Crohn's DiseasePhase 3NCT00409682
Efficacy and Safety of Adalimumab in Pediatric Subjects With Moderate to Severe Crohn's Disease
A Phase 3 study testing Adalimumab in people with Crohn's Disease, run by Abbott at 45 sites in 8 countries.
Trial summary
The purpose of this study is to determine Efficacy, Pharmacokinetics, and Safety of Adalimumab in Pediatric Subjects With Moderate to Severe Crohn's Disease Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- Adalimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 192 participants
- Where
- 45 sitesin 8 countries
- Study dates
- Apr 2007to May 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Subjects between the ages of 6 and 17, inclusive, prior to baseline dosing.
- Subjects with a diagnosis of Crohn's disease for greater than 12 weeks prior to screening, confirmed by endoscopy or radiologic evaluation.
- PCDAI > 30 despite concurrent treatment with an oral corticosteroid, and/or azathioprine (AZA) or 6-mercaptopurine (6-MP) or methotrexate (MTX) as defined below:
- Oral corticosteroid - Prednisone of ≥ 10 mg/day or equivalent, but not exceeding 40 mg, with a stable dose for at least two weeks prior to Baseline.
- Azathioprine or 6-MP - AZA dose of ≥ 1.5 mg/kg/day or 6-MP dose of ≥ 1 mg/kg/day rounded to the nearest available tablet formulation, or a dose that is the highest tolerated for the subject, in the opinion of the investigator (for example due to leukopenia, elevated liver enzymes, nausea, etc.) for at least 8 weeks prior to Baseline with a stable dose for at least 4 weeks prior to Baseline.
- MTX dose of ≥ 5 mg once weekly, either subcutaneously (SC), intramuscularly (IM), or orally for subjects whose body weight is ≥ 20 kg, or a dose that is the highest tolerated for the subject, in the opinion of the investigator (for example due to leukopenia, elevated liver enzymes, nausea, etc.) for at least 8 weeks prior to Baseline with a stable dose for at least 4 weeks prior to Baseline.
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- MTX dose of 0.2 mg/kg, up to 5 mg, once weekly, either SC, IM, or orally for subjects whose body weight is < 20 kg, or a dose that is the highest tolerated for the subject, in the opinion of the investigator (for example due to leukopenia, elevated liver enzymes, nausea, etc.) for at least 8 weeks prior to Baseline with a stable dose for at least 4 weeks prior to Baseline.
- Concurrent therapy will not be required for subjects who within the past 2 years in the opinion of the Investigator have not responded to or could not tolerate systemic corticosteroids, AZA, 6-MP, or MTX as defined below:
- Corticosteroids:
- Failed to successfully respond to corticosteroids, or
- Medical complications and/or adverse events (AEs) from corticosteroids that in the judgment of their physician, precludes their use (e.g. psychosis, uncontrolled diabetes, osteoporosis, or osteonecrosis).
- Azathioprine, 6-MP or MTX: -
- Failed to successfully respond to these drugs or
- Medical complications and/or AEs that in the judgment of their physician, precludes their use (e.g. allergic reaction, pancreatitis, elevated liver enzymes, hepatitis or leukopenia).
- If female, subjects who were sexually active and were of child-bearing potential practicing an approved method of birth control throughout the study and for 150 days after study completion. Examples of approved methods of birth control included the following:
- Condoms, sponge,foam,jellies,diaphragm, or intrauterine device (IUD)
- Oral,parenteral, or intravaginal contraceptives for 12 weeks prior to adalimumab administration
- A vasectomized partner.
- Parent or legal guardian,as required,had voluntarily signed and dated an informed consent form (IFC), approved by an Institutional Review Board (IRB)/ Independent Ethics Committee (IEC).
- Adequate cardiac, renal and hepatic function as determined by principal investigator and demonstrated by Screening laboratory evaluations, questionnaires, and physical examination results that are within normal limits.
- Parent or legal guardian was willing to actively supervise storage and administration of study drug and to ensure that the time of each dose was accurately recorded in the subject's diary.
- Subjects who had previously received infliximab, providing the subject had an initial response and then discontinued use due to a loss of response, or discontinued use due to intolerance.
Who cannot join
- History of cancer or lymphoproliferative disease other than a successfully and completely treated cutaneous squamous cell or basal cell carcinoma or carcinoma-in-situ of the cervix.
- History of listeria, histoplasmosis, chronic or active hepatitis B infection, human immunodeficiency virus (HIV), an immunodeficiency syndrome, central nervous system (CNS) demyelinating disease, or active tuberculosis (TB) (receiving treatment or not receiving treatment), severe infections such as sepsis and opportunistic infections.
- Subject with infectious colitis, ulcerative colitis or indeterminate colitis as determined by the investigator and Abbott Medical Monitor.
- Subject with symptomatic known obstructive strictures.
- Subject who had surgical bowel resections within the past 24 weeks of the Baseline visit or planned any resection at any time point while enrolled in the study.
- Subject with an ostomy or ileo-anal pouch. (Subjects with a previous ileo-rectal anastomosis were not excluded).
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- Subject who had short bowel syndrome as determined by the investigator.
- Subject who was currently receiving total parenteral nutrition (TPN).
- Females who were pregnant or were currently breast-feeding.
- Subject who had received any investigational chemical agent in the past 30 days or 5 half-lives prior to Baseline (whichever was longer).
- Subject who had received any investigational biological agent in the past 16 weeks or 5 half-lives prior to Baseline (whichever was longer).
- Subject who has had systemic antibiotic, antiviral or antifungal treatment(s) within 3 weeks prior to Baseline for any non-Crohn's related infections.
- Subject with a history of clinically significant drug or alcohol abuse in the last year.
- Subjects with a poorly controlled medical condition such as: uncontrolled diabetes, recurrent infections, unstable ischemic heart disease, moderate to severe heart failure, recent cerebrovascular accidents and any other condition which, in the opinion of the investigator or the Sponsor, would put the subject at risk by participation in the protocol.
- Subjects with positive C. difficile stool assay.
- Subject who previously used infliximab within eight weeks of Baseline.
- Subject who previously used infliximab and had not clinically responded at any time ("primary non-responder") unless subject experienced a treatment limiting reaction to infliximab.
- Previous treatment with any other anti-TNF agent except infliximab.
- Received previous treatment with adalimumab or previous participation in an adalimumab clinical study.
- Screening laboratory and other analyses showing any of the following abnormal results:
- Electrocardiogram (ECG) - with clinically significant abnormalities;
- Aspartate transaminase (AST) or alanine transaminase (ALT) >1.75 x the upper limit of the reference range;
- Total bilirubin ≥ 3 mg/dL;
- Serum creatinine > 1.6 mg/dL;
- Subjects on AZA, 6-MP, or MTX who had not been on these medications for at least 8 weeks prior to Baseline and on stable doses of these medications for at least 4 weeks prior to Baseline. Subjects who had been on AZA, 6-MP, or MTX who had discontinued these medications within 8 weeks of Baseline.
- Subjects on aminosalicylates, or Crohn's-related antibiotics (fluoroquinolones such as ciprofloxacin or nitroimidazole derivatives such as metronidazole) that had not been on stable doses of these medications for at least 4 weeks prior to Baseline. In addition, subjects on aminosalicylates or Crohn's-related antibiotic treatments who had discontinued these medications within four weeks of Baseline.
- Subjects on prednisone > 40 mg/day (or equivalent) or subjects on < 10 mg/day prednisone and subjects who were not on a stable dose for at least 2 weeks prior to Baseline. In addition, subjects who discontinued prednisone (or equivalent) within 2 weeks of Baseline.
- Subjects on growth hormone that had not been on a stable dose for at least 12 weeks prior to Baseline. Subjects had to consent to remain on a stable dose through the duration of the study.
- Subjects on budesonide > 9 mg/day and subjects who were not on stable doses for at least 2 weeks prior to Baseline. In addition, subjects who discontinued budesonide within 2 weeks of Baseline.
- Subjects who were currently taking both budesonide and prednisone (or equivalent).
- Subjects who had undergone therapeutic enemas within two weeks prior to Baseline.
- Subjects who had been on cyclosporine (intravenous [IV], oral), tacrolimus (any form), or mycophenolate mofetil within 28 days of Baseline.
- Subjects who had been on Kineret® (anakinra) must discontinue use 2 days prior to Baseline.
- Subjects with any prior exposure to Tysabri (natalizumab).
- Subjects with known hypersensitivity to the excipients of adalimumab as stated in the label.
- Subjects with a previous history of dysplasia of the gastrointestinal tract.
- Subjects who weighed < 17 kg at Screening.
- Subject not in compliance with prior and concomitant medications.
Trial locations and contacts
45 sites in 8 countries.
45 sites in 8 countries
United States26 sites
Site Reference ID/Investigator# 5904
Atlanta, Georgia, 30342
Site Reference ID/Investigator# 5222
Aurora, Colorado, 80045
Site Reference ID/Investigator# 4317
Baltimore, Maryland, 21287
Site Reference ID/Investigator# 8801
Buffalo, New York, 14222
Site Reference ID/Investigator# 6257
Chapel Hill, North Carolina, 27599
Site Reference ID/Investigator# 4316
Chicago, Illinois, 60637
Site Reference ID/Investigator# 4909
Cincinnati, Ohio, 45229
Site Reference ID/Investigator# 4914
Columbus, Ohio, 43205
Site Reference ID/Investigator# 5676
Hartford, Connecticut, 06106
Site Reference ID/Investigator# 4912
Indianapolis, Indiana, 46202
Site Reference ID/Investigator# 3826
Las Vegas, Nevada, 89109
Site Reference ID/Investigator# 10287
Los Angeles, California, 90095-1752
Site Reference ID/Investigator# 5901
Maywood, Illinois, 60153
Site Reference ID/Investigator# 4950
Milwaukee, Wisconsin, 53226
Site Reference ID/Investigator# 3734
Mineola, New York, 11501
Site Reference ID/Investigator# 6182
Morristown, New Jersey, 07962
Site Reference ID/Investigator# 6354
Nashville, Tennessee, 37232
Site Reference ID/Investigator# 4913
New Hyde Park, New York, 11040
Site Reference ID/Investigator# 5223
Orange, California, 92868
Site Reference ID/Investigator# 4911
Orlando, Florida, 32801
Site Reference ID/Investigator# 7640
Orlando, Florida, 32806
Site Reference ID/Investigator# 5892
Philadelphia, Pennsylvania, 19104
Site Reference ID/Investigator# 5102
Rochester, Minnesota, 55905
Site Reference ID/Investigator# 4285
Saint Paul, Minnesota, 55114
Site Reference ID/Investigator# 4984
San Francisco, California, 94143
Site Reference ID/Investigator# 4983
Seattle, Washington, 98105
Canada7 sites
Site Reference ID/Investigator# 5109
Calgary, T3B 6A8
Site Reference ID/Investigator# 4916
Halifax, 83K 6R8
Site Reference ID/Investigator# 10284
Hamilton, L8N 3Z5
Site Reference ID/Investigator# 8391
London, N6A 5W9
Site Reference ID/Investigator# 5169
Ottawa, K1H 8L1
Site Reference ID/Investigator# 6798
Toronto, M5G 1X8
Site Reference ID/Investigator# 5570
Vancouver, V6H 3V4
Belgium3 sites
Site Reference ID/Investigator# 6700
Antwerp, 2020
Site Reference ID/Investigator# 7744
Brussels, 1020
Site Reference ID/Investigator# 6073
Brussels, 1200
Netherlands3 sites
Site Reference ID/Investigator# 16501
Amsterdam, 1100 DD
Site Reference ID/Investigator# 14750
Nijmegen, 6500HB
Site Reference ID/Investigator# 13622
Rotterdam, 3015 GJ
France2 sites
Site Reference ID/Investigator# 6065
Paris, 75015
Site Reference ID/Investigator# 6072
Paris, 75019
Poland2 sites
Site Reference ID/Investigator# 6428
Warsaw, 04-730
Site Reference ID/Investigator# 6430
Wroclaw, 50-369
United Kingdom1 site
Site Reference ID/Investigator# 7742
London, E1 1BB
About this study
Official title: A Multi-Center, Double-Blind Study to Evaluate the Safety, Efficacy and Pharmacokinetics of the Human Anti-TNF Monoclonal Antibody Adalimumab in Pediatric Subjects With Moderate to Severe Crohn's Disease
The purpose of this study is to determine Efficacy, Pharmacokinetics, and Safety of Adalimumab in Pediatric Subjects With Moderate to Severe Crohn's Disease
Read the detailed description
M06-806 (NCT # NCT00409682) was a Phase 3, multi-center, randomized, double-blind (DB), efficacy, safety, and pharmacokinetic (PK) study designed to evaluate the efficacy of 2 dose regimens for the induction and maintenance of clinical remission in pediatric subjects between the ages of 6 and 17 (inclusive) with moderate to severe Crohn's disease (CD) (defined by Pediatric Crohn's Disease Activity Index [PCDAI > 30]). Subjects must have either failed conventional therapy for CD or have previously received infliximab and lost response/had intolerance to infliximab.
Approximately 186 pediatric subjects between the ages of 6 and 17 were planned to be entered into the study at approximately 55 sites in the US, Canada, and Europe. At least 80 subjects were to be ≥ 13 years old at Baseline and one-third to one-half of the study population were to be subjects who had previously lost response or were intolerant to infliximab.
