Safety and Tolerability of AIN457 in Adults (18-65 Years) With Psoriatic Arthritis

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01169844
• Collaborator: (none)
• Enrollment: 28
• Locations: 6
• Arms: 2
• Duration (Months): 29
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Psoriatic Arthritis	Biological: AIN457A; Other: Other	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Non-randomized Extension Study to Evaluate the Safety and Tolerability of AIN457 (Anti Interleukin-17 Monoclonal Antibody) in Patients With Psoriatic Arthritis
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: AIN457A
Placebo Comparator: 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.	Biological: AIN457A; Other: Other

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Total IL-17 Concentration in Blood at Steady-state [Up to 64 weeks]

   Total IL-17 concentration was not reported due to assay limitations.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Hamburg		Germany	22415
2	Novartis Investigative Site	Amsterdam	DE	Netherlands	1100
3	Novartis Investigative Site	Meerssen	KR	Netherlands	6231
4	Novartis Investigative Site	Glasgow		United Kingdom	G12 8TA
5	Novartis Investigative Site	Leeds		United Kingdom	LS7 4SA
6	Novartis Investigative Site	Newcastle upon Tyne		United Kingdom	NE2 4HH

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01169844
• Other Study ID Numbers: CAIN457A2206E1
• First Posted: Jul 26, 2010
• Last Update Posted: Jun 10, 2021
• Last Verified: May 1, 2021

• Keywords provided by Novartis Pharmaceuticals: Psoriatic arthritis; IgG1K monoclonal antibody; Interleukin -17A neutralizing
• Additional relevant MeSH terms: Arthritis; Arthritis, Psoriatic

Study Results

Participant Flow

Pre-assignment Detail	A total of 42 patients were randomized in the (CAIN457A2206) core study, of which 28 patients enrolled into the (CAIN457A2206E1) extension study.

Arm/Group Title	AIN457/AIN457 3 mg/kg.	Placebo/AIN457 3 mg/kg
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	19	9
COMPLETED	14	8
NOT COMPLETED	5	1

Baseline Characteristics

Arm/Group Title	AIN457/AIN457 3 mg/kg	Placebo/AIN457 3 mg/kg	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	19	9	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.6 (10.96)	47.9 (6.81)	46.3 (9.75)
Sex: Female, Male (Count of Participants)
Female	12 63.2%	5 55.6%	17 60.7%
Male	7 36.8%	4 44.4%	11 39.3%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	19 100%	8 88.9%	27 96.4%
Other	0 0%	1 11.1%	1 3.6%
Race/Ethnicity, Customized (Count of Participants)
Other	19 100%	8 88.9%	27 96.4%
Hispanic/Latino	0 0%	1 11.1%	1 3.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events and Serious Adverse Events
Description	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)

Outcome Measure Data

Analysis Population Description

The safety population consisted of all randomized patients who received at least one dose of the study drug.

Arm/Group Title	AIN457/AIN457 3 mg/kg	Placebo/AIN457 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	19	9
Serious Adverse Events	5 26.3%	2 22.2%
Death	0 0%	0 0%

2. Secondary Outcome

Title	Total IL-17 Concentration in Blood at Steady-state
Description	Total IL-17 concentration was not reported due to assay limitations.
Time Frame	Up to 64 weeks

Outcome Measure Data

Analysis Population Description

No participants were evaluated as IL-17 concentration was not reported due to assay limitations

Arm/Group Title	AIN457/AIN457 3 mg/kg	Placebo/AIN457 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	0	0

