Colitis, Ulcerative
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and efficacy of PF-06480605 in subjects with moderate to severe ulcerative colitis.
Detailed description
This is a Phase 2a, single arm, two-stage study in subjects with moderate to severe ulcerative colitis. Subjects will receive 500 mg of PF-06480605 intravenously every 2 weeks for a total of 7 doses. Blood, stool, and tissue samples will be collected at various time points throughout the study to evaluate safety, tolerability, efficacy, pharmacokinetics, and immunogenicity. Duration of participation for subjects will be approximately 8 months.
Interventions
DRUGPF-06480605
PF-06480605 500 mg IV Q2W x 7 Doses
Sponsors
Pfizer
Telavant, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects between ≥ 18 and ≤ 75 years of age at the time of informed consent * Male subjects able to father children and female subjects of childbearing potential must agree to use two highly effective methods of contraception throughout the study and until the Week 26 visit * Diagnosis of ulcerative colitis for ≥ 4 months * Subjects with moderate to severe active ulcerative colitis as defined by screening colonoscopy with total Mayo score of ≥ 6, with rectal bleeding subscore of ≥ 1, and an endoscopic subscore of ≥ 2 on the Mayo * Active disease beyond the rectum (\> 15 cm of active disease at the screening colonoscopy) * Must have inadequate response to, loss of response to, or intolerance to at least one conventional therapy for ulcerative colitis such as: Steroids; Immunosuppressants (AZA, 6-MP, or MTX); Anti -TNF inhibitors (eg, infliximab, adalimumab, or golimumab); Anti-integrin inhibitors (eg, vedolizumab). * Subjects currently receiving the following treatment are eligible provided they have been on stable doses of Oral 5-ASA or sulfasalazine for at least 4 weeks prior to baseline; oral corticosteroids stable dose for at least 2 weeks prior to baseline; 6-MP or AZA stable dose for 8 weeks prior to baseline.
Exclusion criteria
* Diagnosis of indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, microscopic colitis or Crohn's Disease. Subjects with clinical findings suggestive of Crohn's disease (eg, fistulae, granulomas on biopsy) are also excluded. * Subjects with colonic dysplasia or neoplasia, toxic megacolon, primary sclerosing cholangitis, known colonic stricture, history of colonic or small bowel stoma, history of colonic or small bowel obstruction or resection * Presence of active enteric infections (positive stool culture and sensitivity) * Known history of HIV based on documented history with positive serological test, or positive HIV serologic test at screening * Presence of a transplanted organ * Cancer or history of cancer or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell or squamous cell carcinoma that has been treated with no evidence of recurrence); * Acute coronary syndrome (eg., myocardial infarction, unstable angina pectoris); * Any history of cerebrovascular disease within 24 weeks before screening; * Subject with current or a history of QT prolongation * Class III or Class IV heart failure * Prior evidence of liver injury or toxicity due to methotrexate * Abnormality in hematology and/or chemistry profiles during screening (as detailed in the protocol) * Subjects receiving the following therapies within the designated time period: * \> 9 mg/day of oral budesonide or \>20 mg/day prednisone or equivalent within 2 weeks prior to baseline * IV, IM (parenteral), or topical (rectal) treatment of 5-ASA or corticosteroid enemas/suppositories within 2 weeks prior to baseline * Biologics including anti-TNF inhibitors as described: Infliximab, Adalimumab, or Golimumab within 8 weeks prior to baseline * Anti-integrin inhibitors (eg, vedolizumab) within 12 weeks prior to baseline * Other investigational procedures or products, or live attenuated vaccine within 30 days prior to baseline. * Current or history (within 2 years) of serious psychiatric disease or alcohol or drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events, Serious Adverse Events, and Who Withdrew Due to Adverse Events | Day 1 up to final onsite visit (Week 26) | An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. A serious AE (SAE) was any untoward medical occurrence at any dose that (1) resulted in death; (2) was life-threatening (immediate risk of death); (3) required inpatient hospitalization or prolongation of existing hospitalization; (4) resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) resulted in congenital anomaly/birth defect. A treatment-emergent AE (TEAE) was defined as an event that emerged during treatment having been absent pre-treatment, or worsened relative to the pre-treatment state. Causality to study treatment was determined by the investigator. |
