Ankylosing Spondylitis
Conditions
Keywords
Ankylosing spondylitis, IgG1K monoclonal antibody, Interleukin -17A neutralizing
Brief summary
This study is designed as an extension study to the proof-of-concept trial CAIN457A2209 in patients with moderate to severe ankylosing spondylitis 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 Intravenous infusion (IV) 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 ankylosing spondylitis a decision was taken to continue dosing for another 6 month period (Part 2).
Interventions
BIOLOGICALAIN457A
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
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 took part and completed in the core CAIN457A2209 study * Patients who discontinued the core study due to unsatisfactory therapeutic effect at their Visit 14 (Week 16) or later could enter the extension study within 3 weeks of completing the study discontinuation visit of the core study, provided that at their discontinuation visit they fulfilled either one of 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 required to come for an additional baseline visit (Visit 17) and were required to fulfill either one of the criteria below: * No improvement (compared with the core study baseline) in two out of the following four domains: patient global assessment, pain, BASFI and the mean of the two morning stiffness questions from the BASDAI. OR * Deterioration (compared with the core study baseline) in one of the four domains (deterioration defined as \>=20% worsening and an absolute worsening of \>=1 unit)
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 CAIN457A2209 study. * Patients who discontinued from the core CAIN457A2209 study before Visit 14 (Week 16), and patients who completed the core study * 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 Reported Adverse Events (AE's) | From start of the study up to 64 weeks | AEs are 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reported Positive Antibodies for Secukinumab | Pre-dose, Week 0, 8, 24, 40 and Week 64 | Immunogenicity (anti-drug antibodies) was assessed using an MSD bridging assay and a 3-tiered approach (screening, confirmation, titration). |
| Total Interleukin (IL)- 17A Concentration in Blood at Steady-State | Pre-dose and at the end of infusion (up to 64 weeks) | Total serum IL17A was not measured due to assay limitations. |
| Maximum (Peak) Observed in Serum at Steady-State (Cmax,ss) | At end of infusion (Week 64) | Concentration of Secukinumab at the end of infusion (Cmax,ss) was reported. |
| Minimum (Trough) Observed in Serum at Steady State (Cmin,ss) | Pre-dose (Week 0) | The concentration of secukinumab at pre-dose (Cmin,ss) in serum was reported. |
Countries
Germany, Netherlands, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 15 centers in four countries (Germany, Netherlands, United Kingdom, United States).
Pre-assignment details
A total of 39 participants enrolled in the study of which 28 completed the study and 11 discontinued the study. Few participants were enrolled into the extension study (CAIN457A2209E1 \[NCT01109940\]) prior to completion of the core study (CAIN457A2209 \[NCT00809159\]).
Participants by arm
| Arm | Count |
|---|---|
| Dose Group 1 Participants received 3 milligrams per kilogram (mg/kg) of intravenous (IV) secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x10 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]). | 21 |
| Dose Group 2 Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x1.0 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]). | 8 |
| Dose Group 3 Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x0.1 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]). | 7 |
| Secukinumab/Placebo Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received placebo in the core study (CAIN457A2209 \[NCT00809159\]). | 3 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative problems | 2 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | Patient withdrew consent | 1 | 1 | 0 | 0 |
| Overall Study | Serious Adverse Event | 2 | 1 | 0 | 0 |
| Overall Study | Unsatisfactory therapeutic effect | 2 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Dose Group 1 | Dose Group 2 | Dose Group 3 | Secukinumab/Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 39.5 Years STANDARD_DEVIATION 7.56 | 47.9 Years STANDARD_DEVIATION 11.27 | 45.9 Years STANDARD_DEVIATION 8.61 | 41.7 Years STANDARD_DEVIATION 11.59 | 42.5 Years STANDARD_DEVIATION 9.25 |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 18 Participants | 8 Participants | 6 Participants | 3 Participants | 35 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Female | 10 Participants | 4 Participants | 2 Participants | 0 Participants | 16 Participants |
| Sex: Female, Male Male | 11 Participants | 4 Participants | 5 Participants | 3 Participants | 23 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 | 0 / 21 | 0 / 8 | 0 / 7 | 0 / 3 |
| other Total, other adverse events | 18 / 21 | 6 / 8 | 6 / 7 | 3 / 3 |
| serious Total, serious adverse events | 4 / 21 | 1 / 8 | 0 / 7 | 0 / 3 |
Outcome results
Primary
Number of Participants Reported Adverse Events (AE's)
AEs are 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.
Time frame: From start of the study up to 64 weeks
Population: Safety analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Group 1 | Number of Participants Reported Adverse Events (AE's) | 21 Participants |
| Dose Group 2 | Number of Participants Reported Adverse Events (AE's) | 6 Participants |
| Dose Group 3 | Number of Participants Reported Adverse Events (AE's) | 6 Participants |
| Secukinumab/Placebo | Number of Participants Reported Adverse Events (AE's) | 3 Participants |
Secondary
Maximum (Peak) Observed in Serum at Steady-State (Cmax,ss)
Concentration of Secukinumab at the end of infusion (Cmax,ss) was reported.
Time frame: At end of infusion (Week 64)
Population: All completed participants with quantifiable pharmacokinetics (PK) measurements and no major protocol deviations with impact on PK data were included in the PK analysis set. Here, the number of participants analyzed refer to the participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Group 1 | Maximum (Peak) Observed in Serum at Steady-State (Cmax,ss) | 10.5 micrograms per milliliter (μg/mL) | Standard Deviation 3.03 |
| Dose Group 2 | Maximum (Peak) Observed in Serum at Steady-State (Cmax,ss) | 10.6 micrograms per milliliter (μg/mL) | Standard Deviation 3.82 |
| Dose Group 3 | Maximum (Peak) Observed in Serum at Steady-State (Cmax,ss) | 11.3 micrograms per milliliter (μg/mL) | Standard Deviation 4.81 |
| Secukinumab/Placebo | Maximum (Peak) Observed in Serum at Steady-State (Cmax,ss) | 17.1 micrograms per milliliter (μg/mL) | Standard Deviation 10.9 |
Secondary
Minimum (Trough) Observed in Serum at Steady State (Cmin,ss)
The concentration of secukinumab at pre-dose (Cmin,ss) in serum was reported.
Time frame: Pre-dose (Week 0)
Population: All completed participants with quantifiable pharmacokinetics (PK) measurements and no major protocol deviations with impact on PK data were included in the PK analysis set. Here, the number of participants analyzed refer to the participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Group 1 | Minimum (Trough) Observed in Serum at Steady State (Cmin,ss) | 4.73 micrograms per milliliter (μg/mL) | Standard Deviation 10.1 |
| Dose Group 2 | Minimum (Trough) Observed in Serum at Steady State (Cmin,ss) | 15.0 micrograms per milliliter (μg/mL) | Standard Deviation 38.4 |
| Dose Group 3 | Minimum (Trough) Observed in Serum at Steady State (Cmin,ss) | 0.0428 micrograms per milliliter (μg/mL) | Standard Deviation 0.0586 |
| Secukinumab/Placebo | Minimum (Trough) Observed in Serum at Steady State (Cmin,ss) | 27.1 micrograms per milliliter (μg/mL) | Standard Deviation 46.9 |
Secondary
Number of Participants Reported Positive Antibodies for Secukinumab
Immunogenicity (anti-drug antibodies) was assessed using an MSD bridging assay and a 3-tiered approach (screening, confirmation, titration).
Time frame: Pre-dose, Week 0, 8, 24, 40 and Week 64
Population: Safety analysis set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Group 1 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 40 | 0 Participants |
| Dose Group 1 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 8 | 0 Participants |
| Dose Group 1 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 64 | 0 Participants |
| Dose Group 1 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 24 | 0 Participants |
| Dose Group 1 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 0 | 0 Participants |
| Dose Group 2 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 0 | 0 Participants |
| Dose Group 2 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 64 | 0 Participants |
| Dose Group 2 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 8 | 0 Participants |
| Dose Group 2 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 24 | 0 Participants |
| Dose Group 2 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 40 | 0 Participants |
| Dose Group 3 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 64 | 0 Participants |
| Dose Group 3 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 40 | 0 Participants |
| Dose Group 3 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 24 | 0 Participants |
| Dose Group 3 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 8 | 0 Participants |
| Dose Group 3 | Number of Participants Reported Positive Antibodies for Secukinumab | Week 0 | 0 Participants |
| Secukinumab/Placebo | Number of Participants Reported Positive Antibodies for Secukinumab | Week 64 | 0 Participants |
| Secukinumab/Placebo | Number of Participants Reported Positive Antibodies for Secukinumab | Week 0 | 0 Participants |
| Secukinumab/Placebo | Number of Participants Reported Positive Antibodies for Secukinumab | Week 8 | 0 Participants |
| Secukinumab/Placebo | Number of Participants Reported Positive Antibodies for Secukinumab | Week 40 | 0 Participants |
| Secukinumab/Placebo | Number of Participants Reported Positive Antibodies for Secukinumab | Week 24 | 0 Participants |
Secondary
Total Interleukin (IL)- 17A Concentration in Blood at Steady-State
Total serum IL17A was not measured due to assay limitations.
Time frame: Pre-dose and at the end of infusion (up to 64 weeks)
Population: IL-17A measurements were planned for this study but could not be measured because the assay for total IL-17A, samples was not robust.