Efficacy of AIN457 in Adults (18-65 Years) With Psoriatic Arthritis

Randomized, Double-blind Placebo-controlled Multi-center Proof-of-concept Study to Assess the Efficacy of AIN457 in Patients With Psoriatic Arthritis

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00809614

Enrollment

Registered

2008-12-17

Start date

2009-03-31

Completion date

2010-12-31

Last updated

2015-11-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Psoriatic Arthritis

Keywords

Psoriatic arthritis, IgG1K monoclonal antibody, Interleukin -17A neutralizing

Brief summary

This study is designed as a proof of concept of AIN457 in patients with psoriatic arthritis. The study will address the evaluation of the efficacy at 6 and up to 24 weeks after two doses of AIN457 10 mg/kg administered three weeks apart.

Interventions

BIOLOGICALAIN457

The investigational drug, AIN457 50 mg lyophilizate vials was prepared by Novartis. Reconstitution of AIN457 with 1.2 mL SWFI produced a 47 mg/mL concentrate solution for infusion from which at least 1 mL was useable. The AIN457 concentrate was diluted in 5% glucose bags for infusion through a 0.2 micron in-line filter.

BIOLOGICALPlacebo

Matching placebo to AIN457

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* A diagnosis of psoriatic arthritis

Exclusion criteria

* Patients with arthritis or ankylosing spondyitis * Drug-induced psoriasis * Male or female patients who plan to conceive during the time course of the study, or for 6 months after the administration of the second dose. * Participation in any clinical trial within 4 weeks prior to initial dosing or longer. * Previous use of immunosuppressive agents eg cyclosporine, without the necessary wash-out period * History of severe allergy to food or drugs * Positive TB test. Other protocol-defined inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Percentage of ACR Responders Per Treatment at Week 6	week 6	A participant was considered to be a responder according to the ACR20, 50 or 70 criteria if the participant had at least 20% 50% or 70% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)
Percentage of PsARC Responders Per Treatment at Week 6	week 6	Psoriatic Arthritis Response Criteria (PsARC) includes measures of tender and swollen joint counts, patient's assessment of pain, physician's and patient's global assessment of disease activity A subject is defined as a PsARC responder if, and only if, they have an improvement in two of the following four factors (with at least one factor being a joint count) and no worsening in the remaining factors: 1) Patient global assessment (0-100 VAS scale, improvement defined as decrease of at least 20 units) 2) Physician global assessment (0-100 VAS scale, improvement defined as decrease of at least 20 units) 3) Tender 78-joint count (improvement defined as decrease of at least 30%) 4) Swollen 76-joint count (improvement defined as decrease of at least 30%)