The duration of the study was to be up to 65 weeks, which included a 1- to 3-week Screening period, an Induction period, a Maintenance period, and a 70-day follow-up phone call for all subjects that either terminated early from the study or did not rollover into the extension study ([NCT # 00686374], to evaluate the long-term maintenance of clinical response, safety, and tolerability of repeated administration of adalimumab).
All subjects received an induction regimen administered at Baseline (Week 0) and Week 2. The open-label (OL) induction dose was based on the subject's Baseline body weight. Subjects weighing ≥ 40 kg were to receive 160 mg at Week 0 and 80 mg adalimumab at Week 2. Subjects weighing < 40 kg were to receive 80 mg at Week 0 and 40 mg adalimumab at Week 2.
At Week 4, subjects were to be randomized 1:1 to 1 of 2 DB maintenance treatment groups (Low-Dose or High-Dose), stratified by Week 4 clinical responder status (clinical response was defined as decrease in PCDAI of ≥ 15 points from the Baseline score), body weight at Week 4 and prior exposure to infliximab. Subjects randomized to the High-Dose treatment group were to receive either 40 mg adalimumab subcutaneous (SC) every other week (eow) (if Week 4 body weight ≥ 40 kg) or 20 mg adalimumab SC eow (if Week 4 body weight < 40 kg). Subjects randomized to the Low-Dose treatment group were to receive either 20 mg adalimumab SC eow (if Week 4 body weight ≥ 40 kg) or 10 mg adalimumab SC eow (if Week 4 body weight < 40 kg).
Subject's body weight taken at Week 26 was to be used to readjust the maintenance dosing regimen for a subject whose body weight had increased from < 40 kg to ≥ 40 kg during the study.
Subjects were expected to remain on blinded eow therapy throughout the 48-week study DB Maintenance period. However, starting at the Week 12 study visit, subjects who experienced a disease flare (increase in the PCDAI ≥ 15 points when compared to Week 4 and an absolute PCDAI above 30) or were non-responders (not achieving a decrease in the PCDAI score of at least 15 points when compared to the Baseline score for 2 consecutive visits at least 2 weeks apart) could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. During blinded ew treatment, if a subject continued to experience a flare or met the definition of non-response following an 8 week course of DB ew therapy, they were to be switched to OL ew therapy. The dosage of the OL ew therapy was 20 mg for subjects < 40 kg and 40 mg for subjects ≥ 40 kg.
This study used the PCDAI to determine efficacy of the study drug. The primary efficacy endpoint is the proportion of subjects who are in clinical remission at Week 26, as measured by the PCDAI in the intent-to-treat population. Clinical remission is defined as a PCDAI score of ≤ 10.
The clinical response indicators include clinical remission as defined by PCDAI score at Week 52 and clinical response as defined by PCDAI score at Week 26 and at Week 52.
The patient reported outcome is the change from Baseline in total IMPACT III scores at Week 26 and Week 52.
The safety parameters (adverse events, laboratory data, and vital signs) were assessed at all visits throughout the study.
- Conditions
- Crohn's Disease
- Being tested
- Adalimumab
- Keywords
- Crohn's Disease
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdalimumabBiological
Also called ABT-D2E7, adalimumab, Humira
All subjects received an open-label adalimumab induction regimen. Subjects weighing greater than or equal to 40 kg at Baseline received 160 mg at Week 0 and 80 mg at Week 2. Subjects weighing less than 40 kg at Baseline received 80 mg at Week 0 and 40mg at Week 2.
AdalimumabBiological
Also called ABT-D2E7, adalimumab, Humira
Subjects randomized to the Low-Dose treatment group received either 20 mg adalimumab every other week (eow) (if Week 4 body weight [BW] was greater than or equal to 40 kg) or 10 mg adalimumab eow (if Week 4 BW less than 40 kg). Starting at the Week 12 study visit, subjects who experienced a disease flare or were non-responders could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. If a subject continued to experience a flare or met the definition of non-response following an 8-week course of double-blind (DB) ew therapy they could be switched to open-label ew therapy.
AdalimumabBiological
Also called ABT-D2E7, adalimumab, Humira
Subjects randomized to the High-Dose treatment group received either 40 mg adalimumab every other week (eow) (if Week 4 body weight [BW] was greater than or equal to 40 kg) or 20 mg adalimumab eow (if Week 4 BW less than 40 kg). Starting at the Week 12 study visit, subjects who experienced a disease flare or were non-responders could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. If a subject continued to experience a flare or met the definition of non-response following an 8-week course of double-blinded (DB) ew therapy they could be switched to open-label ew therapy.
| Study group | Role | What they receive |
|---|---|---|
| Open-label adalimumab (Week 0 to Week 4) | Active comparator | All subjects received an open-label adalimumab induction regimen. Subjects weighing greater than or equal to 40 kg at Baseline received 160 mg at Week 0 and 80 mg at Week 2. Subjects weighing less than 40 kg at Baseline received 80 mg at Week 0 and 40mg at Week 2. Receives: Biological: Adalimumab |
| Low-Dose Adalimumab: 20 mg or 10 mg eow (Week 4 to Week 52) | Active comparator | Subjects randomized to the Low-Dose treatment group received either 20 mg adalimumab every other week (eow) (if Week 4 body weight [BW] was greater than or equal to 40 kg) or 10 mg adalimumab eow (if Week 4 BW less than 40 kg). Starting at the Week 12 study visit, subjects who experienced a disease flare or were non-responders could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. If a subject continued to experience a flare or met the definition of non-response following an 8-week course of double-blind (DB) ew therapy they could be switched to open-label ew therapy. Receives: Biological: Adalimumab |
| High-Dose Adalimumab: 40 mg or 20 mg eow (Week 4 to Week 52) | Active comparator | Subjects randomized to the High-Dose treatment group received either 40 mg adalimumab every other week (eow) (if Week 4 body weight [BW] was greater than or equal to 40 kg) or 20 mg adalimumab eow (if Week 4 BW less than 40 kg). Starting at the Week 12 study visit, subjects who experienced a disease flare or were non-responders could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. If a subject continued to experience a flare or met the definition of non-response following an 8-week course of double-blinded (DB) ew therapy they could be switched to open-label ew therapy. Receives: Biological: Adalimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of Participants With Clinical Remission as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤ 10 at Week 26
Pediatric Crohn's Disease Activity Index (PCDAI) is an index used to measure disease activity of pediatric patients with Crohn's Disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. The primary endpoint was clinical remission as defined by PCDAI score ≤ 10. The comparison was between High-Dose adalimumab versus Low-Dose adalimumab in the intent-to-treat population.
Measured: Week 26
Secondary outcomes (5)
Percent of Participants With Clinical Remission as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤ 10 at Week 52
Pediatric Crohn's Disease Activity Index (PCDAI) is an index used to measure disease activity of pediatric patients with Crohn's Disease assessing abdominal pain, stool frequency, patient functioning, hematocrit erythrocyte sedimentation rate, albumin, weight, height, examination of abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100 with higher scores indicating more active disease. Clinical remission was defined as PCDAI score of ≤ 10.
The comparison was between High-Dose adalimumab versus Low-Dose adalimumab in the intent-to treat population.
Measured: Week 52
Percent of Participants With Clinical Response as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 26
Pediatric Crohn's Disease Activity Index (PCDAI) is an index used to measure disease activity of pediatric patients with Crohn's Disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, examination of abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. Clinical response was defined as a decrease from Baseline in the PCDAI score of at least 15 points. The comparison was High-Dose adalimumab versus Low-Dose in the ITT population.
Measured: Week 26
Percent of Participants With Clinical Response as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 52
Pediatric Crohn's Disease Activity Index (PCDAI) is an index used to measure disease activity of pediatric patients with Crohn's Disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, examination of abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. Clinical response was defined as a decrease from Baseline in the PCDAI score of at least 15 points. The comparison was High-Dose adalimumab versus Low-Dose in the ITT population.
Measured: Week 52
Change From Baseline IMPACT III Scores at Week 26 (Observed Case)
The IMPACT III questionnaire is a 35-item assessment of health-related quality of life in patients with inflammatory bowel disease (Crohn's disease [CD] or ulcerative colitis). In this study, subjects greater than or equal 10 years old who had CD at baseline completed an IMPACT III questionnaire at Baseline, Week 26, and Week 52. Subjects marked an option from 1 to 5 for each item left to right with numbers 5 (good 'quality of life' condition) through 1 (bad 'quality of life' condition). The total scores, range from 35 to 175 with higher scores representing a better quality of life.
Measured: Baseline and Week 26
Change From Baseline IMPACT III Scores at Week 52 (Observed Case)
The IMPACT III questionnaire is a 35-item assessment of health-related quality of life in patients with inflammatory bowel disease (Crohn's disease [CD] or ulcerative colitis). In this study, subjects greater than or equal 10 years old who had CD at baseline completed an IMPACT III questionnaire at Baseline, Week 26, and Week 52. Subjects marked an option from 1 to 5 for each item left to right with numbers 5 (good 'quality of life' condition) through 1 (bad 'quality of life' condition). The total scores, range from 35 to 175 with higher scores representing a better quality of life.
Measured: Baseline and Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2006 (estimated)
- Study startApr 2007
- Primary completionMay 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abbott
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Roopal Thakkar, Study director, Abbott
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00409682
- Sponsor's protocol ID
- M06-806
- Other IDs
- 2006-004814-41
- Status last verified
- Jul 2011
- First submitted
- 8 Dec 2006
- Last updated
- 4 Aug 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Horneff G, Seyger MMB, Arikan D, Kalabic J, Anderson JK, Lazar A, Williams DA, Wang C, Tarzynski-Potempa R, Hyams JS. Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's Disease. J Pediatr. 2018 Oct;201:166-175.e3. doi: 10.1016/j.jpeds.2018.05.042. Epub 2018 Jul 25.
PubMed 30054164Ruemmele FM, Rosh J, Faubion WA, Dubinsky MC, Turner D, Lazar A, Eichner S, Maa JF, Alperovich G, Robinson AM, Hyams JS. Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn's Disease: Results from IMAgINE 1 and IMAgINE 2. J Crohns Colitis. 2018 Nov 9;12(10):1249-1254. doi: 10.1093/ecco-jcc/jjy087.
PubMed 29939254Hyams JS, Griffiths A, Markowitz J, Baldassano RN, Faubion WA Jr, Colletti RB, Dubinsky M, Kierkus J, Rosh J, Wang Y, Huang B, Bittle B, Marshall M, Lazar A. Safety and efficacy of adalimumab for moderate to severe Crohn's disease in children. Gastroenterology. 2012 Aug;143(2):365-74.e2. doi: 10.1053/j.gastro.2012.04.046. Epub 2012 May 2.
PubMed 22562021
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Double-Blind Study to Evaluate the Safety, Efficacy and Pharmacokinetics of the Human Anti-TNF Monoclonal Antibody Adalimumab in Pediatric Subjects With Moderate to Severe Crohn's Disease
- ClinicalTrials.gov ID
- NCT00409682
- Acronym / sponsor ID
- M06-806
- Conditions
- Crohn's Disease
- Keywords
- Crohn's Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- AbbottIndustry (pharma, biotech, devices)
- Study start
- Apr 2007
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 11 Dec 2006 (estimated)
- Results
- Posted 4 Aug 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine Efficacy, Pharmacokinetics, and Safety of Adalimumab in Pediatric Subjects With Moderate to Severe Crohn's Disease
Detailed description
M06-806 (NCT # NCT00409682) was a Phase 3, multi-center, randomized, double-blind (DB), efficacy, safety, and pharmacokinetic (PK) study designed to evaluate the efficacy of 2 dose regimens for the induction and maintenance of clinical remission in pediatric subjects between the ages of 6 and 17 (inclusive) with moderate to severe Crohn's disease (CD) (defined by Pediatric Crohn's Disease Activity Index [PCDAI > 30]). Subjects must have either failed conventional therapy for CD or have previously received infliximab and lost response/had intolerance to infliximab.
Approximately 186 pediatric subjects between the ages of 6 and 17 were planned to be entered into the study at approximately 55 sites in the US, Canada, and Europe. At least 80 subjects were to be ≥ 13 years old at Baseline and one-third to one-half of the study population were to be subjects who had previously lost response or were intolerant to infliximab.
The duration of the study was to be up to 65 weeks, which included a 1- to 3-week Screening period, an Induction period, a Maintenance period, and a 70-day follow-up phone call for all subjects that either terminated early from the study or did not rollover into the extension study ([NCT # 00686374], to evaluate the long-term maintenance of clinical response, safety, and tolerability of repeated administration of adalimumab).
All subjects received an induction regimen administered at Baseline (Week 0) and Week 2. The open-label (OL) induction dose was based on the subject's Baseline body weight. Subjects weighing ≥ 40 kg were to receive 160 mg at Week 0 and 80 mg adalimumab at Week 2. Subjects weighing < 40 kg were to receive 80 mg at Week 0 and 40 mg adalimumab at Week 2.
At Week 4, subjects were to be randomized 1:1 to 1 of 2 DB maintenance treatment groups (Low-Dose or High-Dose), stratified by Week 4 clinical responder status (clinical response was defined as decrease in PCDAI of ≥ 15 points from the Baseline score), body weight at Week 4 and prior exposure to infliximab. Subjects randomized to the High-Dose treatment group were to receive either 40 mg adalimumab subcutaneous (SC) every other week (eow) (if Week 4 body weight ≥ 40 kg) or 20 mg adalimumab SC eow (if Week 4 body weight < 40 kg). Subjects randomized to the Low-Dose treatment group were to receive either 20 mg adalimumab SC eow (if Week 4 body weight ≥ 40 kg) or 10 mg adalimumab SC eow (if Week 4 body weight < 40 kg).
Subject's body weight taken at Week 26 was to be used to readjust the maintenance dosing regimen for a subject whose body weight had increased from < 40 kg to ≥ 40 kg during the study.
Subjects were expected to remain on blinded eow therapy throughout the 48-week study DB Maintenance period. However, starting at the Week 12 study visit, subjects who experienced a disease flare (increase in the PCDAI ≥ 15 points when compared to Week 4 and an absolute PCDAI above 30) or were non-responders (not achieving a decrease in the PCDAI score of at least 15 points when compared to the Baseline score for 2 consecutive visits at least 2 weeks apart) could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. During blinded ew treatment, if a subject continued to experience a flare or met the definition of non-response following an 8 week course of DB ew therapy, they were to be switched to OL ew therapy. The dosage of the OL ew therapy was 20 mg for subjects < 40 kg and 40 mg for subjects ≥ 40 kg.
This study used the PCDAI to determine efficacy of the study drug. The primary efficacy endpoint is the proportion of subjects who are in clinical remission at Week 26, as measured by the PCDAI in the intent-to-treat population. Clinical remission is defined as a PCDAI score of ≤ 10.
The clinical response indicators include clinical remission as defined by PCDAI score at Week 52 and clinical response as defined by PCDAI score at Week 26 and at Week 52.
The patient reported outcome is the change from Baseline in total IMPACT III scores at Week 26 and Week 52.
The safety parameters (adverse events, laboratory data, and vital signs) were assessed at all visits throughout the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Open-label adalimumab (Week 0 to Week 4) | Active comparator | Biological: AdalimumabAll subjects received an open-label adalimumab induction regimen. Subjects weighing greater than or equal to 40 kg at Baseline received 160 mg at Week 0 and 80 mg at Week 2. Subjects weighing less than 40 kg at Baseline received 80 mg at Week 0 and 40mg at Week 2. |
| Low-Dose Adalimumab: 20 mg or 10 mg eow (Week 4 to Week 52) | Active comparator | Biological: AdalimumabSubjects randomized to the Low-Dose treatment group received either 20 mg adalimumab every other week (eow) (if Week 4 body weight [BW] was greater than or equal to 40 kg) or 10 mg adalimumab eow (if Week 4 BW less than 40 kg). Starting at the Week 12 study visit, subjects who experienced a disease flare or were non-responders could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. If a subject continued to experience a flare or met the definition of non-response following an 8-week course of double-blind (DB) ew therapy they could be switched to open-label ew therapy. |
| High-Dose Adalimumab: 40 mg or 20 mg eow (Week 4 to Week 52) | Active comparator | Biological: AdalimumabSubjects randomized to the High-Dose treatment group received either 40 mg adalimumab every other week (eow) (if Week 4 body weight [BW] was greater than or equal to 40 kg) or 20 mg adalimumab eow (if Week 4 BW less than 40 kg). Starting at the Week 12 study visit, subjects who experienced a disease flare or were non-responders could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. If a subject continued to experience a flare or met the definition of non-response following an 8-week course of double-blinded (DB) ew therapy they could be switched to open-label ew therapy. |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (22 listed)
- Subjects between the ages of 6 and 17, inclusive, prior to baseline dosing.
- Subjects with a diagnosis of Crohn's disease for greater than 12 weeks prior to screening, confirmed by endoscopy or radiologic evaluation.
- PCDAI > 30 despite concurrent treatment with an oral corticosteroid, and/or azathioprine (AZA) or 6-mercaptopurine (6-MP) or methotrexate (MTX) as defined below:
- If female, subjects who were sexually active and were of child-bearing potential practicing an approved method of birth control throughout the study and for 150 days after study completion. Examples of approved methods of birth control included the following:
- Parent or legal guardian,as required,had voluntarily signed and dated an informed consent form (IFC), approved by an Institutional Review Board (IRB)/ Independent Ethics Committee (IEC).
Key exclusion criteria (38 listed)
- History of cancer or lymphoproliferative disease other than a successfully and completely treated cutaneous squamous cell or basal cell carcinoma or carcinoma-in-situ of the cervix.
- History of listeria, histoplasmosis, chronic or active hepatitis B infection, human immunodeficiency virus (HIV), an immunodeficiency syndrome, central nervous system (CNS) demyelinating disease, or active tuberculosis (TB) (receiving treatment or not receiving treatment), severe infections such as sepsis and opportunistic infections.
