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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00809614
First received: December 16, 2008
Last updated: October 14, 2015
Last verified: October 2015
  Purpose
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.

Condition Intervention Phase
Psoriatic Arthritis
Biological: AIN457
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Double-blind Placebo-controlled Multi-center Proof-of-concept Study to Assess the Efficacy of AIN457 in Patients With Psoriatic Arthritis

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of ACR Responders Per Treatment at Week 6 [ Time Frame: week 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: week 6 ] [ Designated as safety issue: No ]

    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 Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 Participants Who Achieved PsARC Response [ Time Frame: Day 8 and 15, Weeks 6, 8, 12, 16 and 24 ] [ Designated as safety issue: No ]
    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%)

  • Mastricht Ankylosing Spondylitis Enthesis Score (MASES) Over Time Per Treatment [ Time Frame: Baseline and Day 8, 15 and weeks 6, 8, 12, 16 and 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Day 8, 15 and weeks 6, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Day 8, 15 and weeks 6, 8, 12, 16 and 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Day 8, 15 and weeks 6, 8, 12, 16 and 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, day 8, 15 and weeks 6, 8, 12, 16 and 24 ] [ Designated as safety issue: No ]
    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.

  • Pharmacokinetic (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) [ Time Frame: Day 1 till end of the study (169) ] [ Designated as safety issue: No ]
    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: Clearance of AIN457 After Single Dose Administration [ Time Frame: Day 1 till end of the study (169) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1 till end of the study (169) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1 till end of the study (169) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1 till end of the study (169) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1 till end of the study (169) ] [ Designated as safety issue: No ]
    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.


Enrollment: 42
Study Start Date: March 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AIN457 (2x 10mg/kg)
Each patient received 10 mg/kg AIN457 intravenously, on Day 1 and Day 22.
Biological: AIN457
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.
Placebo Comparator: Placebo
Each patient received 10 mg/kg of matching placebo intravenously, on Day 1 and Day 22.
Biological: Placebo
Matching placebo to AIN457

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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/exclusion criteria may apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00809614

Locations
Germany
Novartis Investigative Site
Berlin, Germany, 12203
Novartis Investigative Site
Hamburg, Germany, 22081
Novartis Investigative Site
Hamburg, Germany, 22415
Novartis Investigative Site
Herne, Germany, 44649
Novartis Investigative Site
Muenchen, Germany, 80336
Netherlands
Novartis Investigative Site
Amsterdamn, DE, Netherlands, 1100
Novartis Investigative Site
Meerssen, KR, Netherlands, 6231
United Kingdom
Novartis Investigative Site
Glasgow, United Kingdom, G12 8TA
Novartis Investigative Site
Leeds, United Kingdom, LS7 4SA
Novartis Investigative Site
Newcastle upon Tyne, United Kingdom, NE2 4HH
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Principal Investigator: Novartis Novartis Investigator Site
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00809614     History of Changes
Other Study ID Numbers: CAIN457A2206 
Study First Received: December 16, 2008
Results First Received: February 1, 2015
Last Updated: October 14, 2015
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Novartis:
Psoriatic arthritis
IgG1K monoclonal antibody
Interleukin -17A neutralizing

Additional relevant MeSH terms:
Arthritis
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases

ClinicalTrials.gov processed this record on July 25, 2016