Secondary

Measure	Time frame	Description
Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Baseline and Day 8, 15 and weeks 6, 8, 12, 16 and 24	The MASES included assessments of 13 sites. Enthesitis sites included in the MASES index are: 1st costochondral, 7th costochondral, posterior superior iliac spine, anterior superior iliac spine, iliac crest (all above was assessed bilaterally), 5th lumbar spinous process, proximal Achilles (bilateral). The MASES score is defined as the total number of painful MASES entheses. The score was derived as the sum of the 13 scores divided by 3 and the total range is 0 (no tenderness) to 13 (severe tenderness).
Psoriatic Area and Severity Index (PASI) Score in Patients Over Time Per Treatment	Baseline, Day 8, 15 and weeks 6, 8, 12, 16, 20 and 24	The PASI assessed the extent of psoriasis on four body surface areas (head, trunk and upper and lower limbs) and the degree of plaque erythema, scaling and thickness. The PASI score accounted for the extent of body surface area affected by the erythema, scaling and thickness, and the severity of these measures. The score ranged from 0 (no disease) to 72 (maximal disease).
SpA Research Consortium of Canada (SPARCC) Score Score in Patients Over Time Per Treatment	Baseline, Day 8, 15 and weeks 6, 8, 12, 16 and 24	SPARCC evaluated 18 enthesis sites: medial and lateral epicondyle humerus, supraspinatus insertion, proximal Achilles, greater trochanter, medial and lateral condyl femur, insertion of plantar fascia, quadriceps insertion of patella, inferior pole of patella, and tibial tubercle. SPARCC enthesis index is defined as the total number of painful entheses assessed at the SPARCC sites. Total SI joint scores could range from 0 to 78, with a higher score indicating more signs of disease.
Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Baseline, Day 8, 15 and weeks 6, 8, 12, 16 and 24	The LDI basic measured the ratio of the circumference of the affected digit to the circumference of the digit on the opposite hand or foot, using a minimum difference of 10% to define a dactylitic digit. The ratio of circumference was multiplied by a tenderness score, using a modification of LDI which was a binary score (1 for tender, 0 for non-tender). If both sides were considered involved, the number was compared to data provided in a table. This modification was referred to as LDI basic and was applied in this study. The LDI required a tool to measure digital circumference and this tool was provided to the centers.
Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Baseline, day 8, 15 and weeks 6, 8, 12, 16 and 24	The Disease Activity Score (DAS) is a combined index to measure disease activity in arthritic patients. DAS28 is determined using the following variables: 28-joint counts (tender28 and swollen28), CRP, and the participant's general health (GH) Based on the patients global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (0 - 100). Using the data from these variables, DAS28 is calculated using the following formula: DAS28 = 0.56\sqrt(TJC28) + 0.28\sqrt(SJC28) + 0.36\ln(CRP+1) + 0.014\GH + 0.96. The calculation results in a DAS28 score from 0 to 10 indicating the current activity of the rheumatoid arthritis of the patient. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6.
Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Day 8 and 15, Weeks 6, 8, 12, 16 and 24	A participant was considered to be a responder according to the ACR20, 50 or 70 criteria if the participant had at least 20% 50% or 70% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)
Pharmacokinetic (PK) of AIN457: Clearance of AIN457 After Single Dose Administration	Day 1 till end of the study (169)	On dosing days (Day 1 and Day 22) samples were taken at pre-dose (0 h), 2, 3, 4, 24. After the first infusion samples were taken at Day 8 and Day 15. After the second infusion samples were taken at Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 141, Day 169.
Pharmacokinetic (PK) of AIN457: Terminal Elimination Half-life (T1/2)	Day 1 till end of the study (169)	On dosing days (Day 1 and Day 22) samples were taken at pre-dose (0 h), 2, 3, 4, 24. After the first infusion samples were taken at Day 8 and Day 15. After the second infusion samples were taken at Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 141, Day 169.
Pharmacokinetic (PK) of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax)	Day 1 till end of the study (169)	On dosing days (Day 1 and Day 22) samples were taken at pre-dose (0 h), 2, 3, 4, 24. After the first infusion samples were taken at Day 8 and Day 15. After the second infusion samples were taken at Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 141, Day 169.
PK of AIN457: Area Under the Serum Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf)	Day 1 till end of the study (169)	On dosing days (Day 1 and Day 22) samples were taken at pre-dose (0 h), 2, 3, 4, 24. After the first infusion samples were taken at Day 8 and Day 15. After the second infusion samples were taken at Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 141, Day 169.
Pharmacokinetic (PK) of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz)	Day 1 till end of the study (169)	On dosing days (Day 1 and Day 22) samples were taken at pre-dose (0 h), 2, 3, 4, 24. After the first infusion samples were taken at Day 8 and Day 15. After the second infusion samples were taken at Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 141, Day 169.
Pharmacokinetic (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax)	Day 1 till end of the study (169)	On dosing days (Day 1 and Day 22) samples were taken at pre-dose (0 h), 2, 3, 4, 24. After the first infusion samples were taken at Day 8 and Day 15. After the second infusion samples were taken at Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 141, Day 169.
Percentage of Participants Who Achieved PsARC Response	Day 8 and 15, Weeks 6, 8, 12, 16 and 24	responder defined as 20% or more improvement in at least 4 of 6 criteria: 1) swollen joint count, 2) tender joint count, 3) morning stiffness duration (low back), 4) current low back pain, 5) current peripheral joint pain, 6) patient global assessment A subject is defined as a PsARC responder if, and only if, they have an improvement in two of the following four factors (with at least one factor being a joint count) and no worsening in the remaining factors: 1) Patient global assessment (0-100 VAS scale, improvement defined as decrease of at least 20 units) 2) Physician global assessment (0-100 VAS scale, improvement defined as decrease of at least 20 units) 3) Tender 78-joint count (improvement defined as decrease of at least 30%) 4) Swollen 76-joint count (improvement defined as decrease of at least 30%)

Countries

Germany, Netherlands, United Kingdom

Participant flow

Recruitment details

A total of 42 patients were planned and recruited. The patients were randomized to either AIN457 2x10 mg/kg or placebo in a ratio of 2:1. The total sample size of 42 included an additional 3 subjects to allow for drop-outs and/or incomplete data.

