Clinical Trial Results:
A Multi-center, Open-label Study of the Human Anti−TNF Monoclonal Antibody Adalimumab to Evaluate the Efficacy and the Long-term Safety and Tolerability of Repeated Administration of Adalimumab in Pediatric Subjects with Crohn's Disease Who Have Demonstrated a Clinical Response in the M06-806 Study
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Summary
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EudraCT number |
2007-006494-90 |
Trial protocol |
BE CZ GB Outside EU/EEA |
Global end of trial date |
04 Apr 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Oct 2017
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First version publication date |
14 Oct 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
M06-807
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00686374 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
AbbVie
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Sponsor organisation address |
1 North Waukegan Road, North Chicago, IL, United States, 60064
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Public contact |
Global Medical Services, AbbVie, 001 800-633-9110,
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Scientific contact |
Andreas Lazar, AbbVie, andreas.lazar@abbvie.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
04 Apr 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Apr 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the long-term maintenance of clinical response, safety and tolerability of repeated administration of adalimumab in pediatric subjects with Crohn's disease who participated in, and successfully completed, Protocol M06-806 through Week 52 and who met all the inclusion and none of the exclusion criteria of Protocol M06-807.
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Protection of trial subjects |
Prior to any study-related screening procedures being performed, the investigator or his/her representative explained the nature of the study to the parent or guardian of the pediatric subject and answered all questions regarding the study. Subjects were included in all discussions. The informed consent form was reviewed, signed, and dated by the subject's parent or legal guardian, and by the person who administered the informed consent. If a subject became of legal age in the state of residence during the course of the study, another informed consent was to be obtained at that time. Additionally, in keeping with each institution's Institutional Review Board requirements, an informed assent was also to be obtained from the subject, as required. Subjects were to be included in all discussions in order to obtain their signature on an assent form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Feb 2008
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 19
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Country: Number of subjects enrolled |
United Kingdom: 1
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Country: Number of subjects enrolled |
Belgium: 11
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Country: Number of subjects enrolled |
Czech Republic: 8
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Country: Number of subjects enrolled |
United States: 47
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Country: Number of subjects enrolled |
Canada: 14
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Worldwide total number of subjects |
100
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EEA total number of subjects |
39
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
20
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Adolescents (12-17 years) |
80
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects enrolled in and completed Study M06-806 through Week 52 who were responders at any time point during Study M06-806 (defined as having achieved at least a 15-point reduction in Pediatric Crohn's Disease Activity Index from Baseline). | ||||||||||||||||||||
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Pre-assignment
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Screening details |
36 subjects discontinued study drug when adalimumab became commercially available (received regulatory approval for pediatric Crohn’s disease) in their country. These subjects were considered to have completed the study, and are included as study completers in the subject disposition. | ||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||
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Arms
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Arm title
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Any adalimumab | ||||||||||||||||||||
Arm description |
Adalimumab was administered via subcutaneous injection. Dosage was based on body weight and clinical status, and ranged from 10, 20, or 40 mg every other week to 20 or 40 mg every week. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Adalimumab
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Investigational medicinal product code |
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Other name |
ABT-D2E7, Humira
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects who enrolled into the study from blinded therapy in Protocol M06-806 received open-label (OL) therapy at a dose dependent on their body weight. Subjects who weighed ≥ 40 kg received 40 mg of adalimumab every other week (eow), while those who weighed < 40 kg received 20 mg of adalimumab eow. Beginning with Week 8, subjects who had a disease flare may have been switched to every week (ew) treatment at the same dose of adalimumab received while on eow treatment. Subjects who enrolled into the study from OL therapy in Protocol M06-806 continued to receive the same dose they were receiving (i.e., 40 mg ew or 20 mg ew) at the Week 52 visit of Procotol M06-806. Adalimumab dose could have been decreased to the next lower treatment level for those with body weight changes. Subjects who responded to treatment may have also had their dosage frequency decreased from ew to eow dosing, as well as a decrease in dosage.
