Severity Index (PASI) 75 response rate differences at Week12 between GP2015 Etanercept and Enbrel ® Etanercept. PASI 75 response: patients who achieved ≥ 75% improvement (reduction) in PASI score compared to baseline were defined as PASI 75 responders. PASI scores can range from 0, corresponding to no signs of psoriasis up to theoretic maximum of 72.0, which means a higher PASI score reflects a higher psoriasis activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in PASI Score up to Week 12 | 12 weeks | The key secondary efficacy endpoint was the % change from baseline in PASI score up to Week 12. PASI scores can range from 0, corresponding to no signs of psoriasis up to theoretic maximum of 72.0, which means a higher PASI score reflects a higher psoriasis activity. Two approaches (longitudinal approach applying a Mixed Model Repeated Measures and Averaged Treatment Effect approach applying an ANCOVA model) were employed in order to calculate 2-sided 95% confidence intervals (CI) for the difference between the treatment groups. |
| PASI 50, 75 and 90 Response Rates | Week12 | Percentage of patients achieving Psoriasis Area and Severity Index (PASI) 50, PASI 75, and PASI 90 responses at Week 12. PASI 50 response: patients who achieved ≥ 50% improvement (reduction) in PASI score compared to baseline were defined as PASI 50 responders .PASI 90 response: patients who achieved ≥ 90% improvement (reduction) in PASI score compared to baseline were defined as PASI 90 responders . |
| Injection Site Reactions | Week52 | Percentage of patients with injection site reactions up to Week 52 |
| Immunogenicity: Measurement of Rate of ADA Formations Against GP2015 Etanercept and Enbrel ® Etanercept | Week 52 | Immunogenicity was analyzed by the percentage of patients with positive anti-drug antibodies (ADA) to either GP2015 Etanercept or Enbrel ® up to Week 52. |
Countries
Bulgaria, Czechia, Estonia, Germany, Hungary, Poland, Romania, Russia, Slovakia, South Africa, Ukraine, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GP2015 Etanercept Solution for subcutaneous injection in pre-filled syringe. The drug is administered in a dose of 50 mg twice weekly for the first 12 weeks and 50 mg once weekly thereafter
GP2015 Etanercept | 264 |
| Enbrel ® Etanercept Solution for subcutaneous injection in pre-filled syringe. The drug is administered in a dose of 50 mg twice weekly for the first 12 weeks and 50 mg once weekly thereafter
Enbrel ® Etanercept | 267 |
| Total | 531 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Extension Period | Adverse Event | 0 | 0 | 4 | 2 | 2 | 0 |
| Extension Period | Lack of Efficacy | 0 | 0 | 0 | 1 | 1 | 0 |
| Extension Period | Lost to Follow-up | 0 | 0 | 2 | 0 | 0 | 0 |
| Extension Period | Pregnancy | 0 | 0 | 1 | 0 | 0 | 0 |
| Extension Period | Withdrawal by Subject | 0 | 0 | 1 | 2 | 4 | 0 |
| Treatment Period 1 | Adverse Event / Injection Site Reaction | 4 | 4 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Adverse Event, Serious, Fatal | 0 | 1 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Protocol Violation / IMP non-compliance | 1 | 1 | 0 | 0 | 0 | 0 |
| Treatment Period 1 | Withdrawal by Subject | 2 | 5 | 0 | 0 | 0 | 0 |
| Treatment Period 2 | Adverse Event | 0 | 0 | 1 | 2 | 0 | 4 |
| Treatment Period 2 | Lack of Efficacy | 0 | 0 | 1 | 0 | 1 | 0 |
| Treatment Period 2 | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 |
| Treatment Period 2 | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 |
| Treatment Period 2 | Site Termination | 0 | 0 | 1 | 2 | 0 | 0 |
| Treatment Period 2 | Termination of Site | 0 | 0 | 0 | 0 | 2 | 0 |
| Treatment Period 2 | Withdrawal by Subject | 0 | 0 | 3 | 4 | 1 | 1 |
