Double Blind, Placebo Controlled Study to Assess Efficacy of AIN457 in Moderate to Severe Ankylosing Spondylitis
2015년 12월 7일 업데이트: Novartis Pharmaceuticals
Randomized, Placebo Controlled Double Blind, Multi-center Phase II Proof-of-concept Study to Assess the Efficacy of AIN457 in Patients With Moderate to Severe Ankylosing Spondylitis
Evaluate the safety, tolerability and pharmacokinetics of AIN457 when administered as treatment of moderate to severe ankylosing spondylitis (AS).
연구 개요
연구 유형
중재적
등록 (실제)
60
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Amstedam, 네덜란드, 22700
- Novartis Investigative Site
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Maastricht, 네덜란드, 5800
- Novartis Investigative Site
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Meerssen, KR, 네덜란드, 6231
- Novartis Investigative Site
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Berlin, 독일, 12200
- Novartis Investigative Site
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Hamburg, 독일, 22081
- Novartis Investigative Site
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Herne, 독일, 44649
- Novartis Investigative Site
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Munchen, 독일, D-80639
- Novartis Investigative Site
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Arizona
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Paradise Valley, Arizona, 미국, 85253
- Novartis Investigative Site
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Illinois
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Springfield, Illinois, 미국, 62704
- Novartis Investigative Site
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Springfield, Illinois, 미국, 62703
- Novartis Investigative Site
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Oklahoma
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Oklahoma City, Oklahoma, 미국, 73112
- Novartis Investigative Site
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Pennsylvania
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Duncansville, Pennsylvania, 미국, 16635
- Novartis Investigative Site
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South Carolina
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North Charleston, South Carolina, 미국, 29406
- Novartis Investigative Site
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Tennessee
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Jackson, Tennessee, 미국, 38305
- Novartis Investigative Site
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Knoxville, Tennessee, 미국, 37909
- Novartis Investigative Site
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Texas
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Benbrook, Texas, 미국, 76126
- Novartis Investigative Site
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Washington
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Spokane, Washington, 미국, 99204
- Novartis Investigative Site
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Leeds, 영국, LS7 4SA
- Novartis Investigative Site
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Newcastle upon Tyne, 영국, NE2 4HH
- Novartis Investigative Site
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Oxford, 영국, OX3 7LD
- Novartis Investigative Site
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- Patients with moderate to severe AS fulfilling the modified New York criteria for a diagnosis of AS and whose disease was not controlled on NSAIDS (on at least one NSAID over a period of at least 3 months at maximum dose). Minimum disease activity for inclusion of patients was assessed based on the ASAS core set domains: back pain & nocturnal pain score ≥ 4 despite concurrent NSAID use, PLUS a BASDAI score ≥ 4. Elevated CRP or ESR was not mandatory for study inclusion
- No evidence of liver disease or liver injury as indicated by abnormal liver function tests such as serum glutamic oxaloacetic transaminase (SGOT/AST), serum glutamic pyruvic transaminase (SGPT/ALT), gamma glutamyl transpeptidase (GGT), alkaline phosphatase, or serum bilirubin. The investigator was guided by criteria as outlined under exclusion criteria
Exclusion Criteria:
- For patients who were previously treated with TNF blockers, the following washout periods were required for these patients to be eligible to participate in the trial:
- month washout period prior to baseline for alefacept
- month washout period prior to baseline for adalimumab and certolizumab
- month washout prior to baseline for etanercept or infliximab
- For patients who were previously treated with immunosuppressive agents other than MTX, SSZ, and systemic corticosteroids, a 1-month washout period prior to baseline was required. Immunosuppressive agents included but were not limited to cyclosporine, mycophenolate, tacrolimus, and 5-aminosalicylic acid (5-ASA). Prednisone had to be kept at a stable dose 4 weeks before baseline and throughout the study and not to exceed 10 mg/day.
- MTX had to be kept at a stable dose 4 weeks before baseline and throughout the study and not to exceed 25 mg/week.
- SSZ had to be kept at a stable dose 4 weeks before baseline and throughout the study.
- In case of previous leflunomide treatment, a wash-out with oral cholestyramine could be considered as an alternative wash-out procedure to increase the elimination of leflunomide. Based on the notion that cholestyramine reduces plasma levels of the active leflunomide metabolite by approximately 40% in 24 hours and by 49% in 48 hours, cholestyramine was to be given orally at a dose of 8 g t.i.d. daily for 10 days. The patient could then be dosed with study drug not earlier than 2 weeks after the start of the cholestyramine wash-out procedure.
- Patients who were on NSAIDs had to be kept at a stable dose 4 weeks prior to baseline and throughout the study.
- Positive human immunodeficient virus (HIV: ELISA and Western blot) test result, Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. Any active systemic infection within the past 2 weeks including a positive chest X-ray.
