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

27 mars 2015 mis à jour par: Novartis Pharmaceuticals

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

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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

104

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Allemagne
      • Bad Nauheim, Allemagne, 61231
        • Novartis Investigative Site
      • Erlangen, Allemagne, 91054
        • Novartis Investigative Site
      • Muenchen, Allemagne, 80336
        • Novartis Investigative Site
  • Belgique
      • Bruxelles, Belgique, 1200
        • Novartis Investigative Site
      • Merksem, Belgique, 2170
        • Novartis Investigative Site
  • Espagne
      • Guadalajara, Espagne, 19002
        • Novartis Investigative Site
    • Galicia
      • La Coruna, Galicia, Espagne, 15006
        • Novartis Investigative Site
      • Santiago de Compostela, Galicia, Espagne, 15706
        • Novartis Investigative Site
  • Pays-Bas
      • Amsterdam, Pays-Bas, 1105 AZ
        • Novartis Investigative Site
      • Nijmegen, Pays-Bas, 6525 GA
        • Novartis Investigative Site
  • Singapour
      • Singapore, Singapour, 119074
        • Novartis Investigative Site
      • Singapore, Singapour, 529889
        • Novartis Investigative Site
  • États-Unis
    • Alabama
      • Anniston, Alabama, États-Unis, 36207-5710
        • Novartis Investigative Site
    • Arizona
      • Tucson, Arizona, États-Unis, 85724
        • Novartis Investigative Site
    • Florida
      • Largo, Florida, États-Unis, 33773
        • Novartis Investigative Site
      • Ocala, Florida, États-Unis, 34471
        • Novartis Investigative Site
      • Palm Harbor, Florida, États-Unis, 34684
        • Novartis Investigative Site
      • Port Orange, Florida, États-Unis, 32127
        • Novartis Investigative Site
    • Kentucky
      • Madisonville, Kentucky, États-Unis, 42431
        • Novartis Investigative Site
    • Missouri
      • St. Louis, Missouri, États-Unis, 63110
        • Novartis Investigative Site
    • Nebraska
      • Omaha, Nebraska, États-Unis, 68131-2197
        • Novartis Investigative Site
    • Oklahoma
      • Oklahoma City, Oklahoma, États-Unis, 73103
        • Novartis Investigative Site
    • Oregon
      • Bend, Oregon, États-Unis, 97701
        • Novartis Investigative Site
    • Pennsylvania
      • Duncansville, Pennsylvania, États-Unis, 16635
        • Novartis Investigative Site

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 75 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Science basique
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
Biologique: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Expérimental: Part 1 - AIN457A 0.3 mg/kg
AIN457A 0.3 mg/kg was administered intravenously as a single dose.
Biologique: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Expérimental: Part 1 - AIN457A 1.0 mg/kg
AIN457A 1.0 mg/kg was administered intravenously as a single dose.
Biologique: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Expérimental: Part 1 - AIN457A 3.0 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
Biologique: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Comparateur placebo: Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose.
Médicament: Placebo
Placebo to AIN457
Expérimental: Parts 2 and 3 - 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.
Biologique: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Expérimental: Parts 2 and 3 - AIN457A 3.0 mg/kg
AIN457A 3.0 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.
Biologique: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Expérimental: Parts 2 and 3 - AIN457A 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.
Biologique: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Comparateur placebo: Parts 2 and 3 - Placebo
Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.
Médicament: Placebo
Placebo to AIN457
Expérimental: Part 1 - Healthy Volunteers - AIN457A 3 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
Biologique: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Expérimental: Part 1 - Healthy Volunteers - AIN457A 10 mg/kg
AIN457A 10 mg/kg was administered intravenously as a single dose.
Biologique: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Comparateur placebo: Part 1 - Healthy Volunteers - Placebo
Placebo to AIN457A was administered intravenously as a single dose.
Médicament: Placebo
Placebo to AIN457

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Percentage of Parts 2 and 3 Participants Who Achieved American College of Rheumatology Response of 20 (ACR20)
Délai: 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.
Day 43
Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1 Participants
Délai: 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.
Day 113
PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1 Participants
Délai: 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.
Day 113
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
Délai: 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.
Day 113
PK of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) in Part 1 Participants
Délai: 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.
Day 113
PK of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) in Part 1 Participants
Délai: 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.
Day 113
PK of AIN457: Terminal Elimination Half-life (T1/2) in Part 1 Participants
Délai: 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.
Day 113
Pharmacokinetics PK of AIN457: Tmax in Parts 2 and 3 Participants
Délai: 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.
Day 113
Pharmacokinetics PK of AIN457: Cmax in Parts 2 and 3 Participants
Délai: 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.
Day 113
Pharmacokinetics PK of AIN457: AUClast and AUCinf in Parts 2 and 3 Participants
Délai: 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.
Day 113
Pharmacokinetics PK of AIN457: Vz in Parts 2 and 3 Participants
Délai: 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.
Day 113
Pharmacokinetics PK of AIN457: CL in Parts 2 and 3 Participants
Délai: 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.
Day 113
Pharmacokinetics PK of AIN457: T1/2 in Parts 2 and 3 Participants
Délai: 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.
Day 113

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Percentage of Parts 2 and 3 Participants Who Achieved ACR50 and ACR70
Délai: 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
Day 43
Disease Activity Score (DAS28) of Parts 2 and 3 Participants
Délai: 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).
Day 43

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Novartis Pharmaceuticals

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 décembre 2005

Achèvement primaire (Réel)

1 novembre 2008

Achèvement de l'étude (Réel)

1 novembre 2008

Dates d'inscription aux études

Première soumission

29 avril 2008

Première soumission répondant aux critères de contrôle qualité

30 avril 2008

Première publication (Estimation)

1 mai 2008

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

30 mars 2015

Dernière mise à jour soumise répondant aux critères de contrôle qualité

27 mars 2015

Dernière vérification

1 mars 2015

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • CAIN457A2101

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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