| Number of Participants With Laboratory Abnormalities | Day 1 up to final onsite visit (Week 26) | The following parameters were evaluated: hematology (hemoglobin, hematocrit, erythrocytes, erythrocyte mean corpuscular volume, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, and prothrombin time), clinical chemistry (bilirubin, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, blood urea nitrogen, creatinine, urate, sodium, potassium, chloride, calcium, glucose, and creatine kinase), and urinalysis (urine glucose, ketones, urine protein, urine hemoglobin, nitrite, leukocyte esterase, urine erythrocytes, urine leukocytes, hyaline casts, and bacteria). |
| Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Baseline up to final onsite visit (Week 26) | Vital signs evaluation included sitting diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse rate. Sitting blood pressure was measured with the participant's arm supported at the level of the heart, and recorded to the nearest millimeters of mercury (mm Hg). The same size BP cuff which had been properly sized and calibrated was used to measure BP each time. Number of participants with vital signs data meeting pre-specified criteria is presented. |
| Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | Baseline up to final onsite visit (Week 26) | All scheduled 12-lead ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Number of participants with ECG data meeting pre-specified criteria is presented. |
| Percentage of Participants Achieving Endoscopic Improvement at Week 14, Based on Uniformly Minimum-Variance Unbiased Estimator (UMVUE) - Per Protocol Analysis Set | Week 14 | Endoscopic improvement at Week 14 was defined as Mayo endoscopic sub-score of 0 or 1, and without friability. The Mayo scoring system was used to assess ulcerative colitis activity, and it ranges from 0 to 12, calculated as sum of 4 sub-scores, with higher scores indicating more severe disease. The 4 sub-scores are stool frequency (0=normal number of stools; 1=1 to 2 stools more than normal; 2=3 to 4 stools more than normal; 3= 5 or more stools more than normal); rectal bleeding (0=no blood seen; 1=streaks of blood with stools less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes); findings on endoscopy (0=normal or inactive disease; 1=mild disease \[erythema, decreased vascular pattern, mild friability\]; 2=moderate disease \[marked erythema, lack of vascular pattern, friability, erosions\]; 3=severe disease \[spontaneous bleeding, ulceration\]); and physician's global assessment (0=normal; 1=mild disease; 2=moderate disease; 3=severe disease). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lowest Serum Concentration (Cmin) of PF-06480605 | 30 minutes pre-dose and 1 hour post-dose on Day 85 | Lowest serum concentration (Cmin) of PF-06480605 was observed directly from data. |
| Area Under the Concentration-time Profile From Time Zero to Time Tau (AUCtau) of PF-06480605 | 30 minutes pre-dose and 1 hour post-dose on Day 85 | AUCtau of PF-06480605 was calculated using linear/log trapezoidal method; tau was the dosing interval (=14 days). |
| Percentage of Participants Who Developed Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) | Day 1 up to final onsite visit (Week 26) | Serum samples were analyzed using a new ADA assay with acid pre-treatment followed by a more drug-tolerant cell-based NAb assay. For ADA assay with acid pre-treatment, the sample was deemed positive if log titer \>=1.30; for cell-based NAb assay, the sample was deemed positive if log titer \>=0.699. |
| Percentage of Participants Achieving Remission at Week 14 - Full Analysis Set | Week 14 | Remission: total Mayo score \<=2 with no individual subscore \>1. Mayo scoring system was used to assess ulcerative colitis activity (range: 0 to 12, calculated as sum of 4 subscores, higher scores indicating more severe disease). The 4 subscores are stool frequency (0=normal number of stools; 1=1 to 2 stools more than normal; 2= 3 to 4 stools more than normal; 3= 5 or more stools more than normal); rectal bleeding (0=no blood seen; 1=streaks of blood with stools less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes); findings on modified endoscopy (0=normal or inactive disease; 1=mild disease \[erythema, decreased vascular pattern, no friability\]; 2=moderate disease \[marked erythema, lack of vascular pattern, friability, erosions\]; 3=severe disease \[spontaneous bleeding, ulceration\]); and physician's global assessment (0=normal; 1=mild disease; 2=moderate disease; 3=severe disease). |
