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A Study of Adalimumab in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis

3 september 2014 bijgewerkt door: AbbVie (prior sponsor, Abbott)

A Multi-Center, Randomized, Double-Blind, Placebo-controlled Study of Adalimumab in Japanese Subjects With Moderately to Severely Active Ulcerative Colitis.

The purpose of this study is to assess the efficacy and safety of adalimumab in Japanese subjects with moderately to severely active ulcerative colitis (UC).

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Patients who meet all of the inclusion criteria and none of the exclusion criteria are randomized 1:1:1 to receive subcutaneous injections of adalimumab at either 160/80 mg at Week 0/2 and 40 mg every other week (eow) starting at Week 4 to Week 50, 80/40 mg at Week 0/2 and 40 mg eow starting at Week 4 to Week 50, or placebo eow starting at Week 0 to Week 50 under the double-blind condition. At or after Week 8, participants who have inadequate response during the double-blind period can switch to the rescue arm, where participants from the placebo group initially receive adalimumab 160 mg and 80 mg 2 weeks later and those from the adalimumab group receive adalimumab 40 mg initially and 2 weeks later under double-blind conditions. All participants in the rescue arm then receive 40 mg adalimumab eow until Week 50. Participants who complete the 52-week double-blind period receive open-label adalimumab 40 mg eow starting at Week 52 and continuing until the end of the study. Participants who have an inadequate response or disease flare can dose escalate to 80 mg eow at or after Week 60. Participants who dose escalate to 80 mg eow and continue to have an inadequate response or disease flare are withdrawn from the study.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

274

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Japan
      • Asahikawa, Japan
        • Site Reference ID/Investigator# 47136
      • Chiba, Japan
        • Site Reference ID/Investigator# 47159
      • Chikushino, Japan
        • Site Reference ID/Investigator# 47183
      • Fukuoka-shi, Japan
        • Site Reference ID/Investigator# 47135
      • Fukuoka-shi, Japan
        • Site Reference ID/Investigator# 47182
      • Hamamatsu, Japan
        • Site Reference ID/Investigator# 47124
      • Hirakata-shi, Japan
        • Site Reference ID/Investigator# 47130
      • Hirosaki, Japan
        • Site Reference ID/Investigator# 47103
      • Hiroshima, Japan
        • Site Reference ID/Investigator# 47178
      • Hiroshima, Japan
        • Site Reference ID/Investigator# 47179
      • Hiroshima-shi, Japan
        • Site Reference ID/Investigator# 47131
      • Izumo, Japan
        • Site Reference ID/Investigator# 47176
      • Kagoshima, Japan
        • Site Reference ID/Investigator# 47226
      • Kanazawa-shi, Japan
        • Site Reference ID/Investigator# 47123
      • Kashiwa, Japan
        • Site Reference ID/Investigator# 47160
      • Kawagoe, Japan
        • Site Reference ID/Investigator# 47108
      • Koshigaya, Japan
        • Site Reference ID/Investigator# 47107
      • Kurume, Japan
        • Site Reference ID/Investigator# 47181
      • Kurume, Japan
        • Site Reference ID/Investigator# 47222
      • Kurume, Japan
        • Site Reference ID/Investigator# 47223
      • Kyoto, Japan
        • Site Reference ID/Investigator# 47127
      • Kyoto, Japan
        • Site Reference ID/Investigator# 47172
      • Kyoto-shi, Japan
        • Site Reference ID/Investigator# 47170
      • Kyoto-shi, Japan
        • Site Reference ID/Investigator# 47171
      • Matsuyama-shi, Japan
        • Site Reference ID/Investigator# 47134
      • Miyazaki, Japan
        • Site Reference ID/Investigator# 47225
      • Morioka-shi, Japan
        • Site Reference ID/Investigator# 47138
      • Nagakute-shi, Japan
        • Site Reference ID/Investigator# 47168
      • Nagoya-shi, Japan
        • Site Reference ID/Investigator# 47125
      • Nagoya-shi, Japan
        • Site Reference ID/Investigator# 47126
      • Nagoya-shi, Japan
        • Site Reference ID/Investigator# 47166
      • Niigata-shi, Japan
        • Site Reference ID/Investigator# 47122
      • Nishihara, Japan
        • Site Reference ID/Investigator# 47227
      • Nishinomiya-shi, Japan
        • Site Reference ID/Investigator# 47174
      • Oita, Japan
        • Site Reference ID/Investigator# 47224
      • Okayama-shi, Japan
        • Site Reference ID/Investigator# 47177
      • Okinawa, Japan
        • Site Reference ID/Investigator# 47228
      • Osaka, Japan
        • Site Reference ID/Investigator# 47129
      • Osaka-shi, Japan
        • Site Reference ID/Investigator# 47128
      • Otsu-shi, Japan
        • Site Reference ID/Investigator# 47169
      • Sagamihara-shi, Japan
        • Site Reference ID/Investigator# 47118
      • Saitama-shi, Japan
        • Site Reference ID/Investigator# 47158
      • Sakura, Japan
        • Site Reference ID/Investigator# 47109
      • Sapporo, Japan
        • Site Reference ID/Investigator# 47137
      • Sapporo-shi, Japan
        • Site Reference ID/Investigator# 15853
      • Sendai-shi, Japan
        • Site Reference ID/Investigator# 47104
      • Sendai-shi, Japan
        • Site Reference ID/Investigator# 47147
      • Susaki-shi, Japan
        • Site Reference ID/Investigator# 47180
      • Takamatsu, Japan
        • Site Reference ID/Investigator# 47133
      • Takatsuki-shi, Japan
        • Site Reference ID/Investigator# 47173
      • Tokorozawa-shi, Japan
        • Site Reference ID/Investigator# 47106
      • Tokushima, Japan
        • Site Reference ID/Investigator# 47132
      • Tokyo, Japan
        • Site Reference ID/Investigator# 47110
      • Tokyo, Japan
        • Site Reference ID/Investigator# 47111
      • Tokyo, Japan
        • Site Reference ID/Investigator# 47112
      • Tokyo, Japan
        • Site Reference ID/Investigator# 47116
      • Tokyo, Japan
        • Site Reference ID/Investigator# 47117
      • Tokyo, Japan
        • Site Reference ID/Investigator# 47161
      • Tokyo, Japan
        • Site Reference ID/Investigator# 47164
      • Toyama, Japan
        • Site Reference ID/Investigator# 47165
      • Toyoake, Japan
        • Site Reference ID/Investigator# 47167
      • Yamagata-shi, Japan
        • Site Reference ID/Investigator# 47105
      • Yamatotakada, Japan
        • Site Reference ID/Investigator# 47175
      • Yokohama, Japan
        • Site Reference ID/Investigator# 47120
      • Yokohama-shi, Japan
        • Site Reference ID/Investigator# 47121

