Last reviewed · How we verify

NCT02764762

Triple Combination Therapy in High Risk Crohn's Disease (CD)

Completed Phase 4 Results posted Last updated 14 July 2023
What this trial tests

Phase 4 trial testing Vedolizumab in Crohn Disease in 55 participants. Completed in 5 July 2022.

Timeline
18 April 2017
Primary endpoint
22 September 2020
5 July 2022

Quick facts

Lead sponsorTakeda
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment55
Start date18 April 2017
Primary completion22 September 2020
Estimated completion5 July 2022
Sites32 locations across Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

Takeda — full company profile →

Who can join

Adults 18 to 65, any sex, with Crohn Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Achieving Endoscopic Remission at Week 26 Primary · Week 26

Endoscopic remission was defined as simple endoscopic score for Crohn's Disease (SES-CD) scale score from 0-2. The SES-CD evaluated 4 endoscopic variables: ulcer size, proportion of the surface area that was ulcerated, proportion of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was the sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe

GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)34.521.1 – 48.0
Percentage of Participants Achieving Endoscopic Healing at Week 26 Secondary · Week 26

Endoscopic healing was defined as SES-CD score ≤4 and reduction from Baseline in SES-CD score of at least 2 points and no individual SES-CD subscore \>1. The SES-CD evaluated 4 endoscopic variables: ulcer size, proportion of the surface area that is ulcerated, proportion of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was the sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56,

GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)43.629.6 – 57.7
Percentage of Participants Achieving Endoscopic Response at Week 26 Secondary · Week 26

Endoscopic response was defined as 50% reduction in SES-CD score from Baseline. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Percentages are rounded off

GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)56.442.3 – 70.4
Change From Baseline in SES-CD Score at Week 26 Secondary · Baseline and Week 26

The SES-CD evaluated 4 endoscopic variables: ulcer size, proportion of the surface area that is ulcerated, proportion of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left colon, and rectum). The score for each endoscopic variable was the sum of values obtained for each segment. The SES-CD total was the sum of the 4 endoscopic variable scores from 0 to 56, where higher scores indicate more severe disease. Negative change indicates improvement.

Baseline
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)12.6± 5.67
Change From Baseline at Week 26
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)-8.9± 7.29
Percentage of Participants Achieving Deep Remission at Week 26 Secondary · Week 26

Deep remission was defined as Crohn's disease activity index (CDAI) score \<150 and SES-CD score from 0-2. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (ileum, right colon, transverse colon, left

GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)21.810.0 – 33.6
Percentage of Participants Achieving Clinical Remission and Endoscopic Response as a Measure of Mucosal Healing at Week 26 Secondary · Week 26

Clinical remission was defined as CDAI score \<150. Endoscopic response was defined as 50% reduction in SES-CD score from Baseline, as mucosal healing. CDAI was scoring system for assessment of CD activity, index values of 150 and below are associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. The SES-CD evaluated 4 endoscopic variables: ulcer size, percentage of the surface area that is ulcerated, percentage of the surface area affected, and stenosis in 5 colonic segments evaluated during ileocolonoscopy (il

GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)38.224.4 – 51.9
Percentage of Participants Achieving Clinical Remission at Weeks 10 and 26 Secondary · Weeks 10 and 26

Clinical remission was defined as CDAI score \<150. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal.

Week 10
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)60.046.1 – 73.9
Week 26
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)54.540.5 – 68.6
Percentage of Participants Achieving Clinical Response at Weeks 10 and 26 Secondary · Weeks 10 and 26

Clinical response was defined as ≥100-point decrease in CDAI score. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicated active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal.

Week 10
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)49.135.0 – 63.2
Week 26
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)43.629.6 – 57.7
Change From Baseline in C-reactive Protein (CRP) Levels at Weeks 10 and 26 Secondary · Baseline, Weeks 10 and 26

The change between the CRP levels were collected at Weeks 10 and 26 relative to Baseline. Negative change indicates improvement.