| Change From Baseline in High Sensitivity C-reactive Protein (HsCRP) | Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, and 26 | HsCRP is used mainly as a marker of inflammation. |
| Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A) | Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, and 26 | TL1A is a member of the tumor necrosis factor (TNF) family of cytokines. The investigational product of this study PF-06480605 is a fully human neutralizing antibody against TL1A. |
| Change From Baseline in Fecal Calprotectin | Baseline, Weeks 2, 8, 12 and 26 | Fecal calprotectin has been used to detect intestinal inflammation (colitis or enteritis) and can serve as a biomarker for inflammatory bowel diseases. Elevated fecal calprotectin levels indicate migration of neutrophils into the intestinal mucosa, which occurs during intestinal inflammation. |
| Percentage of Participants Achieving Remission at Week 14 - Per Protocol Analysis Set | Week 14 | Remission: total Mayo score \<=2 with no individual subscore \>1. Mayo scoring system was used to assess ulcerative colitis activity (range: 0 to 12, calculated as sum of 4 subscores, higher scores indicating more severe disease). The 4 subscores are stool frequency (0=normal number of stools; 1=1 to 2 stools more than normal; 2= 3 to 4 stools more than normal; 3= 5 or more stools more than normal); rectal bleeding (0=no blood seen; 1=streaks of blood with stools less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes); findings on modified endoscopy (0=normal or inactive disease; 1=mild disease \[erythema, decreased vascular pattern, no friability\]; 2=moderate disease \[marked erythema, lack of vascular pattern, friability, erosions\]; 3=severe disease \[spontaneous bleeding, ulceration\]); and physician's global assessment (0=normal; 1=mild disease; 2=moderate disease; 3=severe disease). |
| Percentage of Participants Achieving Endoscopic Remission at Week 14 - Full Analysis Set | Week 14 | Endoscopic remission at Week 14 was defined as Mayo endoscopic sub-score of 0. The Mayo scoring system was used to assess ulcerative colitis activity, and it ranges from 0 to 12, calculated as sum of 4 sub-scores, with higher scores indicating more severe disease. The 4 sub-scores are stool frequency (0=normal number of stools; 1=1 to 2 stools more than normal; 2= 3 to 4 stools more than normal; 3= 5 or more stools more than normal); rectal bleeding (0=no blood seen; 1=streaks of blood with stools less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes); findings on endoscopy (0=normal or inactive disease; 1=mild disease \[erythema, decreased vascular pattern, mild friability\]; 2=moderate disease \[marked erythema, lack of vascular pattern, friability, erosions\]; 3=severe disease \[spontaneous bleeding, ulceration\]); and physician's global assessment (0=normal; 1=mild disease; 2=moderate disease; 3=severe disease). |
| Maximum Serum Concentration (Cmax) of PF-06480605 | 30 minutes pre-dose and 1 hour post-dose on Day 85 | Maximum serum concentration (Cmax) of PF-06480605 was observed directly from data. |
| Average Serum Concentration (Cav) of PF-06480605 | 30 minutes pre-dose and 1 hour post-dose on Day 85 | Average serum concentration (Cav) of PF-06480605 was calculated as AUCtau/tau, where tau was the dosing interval (tau=14 days), and AUCtau was the area under the concentration-time profile from time 0 to time tau. |
Countries
Belgium, Italy, Netherlands, Poland, South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-06480605 500 mg IV Participants received PF-06480605 500 mg intravenously once every 2 weeks (Q2W) for a total of 7 doses (i.e., 12-week treatment period), and then were followed up for additional 14 weeks after the last dose of PF-06480605. | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow-Up | Lack of Efficacy | 1 |
| Follow-Up | Withdrawal by Subject | 4 |
| Follow-Up | Withdrawal of Consent | 2 |
| Treatment Period | Adverse Event | 1 |
Baseline characteristics
| Characteristic | PF-06480605 500 mg IV |
|---|---|
| Age, Continuous | 40.0 years STANDARD_DEVIATION 14.52 |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized White | 48 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 50 |
| other Total, other adverse events | 20 / 50 |
| serious Total, serious adverse events | 3 / 50 |
Outcome results
Primary
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria
All scheduled 12-lead ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Number of participants with ECG data meeting pre-specified criteria is presented.