Participants by arm

Arm	Count
AIN457 (2x 10mg/kg) Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.	28
Placebo Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.	14
Total	42

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lack of Efficacy	2	3
Overall Study	Withdrawal by Subject	1	1

Baseline characteristics

Characteristic	AIN457 (2x 10mg/kg)	Placebo	Total
Age, Continuous	46.7 Years STANDARD_DEVIATION 11.3	47.6 Years STANDARD_DEVIATION 8.1	47.0 Years STANDARD_DEVIATION 10.2
Sex: Female, Male Female	19 Participants	8 Participants	27 Participants
Sex: Female, Male Male	9 Participants	6 Participants	15 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	23 / 28	11 / 14
serious Total, serious adverse events	4 / 28	1 / 14

Outcome results

Primary

Percentage of ACR Responders Per Treatment at Week 6

A participant was considered to be a responder according to the ACR20, 50 or 70 criteria if the participant had at least 20% 50% or 70% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)

Time frame: week 6

Population: For pharmacodynamic (PD) analysis set five patients were excluded due to protocol deviations.

Arm	Measure	Group	Value (NUMBER)
AIN457 (2x 10mg/kg)	Percentage of ACR Responders Per Treatment at Week 6	ACR20 responders	39 Percentage of ACR responders
AIN457 (2x 10mg/kg)	Percentage of ACR Responders Per Treatment at Week 6	ACR50 responders	17 Percentage of ACR responders
AIN457 (2x 10mg/kg)	Percentage of ACR Responders Per Treatment at Week 6	ACR70 responders	9 Percentage of ACR responders
Placebo	Percentage of ACR Responders Per Treatment at Week 6	ACR20 responders	23 Percentage of ACR responders
Placebo	Percentage of ACR Responders Per Treatment at Week 6	ACR50 responders	8 Percentage of ACR responders
Placebo	Percentage of ACR Responders Per Treatment at Week 6	ACR70 responders	0 Percentage of ACR responders

Primary

Percentage of PsARC Responders Per Treatment at Week 6

Psoriatic Arthritis Response Criteria (PsARC) includes measures of tender and swollen joint counts, patient's assessment of pain, physician's and patient's global assessment of disease activity A subject is defined as a PsARC responder if, and only if, they have an improvement in two of the following four factors (with at least one factor being a joint count) and no worsening in the remaining factors: 1) Patient global assessment (0-100 VAS scale, improvement defined as decrease of at least 20 units) 2) Physician global assessment (0-100 VAS scale, improvement defined as decrease of at least 20 units) 3) Tender 78-joint count (improvement defined as decrease of at least 30%) 4) Swollen 76-joint count (improvement defined as decrease of at least 30%)

Time frame: week 6

Population: For pharmacodynamic (PD) analysis set five patients were excluded due to protocol deviations.

Arm	Measure	Value (NUMBER)
AIN457 (2x 10mg/kg)	Percentage of PsARC Responders Per Treatment at Week 6	43 Percentage of PsARC responders
Placebo	Percentage of PsARC Responders Per Treatment at Week 6	38 Percentage of PsARC responders

Secondary

Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment

The Disease Activity Score (DAS) is a combined index to measure disease activity in arthritic patients. DAS28 is determined using the following variables: 28-joint counts (tender28 and swollen28), CRP, and the participant's general health (GH) Based on the patients global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (0 - 100). Using the data from these variables, DAS28 is calculated using the following formula: DAS28 = 0.56\*sqrt(TJC28) + 0.28\*sqrt(SJC28) + 0.36\*ln(CRP+1) + 0.014\*GH + 0.96. The calculation results in a DAS28 score from 0 to 10 indicating the current activity of the rheumatoid arthritis of the patient. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6.