Baseline
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)7.600.6 – 135.8
Change From Baseline at Week 10
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)-4.80-84.0 – 29.7
Change From Baseline at Week 26
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)-5.50-79.3 – 104.3
Change From Baseline in Fecal Calprotectin Concentrations at Weeks 10, 14, 26, 52, 78, and 102 Secondary · Baseline, Weeks 10, 14, 26, 52, 78 and 102

The change between the fecal calprotectin concentrations collected at Weeks 10, 14, 26, 52, 78, and 102 relative to Baseline were reported. Baseline is defined as the last observation prior to the first dose of the study drug.

Baseline
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)1301.023 – 17707
Vedolizumab 300 mg (IV)1210.023 – 17707
Change From Baseline at Week 10
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)-864.0-16406 – 471
Change From Baseline at Week 14
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)-556.0-14742 – 6892
Change From Baseline at Week 26
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)-860.5-7911 – 440
Change From Baseline at Week 52
GroupValue95% CI
Vedolizumab 300 mg (IV)-350.0-7365 – 8021
Change From Baseline at Week 78
GroupValue95% CI
Vedolizumab 300 mg (IV)-396.5-7844 – 9434
Change From Baseline at Week 102
GroupValue95% CI
Vedolizumab 300 mg (IV)-452.0-8052 – 106
Percentage of Participants Achieving Clinical Remission and CRP <5 Milligram Per Liter (mg/L) at Weeks 26, 52, 78, and 102 Secondary · Weeks 26, 52, 78 and 102

Clinical remission was defined as CDAI score \<150 and CRP level \<5 mg/L in participants with elevated CRP level at Baseline. CDAI was scoring system for the assessment of CD activity, index values of 150 and below were associated with quiescent disease; values above that indicate active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal.

Week 26
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)51.334.3 – 68.3
Week 52
GroupValue95% CI
Vedolizumab 300 mg (IV)44.126.0 – 62.3
Week 78
GroupValue95% CI
Vedolizumab 300 mg (IV)26.510.2 – 42.8
Week 102
GroupValue95% CI
Vedolizumab 300 mg (IV)20.65.5 – 35.7
Percentage of Participants Using Oral Corticosteroids at Baseline Who Have Discontinued Corticosteroids and Are in Clinical Remission at Weeks 10, 26, and 102 Secondary · Weeks 10, 26 and 102

Percentage of participants using oral corticosteroids at Baseline who had discontinued corticosteroids and were in clinical remission at weeks 10, 26, and 102 were reported. Clinical remission was defined as CDAI score \<150. CDAI was scoring system for the assessment of CD activity, index values of 150 and below are associated with quiescent disease; values above that indicate active disease and values above 450 were seen with extremely severe disease. Percentages are rounded off to single decimal.

Week 10
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)50.022.4 – 77.6
Week 26
GroupValue95% CI
Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)56.328.8 – 83.7
Week 102
GroupValue95% CI
Vedolizumab 300 mg (IV)21.40.0 – 46.5

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose up to EOS (up to 120 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Vedolizumab 300 mg (IV) + Adalimumab 160-80-40 mg (SC) + Methotrexate 15 mg (Oral)
Serious: 6/55 (11%)
Deaths: 0/55
Vedolizumab 300 mg (IV)
Serious: 1/45 (2%)
Deaths: 0/45
Safety Follow-up
Serious: 2/53 (4%)
Deaths: 0/53

Serious adverse events (9 terms)

ReactionSystemVedolizumab 300 mg (IV) + …Vedolizumab 300 mg (IV)Safety Follow-up
Small intestinal obstructionGastrointestinal disorders———
Abdominal wall abscessInfections and infestations———
AppendicitisInfections and infestations———
Colonic fistulaGastrointestinal disorders———
Crohn's diseaseGastrointestinal disorders———
GastroenteritisInfections and infestations———
LymphadenopathyBlood and lymphatic system disorders———
Perirectal abscessInfections and infestations———
PyrexiaGeneral disorders———
Other adverse events (19 terms — click to expand)

