Crohn's Disease
Conditions
Brief summary
To evaluate the long-term maintenance of response, safety and tolerability of repeated administration of adalimumab in subjects with Crohn's disease who participated in and successfully completed Protocol M02-404 or Protocol M04-691.
Interventions
BIOLOGICALAdalimumab
Adalimumab 40 mg by subcutaneous injection every other week or every week
Sponsors
Abbott
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subject must have successfully completed either the M02-404 (NCT00077779) or M04-691 (NCT00105300) protocol to be eligible for this study * Diagnosis of Crohn's disease * Willing and able to give informed consent
Exclusion criteria
* Diagnosis of ulcerative colitis * Women cannot be pregnant or breastfeeding * Previous history of listeria infection or untreated tuberculosis * Previous history of cancer other than successfully treated skin cancer or carcinoma-in-situ of the cervix
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving Clinical Remission | Week 156 | Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of \< 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving Clinical Response 100 (CR-100) | Week 156 | A CR-100 is a decrease from baseline in CDAI score of 100 or more points. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity. |
| Percentage of Subjects Achieving Clinical Response 70 (CR-70) | Week 156 | A CR-70 is a decrease from baseline in CDAI score of 70 or more points. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity. |
| Percentage of Subjects Achieving Steroid-free Clinical Remission | Week 156 | Steroid-free remission was achieved if the subject stopped taking steroids before the visit and had a Crohn's Disease Activity Index (CDAI) score of \<150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity. |
| Percentage of Subjects Achieving Steroid-free CR-100 | Week 156 | Steroid-free CR-100 was achieved if the subject stopped taking steroids before the visit and had a decrease from baseline in CDAI score of 100 or more points at that visit. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity. |
| Percentage of Subjects With Fistula Remission | Week 156 | Fistula remission was defined as the absence of draining fistulas in subjects with fistula present at the preceding study's baseline visit. |
| Percentage of Subjects With Infection | Up to 262 weeks of adalimumab treatment | — |
| Percentage of Subjects With Serious Infection | Up to 262 weeks of adalimumab treatment | Serious infections are infectious adverse events that meet at least one criterion for a serious adverse event (e.g., death, life threatening event, hospitalization) including tuberculosis (TB), bacterial sepsis, invasive fungal infections (e.g., histoplasmosis), and infections due to other opportunistic pathogens. |
| Percentage of Subjects With Malignancy | Up to 262 weeks of adalimumab treatment | — |
| Percentage of Subjects With Lymphoma | Up to 262 weeks of adalimumab treatment | — |
| Percentage of Subjects With Nonmelanoma Skin Cancer | Up to 262 weeks of adalimumab treatment | — |
| Percentage of Subjects Achieving Clinical Remission | Week 48 | Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of \< 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity. |
| Percentage of Subjects With Malignancy (Including Lymphoma, Excluding Nonmelanoma Skin Cancer) | Up to 262 weeks of adalimumab treatment | — |
| Percentage of Subjects With Injection Site Reaction-related Adverse Event | Up to 262 weeks of adalimumab treatment | An injection site reaction is any adverse event corresponding to a preferred term beginning with injection site excluding injection site arthritis, injection site movement impairment, injection site photosensitivity, injection site joint effusion, injection site joint inflammation, injection site scab, injection site joint pain, or injection site laceration. |
| Percentage of Subjects With Opportunistic Infection (Excluding Tuberculosis) | Up to 262 weeks of adalimumab treatment | — |
| Percentage of Subjects With Congestive Heart Failure | Up to 262 weeks of adalimumab treatment | — |
| Percentage of Subjects With Demyelinating Disease | Up to 262 weeks of adalimumab treatment | — |
| Percentage of Subjects With Hepatic-related Adverse Event | Up to 262 weeks of adalimumab treatment | — |
| Percentage of Subjects With Allergic Reaction-related Adverse Event | Up to 262 weeks of adalimumab treatment | — |
| Percentage of Subjects With Lupus-like Syndrome | Up to 262 weeks of adalimumab treatment | — |
| Percentage of Subjects With Hematologic-related Adverse Event | Up to 262 weeks of adalimumab treatment | — |
| Percentage of Subjects With Fatal Adverse Event | Up to 262 weeks of adalimumab treatment | — |
| Percentage of Subjects With Malignancy (Excluding Nonmelanoma Skin Cancer and Lymphoma) | Up to 262 weeks of adalimumab treatment | — |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Hungary, Italy, Netherlands, Poland, South Africa, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open-label Adalimumab 40 mg by subcutaneous injection every other week or every week | 777 |
| Total | 777 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative reasons | 2 |
| Overall Study | Adverse Event | 122 |
| Overall Study | Colonic stricture | 1 |
| Overall Study | Increased infection rate | 1 |
| Overall Study | Ineligible | 1 |
| Overall Study | Investigative site closure | 8 |
| Overall Study | Investigator's decision | 2 |
| Overall Study | Lack of Efficacy | 93 |
| Overall Study | Loss of response/no improvement | 3 |
| Overall Study | Lost to Follow-up | 27 |
| Overall Study | Planned surgery | 2 |
| Overall Study | Pregnancy | 14 |
| Overall Study | Protocol Violation | 13 |
| Overall Study | Sponsor discontinued trial | 1 |
| Overall Study | Sponsor discretion - trial ended early | 1 |
| Overall Study | Sponsor stopped study | 1 |
| Overall Study | Subject choice | 3 |
| Overall Study | Subject moved/relocated | 7 |
| Overall Study | Subject non-compliance | 6 |
| Overall Study | Subject started commercial Humira | 5 |
| Overall Study | Subject wants to get pregnant | 4 |
| Overall Study | Use of prohibited medication | 2 |
| Overall Study | Withdrawal by Subject | 58 |
Baseline characteristics
| Characteristic | Open-label Adalimumab |
|---|---|
| Age Continuous | 38.0 years STANDARD_DEVIATION 11.75 |
| Region of Enrollment Australia | 40 participants |
| Region of Enrollment Belgium | 66 participants |
| Region of Enrollment Canada | 197 participants |
| Region of Enrollment Denmark | 18 participants |
| Region of Enrollment France | 24 participants |
| Region of Enrollment Germany | 5 participants |
| Region of Enrollment Hungary | 8 participants |
| Region of Enrollment Italy | 9 participants |
| Region of Enrollment Netherlands | 10 participants |
| Region of Enrollment Poland | 12 participants |
| Region of Enrollment South Africa | 20 participants |
| Region of Enrollment Spain | 3 participants |
| Region of Enrollment Sweden | 5 participants |
| Region of Enrollment United Kingdom | 11 participants |
| Region of Enrollment United States | 349 participants |
| Sex: Female, Male Female | 485 Participants |
| Sex: Female, Male Male | 292 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 720 / 777 |
| serious Total, serious adverse events | 296 / 777 |
Outcome results
Primary
Percentage of Subjects Achieving Clinical Remission
Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of \< 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time frame: Week 156
Population: Intent-to-treat, defined as all subjects who received at least 1 dose of study drug; Observed Cases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects Achieving Clinical Remission | 69.5 Percentage of participants |
Secondary
Percentage of Subjects Achieving Clinical Remission
Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of \< 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time frame: Week 48
Population: Intent-to-treat, Observed Cases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects Achieving Clinical Remission | 59.4 Percentage of participants |
Secondary
Percentage of Subjects Achieving Clinical Remission
Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of \< 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time frame: Week 108
Population: Intent-to-treat, Observed Cases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects Achieving Clinical Remission | 68.8 Percentage of participants |
Secondary
Percentage of Subjects Achieving Clinical Remission
Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of \< 150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time frame: Week 204
Population: Intent-to-treat, Observed Cases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects Achieving Clinical Remission | 46.7 Percentage of participants |
Secondary
Percentage of Subjects Achieving Clinical Response 100 (CR-100)
A CR-100 is a decrease from baseline in CDAI score of 100 or more points. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time frame: Week 156
Population: Intent-to-treat, Observed Cases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects Achieving Clinical Response 100 (CR-100) | 85.7 Percentage of participants |
Secondary
Percentage of Subjects Achieving Clinical Response 70 (CR-70)
A CR-70 is a decrease from baseline in CDAI score of 70 or more points. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time frame: Week 156
Population: Intent-to-treat, Observed Cases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects Achieving Clinical Response 70 (CR-70) | 91.2 Percentage of participants |
Secondary
Percentage of Subjects Achieving Steroid-free Clinical Remission
Steroid-free remission was achieved if the subject stopped taking steroids before the visit and had a Crohn's Disease Activity Index (CDAI) score of \<150. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time frame: Week 156
Population: Intent-to-treat, Subjects with steroid use at baseline of preceding study, Observed Cases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects Achieving Steroid-free Clinical Remission | 63.1 Percentage of participants |
Secondary
Percentage of Subjects Achieving Steroid-free CR-100
Steroid-free CR-100 was achieved if the subject stopped taking steroids before the visit and had a decrease from baseline in CDAI score of 100 or more points at that visit. The CDAI is a weighted composite score of 8 clinical factors measured over a 1-week period. A lower CDAI score indicates lesser disease severity.