Baseline characteristics
| Characteristic | GP2015 Etanercept | Enbrel ® Etanercept | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 18 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 254 Participants | 249 Participants | 503 Participants |
| Age, Continuous | 42.1 years STANDARD_DEVIATION 12.29 | 42.7 years STANDARD_DEVIATION 12.86 | 42.4 years STANDARD_DEVIATION 12.57 |
| Region of Enrollment Bulgaria | 13 participants | 8 participants | 21 participants |
| Region of Enrollment Czech Republic | 25 participants | 16 participants | 41 participants |
| Region of Enrollment Estonia | 41 participants | 40 participants | 81 participants |
| Region of Enrollment Germany | 12 participants | 17 participants | 29 participants |
| Region of Enrollment Hungary | 9 participants | 12 participants | 21 participants |
| Region of Enrollment Poland | 96 participants | 94 participants | 190 participants |
| Region of Enrollment Romania | 9 participants | 24 participants | 33 participants |
| Region of Enrollment Russian Federation | 9 participants | 8 participants | 17 participants |
| Region of Enrollment Slovakia | 17 participants | 20 participants | 37 participants |
| Region of Enrollment South Africa | 4 participants | 1 participants | 5 participants |
| Region of Enrollment Ukraine | 19 participants | 23 participants | 42 participants |
| Region of Enrollment United Kingdom | 10 participants | 4 participants | 14 participants |
| Sex: Female, Male Female | 107 Participants | 95 Participants | 202 Participants |
| Sex: Female, Male Male | 157 Participants | 172 Participants | 329 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 97 / 164 | 57 / 96 | 60 / 100 | 94 / 171 |
| serious Total, serious adverse events | 7 / 164 | 6 / 96 | 6 / 100 | 7 / 171 |
Outcome results
Primary
PASI 75 Response Rate at Week 12 - GP2015 Etanercept vs. Enbrel ® Etanercept
The 95% CI for the Psoriasis Area and Severity Index (PASI) 75 response rate differences at Week12 between GP2015 Etanercept and Enbrel ® Etanercept. PASI 75 response: patients who achieved ≥ 75% improvement (reduction) in PASI score compared to baseline were defined as PASI 75 responders. PASI scores can range from 0, corresponding to no signs of psoriasis up to theoretic maximum of 72.0, which means a higher PASI score reflects a higher psoriasis activity.
Time frame: Week 12
Population: The analysis of the primary outcome measure was based on the per-protocol set (PPS) consisting of patients who completed study until 12 weeks without any major protocol deviation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GP2015 Etanercept | PASI 75 Response Rate at Week 12 - GP2015 Etanercept vs. Enbrel ® Etanercept | 73.4 % of patients achieving PASI75 response |
| Enbrel ® Etanercept | PASI 75 Response Rate at Week 12 - GP2015 Etanercept vs. Enbrel ® Etanercept | 75.7 % of patients achieving PASI75 response |
Comparison: PASI 75 response rate (proportion of patients showing at least a 75% improvement in PASI) after the first 12 weeks of treatment (Treatment Period 1) was the primary endpoint to assess equivalence between GP2015 and Enbrel®. Therapeutic equivalence in terms of PASI75 could be concluded if the exact 95% confidence interval for the difference in the PASI75 rates is completely contained within the interval \[-18%; 18%\]. A logistic regression model was to be employed.95% CI: [-9.85, 5.3]
Secondary
Immunogenicity: Measurement of Rate of ADA Formations Against GP2015 Etanercept and Enbrel ® Etanercept
Immunogenicity was analyzed by the percentage of patients with positive anti-drug antibodies (ADA) to either GP2015 Etanercept or Enbrel ® up to Week 52.
