A Study of the Safety and Efficacy of Ustekinumab (CNTO 1275) in Participants With Crohn's Disease
2014年1月20日 更新者：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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
131
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Arizona
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Scottsdale、Arizona、アメリカ
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California
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Anaheim、California、アメリカ
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Sacramento、California、アメリカ
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San Francisco、California、アメリカ
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Connecticut
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Bristol、Connecticut、アメリカ
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New Haven、Connecticut、アメリカ
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Florida
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Jacksonville、Florida、アメリカ
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Miami、Florida、アメリカ
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Indiana
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Indianapolis、Indiana、アメリカ
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Kansas
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Topeka、Kansas、アメリカ
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Kentucky
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Lexington、Kentucky、アメリカ
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Louisville、Kentucky、アメリカ
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Louisiana
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Baton Rouge、Louisiana、アメリカ
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Metairie、Louisiana、アメリカ
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New Orleans、Louisiana、アメリカ
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Maryland
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Laurel、Maryland、アメリカ
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Michigan
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Chesterfield、Michigan、アメリカ
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Troy、Michigan、アメリカ
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Minnesota
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Rochester、Minnesota、アメリカ
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Nebraska
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Omaha、Nebraska、アメリカ
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New York
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Great Neck、New York、アメリカ
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New York、New York、アメリカ
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North Carolina
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Chapel Hill、North Carolina、アメリカ
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Charlotte、North Carolina、アメリカ
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Ohio
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Cincinnati、Ohio、アメリカ
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Cleveland、Ohio、アメリカ
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Columbus、Ohio、アメリカ
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Oklahoma
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Oklahoma City、Oklahoma、アメリカ
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Oregon
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Portland、Oregon、アメリカ
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Pennsylvania
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Beaver Falls、Pennsylvania、アメリカ
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Pittsburgh、Pennsylvania、アメリカ
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Rhode Island
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Providence、Rhode Island、アメリカ
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South Carolina
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Columbia、South Carolina、アメリカ
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Tennessee
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Germantown、Tennessee、アメリカ
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Knoxville、Tennessee、アメリカ
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Memphis、Tennessee、アメリカ
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Nashville、Tennessee、アメリカ
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Texas
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Austin、Texas、アメリカ
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Dallas、Texas、アメリカ
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Houston、Texas、アメリカ
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Utah
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Ogden、Utah、アメリカ
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Salt Lake City、Utah、アメリカ
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Virginia
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Charlottesville、Virginia、アメリカ
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Christiansburg、Virginia、アメリカ
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Richmond、Virginia、アメリカ
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Washington
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Everett、Washington、アメリカ
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Seattle、Washington、アメリカ
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Tacoma、Washington、アメリカ
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Wisconsin
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Madison、Wisconsin、アメリカ
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Milwaukee、Wisconsin、アメリカ
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Hamilton、カナダ
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London、カナダ
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Alberta
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Edmonton、Alberta、カナダ
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British Columbia
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Vancouver、British Columbia、カナダ
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Manitoba
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Winnipeg、Manitoba、カナダ
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Ontario
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Toronto、Ontario、カナダ
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Leuven、ベルギー
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：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)
他の名前：
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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実験的：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)
他の名前：
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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実験的：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
他の名前：
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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実験的：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
他の名前：
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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実験的：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)
他の名前：
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実験的：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
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Number of Participants in Population 1 With a Clinical Response at Week 8
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Number of Participants in Population 2 With a Clinical Response at Week 8
時間枠：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
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- スタディディレクター：Centocor Clinical Trial、Centocor, Inc.
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2004年4月1日
一次修了 (実際)
2005年11月1日
研究の完了 (実際)
2006年10月1日
試験登録日
最初に提出
2005年12月13日
QC基準を満たした最初の提出物
2005年12月13日
最初の投稿 (見積もり)
2005年12月14日
学習記録の更新
投稿された最後の更新 (見積もり)
2014年2月13日
QC基準を満たした最後の更新が送信されました
2014年1月20日
最終確認日
2014年1月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。