Time frame: Baseline up to final onsite visit (Week 26)
Population: The analysis population included all participants who received at least 1 dose of PF-06480605 and had both baseline and at least 1 post-baseline ECG evaluation performed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06480605 500 mg IV | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | PR interval >=300 milliseconds (msec) | 0 Participants |
| PF-06480605 500 mg IV | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | QRS duration >=140 msec | 0 Participants |
| PF-06480605 500 mg IV | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | QT interval >=500 msec | 0 Participants |
| PF-06480605 500 mg IV | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | QTcF interval: 450 to <480 msec | 5 Participants |
| PF-06480605 500 mg IV | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | QTcF interval: 480 to <500 msec | 0 Participants |
| PF-06480605 500 mg IV | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | QTcF interval: >=500 msec | 0 Participants |
| PF-06480605 500 mg IV | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | PR interval increase from baseline >=25%/50% | 0 Participants |
| PF-06480605 500 mg IV | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | QRS duration increase from baseline >=50% | 0 Participants |
| PF-06480605 500 mg IV | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | QTcF increase from baseline: 30 to <60 msec | 9 Participants |
| PF-06480605 500 mg IV | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | QTcF increase from baseline: >=60 msec | 1 Participants |
Primary
Number of Participants With Laboratory Abnormalities
The following parameters were evaluated: hematology (hemoglobin, hematocrit, erythrocytes, erythrocyte mean corpuscular volume, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, and prothrombin time), clinical chemistry (bilirubin, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, blood urea nitrogen, creatinine, urate, sodium, potassium, chloride, calcium, glucose, and creatine kinase), and urinalysis (urine glucose, ketones, urine protein, urine hemoglobin, nitrite, leukocyte esterase, urine erythrocytes, urine leukocytes, hyaline casts, and bacteria).
Time frame: Day 1 up to final onsite visit (Week 26)
Population: The analysis population included all participants who received at least 1 dose of PF-06480605.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-06480605 500 mg IV | Number of Participants With Laboratory Abnormalities | 38 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events, Serious Adverse Events, and Who Withdrew Due to Adverse Events
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. A serious AE (SAE) was any untoward medical occurrence at any dose that (1) resulted in death; (2) was life-threatening (immediate risk of death); (3) required inpatient hospitalization or prolongation of existing hospitalization; (4) resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) resulted in congenital anomaly/birth defect. A treatment-emergent AE (TEAE) was defined as an event that emerged during treatment having been absent pre-treatment, or worsened relative to the pre-treatment state. Causality to study treatment was determined by the investigator.
Time frame: Day 1 up to final onsite visit (Week 26)
Population: The analysis population included all participants who received at least 1 dose of PF-06480605.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06480605 500 mg IV | Number of Participants With Treatment-Emergent Adverse Events, Serious Adverse Events, and Who Withdrew Due to Adverse Events | All-causality AEs | 33 Participants |
| PF-06480605 500 mg IV | Number of Participants With Treatment-Emergent Adverse Events, Serious Adverse Events, and Who Withdrew Due to Adverse Events | All-causality SAEs | 3 Participants |
| PF-06480605 500 mg IV | Number of Participants With Treatment-Emergent Adverse Events, Serious Adverse Events, and Who Withdrew Due to Adverse Events | Treatment-related AEs | 8 Participants |
| PF-06480605 500 mg IV | Number of Participants With Treatment-Emergent Adverse Events, Serious Adverse Events, and Who Withdrew Due to Adverse Events | Treatment-related SAEs | 1 Participants |
| PF-06480605 500 mg IV | Number of Participants With Treatment-Emergent Adverse Events, Serious Adverse Events, and Who Withdrew Due to Adverse Events | Withdrew due to AEs | 1 Participants |
Primary
Number of Participants With Vital Signs Data Meeting Pre-specified Criteria
Vital signs evaluation included sitting diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse rate. Sitting blood pressure was measured with the participant's arm supported at the level of the heart, and recorded to the nearest millimeters of mercury (mm Hg). The same size BP cuff which had been properly sized and calibrated was used to measure BP each time. Number of participants with vital signs data meeting pre-specified criteria is presented.
