Rapidity of Response to Adalimumab Treatment in Patients With Crohn´s Disease

Rapidity of Onset of Response to Adalimumab in Luminal Crohn's Disease (RAPIDA Study)

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02148718

Acronym

RAPIDA

Enrollment

100

Registered

2014-05-28

Start date

2014-06-30

Completion date

2017-01-31

Last updated

2018-03-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Moderate to Severe Crohn's Disease

Keywords

Crohn's Disease

Brief summary

The purpose of this study is to evaluate the rapidity of onset of clinical response to adalimumab therapy in patients with luminal Crohn's disease.

Interventions

BIOLOGICALadalimumab

Adalimumab pre-filled syringe, administered by subcutaneous injection

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Crohn's disease (CD) diagnosed within, at least, the previous 4 months. * Patients with active luminal (Harvey-Bradshaw Index \[HBI\] ≥ 8) moderate to- severe CD. * No response to a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant. * If receiving any of the following treatments, their dose should be stable during the periods indicated: * Aminosalicylates for, at least, the last 4 weeks * Probiotics for, at least, the last 4 weeks * Analgesics for, at least, the last 4 weeks * Antidiarrheals for, at least, the last 4 weeks * CD-related antibiotics for, at least, the last 4 weeks * Azathioprine, 6-mercaptopurine or methotrexate for, at least, the last 12 weeks * If receiving any of the following treatments, their dose should not have been increase in the past two weeks (the dose reduction is permitted): * Oral budesonide (maximum dose of 9 mg/day) * Oral prednisone or equivalent (maximum dose of 40mg/day)

Exclusion criteria

* Previous treatment with any anti-Tumor Necrosis Factor agent * Surgical bowel resection within the previous 6 months, ostomy, extensive bowel resection (\> 100 cm), short bowel syndrome * Fistulising Crohn's disease * Treatment with cyclosporine or tacrolimus within the previous 8 weeks * Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from screening, congestive heart failure of worse than grade II New York criteria (New York Heart Association Functional Classification). * Subject with an ostomy or ileoanal pouch, proctocolectomy, total colectomy, ileostomy, stoma or ileal pouch-anal anastomosis (Subjects with a previous ileo-rectal anastomosis are not excluded). * Screening laboratory values (according to central laboratory) * Known hepatitis C (HC) infection. * Serologic evidence of hepatitis B (HB) infection based on the results of testing for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) and hepatitis B surface antibody (anti-HBs) antibodies.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Clinical Response at Day 4	Day 4	Clinical response defined as a decrease of at least 3 points in Harvey-Bradshaw Index (HBI) score. The HBI consists of only clinical parameters (general well-being, abdominal pain, number of liquid stools per day, abdominal mass, and complications): The first 3 items are scored for the previous day. Patients with Crohn's disease who scored 3 or less on the HBI are very likely to be in remission. Patients with a score of 8 to 9 or higher are considered to have severe disease.

