Psoriatic Arthritis
Conditions
Keywords
Psoriatic arthritis, IgG1K monoclonal antibody, Interleukin -17A neutralizing
Brief summary
This study is designed as an extension study to the proof-of-concept trial CAIN457A2206 in patients with psoriatic arthritis and aims to provide continuous treatment with AIN457 for patients in the core trial, to obtain safety and tolerability information. The study will address the evaluation of efficacy following doses of 3 mg/kg AIN457 given every 4 weeks over a period initially up to 6 months (Part 1) and based on the risk/benefit balance of AIN457 in psoriatic arthritis a decision will be made as to whether or not to continue dosing for another 6 month period (Part 2).
Interventions
BIOLOGICALAIN457A
OTHEROther
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients who participated and completed the core CAIN457A2206 study up to and including the end of the study (EoS) Visit, i.e. Visit 16 (Week 24), were allowed to enter the extension study upon signing informed consent. * Patients who discontinued the core study due to unsatisfactory therapeutic effect at their Visit 14 (Week 16) or a later visit could enter the extension study within three weeks of completing the study discontinuation visit of the core study, provided that at their discontinuation visit they met the criteria below. Patients who did not enter the extension study within 3 weeks of completing the study discontinuation visit of the core study, were to have an additional baseline visit (Visit 17) and required to meet the criteria below: * The number of tender joints was the same or more than the core study baseline; or, * The number of swollen joints was the same or more than the core study baseline; or, * There was no improvement compared with the core study baseline in at least three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, Health Assessment Questionnaire and CRP
Exclusion criteria
* Patients for whom continued treatment with AIN457 is not considered appropriate by the treating physician. * Patients who were non-compliant or who demonstrated a major protocol deviation in the core CAIN457A2206 study. * Patients who discontinued from the core CAIN457A2206 study before Visit 14 (Week 16), and patients who completed the core study or discontinued the core study more than 2 weeks before the baseline visit. * Pregnant or lactating women * Presence of active infection * Positive PPD or HIV test in patients where repeated testing was deemed appropriate due to their risk profile Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events and Serious Adverse Events | Up to 64 weeks (End of the Study Treatment) | Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total IL-17 Concentration in Blood at Steady-state | Up to 64 weeks | Total IL-17 concentration was not reported due to assay limitations. |
| Mean Serum Concentration Measured at Steady State | Weeks 0, 8, 16, 20, 24, 28, 32, 36, 40 and at 4 and 12 weeks after the last administration at Week 52. | This outcome measure is assessing AIN457 Mean Serum Concentration Measured at Steady State. A competitive ELISA method was used for bioanalytical analyses and the anticipated LLOQ is 80 nanograms/mL serum. |
Countries
Germany, Netherlands, United Kingdom
Participant flow
Pre-assignment details
A total of 42 patients were randomized in the (CAIN457A2206) core study, of which 28 patients enrolled into the (CAIN457A2206E1) extension study.
Participants by arm
| Arm | Count |
|---|---|
| AIN457/AIN457 3 mg/kg Participants who were treated with secukinumab 2x10 mg/kg during the core study were treated with secukinumab at 3mg/kg infused intravenously every 4 weeks during the extension study, over a total period of 52 weeks. | 19 |
| Placebo/AIN457 3 mg/kg Participants who were treated with placebo during the core study were treated with secukinumab at 3mg/kg infused intravenously every 4 weeks during the extension study, over a total period of 52 weeks. | 9 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Patient withdrew consent | 4 | 0 |
| Overall Study | Unsatisfactory therapeutic effect | 1 | 0 |
Baseline characteristics
| Characteristic | AIN457/AIN457 3 mg/kg | Placebo/AIN457 3 mg/kg | Total |
|---|---|---|---|
| Age, Continuous | 45.6 years STANDARD_DEVIATION 10.96 | 47.9 years STANDARD_DEVIATION 6.81 | 46.3 years STANDARD_DEVIATION 9.75 |
| Race/Ethnicity, Customized Ethnicity Hispanic/Latino | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Other | 19 Participants | 8 Participants | 27 Participants |
| Race/Ethnicity, Customized Predominant race Caucasian | 19 Participants | 8 Participants | 27 Participants |
| Race/Ethnicity, Customized Predominant race Other | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 12 Participants | 5 Participants | 17 Participants |
| Sex: Female, Male Male | 7 Participants | 4 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 9 |
| other Total, other adverse events | 19 / 19 | 9 / 9 |
| serious Total, serious adverse events | 5 / 19 | 2 / 9 |
Outcome results
Primary
Number of Participants With Adverse Events and Serious Adverse Events
Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.
Time frame: Up to 64 weeks (End of the Study Treatment)
Population: The safety population consisted of all randomized patients who received at least one dose of the study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AIN457/AIN457 3 mg/kg | Number of Participants With Adverse Events and Serious Adverse Events | Serious Adverse Events | 5 Participants |
| AIN457/AIN457 3 mg/kg | Number of Participants With Adverse Events and Serious Adverse Events | Death | 0 Participants |
| Placebo/AIN457 3 mg/kg | Number of Participants With Adverse Events and Serious Adverse Events | Serious Adverse Events | 2 Participants |
| Placebo/AIN457 3 mg/kg | Number of Participants With Adverse Events and Serious Adverse Events | Death | 0 Participants |
Secondary
Mean Serum Concentration Measured at Steady State
This outcome measure is assessing AIN457 Mean Serum Concentration Measured at Steady State. A competitive ELISA method was used for bioanalytical analyses and the anticipated LLOQ is 80 nanograms/mL serum.
