Crohn's Disease
Conditions
Keywords
Crohn's Disease, Pharmacokinetics
Brief summary
The purpose of this study is to investigate the efficacy, safety, and pharmacokinetics of adalimumab following subcutaneous (SC) administration of 2 dosing regimens in Chinese subjects with Crohn's disease.
Interventions
BIOLOGICALAdalimumab
Adalimumab pre-filled syringe, administered by subcutaneous injection.
BIOLOGICALPlacebo for adalimumab
Placebo for adalimumab pre-filled syringe, administered by subcutaneous injection to maintain double-blind.
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects of Chinese descent with full Chinese parentage. 2. Diagnosis of Crohn's disease (CD) for at least 3 months prior to Week 0 confirmed by endoscopy, radiologic evaluation, and/or histology during the Screening Period. 3. Crohn's Disease Activity Index (CDAI) ≥ 220 and ≤ 450 despite treatment with oral corticosteroids and/or immunosuppressants. 4. Subject has a negative Tuberculosis (TB) Screening Assessment.
Exclusion criteria
1. Subject with ulcerative colitis or indeterminate colitis. 2. Subject who has had a surgical bowel resection within the past 6 months or who is planning any resection at any time point in the future. 3. Subject with an ostomy or ileoanal pouch. 4. Subject who has short bowel syndrome. 5. Subject with symptomatic known obstructive strictures. 6. Subject with an internal or external fistula (with the exception of an anal fistula without abscess). 7. Chronic recurring infections or active TB.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Serum Adalimumab Concentration at Week 8 | Week 8 | Blood samples were drawn prior to drug administration. Adalimumab concentrations in serum were determined using a validated enzyme-linked immunosorbent assay (ELISA) method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Potentially Significant Hematology Parameters During Administration of Adalimumab | 26 weeks | The number of participants with an abnormal laboratory result meeting Common Toxicity Criteria (CTC) Version 3.0 (or later) of Grade 3 or higher is summarized. n=the number of participants with CTC Grade \<3 at baseline and a post-baseline value for each parameter. |
| Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab | From Week 0 to Week 26 | The number of participants with an abnormal laboratory result meeting Common Toxicity Criteria (CTC) Version 3.0 (or later) of Grade 3 or higher is summarized. |
| Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab | 26 weeks | Blood pressure and pulse were measured while the participant was sitting. The number of participants with a postbaseline vital sign result that meets Common Toxicity Criteria (CTC) version 3.0 (or later) Grade 3 or higher and is also more extreme than the baseline value is summarized. Terms abbreviated in the table include systolic blood pressure (SBP) and diastolic blood pressure (DBP). Increase and decrease are signified by ↑ and ↓, respectively. |
| Number of Participants With Adverse Events (AEs) | 35 weeks | An AE is any untoward medical occurrence in a participant which does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs or TESAE) are defined as any event that began or worsened in severity after the first dose of study drug. The investigator assessed the relationship of each event to the use of study drug as either Reasonable possibility or No reasonable possibility of being related to study drug. For more details on adverse events please see the AE section below. |
| Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26 | CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. A score below 150 indicates remission and a score of 220 to 450 reflects moderate to severe disease. Non-responder imputation (NRI) for missing CDAI observations was used. |
| CDAI: Mean Change From Baseline to Each Visit | Baseline (Week 0) and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26 | CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. Scores range from 0 to approximately 600. A score below 150 indicates remission and a score of 220 to 450 reflects moderate to severe disease. Last observation carried forward (LOCF) for missing CDAI observations was used. |
| Fecal Calprotectin: Change From Baseline (Week 0) to Week 8 | Baseline (Week 0) and Weeks 4 and 8 | Stool samples for fecal calprotectin were collected before study drug administration when possible. Decreases in calprotectin are associated with decreased inflammation in the gastrointestinal tract. LOCF was used for missing data. |
| High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Baseline (Week 0) and Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and 26 | hsCRP was measured from blood samples as a marker for inflammation. Higher levels are indicative of more inflammation. Normal concentration in healthy human serum is usually lower than 3 mg/L, slightly increasing with age. LOCF was used for missing data. |
| Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26 | CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. A score below 150 indicates remission and a score of 220 to 450 reflects moderate to severe disease. Non-responder imputation (NRI) for missing CDAI observations was used. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Positive for Anti-Adalimumab Antibodies (AAA) From Baseline to Week 8 | Baseline (Week 0) to Week 8 | Serum samples with adalimumab concentration below 2 μg/mL were selected for AAA analyses. Samples were considered AAA positive if the measured AAA concentration was above 2 μg/mL. A subject was considered to be AAA positive if the subject had at least one AAA positive sample observed within 30 days following the subject's last adalimumab dose. No samples were tested because all samples had adalimumab concentrations \>2 μg/mL. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Induction Dose Participants received the low loading dose of adalimumab (80 mg at Week 0) followed by the standard maintenance dose of adalimumab (40 mg every other week) at Weeks 2, 4, and 6. | 15 |