Time frame: Baseline, day 8, 15 and weeks 6, 8, 12, 16 and 24

Population: For pharmacodynamic (PD) analysis set five patients were excluded due to protocol deviations

Arm	Measure	Group	Value (MEAN)	Dispersion
AIN457 (2x 10mg/kg)	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Baseline (n=24,13)	4.84 Units on a scale	Standard Deviation 1.21
AIN457 (2x 10mg/kg)	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Week 6 (n=28,12)	3.94 Units on a scale	Standard Deviation 1.47
AIN457 (2x 10mg/kg)	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Week 12 (n=23,11)	3.62 Units on a scale	Standard Deviation 1.42
AIN457 (2x 10mg/kg)	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Week 24 (n=23,11)	3.84 Units on a scale	Standard Deviation 1.3
AIN457 (2x 10mg/kg)	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Day 8 (22,12)	4.19 Units on a scale	Standard Deviation 1.27
AIN457 (2x 10mg/kg)	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Day 15 (24,13)	4.09 Units on a scale	Standard Deviation 1.26
AIN457 (2x 10mg/kg)	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Week 8 (n=22,10)	3.66 Units on a scale	Standard Deviation 1.65
AIN457 (2x 10mg/kg)	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Week 16 (n=18,9)	3.54 Units on a scale	Standard Deviation 1.48
Placebo	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Week 16 (n=18,9)	3.83 Units on a scale	Standard Deviation 1.58
Placebo	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Baseline (n=24,13)	4.76 Units on a scale	Standard Deviation 1.19
Placebo	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Day 8 (22,12)	4.43 Units on a scale	Standard Deviation 1.27
Placebo	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Week 6 (n=28,12)	4.20 Units on a scale	Standard Deviation 1.2
Placebo	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Week 8 (n=22,10)	4.64 Units on a scale	Standard Deviation 1.22
Placebo	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Week 12 (n=23,11)	4.36 Units on a scale	Standard Deviation 1.41
Placebo	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Day 15 (24,13)	4.35 Units on a scale	Standard Deviation 1.05
Placebo	Disease Activity Score 28 (DA28) in Patients Over Time Per Treatment	Week 24 (n=23,11)	4.28 Units on a scale	Standard Deviation 1.4

Secondary

Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment

The LDI basic measured the ratio of the circumference of the affected digit to the circumference of the digit on the opposite hand or foot, using a minimum difference of 10% to define a dactylitic digit. The ratio of circumference was multiplied by a tenderness score, using a modification of LDI which was a binary score (1 for tender, 0 for non-tender). If both sides were considered involved, the number was compared to data provided in a table. This modification was referred to as LDI basic and was applied in this study. The LDI required a tool to measure digital circumference and this tool was provided to the centers.

Time frame: Baseline, Day 8, 15 and weeks 6, 8, 12, 16 and 24

Population: Only participants from the pharmacodynamic (PD) analysis set, who had available scores at each given time point, were analyzed for that time point. The PD analysis set included all patients with evaluable PD data with no protocol deviations that impacted PD data analysis.