Time frame: Baseline up to final onsite visit (Week 26)
Population: The analysis population included all participants who received at least 1 dose of PF-06480605.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06480605 500 mg IV | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Sitting DBP <50 mm Hg | 1 Participants |
| PF-06480605 500 mg IV | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Sitting SBP <90 mm Hg | 4 Participants |
| PF-06480605 500 mg IV | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Sitting pulse rate <40 beats per minute (bpm) | 0 Participants |
| PF-06480605 500 mg IV | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Sitting pulse rate >120 bpm | 1 Participants |
| PF-06480605 500 mg IV | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Sitting DBP increase from baseline >=20 mm Hg | 2 Participants |
| PF-06480605 500 mg IV | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Sitting SBP increase from baseline >=30 mm Hg | 5 Participants |
| PF-06480605 500 mg IV | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Sitting DBP decrease from baseline >=20 mm Hg | 7 Participants |
| PF-06480605 500 mg IV | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Sitting SBP decrease from baseline >=30 mm Hg | 1 Participants |
Primary
Percentage of Participants Achieving Endoscopic Improvement at Week 14, Based on Uniformly Minimum-Variance Unbiased Estimator (UMVUE) - Per Protocol Analysis Set
Endoscopic improvement at Week 14 was defined as Mayo endoscopic sub-score of 0 or 1, and without friability. The Mayo scoring system was used to assess ulcerative colitis activity, and it ranges from 0 to 12, calculated as sum of 4 sub-scores, with higher scores indicating more severe disease. The 4 sub-scores are stool frequency (0=normal number of stools; 1=1 to 2 stools more than normal; 2=3 to 4 stools more than normal; 3= 5 or more stools more than normal); rectal bleeding (0=no blood seen; 1=streaks of blood with stools less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes); findings on endoscopy (0=normal or inactive disease; 1=mild disease \[erythema, decreased vascular pattern, mild friability\]; 2=moderate disease \[marked erythema, lack of vascular pattern, friability, erosions\]; 3=severe disease \[spontaneous bleeding, ulceration\]); and physician's global assessment (0=normal; 1=mild disease; 2=moderate disease; 3=severe disease).
Time frame: Week 14
Population: The analysis population included all participants who were eligible for enrollment, not a major protocol violator, with at least 6 out of 7 planned doses received and a final colonoscopy at Week 14.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-06480605 500 mg IV | Percentage of Participants Achieving Endoscopic Improvement at Week 14, Based on Uniformly Minimum-Variance Unbiased Estimator (UMVUE) - Per Protocol Analysis Set | 38.20 percentage of participants |
Secondary
Area Under the Concentration-time Profile From Time Zero to Time Tau (AUCtau) of PF-06480605
AUCtau of PF-06480605 was calculated using linear/log trapezoidal method; tau was the dosing interval (=14 days).
Time frame: 30 minutes pre-dose and 1 hour post-dose on Day 85
Population: The analysis population included all enrolled participants who received at least 1 dose of PF-06480605 and had at least 1 derived value of a specific pharmacokinetic (PK) parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06480605 500 mg IV | Area Under the Concentration-time Profile From Time Zero to Time Tau (AUCtau) of PF-06480605 | 57610000 ng.hr/mL | Geometric Coefficient of Variation 45 |
Secondary
Average Serum Concentration (Cav) of PF-06480605
Average serum concentration (Cav) of PF-06480605 was calculated as AUCtau/tau, where tau was the dosing interval (tau=14 days), and AUCtau was the area under the concentration-time profile from time 0 to time tau.