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

15 jaar en ouder (Kind, Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • Diagnosis of ulcerative colitis for greater than 90 days prior to Baseline.
  • Active ulcerative colitis with a Mayo Score of 6-12 points at Baseline and endoscopy subscore of 2-3 during the Screening Period, despite concurrent treatment with at least one of the following (oral corticosteroids or immunosuppressants or both as defined below):
  • Stable oral corticosteroid dose (prednisolone dose of ≥ 20 mg/day or equivalent) for at least 14 days prior to Baseline or stable oral corticosteroid dose (prednisolone of 5 to less than 20 mg/day) for at least 40 days prior to Baseline. And/or
  • At least a consecutive 90-day course of azathioprine or 6-mercaptopurine (6-MP) prior to Baseline, with a dose of azathioprine ≥ 50 mg/day or 6-MP ≥ 30 mg/day, or a dose that was the highest tolerated by the patient.

Exclusion Criteria:

  • History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, or ileostomy for ulcerative colitis or was planning bowel surgery.
  • Patients with disease limited to the rectum.
  • Indeterminate colitis and/or Crohn's disease.
  • Received any biological therapy (including infliximab) in the past.
  • History of tuberculosis or malignancy.
  • Pregnant women.
  • Patients with positive C. difficile stool assay at Screening.
  • Current diagnosis of fulminant colitis and/or toxic megacolon.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Dubbele

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Placebo-vergelijker: Placebo
Participants received placebo subcutaneous injections every 2 weeks for 52 weeks. From Week 8, participants with an inadequate response could switch to rescue therapy, where they initially received adalimumab 160 mg, 80 mg 2 weeks later, and then 40 mg every other week. Participants who completed the 52-week double-blind period received open-label adalimumab 40 mg every other week, with the possibility to escalate to 80 mg every other week, until drug approval.
Geneesmiddel: placebo
Biologisch: adalimumab
Andere namen:
  • ABT-D2E7 Humira
Experimenteel: Adalimumab 80 mg/40 mg
Participants received adalimumab 80 mg on Day 1, 40 mg at Week 2 and 40 mg every other week from Week 4 to Week 50, via subcutaneous injection. From Week 8, participants with an inadequate response could switch to rescue therapy, where they received adalimumab 40 mg every other week. Participants who completed the 52-week double-blind period received open-label adalimumab 40 mg every other week, with the possibility to escalate to 80 mg every other week, until drug approval.
Biologisch: adalimumab
Andere namen:
  • ABT-D2E7 Humira
Experimenteel: Adalimumab 160 mg/80 mg
Participants received adalimumab 160 mg on Day 1, 80 mg at Week 2 and 40 mg every other week from Week 4 to Week 50, via subcutaneous injection. From Week 8, participants with an inadequate response could switch to rescue therapy, where they received adalimumab 40 mg every other week. Participants who completed the 52-week double-blind period received open-label adalimumab 40 mg every other week, with the possibility to escalate to 80 mg every other week, until drug approval.
Biologisch: adalimumab
Andere namen:
  • ABT-D2E7 Humira

