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NCT Number: NCT00669942

Double Blind, Placebo-controlled, Study of the Safety, Tolerability and Pharmacokinetics of AIN457 in Rheumatoid Arthritis Patients

Evaluate the safety, tolerability and pharmacokinetics of AIN457 when administered as a single dose (intravenous infusion) in patients with active rheumatoid arthritis in combination with a stable dose of methotrexate. And to compare efficacy on the dose groups.

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Key information

Conditions

Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Novartis Investigative Site, Brussels, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male and female patients with active rheumatoid arthritis in combination with a stable dose of methotrexate aged 18-75 years may participate in this trial.
  • Post menopausal or surgically sterile female patients are allowed. Women of child-bearing potential may participate if they are on a stable dose of methotrexate and if they are practicing effective contraception for at least 6 months prior to screening, willing to use 2 forms of contraception, including at least 1 barrier method during the study and for at least 2 months following the completion/discontinuation of the study.
  • Patients must have a diagnosis of active rheumatoid arthritis of stages I, II or III (ACR 1987 revised classification for criteria for RA). Disease duration of at least 6 months prior to randomization is essential;

Exclusion criteria

  • Current treatment with anti-TNF-α or anti IL-1 therapy (or other biological therapy).
  • Patients with congestive heart failure or poorly controlled diabetes mellitus (HbA1c value ≥10%).
  • Presence of any major chronic inflammatory autoimmune diseases like psoriasis, psoriatic arthritis, spondyloarthropathy, inflammatory bowel disease or SLE that can mimic rheumatoid arthritis diagnosis or that can interfere with efficacy evaluation in the study.
  • History of renal trauma, glomerulonephritis or patient with one kidney.
  • Pregnant or breastfeeding women will be excluded.
  • A positive tuberculin skin test.

Other protocol-defined inclusion/exclusion criteria may apply.

Treatment and study plan

AIN457

Biological

AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.

Placebo

Drug

Placebo to AIN457

Primary outcomes

  1. Percentage of Parts 2 and 3 Participants Who Achieved American College of Rheumatology Response of 20 (ACR20)

    Time frame: Day 43

    Clinical response to treatment was assessed according to ACR20 criteria. A participant was defined as an ACR20 responder if the following 3 conditions were met: 1) ≥20% improvement in the number of tender joints, 2) ≥20% improvement in the number of swollen joint and 3) ≥20% improvement in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant.

  2. Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1 Participants

    Time frame: Day 113

    Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 29, 36, 43, 57, 71, 85, 99 and 113.

  3. PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1 Participants

    Time frame: Day 113

    Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  4. 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 Participants

    Time frame: Day 113

    Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  5. PK of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) in Part 1 Participants

    Time frame: Day 113

    Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  6. PK of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) in Part 1 Participants

    Time frame: Day 113

    Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  7. PK of AIN457: Terminal Elimination Half-life (T1/2) in Part 1 Participants

    Time frame: Day 113

    Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  8. Pharmacokinetics PK of AIN457: Tmax in Parts 2 and 3 Participants

    Time frame: Day 113

    Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  9. Pharmacokinetics PK of AIN457: Cmax in Parts 2 and 3 Participants

    Time frame: Day 113

    Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  10. Pharmacokinetics PK of AIN457: AUClast and AUCinf in Parts 2 and 3 Participants

    Time frame: Day 113

    Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  11. Pharmacokinetics PK of AIN457: Vz in Parts 2 and 3 Participants

    Time frame: Day 113

    Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  12. Pharmacokinetics PK of AIN457: CL in Parts 2 and 3 Participants

    Time frame: Day 113

    Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  13. Pharmacokinetics PK of AIN457: T1/2 in Parts 2 and 3 Participants

    Time frame: Day 113

    Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

Secondary outcomes

  1. Percentage of Parts 2 and 3 Participants Who Achieved ACR50 and ACR70

    Time frame: Day 43

    Clinical response to treatment was assessed according to ACR50 and ACR70 criteria. A participant was defined as an ACR50 or ACR70 responder if the following 3 conditions were met: 1) improvement of ≥50% or ≥ 70%, respectively, in the number of tender joints, 2) improvement of ≥50% or ≥ 70%, respectively, in the number of swollen joints and 3) improvement of ≥50% or ≥ 70%, respectively, in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant

  2. Disease Activity Score (DAS28) of Parts 2 and 3 Participants

    Time frame: Day 43

    The DAS28 is a composite score based on tender and swollen joint counts, C reactive protein (CRP) concentrations, and the participant's global disease activity based on a visual analogue scale (VAS). The tender joint count (based on 28 joints) was calculated by scoring several different aspects of tenderness as assessed by pressure and joint manipulation on physical examination. The information on various types of tenderness was then collapsed into a single tender versus non-tender dichotomy, and the number of joints that were classified as tender was recorded. The swollen joint count was calculated in the same manner. For CRP concentrations, blood samples were collected and sent to a central laboratory for assessment. For the VAS assessment, the participant used a 100 mm horizontal VAS to assess the severity of his or her arthritis where 0 = none and 100 = most severe. DAS28 scores range from <2.6 (disease remission) to >5.1 (high disease activity).

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Randomized, Double Blind, Placebo-controlled, Dose Escalation Study of the Safety, Tolerability and Pharmacokinetics of AIN457 in Rheumatoid Arthritis Patients With Pharmacodynamics Assessed in an Expanded Cohort at the Maximum Tolerated Dose

Important dates

Study start
2005
Primary completion
2008
Study completion
2008
First posted
May 1, 2008
Registry last updated
Mar 30, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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