Arm	Measure	Group	Value (MEAN)	Dispersion
AIN457 (2x 10mg/kg)	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Week 12 (n=3,6)	2.52 total score	Standard Deviation 1.57
AIN457 (2x 10mg/kg)	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Week 8 (n=3,5)	2.96 total score	Standard Deviation 1.03
AIN457 (2x 10mg/kg)	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Day 8 (n=5,5)	2.65 total score	Standard Deviation 1.6
AIN457 (2x 10mg/kg)	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Week 16 (n=3,4)	2.65 total score	Standard Deviation 1.82
AIN457 (2x 10mg/kg)	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Week 24 (n=2,6)	3.08 total score	Standard Deviation 1.54
AIN457 (2x 10mg/kg)	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Day 15 (n=4,5)	2.67 total score	Standard Deviation 2.61
AIN457 (2x 10mg/kg)	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Week 6 (n=4,5)	2.92 total score	Standard Deviation 2.37
AIN457 (2x 10mg/kg)	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Baseline (n=6,5)	2.74 total score	Standard Deviation 2.32
Placebo	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Week 6 (n=4,5)	2.14 total score	Standard Deviation 2.56
Placebo	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Week 12 (n=3,6)	0.73 total score	Standard Deviation 0.58
Placebo	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Week 24 (n=2,6)	1.88 total score	Standard Deviation 2.19
Placebo	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Day 8 (n=5,5)	1.32 total score	Standard Deviation 0.94
Placebo	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Day 15 (n=4,5)	1.72 total score	Standard Deviation 2.25
Placebo	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Week 8 (n=3,5)	1.54 total score	Standard Deviation 2.35
Placebo	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Week 16 (n=3,4)	2.08 total score	Standard Deviation 2.4
Placebo	Leeds Dactylitis Instrument (LDI) Score in Patients Over Time Per Treatment	Baseline (n=6,5)	1.56 total score	Standard Deviation 2.35

Secondary

Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment

The MASES included assessments of 13 sites. Enthesitis sites included in the MASES index are: 1st costochondral, 7th costochondral, posterior superior iliac spine, anterior superior iliac spine, iliac crest (all above was assessed bilaterally), 5th lumbar spinous process, proximal Achilles (bilateral). The MASES score is defined as the total number of painful MASES entheses. The score was derived as the sum of the 13 scores divided by 3 and the total range is 0 (no tenderness) to 13 (severe tenderness).

Time frame: Baseline and Day 8, 15 and weeks 6, 8, 12, 16 and 24

Population: For pharmacodynamic (PD) analysis set five patients were excluded due to protocol deviations

Arm	Measure	Group	Value (MEAN)	Dispersion
AIN457 (2x 10mg/kg)	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Baseline (n=24,13)	3.0 Units on a scale	Standard Deviation 4.12
AIN457 (2x 10mg/kg)	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Day 8 (n=23,13)	2.6 Units on a scale	Standard Deviation 4.3
AIN457 (2x 10mg/kg)	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Day 15 (24,13)	2.9 Units on a scale	Standard Deviation 4.81
AIN457 (2x 10mg/kg)	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Week 6 (n=23,11)	2.6 Units on a scale	Standard Deviation 4.68
AIN457 (2x 10mg/kg)	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Week 8 (n=22,11)	2.7 Units on a scale	Standard Deviation 4.14
AIN457 (2x 10mg/kg)	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Week 12 (n=20,11)	2.4 Units on a scale	Standard Deviation 4.06
AIN457 (2x 10mg/kg)	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Week 16 (n=19,9)	2.6 Units on a scale	Standard Deviation 4.78
AIN457 (2x 10mg/kg)	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Week 24 (n=23,11)	1.6 Units on a scale	Standard Deviation 3.88
Placebo	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Week 24 (n=23,11)	2.7 Units on a scale	Standard Deviation 3.32
Placebo	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Baseline (n=24,13)	3.4 Units on a scale	Standard Deviation 2.33
Placebo	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Week 8 (n=22,11)	2.6 Units on a scale	Standard Deviation 3.32
Placebo	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Day 8 (n=23,13)	2.7 Units on a scale	Standard Deviation 2.59
Placebo	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Week 16 (n=19,9)	2.0 Units on a scale	Standard Deviation 2.4
Placebo	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Day 15 (24,13)	2.8 Units on a scale	Standard Deviation 3.42
Placebo	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Week 12 (n=20,11)	2.5 Units on a scale	Standard Deviation 2.62
Placebo	Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment	Week 6 (n=23,11)	2.8 Units on a scale	Standard Deviation 3.34

Secondary

Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria

Time frame: Day 8 and 15, Weeks 6, 8, 12, 16 and 24

Population: For pharmacodynamic (PD) analysis set five patients were excluded due to protocoldeviations.