- Current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, psychiatric, chronic inflammatory diseases with the exception of psoriatic arthritis or other disease which in the clinical judgment of the investigator would make the patient unsuitable for the trial
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 더블
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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위약 비교기: Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose
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Placebo to AIN457
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실험적: Parts 1 and 2 - AIN457A 1.0 mg/kg
AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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실험적: Part 1 and 2 - AIN457 0.1 mg/kg
AIN457A 0.1 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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실험적: Part 1 and 2 - AIN457 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
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AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Percentage of Participants Who Achieved ASAS20 Response
기간: 6 Weeks
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Clinical response to treatment was assessed according to ASAS20 criteria.
ASAS20 responder had improvement of 20% or more and absolute improvement of at least 1 units (on a scale of 0 [least] to 10 [worst]) from Baseline in at least 3 of the following 4 domains, with absence of deterioration (worsening of at least 20% an absolute Worsening of at least 1 unit) in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores
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6 Weeks
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Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score From Baseline to 6 Weeks After First Infusion in Part 2
기간: 6 Weeks
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ASAS20 as described in Primary Outcome.
ASAS40 responder had improvement of 40% or more and absolute improvement of at least 2 units (on a scale of 0 [least] to 10 [worst]) from Baseline in at least 3 of the following 4 domains, with no deterioration in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores).
ASAS 5/6 responder had improvement of 20% or more) from Baseline in at least 5 of the following 6 domains: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (BASFI); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores); Spinal Mobility (BASFI); Acute phase reactant (CRP)
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6 Weeks
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 Over Time in Part 1
기간: Day8,15,29,week 6, 8, 10, 12, 16, 20, 24, 28
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ASAS20 responder had improvement of 40% or more and absolute improvement of at least 2 units (scale of 0 [least] to 10 [worst]) from Baseline in at least 3 of the following 4 domains, with no deterioration in the potential remaining domain: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores).
ASAS 5/6 responder had improvement of 20% or more) from Baseline in at least 5 of the following 6 domains: Patient's Global Assessment of Disease Activity; Total Back Pain visual analog scale (VAS); Function (Bath Ankylosing Spondylitis Functional Index (BASFI)); and Inflammation (mean of 2 morning stiffness-related Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] scores); Spinal Mobility (BASFI); Acute phase reactant (CRP)
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Day8,15,29,week 6, 8, 10, 12, 16, 20, 24, 28
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Number of Participants Who Achieved ASAS20, ASAS40, and ASAS 5/6 in Part 1 and 2 Combined
기간: Day 8,15,29,week 6, 8, 10, 12, 16, 20, 24, 28
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a Bayesian model was fitted to the ASAS20 , ASAS40 and ASAS 5/6 response rates on active and placebo treatments.
A Bayesian analysis had been chosen to allow the direct incorporation into the analysis of information about placebo response rates from historical data
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Day 8,15,29,week 6, 8, 10, 12, 16, 20, 24, 28
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Magnetic Resonance Imaging (MRI) Inflammatory Scores at Baseline, Week 6 in Part 1
기간: Baseline, week 6, week 28
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The study used MRI with fat-saturating techniques such as short tau inversion recovery (STIR) to look for the presence of bone marrow edema.
The Berlin modification of ASspiMRI-a (ASspiMRI-a) scoring technique assesses inflammation in each of the 23 disc vertebral units (DVU), capturing edema and erosion.
Scores for each DVU range from 0-3 (0=normal; 1=minor bone marrow edema (less than25% of DVU; 3=severe bone marrow edema (more that 50% of DVU).
The composite score ranges from 0 to 69, with higher scores indicating more severe inflammation
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Baseline, week 6, week 28
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Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1
기간: Week 28
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Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28.
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Week 28
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Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1 and 2
기간: Week 28
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Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28.
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Week 28
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PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1
기간: Week 28
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Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
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Week 28
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PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1 and 2
기간: Week 28
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Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
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Week 28
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PK of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) in Part 1
기간: Week 28
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Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
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Week 28
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PK of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) in Part 1 and 2
기간: Week 28
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Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
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Week 28
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PK of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) in Part 1
기간: Week 28
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Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
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Week 28
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PK of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) in Part 1 and 2
기간: Week 28
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Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
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Week 28
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PK of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) in Part 1
기간: Week 28
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Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
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Week 28
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PK of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) in Part 1 and 2
기간: Week 28
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Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
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Week 28
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PK of AIN457: Terminal Elimination Half-life (T1/2) in Part 1
기간: Week 28
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Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
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Week 28
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PK of AIN457: Terminal Elimination Half-life (T1/2) in Part 1 and 2
기간: Week 28
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Serum samples were collected pre-dose 2, 3, 4 and 24 hours after initiation of the infusions (Days 1 and 22), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24 and end of study/Week 28
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Week 28
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Mean Change Bath Ankylosing Spondylitis Metrology Index (BASMI) Score in Part 1 and 2
기간: Baseline, day 8,15,29, week 6,8,10,12,16,20,24,28
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BASMI measures the range of motion based on five clinical measurements: 1) cervical rotation, 2) tragus to wall distance, 3) lumbar side flexion, 4) lumbar flexion (modified Schober's) and 5) intermalleolar distance.