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Baseline characteristics reporting groups
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Reporting group title |
Any adalimumab
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Reporting group description |
Adalimumab was administered via subcutaneous injection. Dosage was based on body weight and clinical status, and ranged from 10, 20, or 40 mg every other week to 20 or 40 mg every week. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Any adalimumab
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Reporting group description |
Adalimumab was administered via subcutaneous injection. Dosage was based on body weight and clinical status, and ranged from 10, 20, or 40 mg every other week to 20 or 40 mg every week. | ||
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End point title |
Number of subjects who achieved Pediatric Crohn's Disease Activity Index (PCDAI) clinical remission over time [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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. Clinical remission was defined as PCDAI ≤ 10.
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End point type |
Primary
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End point timeframe |
Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics are presented, per protocol. |
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| Notes [2] - ITT population:subjects who rcvd ≥ 1 dose of adalimumab and had ≥ 1 non-missing efficacy measurement |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of subjects with clinical response as defined by Pediatric Crohn's Disease Activity Index (PCDAI) score over time [3] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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 baseline PCDAI value was defined as the last non-missing value on or before the date of the first dose of study drug during Protocol M06-806. Clinical response was defined as a PCDAI ≥ 15 points lower than the Protocol M06-806 baseline PCDAI value.
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End point type |
Primary
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End point timeframe |
Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics are presented, per protocol. |
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| Notes [4] - ITT population:subjects who rcvd ≥ 1 dose of adalimumab and had ≥ 1 non-missing efficacy measurement |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of subjects who were in Crohn’s Disease Activity Index (CDAI) clinical remission over time | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The CDAI includes 8 variables encompassing both subject-reported (symptoms, general well-being) and objective (medication usage, laboratory variables, presence of abdominal mass or complications, and weight) variables. For symptoms scores, subjects kept track of daily symptoms on a diary card, and the daily symptom scores were summed for the week. Each item in the CDAI is assigned a specific weight, and the weighted values of the items are totaled to produce the CDAI score. Higher CDAI scores indicate greater disease activity; 0 is the lower limit with no set upper limit. The scale for the score is as follows: < 150 to indicate remission, 150 - 219 to define mildly active disease, 220 - 450 to define moderately active disease, and > 450 to define severely active disease. A CDAI was calculated at each visit for subjects who were age 13 or older at Protocol M06-806 entry. The Protocol M06-806 Week 52 visit served as the baseline visit for this study.
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End point type |
Secondary
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End point timeframe |
Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408
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| Notes [5] - Subjects ≥ 13 years old at M06-806 entry;rcvd ≥ 1 dose adalimumab;had ≥ 1 non-missing efficacy meas |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of subjects who were in Crohn’s Disease Activity Index (CDAI) clinical response over time | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The CDAI includes 8 variables: subject-reported (symptoms, general well-being) and objective (medication usage, laboratory variables, presence of abdominal mass or complications, and weight). Subjects kept track of symptoms on a diary card, and scores were summed for the week. Each item is assigned a specific weight, and the weighted values of the items are totaled to produce the CDAI score. Higher CDAI scores indicate greater disease activity; 0 is the lower limit with no set upper limit. Scale: < 150 (remission), 150 - 219 (mildly active disease), 220 - 450 (moderately active disease), and > 450 (severely active disease). A CDAI was calculated at each visit for subjects ≥ 13 yrs old at M06-806 entry. Clinical response was defined as a decrease from M06-806 Baseline CDAI value of ≥ 70 pts. The M06-806 Baseline value was defined as the last non-missing value on or before the date of the 1st dose of study drug in M06-806.
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End point type |
Secondary
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End point timeframe |
Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408
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| Notes [6] - Subjects ≥ 13 years old at M06-806 entry;rcvd ≥ 1 dose adalimumab;had ≥ 1 non-missing efficacy meas |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of subjects in Steroid-free Pediatric Crohn's Disease Activity Index (PCDAI) remission over time | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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. PCDAI corticosteroid-free remission was defined as discontinued corticosteroid use at least 90 consecutive days prior to the respective visit, with a PCDAI ≤ 10 at that visit.
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End point type |
Secondary
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End point timeframe |
Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384
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| Notes [7] - Corticosteroid use at M06-806 entry; rcvd ≥ 1 dose adalimumab; ≥ 1 non-missing efficacy measurement |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of subjects in Steroid-free Crohn's Disease Activity Index (CDAI) remission over time | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The CDAI includes 8 variables encompassing subject-reported (symptoms, general well-being) and objective (medication usage, laboratory variables, presence of abdominal mass or complications, and weight) variables. Subjects kept track of daily symptoms on a diary card, and the scores were summed for the week. Each item in the CDAI is assigned a specific weight, and the items are totaled to produce the CDAI score. Higher CDAI scores indicate greater disease activity; 0 is the lower limit with no set upper limit. The scale for the score is as follows: < 150 (remission), 150 - 219 (mildly active disease), 220 - 450 (moderately active disease), and > 450 (severely active disease). A CDAI was calculated at each visit for subjects ≥ 13 years old at M06-806 entry. CDAI corticosteroid-free remission was defined as discontinued use at least 90 consecutive days prior to the respective visit and a CDAI < 150 at that visit.
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End point type |
Secondary
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End point timeframe |
Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384
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| Notes [8] - ≥ 13 yrs, corticosteroid use at M06-806 entry;rcvd ≥ 1 dose adalimumab;≥ 1 non-missing efficacy meas |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Mean change from baseline in Pediatric Crohn's Disease Activity Index (PCDAI) over time | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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 baseline value was defined as the last non-missing value on or before the date of the first dose of study drug in Study M06-806. Negative changes indicate reductions (improvement) in disease activity.
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End point type |
Secondary
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End point timeframe |
Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384
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| Notes [9] - ITT population:subjects who rcvd ≥ 1 dose of adalimumab and had ≥ 1 non-missing efficacy measurement |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Mean change from baseline in Crohn's Disease Activity Index (CDAI) over time | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The CDAI includes 8 variables: subject-reported (symptoms, general well-being) and objective (medication usage, laboratory variables, presence of abdominal mass or complications, and weight) variables. For symptoms scores, subjects kept track of daily symptoms on a diary card, and the scores were summed for the week. Each item in the CDAI is assigned a specific weight, and the items are totaled to produce the CDAI score. Higher CDAI scores indicate greater disease activity; 0 is the lower limit with no set upper limit. The scale for the score is as follows: < 150 (remission), 150 - 219 (mildly active disease), 220 - 450 (moderately active disease) and > 450 (severely active disease). A CDAI was calculated at each visit for subjects who were ≥ 13 years old at Protocol M06-806 entry. The baseline value was defined as the last non-missing value on or before the date of the first dose of study drug in Study M06-806. Negative changes indicate reductions (improvement) in disease activity.
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End point type |
Secondary
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End point timeframe |
Week 0, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384
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| Notes [10] - Subjects ≥ 13 years old at M06-806 entry;rcvd ≥ 1 dose adalimumab;had ≥ 1 non-missing efficacy meas |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration in Protocol M06-806 until 70 days after the last dose of study drug in Protocol M06-807 (up to 470 weeks).
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Adverse event reporting additional description |
TEAEs and TESAEs are defined as any adverse event (AE) or serious adverse event (SAE) with an onset date that is after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Any adalimumab
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Reporting group description |
Adalimumab was administered via subcutaneous injection. Dosage was based on body weight and clinical status, and ranged from 10, 20, or 40 mg every other week to 20 or 40 mg every week. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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10 Oct 2008 |
Amendment 1
● Updated Inclusion Criterion #2 to clarify that subject must be responder during Study M06-806.
● Amended the stopping rules as follows: The rate of possibly related SAEs or higher, on a per subject per year basis in excess of 0.45, was changed to the proportion of SAEs, possibly related or higher, on a per subject basis in excess of 0.20.
● Changed overall rate, in excess of 0.09 infectious SAEs on a per subject per year basis to the overall proportion of infectious SAEs in excess of 0.20 on a per subject basis.
● Changed the protocol paragraph with text "If either of these criteria is met, no new enrollment will occur until the Data Monitoring Committee (DMC) or the Sponsor Steering Committee makes their recommendations" to "If either of the above criteria is met, the DMC will meet within 2 weeks to consider whether or not to recommend a temporary suspension of enrollment."