3. Secondary Outcome

Title	Mean Serum Concentration Measured at Steady State
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	AIN457/AIN457 3 mg/kg	Placebo/AIN457 3 mg/kg
Arm/Group Description	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.	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.
Measure Participants	19	9
0/pre-inf	2.76 (4.73)	0.00 (0.00)
0/post-inf	80.0 (17.7)	68.8 (19.1)
8/pre-inf	29.6 (10.3)	19.5 (7.68)
8 /post-inf	99.7 (22.1)	88.9 (25.5)
16/pre-inf	32.9 (12.1)	23.3 (10.3)
16/post-inf	110 (25.3)	82.9 (24.7)
20/pre-inf	31.3 (9.00)	25.4 (13.0)
20/post-inf	111 (29.9)	85.5 (19.9)
24/pre-inf	37.2 (11.9)	25.5 (11.6)
24/post-inf	109 (24.5)	89.1 (23.2)
28/pre-inf	37.4 (10.2)	22.1 (9.45)
28/post-inf	122 (20.2)	96.9 (18.5)
32/pre-inf	37.4 (13.0)	26.7 (8.05)
32/post-inf	112 (15.1)	92.8 (23.2)
36/pre-inf	33.4 (9.49)	27.3 (7.06)
36/post-inf	109 (24.4)	88.9 (13.9)
40/pre-inf	46.4 (28.2)	28.7 (9.00)
40/post-inf	84.8 (30.5)	105 (24.9)
56	33.8 (8.93)	31.6 (7.62)
64	11.0 (3.46)	10.3 (8.31)

Adverse Events

Time Frame	Adverse events were collected from first dose of study treatment until end of study treatment (Week 52), and continued up to Week 64
Arm/Group Title	AIN457/AIN457 3 mg/kg		Placebo/AIN457 3 mg/kg
Arm/Group Description	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.		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.
All Cause Mortality
	AIN457/AIN457 3 mg/kg		Placebo/AIN457 3 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/9 (0%)
Serious Adverse Events
	AIN457/AIN457 3 mg/kg		Placebo/AIN457 3 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/19 (26.3%)		2/9 (22.2%)
Cardiac disorders
Myocardial infarction	0/19 (0%)		1/9 (11.1%)
Infections and infestations
Viral sinusitis	1/19 (5.3%)		0/9 (0%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/19 (5.3%)		0/9 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/19 (5.3%)		0/9 (0%)
Bursitis	1/19 (5.3%)		0/9 (0%)
Osteoarthritis	2/19 (10.5%)		0/9 (0%)
Nervous system disorders
Sciatica	0/19 (0%)		1/9 (11.1%)
Other (Not Including Serious) Adverse Events
	AIN457/AIN457 3 mg/kg		Placebo/AIN457 3 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/19 (100%)		9/9 (100%)
Blood and lymphatic system disorders
Anaemia	1/19 (5.3%)		0/9 (0%)
Leukopenia	1/19 (5.3%)		0/9 (0%)
Cardiac disorders
Palpitations	1/19 (5.3%)		0/9 (0%)
Ear and labyrinth disorders
Ear pain	1/19 (5.3%)		0/9 (0%)
Sudden hearing loss	1/19 (5.3%)		0/9 (0%)
Eye disorders
Dry eye	1/19 (5.3%)		0/9 (0%)
Eye pruritus	1/19 (5.3%)		0/9 (0%)
Vision blurred	1/19 (5.3%)		0/9 (0%)
Gastrointestinal disorders
Abdominal pain	1/19 (5.3%)		0/9 (0%)
Abdominal pain upper	2/19 (10.5%)		0/9 (0%)
Anal fissure	1/19 (5.3%)		0/9 (0%)
Change of bowel habit	1/19 (5.3%)		0/9 (0%)
Diarrhoea	1/19 (5.3%)		1/9 (11.1%)
Gastrooesophageal reflux disease	0/19 (0%)		1/9 (11.1%)
Mouth ulceration	1/19 (5.3%)		1/9 (11.1%)
Nausea	1/19 (5.3%)		1/9 (11.1%)
Toothache	0/19 (0%)		1/9 (11.1%)
Vomiting	2/19 (10.5%)		0/9 (0%)
General disorders
Chills	1/19 (5.3%)		0/9 (0%)
Fatigue	1/19 (5.3%)		0/9 (0%)
Inflammation	0/19 (0%)		1/9 (11.1%)
Local swelling	1/19 (5.3%)		0/9 (0%)
Malaise	1/19 (5.3%)		0/9 (0%)
Non-cardiac chest pain	1/19 (5.3%)		0/9 (0%)
Oedema peripheral	1/19 (5.3%)		0/9 (0%)
Pyrexia	1/19 (5.3%)		1/9 (11.1%)
Thirst	1/19 (5.3%)		0/9 (0%)
Immune system disorders
Hypersensitivity	0/19 (0%)		1/9 (11.1%)
Infections and infestations
Bronchitis	1/19 (5.3%)		0/9 (0%)
Device related infection	0/19 (0%)		1/9 (11.1%)
Gastroenteritis	1/19 (5.3%)		0/9 (0%)
Influenza	0/19 (0%)		3/9 (33.3%)
Laryngitis	1/19 (5.3%)		0/9 (0%)
Lower respiratory tract infection	1/19 (5.3%)		0/9 (0%)
Nasopharyngitis	7/19 (36.8%)		4/9 (44.4%)
Onychomycosis	0/19 (0%)		1/9 (11.1%)
Respiratory tract infection	1/19 (5.3%)		0/9 (0%)
Rhinitis	1/19 (5.3%)		0/9 (0%)
Tooth abscess	1/19 (5.3%)		1/9 (11.1%)
Tooth infection	2/19 (10.5%)		0/9 (0%)
Upper respiratory tract infection	2/19 (10.5%)		0/9 (0%)
Urinary tract infection	1/19 (5.3%)		0/9 (0%)
Injury, poisoning and procedural complications
Contusion	1/19 (5.3%)		0/9 (0%)
Fall	2/19 (10.5%)		0/9 (0%)
Infusion related reaction	1/19 (5.3%)		0/9 (0%)
Laceration	1/19 (5.3%)		0/9 (0%)
Procedural pain	0/19 (0%)		1/9 (11.1%)
Investigations
Blood immunoglobulin G increased	1/19 (5.3%)		0/9 (0%)
Blood pressure increased	1/19 (5.3%)		2/9 (22.2%)
Weight decreased	1/19 (5.3%)		0/9 (0%)
Metabolism and nutrition disorders
Gout	1/19 (5.3%)		0/9 (0%)
Hypercholesterolaemia	1/19 (5.3%)		0/9 (0%)
Overweight	0/19 (0%)		1/9 (11.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/19 (26.3%)		2/9 (22.2%)
Arthritis	3/19 (15.8%)		0/9 (0%)
Back pain	2/19 (10.5%)		2/9 (22.2%)
Bone pain	0/19 (0%)		1/9 (11.1%)
Joint swelling	2/19 (10.5%)		0/9 (0%)
Muscle tightness	1/19 (5.3%)		0/9 (0%)
Myalgia	2/19 (10.5%)		0/9 (0%)
Neck pain	1/19 (5.3%)		0/9 (0%)
Osteoarthritis	1/19 (5.3%)		0/9 (0%)
Pain in extremity	0/19 (0%)		1/9 (11.1%)
Pain in jaw	1/19 (5.3%)		0/9 (0%)
Psoriatic arthropathy	1/19 (5.3%)		0/9 (0%)
Spinal column stenosis	1/19 (5.3%)		0/9 (0%)
Nervous system disorders
Burning sensation	1/19 (5.3%)		0/9 (0%)
Dizziness	3/19 (15.8%)		1/9 (11.1%)
Headache	2/19 (10.5%)		1/9 (11.1%)
Lethargy	1/19 (5.3%)		0/9 (0%)
Paraesthesia	1/19 (5.3%)		0/9 (0%)
Sciatica	0/19 (0%)		1/9 (11.1%)
Renal and urinary disorders
Haematuria	0/19 (0%)		1/9 (11.1%)
Nephrolithiasis	1/19 (5.3%)		0/9 (0%)
Renal colic	0/19 (0%)		1/9 (11.1%)
Reproductive system and breast disorders
Epididymitis	1/19 (5.3%)		0/9 (0%)
Metrorrhagia	1/19 (5.3%)		0/9 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	3/19 (15.8%)		0/9 (0%)
Dry throat	0/19 (0%)		1/9 (11.1%)
Dyspnoea exertional	0/19 (0%)		1/9 (11.1%)
Oropharyngeal pain	5/19 (26.3%)		3/9 (33.3%)
Tonsillar hypertrophy	0/19 (0%)		1/9 (11.1%)
Skin and subcutaneous tissue disorders
Dry skin	1/19 (5.3%)		0/9 (0%)
Pruritus	3/19 (15.8%)		0/9 (0%)
Skin warm	1/19 (5.3%)		0/9 (0%)
Vascular disorders
Raynaud's phenomenon	1/19 (5.3%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.