Time frame: Week 52
Population: The analysis was performed on immunogenicity set consisting of patients who provided data for ADA assessment of etanercept at baseline visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GP2015 Etanercept | Immunogenicity: Measurement of Rate of ADA Formations Against GP2015 Etanercept and Enbrel ® Etanercept | 0 percentage patients with positive ADA |
| Enbrel ® Etanercept | Immunogenicity: Measurement of Rate of ADA Formations Against GP2015 Etanercept and Enbrel ® Etanercept | 1.1 percentage patients with positive ADA |
| GP2015 Etanercept Switched | Immunogenicity: Measurement of Rate of ADA Formations Against GP2015 Etanercept and Enbrel ® Etanercept | 0 percentage patients with positive ADA |
| Enbrel ® Etanercept Continued | Immunogenicity: Measurement of Rate of ADA Formations Against GP2015 Etanercept and Enbrel ® Etanercept | 3.5 percentage patients with positive ADA |
Secondary
Injection Site Reactions
Percentage of patients with injection site reactions up to Week 52
Time frame: Week52
Population: The analysis was performed on safety set including all patients who took at least 1 dose of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GP2015 Etanercept | Injection Site Reactions | 8.5 percentage of patients with ISRs |
| Enbrel ® Etanercept | Injection Site Reactions | 16.7 percentage of patients with ISRs |
| GP2015 Etanercept Switched | Injection Site Reactions | 9.0 percentage of patients with ISRs |
| Enbrel ® Etanercept Continued | Injection Site Reactions | 15.8 percentage of patients with ISRs |
Secondary
PASI 50, 75 and 90 Response Rates
Percentage of patients achieving Psoriasis Area and Severity Index (PASI) 50, PASI 75, and PASI 90 responses at Week 12. PASI 50 response: patients who achieved ≥ 50% improvement (reduction) in PASI score compared to baseline were defined as PASI 50 responders .PASI 90 response: patients who achieved ≥ 90% improvement (reduction) in PASI score compared to baseline were defined as PASI 90 responders .
Time frame: Week12
Population: The analysis of this secondary outcome measure was based on the per-protocol set (PPS) consisting of patients who completed study until 12 weeks without any major protocol deviation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GP2015 Etanercept | PASI 50, 75 and 90 Response Rates | % of patients achieving PASI50 response at Week 12 | 99.2 percentage of patients |
| GP2015 Etanercept | PASI 50, 75 and 90 Response Rates | % of patients achieving PASI75 response at Week 12 | 73.4 percentage of patients |
| GP2015 Etanercept | PASI 50, 75 and 90 Response Rates | % of patients achieving PASI90 response at Week 12 | 39.2 percentage of patients |
| Enbrel ® Etanercept | PASI 50, 75 and 90 Response Rates | % of patients achieving PASI50 response at Week 12 | 97.9 percentage of patients |
| Enbrel ® Etanercept | PASI 50, 75 and 90 Response Rates | % of patients achieving PASI75 response at Week 12 | 75.7 percentage of patients |
| Enbrel ® Etanercept | PASI 50, 75 and 90 Response Rates | % of patients achieving PASI90 response at Week 12 | 34.1 percentage of patients |
Secondary
Percent Change From Baseline in PASI Score up to Week 12
The key secondary efficacy endpoint was the % change from baseline in PASI score up to Week 12. PASI scores can range from 0, corresponding to no signs of psoriasis up to theoretic maximum of 72.0, which means a higher PASI score reflects a higher psoriasis activity. Two approaches (longitudinal approach applying a Mixed Model Repeated Measures and Averaged Treatment Effect approach applying an ANCOVA model) were employed in order to calculate 2-sided 95% confidence intervals (CI) for the difference between the treatment groups.
Time frame: 12 weeks
Population: The analysis was based on the per-protocol set (PPS) consisting of patients who completed study until 12 weeks without any major protocol deviation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GP2015 Etanercept | Percent Change From Baseline in PASI Score up to Week 12 | -56.11 percentage difference | Standard Error 1.0578 |
| Enbrel ® Etanercept | Percent Change From Baseline in PASI Score up to Week 12 | -55.48 percentage difference | Standard Error 1.0511 |
95% CI: [-3.474, 2.204]
95% CI: [-3.61, 1.845]