| Standard Induction Dose Participants received the standard loading dose of adalimumab (160 mg at Week 0 and 80 mg at Week 2) followed by the standard maintenance dose of adalimumab (40 mg every other week) at Weeks 4 and 6. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Low Induction Dose | Standard Induction Dose | Total |
|---|---|---|---|
| Age, Continuous | 33.5 years STANDARD_DEVIATION 14.6 | 35.6 years STANDARD_DEVIATION 13 | 34.5 years STANDARD_DEVIATION 13.63 |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 15 | 7 / 15 | 6 / 13 | 6 / 14 |
| serious Total, serious adverse events | 1 / 15 | 1 / 15 | 1 / 13 | 2 / 14 |
Outcome results
Primary
Mean Serum Adalimumab Concentration at Week 8
Blood samples were drawn prior to drug administration. Adalimumab concentrations in serum were determined using a validated enzyme-linked immunosorbent assay (ELISA) method.
Time frame: Week 8
Population: All participants in the intent-to-treat (ITT) population, defined as all randomized participants who received at least 1 dose of double-blind study drug, who had evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Induction Dose | Mean Serum Adalimumab Concentration at Week 8 | 7.99 μg/mL | Standard Deviation 3.48 |
| Standard Induction Dose | Mean Serum Adalimumab Concentration at Week 8 | 10.0 μg/mL | Standard Deviation 4.57 |
Secondary
CDAI: Mean Change From Baseline to Each Visit
CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. Scores range from 0 to approximately 600. A score below 150 indicates remission and a score of 220 to 450 reflects moderate to severe disease. Last observation carried forward (LOCF) for missing CDAI observations was used.
Time frame: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26
Population: ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 14 | -193.63 units on a scale | Standard Deviation 97.13 |
| Low Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 26 | -215.79 units on a scale | Standard Deviation 101.879 |
| Low Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 2 | -108.91 units on a scale | Standard Deviation 76.196 |
| Low Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 4 | -152.96 units on a scale | Standard Deviation 71.589 |
| Low Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 6 | -163.53 units on a scale | Standard Deviation 80.868 |
| Low Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 8 | -181.50 units on a scale | Standard Deviation 81.611 |
| Low Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 10 | -185.24 units on a scale | Standard Deviation 81.532 |
| Low Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 12 | -200.33 units on a scale | Standard Deviation 88.612 |
| Low Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 16 | -198.07 units on a scale | Standard Deviation 96.381 |
| Low Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 18 | -200.17 units on a scale | Standard Deviation 93.758 |
| Low Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 20 | -214.43 units on a scale | Standard Deviation 96.417 |
| Low Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 22 | -213.95 units on a scale | Standard Deviation 98.357 |
| Low Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 24 | -215.47 units on a scale | Standard Deviation 99.278 |
| Standard Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 18 | -188.31 units on a scale | Standard Deviation 109.516 |
| Standard Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 14 | -194.96 units on a scale | Standard Deviation 111.444 |
| Standard Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 10 | -182.87 units on a scale | Standard Deviation 96.039 |
| Standard Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 26 | -200.17 units on a scale | Standard Deviation 110.999 |
| Standard Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 16 | -191.37 units on a scale | Standard Deviation 108.932 |
| Standard Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 22 | -194.53 units on a scale | Standard Deviation 111.046 |
| Standard Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 2 | -143.79 units on a scale | Standard Deviation 86.193 |
| Standard Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 12 | -191.09 units on a scale | Standard Deviation 98.035 |
| Standard Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 4 | -163.21 units on a scale | Standard Deviation 95.545 |
| Standard Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 20 | -189.83 units on a scale | Standard Deviation 110.845 |
| Standard Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 6 | -178.23 units on a scale | Standard Deviation 103.159 |
| Standard Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 24 | -187.98 units on a scale | Standard Deviation 107.702 |
| Standard Induction Dose | CDAI: Mean Change From Baseline to Each Visit | Week 8 | -181.87 units on a scale | Standard Deviation 100.077 |
Secondary
Fecal Calprotectin: Change From Baseline (Week 0) to Week 8
Stool samples for fecal calprotectin were collected before study drug administration when possible. Decreases in calprotectin are associated with decreased inflammation in the gastrointestinal tract. LOCF was used for missing data.