ReactionSystemVedolizumab 300 mg (IV) + …Vedolizumab 300 mg (IV)Safety Follow-up
Crohn's diseaseGastrointestinal disorders———
ArthralgiaMusculoskeletal and connective tissue disorders———
NasopharyngitisInfections and infestations———
Abdominal painGastrointestinal disorders———
HeadacheNervous system disorders———
RashSkin and subcutaneous tissue disorders———
C-reactive protein increasedInvestigations———
CoughRespiratory, thoracic and mediastinal disorders———
Faecal calprotectin increasedInvestigations———
FatigueGeneral disorders———
NauseaGastrointestinal disorders———
Abdominal pain upperGastrointestinal disorders———
Anal fissureGastrointestinal disorders———
Blood creatine phosphokinase increasedInvestigations———
DizzinessNervous system disorders———
GastroenteritisInfections and infestations———
HaematocheziaGastrointestinal disorders———
Oropharyngeal painRespiratory, thoracic and mediastinal disorders———
Urinary tract infectionInfections and infestations———

Most-reported serious reactions: Small intestinal obstruction, Abdominal wall abscess, Appendicitis, Colonic fistula, Crohn's disease, Gastroenteritis, Lymphadenopathy, Perirectal abscess.

Data from ClinicalTrials.gov NCT02764762 adverse events section.

Sponsor's own description

The purpose of this study is to determine the effect of triple combination therapy with an anti-integrin (vedolizumab intravenous \[IV\]), a tumor necrosis factor (TNF) antagonist (adalimumab subcutaneously \[SC\]), and an immunomodulator (oral methotrexate) on endoscopic remission in participants with newly-diagnosed CD stratified at higher risk for complications.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Perspectives on Current and Novel Treatments for Inflammatory Bowel Disease.
    Na SY, Moon W. · · 2019 · cited 99× · PMID 31195433 · DOI 10.5009/gnl19019
  2. Combining Biologics in Inflammatory Bowel Disease and Other Immune Mediated Inflammatory Disorders.
    Hirten RP, Iacucci M, Shah S, Ghosh S, et al · · 2018 · cited 89× · PMID 29481970 · DOI 10.1016/j.cgh.2018.02.024
  3. The current state of the art for biological therapies and new small molecules in inflammatory bowel disease.
    Paramsothy S, Rosenstein AK, Mehandru S, Colombel JF. · · 2018 · cited 82× · PMID 29907872 · DOI 10.1038/s41385-018-0050-3
  4. Anti-integrin therapy for inflammatory bowel disease.
    Park SC, Jeen YT. · · 2018 · cited 82× · PMID 29740202 · DOI 10.3748/wjg.v24.i17.1868
  5. Novel Pharmacological Therapy in Inflammatory Bowel Diseases: Beyond Anti-Tumor Necrosis Factor.
    Pagnini C, Pizarro TT, Cominelli F. · · 2019 · cited 59× · PMID 31316377 · DOI 10.3389/fphar.2019.00671
  6. Vedolizumab, Adalimumab, and Methotrexate Combination Therapy in Crohn's Disease (EXPLORER).
    Colombel JF, Ungaro RC, Sands BE, Siegel CA, et al · · 2024 · cited 57× · PMID 37743037 · DOI 10.1016/j.cgh.2023.09.010
  7. Systematic Review With Meta-analysis: Safety and Effectiveness of Combining Biologics and Small Molecules in Inflammatory Bowel Disease.
    Alayo QA, Fenster M, Altayar O, Glassner KL, et al · · 2022 · cited 55× · PMID 35310082 · DOI 10.1093/crocol/otac002
  8. Combination of Biological Agents in Moderate to Severe Pediatric Inflammatory Bowel Disease: A Case Series and Review of the Literature.
    Olbjørn C, Rove JB, Jahnsen J. · · 2020 · cited 45× · PMID 32378002 · DOI 10.1007/s40272-020-00396-1

Verify or expand the search:

Other trials of Vedolizumab

Trials testing the same drug.

Other recruiting trials for Crohn Disease

Currently open trials in the same condition.

Other Takeda trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02764762.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing