A Study of the Safety and Efficacy of Ustekinumab (CNTO 1275) in Participants With Crohn's Disease
20 janvier 2014 mis à jour par: Centocor, Inc.
A Multicenter, Randomized, Phase 2a Study of Human Monoclonal Antibody to IL-12p40 (CNTO 1275) in Subjects With Moderately to Severely Active Crohn's Disease
The purpose of this study is to examine the safety and efficacy of CNTO 1275 in participants with active Crohn's Disease.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
This is a multicenter, randomized study of IL-12p40 (CNTO 1275), hereafter referred to as ustekinumab, in 2 populations of participants with moderately to severely active Crohn's disease of at least 6 weeks duration.
A total of approximately 120 volunteers will participate in this study in Canada, Belgium, and the United States.
Two separate groups of participants (Population 1 and Population 2) will be evaluated.
The primary population of participants (Population 1) will consist of approximately 100 participants with Crohn's disease despite treatment with standard Crohn's disease medications (includes agents to decrease intestinal inflammation such as 5-ASA medications such as PENTASA, ASACOL), corticosteroids such as prednisone and/or other drugs known to suppress the immune system called immunomodulators such as azathioprine, 6-mercaptopurine, methotrexate, infliximab or adalimumab [marketed under the trade name of HUMMIRA]).
Participants in Population 1 will be randomly assigned (assigned by chance, like "flipping a coin") to double-blind treatment (participants and study staff will not know the identity of the treatments) with ustekinumab and placebo (inactive substance) in 1 of 4 treatment groups as follows: (1) 4 weeks of treatment with ustekinumab 90 mg followed by 4 weeks of treatment with placebo injected subcutaneously (SC, under the skin), (II) 4 weeks of placebo followed by 4 weeks of ustekinumab 90 mg injected SC, (III) 1 intravenous (IV, in the vein) infusion of ustekinumab 4.5 mg/kg followed by 1 IV infusion of placebo, and (IV) 1 IV infusion of placebo followed by 1 IV infusion of ustekinumab 4.5 mg/kg.
Population 2 consists of approximately 20 participants who failed to respond to previous therapy with infliximab (trade name REMICADE), a type of antibody that decreases inflammation in patients with moderate to severe Crohn's disease).
All participants in Population 2 will receive open-label (un-blinded) treatment with ustekinumab 4.5 mg/kg administered SC for 4 weeks or as one IV infusion.
Placebo will not be given to participants in Population 2. The duration of the study for each participant is 28 weeks (not including a screening period of up to 2 weeks) with participants returning at Week 54 to have blood samples collected to assess the concentration of ustekinumab and antibodies to ustekinumab.
Adverse events (side-effects) as a measure of safety and tolerability and results from routine laboratory tests will be monitored and reported throughout the study from the time that informed consent is documented up to 3 days after the final blood sample collection at Week 54.
Note: doses of ustekinumab used in the study were adjusted by a factor of 0.9 to be consistent with the corrected absorptivity constant for ustekinumab.
Therefore, ustekinumab doses of 100 mg and 5 mg/kg previously stated in the study protocol have been restated as 90 mg and 4.5 mg/kg, respectively.
No change was made to the amount of ustekinumab given to participants in this study.
Type d'étude
Interventionnel
Inscription (Réel)
131
Phase
- Phase 2
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
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Leuven, Belgique
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Hamilton, Canada
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London, Canada
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Alberta
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Edmonton, Alberta, Canada
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British Columbia
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Vancouver, British Columbia, Canada
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Manitoba
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Winnipeg, Manitoba, Canada
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Ontario
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Toronto, Ontario, Canada
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Arizona
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Scottsdale, Arizona, États-Unis
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California
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Anaheim, California, États-Unis
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Sacramento, California, États-Unis
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San Francisco, California, États-Unis
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Connecticut
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Bristol, Connecticut, États-Unis
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New Haven, Connecticut, États-Unis
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Florida
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Jacksonville, Florida, États-Unis
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Miami, Florida, États-Unis
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Indiana
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Indianapolis, Indiana, États-Unis
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Kansas
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Topeka, Kansas, États-Unis
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Kentucky
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Lexington, Kentucky, États-Unis
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Louisville, Kentucky, États-Unis
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Louisiana
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Baton Rouge, Louisiana, États-Unis
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Metairie, Louisiana, États-Unis
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New Orleans, Louisiana, États-Unis
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Maryland
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Laurel, Maryland, États-Unis
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Michigan
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Chesterfield, Michigan, États-Unis
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Troy, Michigan, États-Unis
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Minnesota
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Rochester, Minnesota, États-Unis
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Nebraska
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Omaha, Nebraska, États-Unis
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New York
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Great Neck, New York, États-Unis
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New York, New York, États-Unis
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North Carolina
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Chapel Hill, North Carolina, États-Unis
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Charlotte, North Carolina, États-Unis
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Ohio
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Cincinnati, Ohio, États-Unis
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Cleveland, Ohio, États-Unis
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Columbus, Ohio, États-Unis
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Oklahoma
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Oklahoma City, Oklahoma, États-Unis
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Oregon
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Portland, Oregon, États-Unis
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Pennsylvania
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Beaver Falls, Pennsylvania, États-Unis
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Pittsburgh, Pennsylvania, États-Unis
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Rhode Island
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Providence, Rhode Island, États-Unis
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South Carolina
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Columbia, South Carolina, États-Unis
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Tennessee
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Germantown, Tennessee, États-Unis
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Knoxville, Tennessee, États-Unis
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Memphis, Tennessee, États-Unis
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Nashville, Tennessee, États-Unis
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Texas
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Austin, Texas, États-Unis
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Dallas, Texas, États-Unis
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Houston, Texas, États-Unis
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Utah
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Ogden, Utah, États-Unis
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Salt Lake City, Utah, États-Unis
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Virginia
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Charlottesville, Virginia, États-Unis
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Christiansburg, Virginia, États-Unis
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Richmond, Virginia, États-Unis
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Washington
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Everett, Washington, États-Unis
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Seattle, Washington, États-Unis
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Tacoma, Washington, États-Unis
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Wisconsin
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Madison, Wisconsin, États-Unis
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Milwaukee, Wisconsin, États-Unis
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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 et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Have moderately to severly active Crohn's disease or fistulizing Crohn's disease for at least 6 weeks' duration with a Crohn's disease activity index (CDAI) score of >=220 and <=450
- In Population 1, participants must have had active disease despite treatment with 5-ASA compounds, antibiotics, corticosteroids, and/or immunomodulators, including anti-TNF agents. In Population 2, participants must have had active disease and have failed to respond to infliximab at the maximum approved dose and treatment regimen for Crohn's disease as defined in the US package insert.
Exclusion Criteria:
- Have local manifestations of Crohn's disease such as strictures, abscesses, or other disease complications for which surgery might be indicated
- Had intra-abdominal surgery within 6 months prior to entering the study
- Have received treatment with parenteral nutrition (ie, introduction of nutrition into the body via a route other than the mouth) (total parenteral nutrition [TPN]) within 6 weeks of baseline
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: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: Population 1: Placebo SC followed by ustekinumab SC
Placebo injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by ustekinumab 90 mg SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2.
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one 90 mg SC injection each week for 4 weeks (Weeks 0-3 during Intervention Period 1 or Weeks 8-11 during Intervention Period 2 for Population 1 or Weeks 0-3 during Intervention Period 1 for Population 2)
Autres noms:
one SC injection each week for 4 weeks (Weeks 0-3 in Intervention Period 1 or Weeks 8-11 in Intervention Period 2 for Population 1 or at Weeks 0-3 in Intervention Period 1 for Population 2)
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Expérimental: Population 1: Ustekinumab SC followed by Placebo SC:
Ustekinumab 90 mg injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by ustekinumab 90 mg SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2.
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one 90 mg SC injection each week for 4 weeks (Weeks 0-3 during Intervention Period 1 or Weeks 8-11 during Intervention Period 2 for Population 1 or Weeks 0-3 during Intervention Period 1 for Population 2)
Autres noms:
one SC injection each week for 4 weeks (Weeks 0-3 in Intervention Period 1 or Weeks 8-11 in Intervention Period 2 for Population 1 or at Weeks 0-3 in Intervention Period 1 for Population 2)
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Expérimental: Population 1: Placebo IV followed by ustekinumab IV
Placebo given as 1 intravenous (IV) infusion at Week 0 during Intervention Period 1 and ustekinumab 4.5 mg/kg given as one IV infusion at Week 8 during Intervention Period 2.
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one IV infusion of 4.5 mg/kg over a period of not less than 2 hours at Week 0 in Intervention Period 1 or Week 8 in Intervention Period 2 for Population 1 or at Week 0 in Intervention Period 1 for Population 2
Autres noms:
one IV infusion over a period of not less than 2 hours at Week 0 in Intervention Period 1 for Population 1 and Population 2 or at Week 8 in Intervention Period 2 for Population 1
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Expérimental: Population 1: Ustekinumab IV followed by Placebo IV:
Ustekinumab 4.5 mg/kg given as one intravenous(IV) infusion at Week 0 during Intervention Period 1 followed by placebo given as one IV infusion at Week 8 during Intervention Period 2.
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one IV infusion of 4.5 mg/kg over a period of not less than 2 hours at Week 0 in Intervention Period 1 or Week 8 in Intervention Period 2 for Population 1 or at Week 0 in Intervention Period 1 for Population 2
Autres noms:
one IV infusion over a period of not less than 2 hours at Week 0 in Intervention Period 1 for Population 1 and Population 2 or at Week 8 in Intervention Period 2 for Population 1
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Expérimental: Population 2: Ustekinumab SC
Ustekinumab 90 mg injected subcutaneously (SC) once a week at Weeks 0-3 during Intervention Period 1.
No intervention given during Intervention Period 2.
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one 90 mg SC injection each week for 4 weeks (Weeks 0-3 during Intervention Period 1 or Weeks 8-11 during Intervention Period 2 for Population 1 or Weeks 0-3 during Intervention Period 1 for Population 2)
Autres noms:
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Expérimental: Population 2: Ustekinumab IV
Ustekinumab 4.5 mg given as one intravenous (IV) infusion at Week 0 during Intervention Period 1.
No intervention given during Intervention Period 2.
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one IV infusion of 4.5 mg/kg over a period of not less than 2 hours at Week 0 in Intervention Period 1 or Week 8 in Intervention Period 2 for Population 1 or at Week 0 in Intervention Period 1 for Population 2
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Number of Participants in Population 1 With a Clinical Response at Week 8
Délai: Week 8
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The table below provides the number of participants in Population 1 with a clinical response at Week 8 defined as a reduction from baseline in the CDAI (Crohn's disease activity index) score of >= 25% and >= 70 points at Week 8.
A reduction in CDAI score correlates with improvement in the severity of illness.
The CDAI is derived as a weighted sum of 8 different Crohn's disease related variables: extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools (or bags emptied for participants with a stoma), abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well being.
The primary endpoint analysis was based on the comparison between the combined SC and IV Placebo and combined SC and IV ustekinumab treatment groups in Population 1.
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Week 8
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Number of Participants in Population 2 With a Clinical Response at Week 8
Délai: Week 8
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The table below provides the number of participants in Population 2 with a clinical response at Week 8 defined as a reduction from baseline in the CDAI (Crohn's disease activity index) score of >= 25% and >= 70 points at Week 8.
A reduction in CDAI score correlates with improvement in the severity of illness.
The CDAI is derived as a weighted sum of 8 different Crohn's disease related variables: extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools (or bags emptied for participants with a stoma), abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being.
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Week 8
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Number of Participants in Population 1 With Clinical Remission at Week 8
Délai: Week 8
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The table below shows the number of participants in Population 1 with clinical remission at Week 8 defined a CDAI (Crohn's disease activity index) score < 150 points at Week 8.
A reduction in CDAI score correlates with improvement in the severity of illness.
The CDAI is derived as a weighted sum of 8 different Crohn's disease related variables: extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools (or bags emptied for participants with a stoma), abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being.
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Week 8
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Directeur d'études: Centocor Clinical Trial, Centocor, Inc.
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
- Ghosh S, Gensler LS, Yang Z, Gasink C, Chakravarty SD, Farahi K, Ramachandran P, Ott E, Strober BE. Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn's Disease: An Integrated Analysis of Phase II/III Clinical Development Programs. Drug Saf. 2019 Jun;42(6):751-768. doi: 10.1007/s40264-019-00797-3. Erratum In: Drug Saf. 2019 Apr 22;:
- Sandborn WJ, Feagan BG, Fedorak RN, Scherl E, Fleisher MR, Katz S, Johanns J, Blank M, Rutgeerts P; Ustekinumab Crohn's Disease Study Group. A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease. Gastroenterology. 2008 Oct;135(4):1130-41. doi: 10.1053/j.gastro.2008.07.014. Epub 2008 Jul 17.
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 avril 2004
Achèvement primaire (Réel)
1 novembre 2005
Achèvement de l'étude (Réel)
1 octobre 2006
Dates d'inscription aux études
Première soumission
13 décembre 2005
Première soumission répondant aux critères de contrôle qualité
13 décembre 2005
Première publication (Estimation)
14 décembre 2005
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
13 février 2014
Dernière mise à jour soumise répondant aux critères de contrôle qualité
20 janvier 2014
Dernière vérification
1 janvier 2014
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- CR005287
- C0379T07 (Autre identifiant: Centocor, Inc.)
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 .