Time frame: 30 minutes pre-dose and 1 hour post-dose on Day 85
Population: The analysis population included all enrolled participants who received at least 1 dose of PF-06480605 and had at least 1 derived value of a specific pharmacokinetic (PK) parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06480605 500 mg IV | Average Serum Concentration (Cav) of PF-06480605 | 171400 nanograms (ng)/milliliters (mL) | Geometric Coefficient of Variation 45 |
Secondary
Change From Baseline in Fecal Calprotectin
Fecal calprotectin has been used to detect intestinal inflammation (colitis or enteritis) and can serve as a biomarker for inflammatory bowel diseases. Elevated fecal calprotectin levels indicate migration of neutrophils into the intestinal mucosa, which occurs during intestinal inflammation.
Time frame: Baseline, Weeks 2, 8, 12 and 26
Population: The analysis population included all participants who received at least 1 dose of PF 06480605 with at least 1 fecal calprotectin measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06480605 500 mg IV | Change From Baseline in Fecal Calprotectin | Baseline | 3662.25 micrograms/grams | Standard Deviation 3556.331 |
| PF-06480605 500 mg IV | Change From Baseline in Fecal Calprotectin | Week 2 change from baseline | -1861.38 micrograms/grams | Standard Deviation 3565.861 |
| PF-06480605 500 mg IV | Change From Baseline in Fecal Calprotectin | Week 8 change from baseline | -2509.43 micrograms/grams | Standard Deviation 3751.843 |
| PF-06480605 500 mg IV | Change From Baseline in Fecal Calprotectin | Week 12 change from baseline | -2844.26 micrograms/grams | Standard Deviation 3623.922 |
| PF-06480605 500 mg IV | Change From Baseline in Fecal Calprotectin | Week 26 change from baseline | -2726.97 micrograms/grams | Standard Deviation 3673.063 |
Secondary
Change From Baseline in High Sensitivity C-reactive Protein (HsCRP)
HsCRP is used mainly as a marker of inflammation.
Time frame: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, and 26
Population: The analysis population included all participants who received at least 1 dose of PF 06480605 with 1 hsCRP measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06480605 500 mg IV | Change From Baseline in High Sensitivity C-reactive Protein (HsCRP) | Baseline | 0.9316 micrograms/deciliter | Standard Deviation 1.15545 |
| PF-06480605 500 mg IV | Change From Baseline in High Sensitivity C-reactive Protein (HsCRP) | Week 2 change from baseline | -0.2136 micrograms/deciliter | Standard Deviation 1.43785 |
| PF-06480605 500 mg IV | Change From Baseline in High Sensitivity C-reactive Protein (HsCRP) | Week 4 change from baseline | -0.4883 micrograms/deciliter | Standard Deviation 1.1082 |
| PF-06480605 500 mg IV | Change From Baseline in High Sensitivity C-reactive Protein (HsCRP) | Week 6 change from baseline | -0.3314 micrograms/deciliter | Standard Deviation 1.39605 |
| PF-06480605 500 mg IV | Change From Baseline in High Sensitivity C-reactive Protein (HsCRP) | Week 8 change from baseline | -0.4875 micrograms/deciliter | Standard Deviation 1.0087 |
| PF-06480605 500 mg IV | Change From Baseline in High Sensitivity C-reactive Protein (HsCRP) | Week 10 change from baseline | -0.5738 micrograms/deciliter | Standard Deviation 0.97608 |
| PF-06480605 500 mg IV | Change From Baseline in High Sensitivity C-reactive Protein (HsCRP) | Week 12 change from baseline | -0.4242 micrograms/deciliter | Standard Deviation 1.18416 |
| PF-06480605 500 mg IV | Change From Baseline in High Sensitivity C-reactive Protein (HsCRP) | Week 14 change from baseline | -0.3983 micrograms/deciliter | Standard Deviation 1.21181 |
| PF-06480605 500 mg IV | Change From Baseline in High Sensitivity C-reactive Protein (HsCRP) | Week 16 change from baseline | -0.5070 micrograms/deciliter | Standard Deviation 1.37798 |
| PF-06480605 500 mg IV | Change From Baseline in High Sensitivity C-reactive Protein (HsCRP) | Week 20 change from baseline | -0.4728 micrograms/deciliter | Standard Deviation 1.1195 |
| PF-06480605 500 mg IV | Change From Baseline in High Sensitivity C-reactive Protein (HsCRP) | Week 24 change from baseline | -0.5334 micrograms/deciliter | Standard Deviation 1.03224 |
| PF-06480605 500 mg IV | Change From Baseline in High Sensitivity C-reactive Protein (HsCRP) | Week 26 change from baseline | -0.3453 micrograms/deciliter | Standard Deviation 1.37576 |
Secondary
Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A)
TL1A is a member of the tumor necrosis factor (TNF) family of cytokines. The investigational product of this study PF-06480605 is a fully human neutralizing antibody against TL1A.