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Percentage of Participants With Clinical Remission at 8 Weeks
Tijdsspanne: Week 8

Clinical remission was defined as a Mayo score ≤ 2 with no individual subscore > 1. The Mayo score is a composite score of ulcerative colitis disease activity calculated as the sum of four subscores:

  • Stool Frequency Subscore (SFS), based on the participant's diary and scored from zero (normal number of stools) to three (5 or more stools than normal);
  • Rectal Bleeding Subscore (RBS), based on the participant's diary and scored from zero (no blood) to three (blood only passed);
  • Endoscopy Subscore (ESS), based on colonoscopy or sigmoidoscopy and scored from zero (normal or inactive disease) to three (severe disease, spontaneous bleeding, ulceration);
  • Physician's Global Assessment (PGA) subscore, based on the physician's overall assessment, and scored from zero (normal) to three (severe disease).

The total Mayo score ranges from 0 to 12 points, with higher scores representing more severe disease.
Week 8
Percentage of Participants With Clinical Remission at 52 Weeks
Tijdsspanne: Week 52

Clinical remission was defined as a Mayo score ≤ 2 with no individual subscore > 1. The Mayo score is a composite score of ulcerative colitis disease activity calculated as the sum of four subscores:

  • Stool Frequency Subscore (SFS), based on the participant's diary and scored from zero (normal number of stools) to three (5 or more stools than normal);
  • Rectal Bleeding Subscore (RBS), based on the participant's diary and scored from zero (no blood) to three (blood only passed);
  • Endoscopy Subscore (ESS), based on colonoscopy or sigmoidoscopy and scored from zero (normal or inactive disease) to three (severe disease, spontaneous bleeding, ulceration);
  • Physician's Global Assessment (PGA) subscore, based on the physician's overall assessment, and scored from zero (normal) to three (severe disease).

The total Mayo score ranges from 0 to 12 points, with higher scores representing more severe disease.
Week 52

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Percentage of Participants With Clinical Remission at 8, 32, and 52 Weeks
Tijdsspanne: Weeks 8, 32, and 52

Clinical remission was defined as a Mayo score ≤ 2 with no individual subscore > 1. The Mayo score is a composite score of ulcerative colitis disease activity calculated as the sum of four subscores:

  • Stool Frequency Subscore (SFS), based on the participant's diary and scored from zero (normal number of stools) to three (5 or more stools than normal);
  • Rectal Bleeding Subscore (RBS), based on the participant's diary and scored from zero (no blood) to three (blood only passed);
  • Endoscopy Subscore (ESS), based on colonoscopy or sigmoidoscopy and scores from zero (normal or inactive disease) to three (severe disease, spontaneous bleeding, ulceration);
  • Physician's Global Assessment (PGA) subscore, based on the physician's overall assessment, and scored from zero (normal) to three (severe disease).

The total Mayo score ranges from 0 to 12 points, with higher scores representing more severe disease.
Weeks 8, 32, and 52
Percentage of Participants With a Clinical Response
Tijdsspanne: Baseline and Weeks 8, 32, and 52

A clinical response was defined as a decrease in Mayo score of ≥ 3 points and ≥ 30% from Baseline PLUS a decrease in the Rectal Bleeding Subscore (RBS) ≥ 1 or an absolute RBS of 0 or 1.

The Mayo score is a composite score of ulcerative colitis disease activity calculated as the sum of four subscores:

  • Stool Frequency Subscore, based on the participant's diary and scored from zero (normal number of stools) to three (5 or more stools than normal);
  • Rectal Bleeding Subscore, based on the participant's diary and scored from zero (no blood) to three (blood only passed);
  • Endoscopy Subscore, based on colonoscopy or sigmoidoscopy and scored from zero (normal or inactive disease) to three (severe disease, spontaneous bleeding, ulceration);
  • Physician's Global Assessment subscore, based on the physician's overall assessment, and scored from zero (normal) to three (severe disease).