BASMI 0 = indicates mild disease involvement, 1 = moderate disease, and 2 = severe disease involvement.
The results for cervical rotation and lumbar side flexion are the means of the left and right measurements.
Scoring range 0-10.
The higher the BASMI score, the more severe was the subject's limitation of movement
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Baseline, day 8,15,29, week 6,8,10,12,16,20,24,28
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Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in Part 1 and 2
기간: Baseline, day 8,15,29,week 6,8,10,12,16,20,24,28
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The BASDAI consists of a 1 through 10 scale (1 being no problem and 10 being the worst problem), which was used to answer 6 questions pertaining to the 5 major symptoms of AS: Fatigue, Spinal pain, Joint pain / swelling, areas of localized tenderness (called enthesitis, or inflammation of insertion sites of tendons and ligaments), morning stiffness duration, and morning stiffness severity.
The physician will globally assess the subject's current disease state using a visual analog scale (VAS) scale with 0 being very good and 100 being very bad.
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Baseline, day 8,15,29,week 6,8,10,12,16,20,24,28
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Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1
기간: Baseline, day 8,15,29,week, 6, 8,10,12,16,20,24,28
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MASES is measured by scoring of entheses of 0 (no tenderness) to 3 (severe tenderness) at 13 sites on the body.
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).
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Baseline, day 8,15,29,week, 6, 8,10,12,16,20,24,28
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Mean Change in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in Part 1 and 2
기간: Day 8,15,29,week, 6, 10,12,16,20,24,28
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MASES is measured by scoring of entheses of 0 (no tenderness) to 3 (severe tenderness) at 13 sites on the body.
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).
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Day 8,15,29,week, 6, 10,12,16,20,24,28
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Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1.
기간: SF-36:Baseline, week 12, week 28; ASQoL: Baseline, Day 29, week 12, week 28
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The Short Form (36) Health Survey (SF-36) measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score.
Scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health.
ASQoL determined subject's quality of life and is comprised of 18 questions (yes or no) to be completed by the subject.
Each statement on the ASQoL is given a score of "1" or "0."
All item scores were summed to give a total score or index.
Total scores ranged from 0 (good quality of life) to 18 (poor quality of life) related to ability to cope, relationships, mood, sleep, motivation, activities of everyday living, independence, and social life.
Decrease in ASQoL score represents improvement.
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SF-36:Baseline, week 12, week 28; ASQoL: Baseline, Day 29, week 12, week 28
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Change From Baseline in the Health Related Quality of Life (HRQoL) by Using the SF-36 Physical Component, and the ASQoL (Ankylosing Spondylitis Quality of Life Instrument) in Part 1 and 2.
기간: SF-36: Baseline, week 12, week 28; ASQoL: Baseline, day 29, week 12, week 8
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The SF-36 measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score.
ASQoL determined subject's quality of life and is comprised of 18 questions (yes or no) to be completed by the subject.
Each statement on the ASQoL is given a score of "1" or "0."
All item scores were summed to give a total score or index.
Total scores ranged from 0 (good quality of life) to 18 (poor quality of life) related to ability to cope, relationships, mood, sleep, motivation, activities of everyday living, independence, and social life.
Decrease in ASQoL score represents improvement.
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SF-36: Baseline, week 12, week 28; ASQoL: Baseline, day 29, week 12, week 8
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- Baraliakos X, Borah B, Braun J, Baeten D, Laurent D, Sieper J, Emery P, McInnes IB, van Laar JM, Wordsworth P, Wollenhaupt J, Kellner H, Colin L, Vandenhende F, Radford K, Hueber W. Long-term effects of secukinumab on MRI findings in relation to clinical efficacy in subjects with active ankylosing spondylitis: an observational study. Ann Rheum Dis. 2016 Feb;75(2):408-12. doi: 10.1136/annrheumdis-2015-207544. Epub 2015 Aug 6.
- Baeten D, Baraliakos X, Braun J, Sieper J, Emery P, van der Heijde D, McInnes I, van Laar JM, Landewe R, Wordsworth P, Wollenhaupt J, Kellner H, Paramarta J, Wei J, Brachat A, Bek S, Laurent D, Li Y, Wang YA, Bertolino AP, Gsteiger S, Wright AM, Hueber W. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2013 Nov 23;382(9906):1705-13. doi: 10.1016/S0140-6736(13)61134-4. Epub 2013 Sep 13. Erratum In: Lancet. 2014 May 3;383(9928):1548.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작
2009년 3월 1일
기본 완료 (실제)
2011년 5월 1일
연구 완료 (실제)
2011년 5월 1일
연구 등록 날짜
최초 제출
2008년 12월 16일
QC 기준을 충족하는 최초 제출
2008년 12월 16일
처음 게시됨 (추정)
2008년 12월 17일
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
2015년 12월 9일
QC 기준을 충족하는 마지막 업데이트 제출
2015년 12월 7일
마지막으로 확인됨
2015년 8월 1일
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .