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

27 marzo 2015 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Effettivo)

104

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 75 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Scienza basilare
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Doppio

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Part 1 - AIN457A 10 mg/kg
AIN457A 10.0 mg/kg was administered intravenously as a single dose.
Biologico: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Sperimentale: Part 1 - AIN457A 0.3 mg/kg
AIN457A 0.3 mg/kg was administered intravenously as a single dose.
Biologico: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Sperimentale: Part 1 - AIN457A 1.0 mg/kg
AIN457A 1.0 mg/kg was administered intravenously as a single dose.
Biologico: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Sperimentale: Part 1 - AIN457A 3.0 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
Biologico: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Comparatore placebo: Part 1 - Placebo
Placebo to AIN457A was administered intravenously as a single dose.
Droga: Placebo
Placebo to AIN457
Sperimentale: 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.
Biologico: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Sperimentale: 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.
Biologico: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Sperimentale: 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.
Biologico: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Comparatore 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.
Droga: Placebo
Placebo to AIN457
Sperimentale: Part 1 - Healthy Volunteers - AIN457A 3 mg/kg
AIN457A 3.0 mg/kg was administered intravenously as a single dose.
Biologico: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Sperimentale: Part 1 - Healthy Volunteers - AIN457A 10 mg/kg
AIN457A 10 mg/kg was administered intravenously as a single dose.
Biologico: AIN457
AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.
Comparatore placebo: Part 1 - Healthy Volunteers - Placebo
Placebo to AIN457A was administered intravenously as a single dose.
Droga: Placebo
Placebo to AIN457

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Percentage of Parts 2 and 3 Participants Who Achieved American College of Rheumatology Response of 20 (ACR20)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Percentage of Parts 2 and 3 Participants Who Achieved ACR50 and ACR70
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Novartis Pharmaceuticals

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 dicembre 2005

Completamento primario (Effettivo)

1 novembre 2008

Completamento dello studio (Effettivo)

1 novembre 2008

Date di iscrizione allo studio

Primo inviato

29 aprile 2008

Primo inviato che soddisfa i criteri di controllo qualità

30 aprile 2008

Primo Inserito (Stima)

1 maggio 2008

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

30 marzo 2015

Ultimo aggiornamento inviato che soddisfa i criteri QC

27 marzo 2015

Ultimo verificato

1 marzo 2015

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • CAIN457A2101

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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