Time frame: Weeks 0, 8, 16, 20, 24, 28, 32, 36, 40 and at 4 and 12 weeks after the last administration at Week 52.
Population: All participants from the safety set with quantifiable pharmacokinetic (PK) measurements and no major protocol deviations with impact on PK data were included in the Pharmacokinetic Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 0/pre-inf | 2.76 Microgram/millilitre (μg/mL) | Standard Deviation 4.73 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 0/post-inf | 80.0 Microgram/millilitre (μg/mL) | Standard Deviation 17.7 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 8/pre-inf | 29.6 Microgram/millilitre (μg/mL) | Standard Deviation 10.3 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 8 /post-inf | 99.7 Microgram/millilitre (μg/mL) | Standard Deviation 22.1 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 16/pre-inf | 32.9 Microgram/millilitre (μg/mL) | Standard Deviation 12.1 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 16/post-inf | 110 Microgram/millilitre (μg/mL) | Standard Deviation 25.3 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 20/pre-inf | 31.3 Microgram/millilitre (μg/mL) | Standard Deviation 9 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 20/post-inf | 111 Microgram/millilitre (μg/mL) | Standard Deviation 29.9 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 24/pre-inf | 37.2 Microgram/millilitre (μg/mL) | Standard Deviation 11.9 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 24/post-inf | 109 Microgram/millilitre (μg/mL) | Standard Deviation 24.5 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 28/pre-inf | 37.4 Microgram/millilitre (μg/mL) | Standard Deviation 10.2 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 28/post-inf | 122 Microgram/millilitre (μg/mL) | Standard Deviation 20.2 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 32/pre-inf | 37.4 Microgram/millilitre (μg/mL) | Standard Deviation 13 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 32/post-inf | 112 Microgram/millilitre (μg/mL) | Standard Deviation 15.1 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 36/pre-inf | 33.4 Microgram/millilitre (μg/mL) | Standard Deviation 9.49 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 36/post-inf | 109 Microgram/millilitre (μg/mL) | Standard Deviation 24.4 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 40/pre-inf | 46.4 Microgram/millilitre (μg/mL) | Standard Deviation 28.2 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 40/post-inf | 84.8 Microgram/millilitre (μg/mL) | Standard Deviation 30.5 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 56 | 33.8 Microgram/millilitre (μg/mL) | Standard Deviation 8.93 |
| AIN457/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 64 | 11.0 Microgram/millilitre (μg/mL) | Standard Deviation 3.46 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 40/post-inf | 105 Microgram/millilitre (μg/mL) | Standard Deviation 24.9 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 0/pre-inf | 0.00 Microgram/millilitre (μg/mL) | Standard Deviation 0 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 28/pre-inf | 22.1 Microgram/millilitre (μg/mL) | Standard Deviation 9.45 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 0/post-inf | 68.8 Microgram/millilitre (μg/mL) | Standard Deviation 19.1 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 36/post-inf | 88.9 Microgram/millilitre (μg/mL) | Standard Deviation 13.9 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 8/pre-inf | 19.5 Microgram/millilitre (μg/mL) | Standard Deviation 7.68 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 28/post-inf | 96.9 Microgram/millilitre (μg/mL) | Standard Deviation 18.5 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 8 /post-inf | 88.9 Microgram/millilitre (μg/mL) | Standard Deviation 25.5 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 64 | 10.3 Microgram/millilitre (μg/mL) | Standard Deviation 8.31 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 16/pre-inf | 23.3 Microgram/millilitre (μg/mL) | Standard Deviation 10.3 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 32/pre-inf | 26.7 Microgram/millilitre (μg/mL) | Standard Deviation 8.05 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 16/post-inf | 82.9 Microgram/millilitre (μg/mL) | Standard Deviation 24.7 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 40/pre-inf | 28.7 Microgram/millilitre (μg/mL) | Standard Deviation 9 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 20/pre-inf | 25.4 Microgram/millilitre (μg/mL) | Standard Deviation 13 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 32/post-inf | 92.8 Microgram/millilitre (μg/mL) | Standard Deviation 23.2 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 20/post-inf | 85.5 Microgram/millilitre (μg/mL) | Standard Deviation 19.9 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 56 | 31.6 Microgram/millilitre (μg/mL) | Standard Deviation 7.62 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 24/pre-inf | 25.5 Microgram/millilitre (μg/mL) | Standard Deviation 11.6 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 36/pre-inf | 27.3 Microgram/millilitre (μg/mL) | Standard Deviation 7.06 |
| Placebo/AIN457 3 mg/kg | Mean Serum Concentration Measured at Steady State | 24/post-inf | 89.1 Microgram/millilitre (μg/mL) | Standard Deviation 23.2 |
Secondary
Total IL-17 Concentration in Blood at Steady-state
Total IL-17 concentration was not reported due to assay limitations.
Time frame: Up to 64 weeks
Population: No participants were evaluated as IL-17 concentration was not reported due to assay limitations