Time frame: Week 156
Population: Intent-to-treat, Subjects with corticosteroid use at baseline of preceding study, Observed Cases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects Achieving Steroid-free CR-100 | 74.8 Percentage of participants |
Secondary
Percentage of Subjects With Allergic Reaction-related Adverse Event
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Allergic Reaction-related Adverse Event | 2.7 Percentage of participants |
Secondary
Percentage of Subjects With Congestive Heart Failure
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Congestive Heart Failure | 0 Percentage of subjects |
Secondary
Percentage of Subjects With Demyelinating Disease
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Demyelinating Disease | 0.3 Percentage of participants |
Secondary
Percentage of Subjects With Fatal Adverse Event
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Fatal Adverse Event | 0.3 Percentage of participants |
Secondary
Percentage of Subjects With Fistula Remission
Fistula remission was defined as the absence of draining fistulas in subjects with fistula present at the preceding study's baseline visit.
Time frame: Week 156
Population: Intent-to-treat, Subjects with fistulas present at baseline of the preceding study, Observed Cases
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Fistula Remission | 55.8 Percentage of participants |
Secondary
Percentage of Subjects With Hematologic-related Adverse Event
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Hematologic-related Adverse Event | 1.5 Percentage of participants |
Secondary
Percentage of Subjects With Hepatic-related Adverse Event
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Hepatic-related Adverse Event | 8.1 Percentage of participants |
Secondary
Percentage of Subjects With Infection
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population, defined as all subjects who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Infection | 80.2 Percentage of participants |
Secondary
Percentage of Subjects With Injection Site Reaction-related Adverse Event
An injection site reaction is any adverse event corresponding to a preferred term beginning with injection site excluding injection site arthritis, injection site movement impairment, injection site photosensitivity, injection site joint effusion, injection site joint inflammation, injection site scab, injection site joint pain, or injection site laceration.
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Injection Site Reaction-related Adverse Event | 22.8 Percentage of participants |
Secondary
Percentage of Subjects With Lupus-like Syndrome
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Lupus-like Syndrome | 0.4 Percentage of participants |
Secondary
Percentage of Subjects With Lymphoma
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Lymphoma | 0.1 Percentage of participants |
Secondary
Percentage of Subjects With Malignancy
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Malignancy | 4.1 Percentage of participants |
Secondary
Percentage of Subjects With Malignancy (Excluding Nonmelanoma Skin Cancer and Lymphoma)
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Malignancy (Excluding Nonmelanoma Skin Cancer and Lymphoma) | 2.3 Percentage of participants |
Secondary
Percentage of Subjects With Malignancy (Including Lymphoma, Excluding Nonmelanoma Skin Cancer)
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Malignancy (Including Lymphoma, Excluding Nonmelanoma Skin Cancer) | 2.4 Percentage of participants |
Secondary
Percentage of Subjects With Nonmelanoma Skin Cancer
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Nonmelanoma Skin Cancer | 1.8 Percentage of participants |
Secondary
Percentage of Subjects With Opportunistic Infection (Excluding Tuberculosis)
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Opportunistic Infection (Excluding Tuberculosis) | 4.9 Percentage of participants |
Secondary
Percentage of Subjects With Serious Infection
Serious infections are infectious adverse events that meet at least one criterion for a serious adverse event (e.g., death, life threatening event, hospitalization) including tuberculosis (TB), bacterial sepsis, invasive fungal infections (e.g., histoplasmosis), and infections due to other opportunistic pathogens.
Time frame: Up to 262 weeks of adalimumab treatment
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Adalimumab | Percentage of Subjects With Serious Infection | 10.6 Percentage of participants |