Arm	Measure	Group	Value (NUMBER)
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Day 8 ACR20 responders	17 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Day 8 ACR50 responders	0 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Day 8 ACR70 responders	0 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Day 15 ACR20 responders	25 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Day 15 ACR50 responders	13 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Day 15 ACR70 responders	0 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 6 ACR20 responders	39 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 6 ACR50 responders	17 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 6 ACR70 responders	9 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 8 ACR20 responders	42 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 8 ACR50 responders	29 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 8 ACR70 responders	17 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 12 ACR20 responders	39 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 12 ACR50 responders	22 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 12 ACR70 responders	9 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 16 ACR20 responders	41 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 16 ACR50 responders	27 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 16 ACR70 responders	18 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 24 ACR20 responders	43 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 24 ACR50 responders	17 Percentage of particpants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 24 ACR70 responders	13 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 8 ACR50 responders	8 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Day 8 ACR20 responders	8 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 24 ACR20 responders	18 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Day 8 ACR50 responders	0 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 8 ACR70 responders	0 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Day 8 ACR70 responders	0 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 16 ACR50 responders	18 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Day 15 ACR20 responders	17 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 12 ACR20 responders	15 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Day 15 ACR50 responders	0 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 24 ACR70 responders	9 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Day 15 ACR70 responders	0 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 12 ACR50 responders	8 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 6 ACR20 responders	23 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 16 ACR70 responders	9 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 6 ACR50 responders	8 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 12 ACR70 responders	8 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 6 ACR70 responders	0 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 24 ACR50 responders	9 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 8 ACR20 responders	23 Percentage of particpants
Placebo	Percentage of Participants Who Achieved 20%, 50% or 70% Improvement as Measured by ACR Response Criteria	Week 16 ACR20 responders	27 Percentage of particpants

Secondary

Percentage of Participants Who Achieved PsARC Response

responder defined as 20% or more improvement in at least 4 of 6 criteria: 1) swollen joint count, 2) tender joint count, 3) morning stiffness duration (low back), 4) current low back pain, 5) current peripheral joint pain, 6) patient global assessment A subject is defined as a PsARC responder if, and only if, they have an improvement in two of the following four factors (with at least one factor being a joint count) and no worsening in the remaining factors: 1) Patient global assessment (0-100 VAS scale, improvement defined as decrease of at least 20 units) 2) Physician global assessment (0-100 VAS scale, improvement defined as decrease of at least 20 units) 3) Tender 78-joint count (improvement defined as decrease of at least 30%) 4) Swollen 76-joint count (improvement defined as decrease of at least 30%)

Time frame: Day 8 and 15, Weeks 6, 8, 12, 16 and 24

Population: For pharmacodynamic (PD) analysis set five patients were excluded due to protocol deviations.

Arm	Measure	Group	Value (NUMBER)
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved PsARC Response	Week 6	43 Percentage of participants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved PsARC Response	Week 12	52 Percentage of participants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved PsARC Response	Day 15	33 Percentage of participants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved PsARC Response	Week 16	55 Percentage of participants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved PsARC Response	Week 8	52 Percentage of participants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved PsARC Response	Week 24	50 Percentage of participants
AIN457 (2x 10mg/kg)	Percentage of Participants Who Achieved PsARC Response	Day 8	27 Percentage of participants
Placebo	Percentage of Participants Who Achieved PsARC Response	Week 24	36 Percentage of participants
Placebo	Percentage of Participants Who Achieved PsARC Response	Day 8	23 Percentage of participants
Placebo	Percentage of Participants Who Achieved PsARC Response	Day 15	15 Percentage of participants
Placebo	Percentage of Participants Who Achieved PsARC Response	Week 6	38 Percentage of participants
Placebo	Percentage of Participants Who Achieved PsARC Response	Week 8	38 Percentage of participants
Placebo	Percentage of Participants Who Achieved PsARC Response	Week 12	15 Percentage of participants
Placebo	Percentage of Participants Who Achieved PsARC Response	Week 16	36 Percentage of participants

Secondary

Pharmacokinetic (PK) of AIN457: Clearance of AIN457 After Single Dose Administration

On dosing days (Day 1 and Day 22) samples were taken at pre-dose (0 h), 2, 3, 4, 24. After the first infusion samples were taken at Day 8 and Day 15. After the second infusion samples were taken at Day 29, Day 43, Day 57, Day 71, Day 85, Day 113, Day 141, Day 169.