Time frame: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, and 26
Population: The analysis population included all participants who received at least 1 dose of PF 06480605 with 1 sTL1A measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-06480605 500 mg IV | Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A) | Baseline | 103.9 picograms/mL | Standard Deviation 32.05 |
| PF-06480605 500 mg IV | Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A) | Week 2 change from baseline | 3390.4 picograms/mL | Standard Deviation 1349.87 |
| PF-06480605 500 mg IV | Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A) | Week 4 change from baseline | 5308.9 picograms/mL | Standard Deviation 2073.59 |
| PF-06480605 500 mg IV | Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A) | Week 6 change from baseline | 6908.7 picograms/mL | Standard Deviation 3278.23 |
| PF-06480605 500 mg IV | Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A) | Week 8 change from baseline | 7319.3 picograms/mL | Standard Deviation 3587.14 |
| PF-06480605 500 mg IV | Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A) | Week 10 change from baseline | 7175.7 picograms/mL | Standard Deviation 4095.36 |
| PF-06480605 500 mg IV | Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A) | Week 12 change from baseline | 6446.3 picograms/mL | Standard Deviation 4422.46 |
| PF-06480605 500 mg IV | Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A) | Week 14 change from baseline | 6539.1 picograms/mL | Standard Deviation 4836.21 |
| PF-06480605 500 mg IV | Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A) | Week 16 change from baseline | 5316.6 picograms/mL | Standard Deviation 4941.13 |
| PF-06480605 500 mg IV | Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A) | Week 20 change from baseline | 3903.3 picograms/mL | Standard Deviation 4092.26 |
| PF-06480605 500 mg IV | Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A) | Week 24 change from baseline | 3190.2 picograms/mL | Standard Deviation 3172.22 |
| PF-06480605 500 mg IV | Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A) | Week 26 change from baseline | 3084.3 picograms/mL | Standard Deviation 2964.75 |
Secondary
Lowest Serum Concentration (Cmin) of PF-06480605
Lowest serum concentration (Cmin) of PF-06480605 was observed directly from data.
Time frame: 30 minutes pre-dose and 1 hour post-dose on Day 85
Population: The analysis population included all enrolled participants who received at least 1 dose of PF-06480605 and in whom at least 1 concentration value was reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06480605 500 mg IV | Lowest Serum Concentration (Cmin) of PF-06480605 | 87650 ng/mL | Geometric Coefficient of Variation 50 |
Secondary
Maximum Serum Concentration (Cmax) of PF-06480605
Maximum serum concentration (Cmax) of PF-06480605 was observed directly from data.
Time frame: 30 minutes pre-dose and 1 hour post-dose on Day 85
Population: The analysis population included all enrolled participants who received at least 1 dose of PF-06480605 and in whom at least 1 concentration value was reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-06480605 500 mg IV | Maximum Serum Concentration (Cmax) of PF-06480605 | 263400 nanograms (ng)/milliliters (mL) | Geometric Coefficient of Variation 54 |
Secondary
Percentage of Participants Achieving Endoscopic Remission at Week 14 - Full Analysis Set
Endoscopic remission at Week 14 was defined as Mayo endoscopic sub-score of 0. The Mayo scoring system was used to assess ulcerative colitis activity, and it ranges from 0 to 12, calculated as sum of 4 sub-scores, with higher scores indicating more severe disease. The 4 sub-scores are stool frequency (0=normal number of stools; 1=1 to 2 stools more than normal; 2= 3 to 4 stools more than normal; 3= 5 or more stools more than normal); rectal bleeding (0=no blood seen; 1=streaks of blood with stools less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes); findings on endoscopy (0=normal or inactive disease; 1=mild disease \[erythema, decreased vascular pattern, mild friability\]; 2=moderate disease \[marked erythema, lack of vascular pattern, friability, erosions\]; 3=severe disease \[spontaneous bleeding, ulceration\]); and physician's global assessment (0=normal; 1=mild disease; 2=moderate disease; 3=severe disease).