The total Mayo score ranges from 0 to 12 points, with higher scores representing more severe disease.
Baseline and Weeks 8, 32, and 52
Percentage of Participants With Mucosal Healing
Tijdsspanne: Weeks 8, 32, and 52

Mucosal healing was defined as an endoscopy subscore of ≤ 1 and was assessed using flexible sigmoidoscopy performed at Weeks 8, 32, and 52.

The endoscopy subscore ranges from zero to three as follows:

0 = Normal or inactive disease, 1 = Mild disease (erythema, decreased vascular pattern, mild friability), 2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions), 3 = Severe disease (spontaneous bleeding, ulceration).
Weeks 8, 32, and 52
Percentage of Participants With Rectal Bleeding Subscore Indicative of Mild Disease (≤ 1)
Tijdsspanne: Weeks 8, 32, and 52

Rectal bleeding was assessed from the participant's diary, taking the worst score from the 3 days prior to each study visit. The rectal bleeding subscore ranges from zero to three, according to the following scale:

0 = no blood seen, 1 = streaks of blood with stool less than half the time, 2 = obvious blood with stool most of the time, 3 = blood alone passed.
Weeks 8, 32, and 52
Percentage of Participants With Physician's Global Assessment Subscore Indicative of Mild Disease (≤ 1)
Tijdsspanne: Weeks 8, 32, and 52

The Physician's Global Assessment Subscore acknowledges the three other subscores (Stool Frequency, Rectal Bleeding, and Endoscopy), the participant's daily record of abdominal discomfort and functional assessment, and other observations such as physical findings and the participant's performance status. Possible scores range from zero to three as follows:

0 = Normal (other subscores are 0), 1 = Mild disease (other subscores are mostly 1), 2 = Moderate disease (other subscores are 1 to 2), 3 = Severe disease (other subscores are 2 to 3).
Weeks 8, 32, and 52
Percentage of Participants With Stool Frequency Subscore Indicative of Mild Disease (≤ 1)
Tijdsspanne: Weeks 8, 32, and 52

Stool frequency was assessed from the participant's diary, taking the worst score from the 3 days prior to each study visit. The stool frequency subscore ranges from zero to three, according to the following scale:

0 = Normal number of stools for this participant, 1 = 1-2 stools more than normal, 2 = 3-4 stools more than normal, 3 = 5 or more stools more than normal.
Weeks 8, 32, and 52
Percentage of Inflammatory Bowel Disease Questionnaire (IBDQ) Responders
Tijdsspanne: Baseline and Weeks 8, 32, and 52
An inflammatory bowel disease questionnaire responder was defined as a participant with at least a 16-point increase from Baseline in total Inflammatory Bowel Disease Questionnaire (IBDQ) score. The IBDQ is a 32-item questionnaire consisting of 4 dimensions: bowel-related symptoms, systemic function, social function, and emotional status. The responses to each question within each domain range from 1 (significant impairment) to 7 (no impairment), with the total score ranging from 32 (very poor) to 224 (perfect health-related quality of life).
Baseline and Weeks 8, 32, and 52
Number of Participants With Adverse Events up to Week 8
Tijdsspanne: 8 weeks

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related.

A serious adverse event is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.

For more details on adverse events please see the Adverse Event section below.
8 weeks
Number of Participants With Adverse Events up to Week 52
Tijdsspanne: 52 weeks

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related.

A serious adverse event is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.

For more details on adverse events please see the Adverse Event section below.
52 weeks
Number of Participants With Adverse Events During the Adalimumab Treatment Period
Tijdsspanne: 221 weeks

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related.

A serious adverse event is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.

For more details on adverse events please see the Adverse Event section below.
221 weeks

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

AbbVie (prior sponsor, Abbott)

Medewerkers

Eisai Co., Ltd.

Onderzoekers

  • Studie directeur: Morio Ozawa, MS, AbbVie GK.

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 februari 2009

Primaire voltooiing (Werkelijk)

1 mei 2011

Studie voltooiing (Werkelijk)

1 augustus 2013

Studieregistratiedata

Eerst ingediend

27 februari 2009

Eerst ingediend dat voldeed aan de QC-criteria

27 februari 2009

Eerst geplaatst (Schatting)

2 maart 2009

Updates van studierecords

Laatste update geplaatst (Schatting)

5 september 2014

Laatste update ingediend die voldeed aan QC-criteria

3 september 2014

Laatst geverifieerd

1 september 2014

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • M10-447

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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