Secondary

Measure	Time frame	Description
Percentage of Participants With Clinical Remission at Weeks 2 and 4	Weeks 2 and 4	Clinical remission defined as HBI \< 5. The HBI consists of only clinical parameters (general well-being, abdominal pain, number of liquid stools per day, abdominal mass, and complications): The first 3 items are scored for the previous day. Patients with Crohn's disease who scored 3 or less on the HBI are very likely to be in remission. Patients with a score of 8 to 9 or higher are considered to have severe disease.
European Quality of Life (EuroQol) 5 Dimensions 3 Levels Questionnaire (EQ-5D-3L) Index Score: Change From Baseline to Week 12	Baseline (Week 0) and Week 12	The EQ-5D-3L is a standardized instrument for use as a measure of health-related quality of life (HRQoL) and consists of 2 components: 1. The EQ-5D-3L Index Score has five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) with 3 levels of severity for each dimension ('no problems', 'some problems', and 'extreme problems'). The level of severity reported on each of the EQ-5D-3L dimensions determines a unique health state. Health states are converted into a weighted health state index. These weights lie on a scale on which full health has a value of 1 and dead has a value of 0. 2. The EQ-5D visual analog scale (VAS) is a 20-cm scale with endpoints labeled best imaginable health and worst imaginable health anchored at 100 and 0, respectively. A positive change represents an improvement in HRQoL. Mean Baseline and mean change from Baseline to Week 12 in the EQ-5D-3L Index Score are presented.
European Quality of Life (EuroQol) 5 Dimensions 3 Levels Questionnaire (EQ-5D-3L) Visual Analog Scale (VAS): Change From Baseline to Week 12	Baseline (Week 0) and Week 12	The EQ-5D-3L is a standardized instrument for use as a measure of HRQoL and consists of 2 components: 1. The EQ-5D-3L Index Score has five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) with 3 levels of severity for each dimension ('no problems', 'some problems', and 'extreme problems'). The level of severity reported on each of the EQ-5D-3L dimensions determines a unique health state. Health states are converted into a weighted health state index. These weights lie on a scale on which full health has a value of 1 and dead has a value of 0. 2. The EQ-5D VAS is a 20-cm scale with endpoints labeled best imaginable health and worst imaginable health anchored at 100 and 0, respectively. A positive change represents an improvement in HRQoL. Mean Baseline and mean change from Baseline to Week 12 in the EQ-5D-3L VAS are presented.
Inflammatory Bowel Disease Quality-36 (IBDQ-36) Questionnaire Overall Score: Change From Baseline to Week 12	Baseline (Week 0) and Week 12	The IBDQ-36 is used to assess the HRQoL related to bowel symptoms. The IBDQ-36 overall score is calculated as the sum of thirty-six items, each scored on a 1 to 7 likert point scale, and ranges from 7 to 252. The highest score indicates the best HRQoL related to bowel symptoms. A positive change in IBDQ-36 overall score indicates an improvement in HRQoL due to inflammatory bowel disease. Mean Baseline and mean change from Baseline to Week 12 in the EQ-5D-3L VAS are presented.
Fatigue Impact Scale for Daily Use (D-FIS): Change From Baseline to Week 12	Baseline (Week 0) and Week 12	The D-FIS is used to measure the impact of fatigue on the daily lives of persons. The D-FIS overall score was calculated as the sum of eight items, each scored on a 0 to 4 point scale, and ranges from 0 to 32. A higher score indicates a higher impact of fatigue on daily life. A negative change in D-FIS Overall Score means an improvement in HRQoL due to fatigue. Mean Baseline and mean change from Baseline to Week 12 are presented.
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Hemoglobin	Baseline (Week 0) and Week 12	Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes sedimentation rate (ESR), C-reactive protein (CRP), fecal calprotectin, and coagulation (activated partial thromboplastin time \[aPTT\], international normalized ratio \[INR\], and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 are presented.
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Hematocrit	Baseline (Week 0) and Week 12	Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Leukocytes, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets	Baseline (Week 0) and Week 12	Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Percentage of Participants With Clinical Response at Week 1	Week 1	Clinical response defined as a decrease of at least 3 points in HBI score. The HBI consists of only clinical parameters (general well-being, abdominal pain, number of liquid stools per day, abdominal mass, and complications): The first 3 items are scored for the previous day. Patients with Crohn's disease who scored 3 or less on the HBI are very likely to be in remission. Patients with a score of 8 to 9 or higher are considered to have severe disease.
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Sedimentation Rate (ESR)	Baseline (Week 0) and Week 12	Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Change From Baseline to Week 12 in Analytic Markers of Inflammation: C-reactive Protein (CRP)	Baseline (Week 0) and Week 12	Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Fecal Calprotectin	Baseline (Week 0) and Week 12	Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Activated Partial Thromboplastin Time (aPTT)	Baseline (Week 0) and Week 12	Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Change From Baseline to Week 12 in Analytic Markers of Inflammation: International Normalized Ratio (INR)	Baseline (Week 0) and Week 12	Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Fibrinogen	Baseline (Week 0) and Week 12	Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.
Percentage of Participants With Clinical Response at Day 4 or Week 12 and Clinical Remission at Week 12	Up to Week 12	The percentage of participants with clinical response (defined as decrease of at least 3 points in HBI score) at Day 4 or Week 1 and clinical remission (defined as a HBI \< 5) at Week 12.
Change From Baseline to Week 12 in Analytic Markers of Inflammation: Erythrocytes	Baseline (Week 0) and Week 12	Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.

Participant flow

Pre-assignment details

A total of 100 participants were enrolled in the study; 14 participants did not receive study drug and are excluded from the analyses.

Participants by arm

Arm	Count
Adalimumab Participants received adalimumab for 12 weeks (160 mg at Week 0; 80 mg at week 2; then adalimumab 40 mg every other week starting at Week 4).	86
Total	86

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Discontinued Study Prematurely	5
Overall Study	Protocol Violation	26

Baseline characteristics

Characteristic	Adalimumab
Age, Continuous	37.73 years STANDARD_DEVIATION 12.16
Region of Enrollment Spain	86 participants
Sex: Female, Male Female	49 Participants
Sex: Female, Male Male	37 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	35 / 86
serious Total, serious adverse events	2 / 86

Outcome results

Primary

Percentage of Participants With Clinical Response at Day 4

Clinical response defined as a decrease of at least 3 points in Harvey-Bradshaw Index (HBI) score. The HBI consists of only clinical parameters (general well-being, abdominal pain, number of liquid stools per day, abdominal mass, and complications): The first 3 items are scored for the previous day. Patients with Crohn's disease who scored 3 or less on the HBI are very likely to be in remission. Patients with a score of 8 to 9 or higher are considered to have severe disease.

Time frame: Day 4

Population: Intent to Treat (ITT) population: all enrolled participants who received at least 1 dose of study drug

Arm	Measure	Value (NUMBER)
Adalimumab	Percentage of Participants With Clinical Response at Day 4	61.63 percentage of participants

Secondary

Change From Baseline to Week 12 in Analytic Markers of Inflammation: Activated Partial Thromboplastin Time (aPTT)

Analytic markers of inflammation are hemogram (hemoglobin, hematocrit, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, and platelets), erythrocytes, ESR, CRP, fecal calprotectin, and coagulation (aPTT, INR, and fibrinogen). Mean Baseline and mean change from Baseline to Week 12 for each parameter are presented.