Time frame: Week 14
Population: The analysis population included all participants who received at least 1 dose of PF-06480605.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-06480605 500 mg IV | Percentage of Participants Achieving Endoscopic Remission at Week 14 - Full Analysis Set | 10.00 percentage of participants |
Secondary
Percentage of Participants Achieving Remission at Week 14 - Full Analysis Set
Remission: total Mayo score \<=2 with no individual subscore \>1. Mayo scoring system was used to assess ulcerative colitis activity (range: 0 to 12, calculated as sum of 4 subscores, higher scores indicating more severe disease). The 4 subscores are stool frequency (0=normal number of stools; 1=1 to 2 stools more than normal; 2= 3 to 4 stools more than normal; 3= 5 or more stools more than normal); rectal bleeding (0=no blood seen; 1=streaks of blood with stools less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes); findings on modified endoscopy (0=normal or inactive disease; 1=mild disease \[erythema, decreased vascular pattern, no friability\]; 2=moderate disease \[marked erythema, lack of vascular pattern, friability, erosions\]; 3=severe disease \[spontaneous bleeding, ulceration\]); and physician's global assessment (0=normal; 1=mild disease; 2=moderate disease; 3=severe disease).
Time frame: Week 14
Population: The analysis population included all participants who received at least 1 dose of PF-06480605.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-06480605 500 mg IV | Percentage of Participants Achieving Remission at Week 14 - Full Analysis Set | 24.00 percentage of participants |
Secondary
Percentage of Participants Achieving Remission at Week 14 - Per Protocol Analysis Set
Remission: total Mayo score \<=2 with no individual subscore \>1. Mayo scoring system was used to assess ulcerative colitis activity (range: 0 to 12, calculated as sum of 4 subscores, higher scores indicating more severe disease). The 4 subscores are stool frequency (0=normal number of stools; 1=1 to 2 stools more than normal; 2= 3 to 4 stools more than normal; 3= 5 or more stools more than normal); rectal bleeding (0=no blood seen; 1=streaks of blood with stools less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes); findings on modified endoscopy (0=normal or inactive disease; 1=mild disease \[erythema, decreased vascular pattern, no friability\]; 2=moderate disease \[marked erythema, lack of vascular pattern, friability, erosions\]; 3=severe disease \[spontaneous bleeding, ulceration\]); and physician's global assessment (0=normal; 1=mild disease; 2=moderate disease; 3=severe disease).
Time frame: Week 14
Population: The analysis population included all participants who were eligible for enrollment, not a major protocol violator, with at least 6 out of 7 planned doses received and a final colonoscopy at Week 14.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-06480605 500 mg IV | Percentage of Participants Achieving Remission at Week 14 - Per Protocol Analysis Set | 26.67 percentage of participants |
Secondary
Percentage of Participants Who Developed Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)
Serum samples were analyzed using a new ADA assay with acid pre-treatment followed by a more drug-tolerant cell-based NAb assay. For ADA assay with acid pre-treatment, the sample was deemed positive if log titer \>=1.30; for cell-based NAb assay, the sample was deemed positive if log titer \>=0.699.
Time frame: Day 1 up to final onsite visit (Week 26)
Population: The analysis population included all enrolled participants who received at least 1 dose of PF 06480605 with at least 1 post-treatment ADA determination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-06480605 500 mg IV | Percentage of Participants Who Developed Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) | ADA | 82.0 percentage of participants |
| PF-06480605 500 mg IV | Percentage of Participants Who Developed Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) | NAb | 10.0 percentage of participants |