- Subject with infectious colitis, ulcerative colitis or indeterminate colitis as determined by the investigator and Abbott Medical Monitor.
- Subject with symptomatic known obstructive strictures.
- Subject who had surgical bowel resections within the past 24 weeks of the Baseline visit or planned any resection at any time point while enrolled in the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdalimumabAlso: ABT-D2E7, adalimumab, HumiraAll subjects received an open-label adalimumab induction regimen. Subjects weighing greater than or equal to 40 kg at Baseline received 160 mg at Week 0 and 80 mg at Week 2. Subjects weighing less than 40 kg at Baseline received 80 mg at Week 0 and 40mg at Week 2. | Biological | Open-label adalimumab (Week 0 to Week 4) |
| AdalimumabAlso: ABT-D2E7, adalimumab, HumiraSubjects randomized to the Low-Dose treatment group received either 20 mg adalimumab every other week (eow) (if Week 4 body weight [BW] was greater than or equal to 40 kg) or 10 mg adalimumab eow (if Week 4 BW less than 40 kg). Starting at the Week 12 study visit, subjects who experienced a disease flare or were non-responders could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. If a subject continued to experience a flare or met the definition of non-response following an 8-week course of double-blind (DB) ew therapy they could be switched to open-label ew therapy. | Biological | Low-Dose Adalimumab: 20 mg or 10 mg eow (Week 4 to Week 52) |
| AdalimumabAlso: ABT-D2E7, adalimumab, HumiraSubjects randomized to the High-Dose treatment group received either 40 mg adalimumab every other week (eow) (if Week 4 body weight [BW] was greater than or equal to 40 kg) or 20 mg adalimumab eow (if Week 4 BW less than 40 kg). Starting at the Week 12 study visit, subjects who experienced a disease flare or were non-responders could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. If a subject continued to experience a flare or met the definition of non-response following an 8-week course of double-blinded (DB) ew therapy they could be switched to open-label ew therapy. | Biological | High-Dose Adalimumab: 40 mg or 20 mg eow (Week 4 to Week 52) |
Primary outcome
Percent of Participants With Clinical Remission as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤ 10 at Week 26
Time frame: Week 26
Pediatric Crohn's Disease Activity Index (PCDAI) is an index used to measure disease activity of pediatric patients with Crohn's Disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. The primary endpoint was clinical remission as defined by PCDAI score ≤ 10. The comparison was between High-Dose adalimumab versus Low-Dose adalimumab in the intent-to-treat population.
5 secondary outcomes
Percent of Participants With Clinical Remission as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤ 10 at Week 52
Time frame: Week 52
Percent of Participants With Clinical Response as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 26
Time frame: Week 26
Percent of Participants With Clinical Response as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 52
Time frame: Week 52
Change From Baseline IMPACT III Scores at Week 26 (Observed Case)
Time frame: Baseline and Week 26
Change From Baseline IMPACT III Scores at Week 52 (Observed Case)
Time frame: Baseline and Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30054164Horneff G, Seyger MMB, Arikan D, Kalabic J, Anderson JK, Lazar A, Williams DA, Wang C, Tarzynski-Potempa R, Hyams JS. Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's Disease. J Pediatr. 2018 Oct;201:166-175.e3. doi: 10.1016/j.jpeds.2018.05.042. Epub 2018 Jul 25.
- Derived from this study: PubMed 29939254Ruemmele FM, Rosh J, Faubion WA, Dubinsky MC, Turner D, Lazar A, Eichner S, Maa JF, Alperovich G, Robinson AM, Hyams JS. Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn's Disease: Results from IMAgINE 1 and IMAgINE 2. J Crohns Colitis. 2018 Nov 9;12(10):1249-1254. doi: 10.1093/ecco-jcc/jjy087.
- Derived from this study: PubMed 22562021Hyams JS, Griffiths A, Markowitz J, Baldassano RN, Faubion WA Jr, Colletti RB, Dubinsky M, Kierkus J, Rosh J, Wang Y, Huang B, Bittle B, Marshall M, Lazar A. Safety and efficacy of adalimumab for moderate to severe Crohn's disease in children. Gastroenterology. 2012 Aug;143(2):365-74.e2. doi: 10.1053/j.gastro.2012.04.046. Epub 2012 May 2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roopal Thakkar study director
Abbott
45 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Adalimumab in people with Crohn's Disease, run by Abbott at 45 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States, Canada, Belgium, Netherlands, France and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Aug 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent of Participants With Clinical Remission as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤ 10 at Week 26 (time frame: Week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00409682, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2011.