Time frame: Baseline (Week 0) and Weeks 4 and 8
Population: ITT population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Low Induction Dose | Fecal Calprotectin: Change From Baseline (Week 0) to Week 8 | Week 8 | -44.0 μg/g |
| Low Induction Dose | Fecal Calprotectin: Change From Baseline (Week 0) to Week 8 | Week 4 | -135.0 μg/g |
| Standard Induction Dose | Fecal Calprotectin: Change From Baseline (Week 0) to Week 8 | Week 4 | -207.0 μg/g |
| Standard Induction Dose | Fecal Calprotectin: Change From Baseline (Week 0) to Week 8 | Week 8 | -274.0 μg/g |
Secondary
High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26
hsCRP was measured from blood samples as a marker for inflammation. Higher levels are indicative of more inflammation. Normal concentration in healthy human serum is usually lower than 3 mg/L, slightly increasing with age. LOCF was used for missing data.
Time frame: Baseline (Week 0) and Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and 26
Population: ITT population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Low Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 1 | -7.70 mg/L |
| Low Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 2 | -14.10 mg/L |
| Low Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 4 | -12.05 mg/L |
| Low Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 6 | -12.66 mg/L |
| Low Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 8 | -11.90 mg/L |
| Low Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 12 | -9.40 mg/L |
| Low Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 16 | -14.00 mg/L |
| Low Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 20 | -9.50 mg/L |
| Low Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 24 | -12.90 mg/L |
| Low Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 26 | -11.20 mg/L |
| Standard Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 20 | -12.80 mg/L |
| Standard Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 1 | -24.51 mg/L |
| Standard Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 12 | -15.00 mg/L |
| Standard Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 2 | -25.37 mg/L |
| Standard Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 26 | -6.90 mg/L |
| Standard Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 4 | -21.12 mg/L |
| Standard Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 16 | -15.10 mg/L |
| Standard Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 6 | -21.61 mg/L |
| Standard Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 24 | -12.90 mg/L |
| Standard Induction Dose | High-sensitivity C-reactive Protein (hsCRP): Median Change From Baseline (Week 0) to Week 26 | Week 8 | -21.58 mg/L |
Secondary
Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant which does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs or TESAE) are defined as any event that began or worsened in severity after the first dose of study drug. The investigator assessed the relationship of each event to the use of study drug as either Reasonable possibility or No reasonable possibility of being related to study drug. For more details on adverse events please see the AE section below.
Time frame: 35 weeks
Population: Safety Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Induction Dose | Number of Participants With Adverse Events (AEs) | Any TEAE | 6 participants |
| Low Induction Dose | Number of Participants With Adverse Events (AEs) | Any TESAE | 1 participants |
| Low Induction Dose | Number of Participants With Adverse Events (AEs) | TEAE leading to discontinuation | 2 participants |
| Low Induction Dose | Number of Participants With Adverse Events (AEs) | Severe TEAE | 0 participants |
| Low Induction Dose | Number of Participants With Adverse Events (AEs) | TEAEs with reasonable possibility of being related | 3 participants |
| Low Induction Dose | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| Standard Induction Dose | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| Standard Induction Dose | Number of Participants With Adverse Events (AEs) | Severe TEAE | 1 participants |
| Standard Induction Dose | Number of Participants With Adverse Events (AEs) | Any TEAE | 7 participants |
| Standard Induction Dose | Number of Participants With Adverse Events (AEs) | TEAE leading to discontinuation | 1 participants |
| Standard Induction Dose | Number of Participants With Adverse Events (AEs) | Any TESAE | 1 participants |
| Standard Induction Dose | Number of Participants With Adverse Events (AEs) | TEAEs with reasonable possibility of being related | 6 participants |
| Low Induction Dose (Open-label Extension Period) | Number of Participants With Adverse Events (AEs) | Any TESAE | 1 participants |
| Low Induction Dose (Open-label Extension Period) | Number of Participants With Adverse Events (AEs) | TEAE leading to discontinuation | 1 participants |
| Low Induction Dose (Open-label Extension Period) | Number of Participants With Adverse Events (AEs) | Severe TEAE | 0 participants |
| Low Induction Dose (Open-label Extension Period) | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| Low Induction Dose (Open-label Extension Period) | Number of Participants With Adverse Events (AEs) | TEAEs with reasonable possibility of being related | 5 participants |
| Low Induction Dose (Open-label Extension Period) | Number of Participants With Adverse Events (AEs) | Any TEAE | 7 participants |
| Standard Induction Dose (Open-label Extension) | Number of Participants With Adverse Events (AEs) | TEAEs with reasonable possibility of being related | 6 participants |
| Standard Induction Dose (Open-label Extension) | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| Standard Induction Dose (Open-label Extension) | Number of Participants With Adverse Events (AEs) | Any TESAE | 2 participants |
| Standard Induction Dose (Open-label Extension) | Number of Participants With Adverse Events (AEs) | Severe TEAE | 1 participants |
| Standard Induction Dose (Open-label Extension) | Number of Participants With Adverse Events (AEs) | Any TEAE | 7 participants |
| Standard Induction Dose (Open-label Extension) | Number of Participants With Adverse Events (AEs) | TEAE leading to discontinuation | 2 participants |
Secondary
Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab
The number of participants with an abnormal laboratory result meeting Common Toxicity Criteria (CTC) Version 3.0 (or later) of Grade 3 or higher is summarized.
Time frame: From Week 0 to Week 26
Population: Safety Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Induction Dose | Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab | Sodium <130 mmol/L | 0 participants |
| Low Induction Dose | Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab | Calcium <1.75 mmol/L | 0 participants |
| Low Induction Dose | Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab | Albumin <20 g/L | 0 participants |
| Low Induction Dose | Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab | Uric Acid >500µmol/L | 0 participants |
| Low Induction Dose | Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab | Potassium <3.0 mmol/L | 0 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab | Uric Acid >500µmol/L | 1 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab | Potassium <3.0 mmol/L | 1 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab | Sodium <130 mmol/L | 1 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab | Albumin <20 g/L | 1 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Clinical Chemistry Parameters During Administration of Adalimumab | Calcium <1.75 mmol/L | 1 participants |
Secondary
Number of Participants With Potentially Significant Hematology Parameters During Administration of Adalimumab
The number of participants with an abnormal laboratory result meeting Common Toxicity Criteria (CTC) Version 3.0 (or later) of Grade 3 or higher is summarized. n=the number of participants with CTC Grade \<3 at baseline and a post-baseline value for each parameter.
Time frame: 26 weeks
Population: Safety Analysis Set: all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Induction Dose | Number of Participants With Potentially Significant Hematology Parameters During Administration of Adalimumab | Haemoglobin <80 g/L (n=15,15) | 1 participants |
| Low Induction Dose | Number of Participants With Potentially Significant Hematology Parameters During Administration of Adalimumab | White Blood Cells ≥1 x10^9/L (n=15,15) | 1 participants |
| Low Induction Dose | Number of Participants With Potentially Significant Hematology Parameters During Administration of Adalimumab | Neutrophils <1.0x10^9/mcL (n=15,15) | 1 participants |
| Low Induction Dose | Number of Participants With Potentially Significant Hematology Parameters During Administration of Adalimumab | Lymphocytes <0.5x10^3/mcL (n=15,13) | 2 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Hematology Parameters During Administration of Adalimumab | Lymphocytes <0.5x10^3/mcL (n=15,13) | 0 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Hematology Parameters During Administration of Adalimumab | Haemoglobin <80 g/L (n=15,15) | 1 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Hematology Parameters During Administration of Adalimumab | Neutrophils <1.0x10^9/mcL (n=15,15) | 0 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Hematology Parameters During Administration of Adalimumab | White Blood Cells ≥1 x10^9/L (n=15,15) | 0 participants |
Secondary
Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab
Blood pressure and pulse were measured while the participant was sitting. The number of participants with a postbaseline vital sign result that meets Common Toxicity Criteria (CTC) version 3.0 (or later) Grade 3 or higher and is also more extreme than the baseline value is summarized. Terms abbreviated in the table include systolic blood pressure (SBP) and diastolic blood pressure (DBP). Increase and decrease are signified by ↑ and ↓, respectively.
Time frame: 26 weeks
Population: Safety Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Induction Dose | Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab | SBP ≤90 mm Hg or ≥20 mm Hg ↓ from BL | 7 participants |
| Low Induction Dose | Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab | SBP ≥180 mm Hg or ≥20 mm Hg ↑ from BL | 8 participants |
| Low Induction Dose | Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab | DBP ≤50 mm Hg or ≥15 mm Hg ↓ from BL | 3 participants |
| Low Induction Dose | Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab | SBP ≥105 mm Hg or ≥15 mm Hg ↑ from BL | 6 participants |
| Low Induction Dose | Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab | Pulse ≤50 bpm or ≥15 bpm ↓ from BL | 6 participants |
| Low Induction Dose | Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab | Pulse SBP ≥120 bpm or ≥15 bpm ↑ from BL | 7 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab | Pulse ≤50 bpm or ≥15 bpm ↓ from BL | 7 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab | SBP ≤90 mm Hg or ≥20 mm Hg ↓ from BL | 5 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab | SBP ≥105 mm Hg or ≥15 mm Hg ↑ from BL | 4 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab | SBP ≥180 mm Hg or ≥20 mm Hg ↑ from BL | 3 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab | Pulse SBP ≥120 bpm or ≥15 bpm ↑ from BL | 6 participants |
| Standard Induction Dose | Number of Participants With Potentially Significant Vital Signs Parameters During Administration of Adalimumab | DBP ≤50 mm Hg or ≥15 mm Hg ↓ from BL | 4 participants |
Secondary
Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26
CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. A score below 150 indicates remission and a score of 220 to 450 reflects moderate to severe disease. Non-responder imputation (NRI) for missing CDAI observations was used.
Time frame: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26
Population: ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 4 | 40.0 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 16 | 60.0 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 8 | 60.0 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 18 | 60.0 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 12 | 60.0 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 20 | 66.7 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 10 | 66.7 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 22 | 66.7 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 6 | 60.0 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 24 | 66.7 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 14 | 60.0 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 26 | 66.7 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 2 | 26.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 26 | 66.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 10 | 66.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 2 | 46.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 4 | 66.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 6 | 73.3 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 8 | 66.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 12 | 73.3 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 14 | 73.3 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 16 | 73.3 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 18 | 73.3 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 20 | 66.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 22 | 66.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Remission (Crohn's Disease Activity Index [CDAI] < 150) Every 2 Weeks up to Week 26 | Week 24 | 66.7 percentage of participants |
Secondary
Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26
CDAI is used to quantify the signs and symptoms of patients with Crohn's Disease. A score below 150 indicates remission and a score of 220 to 450 reflects moderate to severe disease. Non-responder imputation (NRI) for missing CDAI observations was used.
Time frame: Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26
Population: ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 6 | 93.3 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 14 | 73.7 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 24 | 66.7 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 16 | 80.0 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 8 | 93.3 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 18 | 80.0 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 4 | 93.3 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 20 | 73.7 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 10 | 86.7 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 22 | 66.7 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 2 | 66.7 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 26 | 66.7 percentage of participants |
| Low Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 12 | 80.0 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 26 | 66.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 2 | 80.0 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 4 | 93.3 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 6 | 86.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 8 | 86.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 10 | 86.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 12 | 80.0 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 14 | 73.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 16 | 73.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 18 | 73.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 20 | 66.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 24 | 66.7 percentage of participants |
| Standard Induction Dose | Percentage of Participants Who Achieved Clinical Response (CDAI Decrease ≥ 70 From Week 0) Every 2 Weeks up to Week 26 | Week 22 | 66.7 percentage of participants |
Other Pre-specified
Number of Subjects Positive for Anti-Adalimumab Antibodies (AAA) From Baseline to Week 8
Serum samples with adalimumab concentration below 2 μg/mL were selected for AAA analyses. Samples were considered AAA positive if the measured AAA concentration was above 2 μg/mL. A subject was considered to be AAA positive if the subject had at least one AAA positive sample observed within 30 days following the subject's last adalimumab dose. No samples were tested because all samples had adalimumab concentrations \>2 μg/mL.
Time frame: Baseline (Week 0) to Week 8
Population: ITT population.