● Removed Section 12.2 re: publication.
● Administrative Changes:
○ Updated approvals from other indications to reflect the most current data available.
○ Updated Safety Hotline address and contact information for AE reporting.
○ Updated to add reference for current guidelines for treatment of latent TB to reference list.
○ Appendix C (Documents Required Prior to Initiation of the Study): updated to reflect current regulatory requirements.
○ Appendix D (Responsibilities of the Clinical investigator): updated to reflect current regulatory requirements.
○ Appendix E (Centers for Disease Control [CDC] Treatment of Tuberculosis Infection [Preventive Therapy]): updated with current guidelines for treatment of latent TB.
○ Appendix H (PCDAI User's Guide and Guideline for Reference Weight and Height): updated to clarify from Wk 48 to Wk 72 and from post Wk 72, using height from Wk 48.
○ Appendix L (Excluded Medications): updated to state any previous anti TNF medication except infliximab before Study M06-806
○ Appendix M (Day 70 Phone Call): updated faxing contact info. |
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26 Aug 2010 |
Amendment 2
● Added blood sample collections for adalimumab concentration and AAA assays.
● Changed the stopping criteria for study based on discussion and recommendation by the DMC members.
● Added subject visits through Week 264 and provided for study to continue until local regulatory approval.
● Incorporated Administrative Changes 3 through 6 into this protocol.
● Added a new required template for protocol signatories (Appendix B).
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14 Dec 2010 |
Amendment 3
● Included an interim analysis.
● Clarified that the x-ray for bone age was not to be performed at the unscheduled visit.
● Added a statement allowing the investigator to omit the x-ray for bone age and the determination of serum bone markers if the subject was no longer growing.
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29 Jun 2011 |
Amendment 4
● Allowed dose and frequency decrease in subjects who responded well to treatment, allowed dose adjustment due to weight loss, and added 10 mg eow dosage. |
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03 Jan 2012 |
Amendment 5
● Added in regular TB testing in response to the US Food and Drug Administration required labeling change based on cases of reactivation of TB/occurrence or new TB infections in patients receiving Humira. The US package insert now says retest should be done "periodically" during therapy, without specifying the interval. Based on the actual US package insert and on literature search, annual TB rescreening was implemented as a reasonable interval. |
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12 Apr 2013 |
Amendment 6
● Added subject visits through Week 336 to extend the study.
● Section 3.0, Section 5.2.3.1, and Section 6.5 were revised to include additional anti-TNF information per Humira standards, and provided background information about enhanced data collection to understand the risks of malignancy in subjects 30 and younger.
● Section 5.2.3.2 Concomitant Therapy was revised to allow immunosuppressant to be started or restarted during the study. In addition, a sentence regarding the use of therapeutic enemas, suppositories and TPN was added to encourage the investigator to discuss with the Medical Monitor prior to use.
● In Section 5.2.3.4 Prohibited Medication, the use of therapeutic enemas and suppositories was removed.
● Section 5.3.1.1 Study Procedures (Outcomes): A clarification on the completion procedure of the WPAI-CD Caregiver was added.
● Section 5.3.2.1 Collection of samples for analysis: A clarification on collecting samples for subjects who require switching or change dose was added.
● Section 5.5.2.1 Packaging and Labeling was revised.
● Section 6.6 Pregnancy: The verbiage regarding the pregnancy registry was removed, as the registry is closed to Humira subjects and is only enrolling in the comparator (non-Humira) arm.
● Incorporated Administrative Change 7 into this protocol.
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26 May 2015 |
Amendment 7
● Added subject visits through Week 408 (approximately 8 years) to extend the study and provide for study to continue until local regulatory approval.
● Added the Complaint and Product Complaint definition to Sections 6.0, 6.2.1, and 6.2.2 as well as the reporting requirements for Product Complaints.
● Updated Section 8.1.5, Interim Analysis.
● Incorporated Administrative Changes 8 and 9 into this protocol.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/28129288 |
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