Trial Outcomes & Findings for Evaluate PF-00547659 On Cerebrospinal Fluid Lymphocytes In Volunteers With Crohn's Disease Or Ulcerative Colitis Who Failed Or Did Not Tolerate Anti-TNFs (NCT NCT01387594)

Last Updated: 2021-06-03

Results Overview

The primary CSF endpoint of Cohort 2 was the percent change from baseline in absolute lymphocyte counts in CSF after 3 doses of PF-00547659. The hypothesis for the primary endpoint was evaluated using the CSF evaluable population in Cohort 2. CSF samples were obtained via lumbar puncture and analyzed by fluorescence-activated cell sorting (FACS) for total lymphocyte counts. Lumbar punctures were performed by a highly qualified physician using a 20-22 gauge needle, preferably an atraumatic needle.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

49 participants

Primary outcome timeframe

Baseline

Results posted on

2021-06-03

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1: PF-00547659 Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Prior to treatment, participants underwent 2 lumbar punctures (LP) 2-4 weeks apart. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) (Days 1, 29, 57). At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.	Cohort 2: PF-00547659 Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Participants underwent 2 lumbar punctures (LP), 1 prior to treatment and another 1-3 weeks after the last dose. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) on Days 1, 29, and 57. At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.
Overall Study STARTED	10	39
Overall Study COMPLETED	10	36
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: PF-00547659 Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Prior to treatment, participants underwent 2 lumbar punctures (LP) 2-4 weeks apart. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) (Days 1, 29, 57). At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.	Cohort 2: PF-00547659 Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Participants underwent 2 lumbar punctures (LP), 1 prior to treatment and another 1-3 weeks after the last dose. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) on Days 1, 29, and 57. At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.
Overall Study Withdrawal by Subject	0	2
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Evaluate PF-00547659 On Cerebrospinal Fluid Lymphocytes In Volunteers With Crohn's Disease Or Ulcerative Colitis Who Failed Or Did Not Tolerate Anti-TNFs

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: PF-00547659 n=10 Participants Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Prior to treatment, participants underwent 2 lumbar punctures (LP) 2-4 weeks apart. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) (Days 1, 29, 57). At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.	Cohort 2: PF-00547659 n=39 Participants Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Participants underwent 2 lumbar punctures (LP), 1 prior to treatment and another 1-3 weeks after the last dose. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) on Days 1, 29, and 57. At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.	Total n=49 Participants Total of all reporting groups
Age, Continuous	40.9 years STANDARD_DEVIATION 15.9 • n=5 Participants	37.4 years STANDARD_DEVIATION 10.6 • n=7 Participants	38.1 years STANDARD_DEVIATION 11.8 • n=5 Participants
Age, Customized 18-44 years	6 Participants n=5 Participants	27 Participants n=7 Participants	33 Participants n=5 Participants
Age, Customized 45-64 years	4 Participants n=5 Participants	12 Participants n=7 Participants	16 Participants n=5 Participants
Age, Customized More than or equal to (>=) 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	26 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	13 Participants n=7 Participants	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline

Population: All Cohort 2 participants who were enrolled, had 2 evaluable LPs, and who received all 3 doses of study drug.

Outcome measures

Outcome measures
Measure	Cohort 2: PF-00547659 n=32 Participants Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Participants underwent 2 lumbar punctures (LP), 1 prior to treatment and another 1-3 weeks after the last dose. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) on Days 1, 29, and 57. At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.	Cohort 2: PF-00547659 Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Participants underwent 2 lumbar punctures (LP), 1 prior to treatment and another 1-3 weeks after the last dose. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) on Days 1, 29, and 57. At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.
Cohort 2: Baseline Absolute Lymphocyte Count in Cerebrospinal Fluid (CSF)	338.5 cells per milliliter (cells/mL) Full Range 689.69 • Interval 67.0 to 2100.0	—

PRIMARY outcome

Timeframe: Baseline, Month 3

Population: All Cohort 2 participants who were enrolled, had 2 evaluable lumbar punctures, and who received all 3 doses of study drug.

The primary CSF endpoint of Cohort 2 was the percent change from baseline in absolute lymphocyte counts in CSF after 3 doses of PF-00547659. The hypothesis for the primary endpoint was evaluated using the CSF evaluable population in Cohort 2. CSF samples were obtained via lumbar puncture and analyzed by FACS for total lymphocyte counts. Lumbar punctures were performed by a highly qualified physician using a 20-22 gauge needle, preferably an atraumatic needle.

Outcome measures

Outcome measures
Measure	Cohort 2: PF-00547659 n=32 Participants Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Participants underwent 2 lumbar punctures (LP), 1 prior to treatment and another 1-3 weeks after the last dose. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) on Days 1, 29, and 57. At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.	Cohort 2: PF-00547659 Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Participants underwent 2 lumbar punctures (LP), 1 prior to treatment and another 1-3 weeks after the last dose. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) on Days 1, 29, and 57. At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.
Cohort 2: Percent Change From Baseline in Absolute Lymphocyte Count in CSF at Month 3	35.2 percent change Full Range 92.67 • Interval -70.2 to 267.8	—

SECONDARY outcome

Timeframe: Baseline up to Week 12

Population: All participants who received at least one dose of study drug were analyzed for AEs/safety. Combined data for both cohorts is presented.

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent for this measure are events between first dose of study drug and up to 85 days (Week 12) after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included serious and non-serious AEs.

Outcome measures

Outcome measures
Measure	Cohort 2: PF-00547659 n=10 Participants Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Participants underwent 2 lumbar punctures (LP), 1 prior to treatment and another 1-3 weeks after the last dose. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) on Days 1, 29, and 57. At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.	Cohort 2: PF-00547659 n=39 Participants Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Participants underwent 2 lumbar punctures (LP), 1 prior to treatment and another 1-3 weeks after the last dose. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) on Days 1, 29, and 57. At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.
Cohorts 1 and 2: Total Number of Participants With Non-Lumbar Puncture (LP) Related Treatment-Emergent Adverse Events (AEs), Withdrawals Due to AEs, and Serious Adverse Events (SAEs) During the 12-week Treatment Period AEs	9 participants	36 participants
Cohorts 1 and 2: Total Number of Participants With Non-Lumbar Puncture (LP) Related Treatment-Emergent Adverse Events (AEs), Withdrawals Due to AEs, and Serious Adverse Events (SAEs) During the 12-week Treatment Period Withdrawals due to AEs	0 participants	0 participants
Cohorts 1 and 2: Total Number of Participants With Non-Lumbar Puncture (LP) Related Treatment-Emergent Adverse Events (AEs), Withdrawals Due to AEs, and Serious Adverse Events (SAEs) During the 12-week Treatment Period SAEs	1 participants	3 participants

SECONDARY outcome

Timeframe: Day 1; Weeks 4, 8, 9-11 (Cohort 2 only), 12, 20, 28, and 36; Early Withdrawal

Population: All participants who received at least one dose of study drug.

Serum samples were analysed for presence of ADAs to PF-00547659. Participants who showed positive results for PF-00547659 were reported.

Outcome measures

Outcome measures
Measure	Cohort 2: PF-00547659 n=10 Participants Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Participants underwent 2 lumbar punctures (LP), 1 prior to treatment and another 1-3 weeks after the last dose. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) on Days 1, 29, and 57. At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.	Cohort 2: PF-00547659 n=39 Participants Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Participants underwent 2 lumbar punctures (LP), 1 prior to treatment and another 1-3 weeks after the last dose. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) on Days 1, 29, and 57. At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.
Cohorts 1 and 2: Number of Participants Who Developed Anti-Drug Antibodies (ADAs) to PF-00547659	4 participants	11 participants

SECONDARY outcome

Timeframe: Baseline till End of Study/Early Withdrawal, up to Week 12

Population: All participants who received at least one dose of study drug.

Injection site reaction AEs include: injection site irritation, injection site pain, injection site rash, contusion, and erythema.

Outcome measures

Outcome measures
Measure	Cohort 2: PF-00547659 n=10 Participants Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Participants underwent 2 lumbar punctures (LP), 1 prior to treatment and another 1-3 weeks after the last dose. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) on Days 1, 29, and 57. At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.	Cohort 2: PF-00547659 n=39 Participants Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Participants underwent 2 lumbar punctures (LP), 1 prior to treatment and another 1-3 weeks after the last dose. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) on Days 1, 29, and 57. At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.
Cohorts 1 and 2: Number of Participants With Injection Site Reactions by Severity Mild	1 participants	6 participants
Cohorts 1 and 2: Number of Participants With Injection Site Reactions by Severity Moderate	0 participants	1 participants
Cohorts 1 and 2: Number of Participants With Injection Site Reactions by Severity Severe	0 participants	0 participants

Adverse Events

Cohort 1: PF-00547659

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Cohort 2: PF-00547659

Serious events: 3 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: PF-00547659 n=10 participants at risk Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Prior to treatment, participants underwent 2 lumbar punctures (LP) 2-4 weeks apart. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) (Days 1, 29, 57). At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.	Cohort 2: PF-00547659 n=39 participants at risk Participants who had Crohn's disease (CD) and who satisfied all study entry criteria were enrolled into the study. Participants underwent 2 lumbar punctures (LP), 1 prior to treatment and another 1-3 weeks after the last dose. All participants received 3 monthly subcutaneous (SC) doses of PF-00547659 225 milligrams (mg) on Days 1, 29, and 57. At Week 12, participants who had a clinical response to treatment could enter the open-label extension study. Otherwise, participants would enter a 6-month follow-up period onsite.
Gastrointestinal disorders Crohn's disease	0.00% 0/10 • Screening till end of study or at early withdrawal, whichever was earlier, up to Week 12. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.1% 2/39 • Screening till end of study or at early withdrawal, whichever was earlier, up to Week 12. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Enterocutaneous fistula	10.0% 1/10 • Screening till end of study or at early withdrawal, whichever was earlier, up to Week 12. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/39 • Screening till end of study or at early withdrawal, whichever was earlier, up to Week 12. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	10.0% 1/10 • Screening till end of study or at early withdrawal, whichever was earlier, up to Week 12. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/39 • Screening till end of study or at early withdrawal, whichever was earlier, up to Week 12. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Nephrolithiasis	0.00% 0/10 • Screening till end of study or at early withdrawal, whichever was earlier, up to Week 12. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	2.6% 1/39 • Screening till end of study or at early withdrawal, whichever was earlier, up to Week 12. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER