Clinical trial NCT02743871: Study Of PF-06817024 In Healthy Subjects, In Patients With Chronic Rhinosinusitis With Nasal Polyps And in Patients With Atopic Dermatitis
Official title: A PHASE 1, RANDOMIZED, DOUBLE-BLIND, THIRD-PARTY OPEN, PLACEBO-CONTROLLED, DOSE ESCALATING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF SINGLE AND/OR MULTIPLE INTRAVENOUS AND/OR SUBCUTANEOUS DOSES OF PF-06817024 IN HEALTHY SUBJECTS WHO MAY BE MILDLY ATOPIC, SUBJECTS WITH CHRONIC RHINOSINUSITIS WITH NASAL POLYPS, AND SUBJECTS WITH MODERATE-SEVERE ATOPIC DERMATITIS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Chronic Rhinosinusitis With Nasal Polyps
Atopic Dermatitis
Keywords: FIH, Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, Atopic Dermatitis, Chronic Rhinosinusitis, Nasal Polyps
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-04-19
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06817024 in healthy volunteers, in participants with chronic rhinosinusitis, with nasal polyps and in participants with moderate-to-severe Atopic Dermatitis

Detailed description: The purpose of the study for Part 1 is to evaluate the safety and tolerability of PF-06817024 in healthy subjects.

The purpose of the study for Part 2 is to evaluate the safety and tolerability of PF-06817024 in patients with chronic rhinosinusitis with nasal polyps.

The purpose of the study for Part 3 is to evaluate the safety and tolerability of PF-06817024 in patients with moderate-to-severe Atopic Dermatitis

Eligibility criteria: Inclusion Criteria

* Healthy male subjects, healthy female subjects of non-childbearing potential, 18-55 years of age (Part 1)
* Male subjects, female subjects of non-childbearing potential, female subjects of childbearing potential with documented bilateral tubal ligation (tubes tied) or bilateral salpingectomy (tubes removed), 18-65 years of age, and 2 of the following symptoms: nasal congestion/obstruction, nasal discharge, face pain/pressure,or reduction/loss of smell (Part 2)
* Male or female subjects between the ages of 18 and 75 years, inclusive with moderate-to-severe Atopic Dermatitis, agree to avoid prolonged exposure to the sun and not to use tanning booths, sun lamps, or other ultraviolet light sources during the study (Part 3)

Exclusion Criteria:

* Clinically significant diseases (cardiac, psychiatric, autoimmune, renal, etc.), positive urine drug test, fever within 7 days of dosing, active infections within 28 days of dosing (Part 1 and 2 and 3)
* History of allergic reaction to topical lidocaine, nasal surgery within 6 months (Part 2)
* Exposure to live or attenuated vaccines, have skin conditions other than Atopic Dermatitis, use of JAK inhibitors and biologics (Part 3)

Primary outcomes:
measure: Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Part 1
timeFrame: From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7).
measure: Number of Participants With Treatment-Related TEAEs and SAEs in Part 1
timeFrame: From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7).
measure: Number of All-Causality TEAEs According to Severity in Part 1
timeFrame: From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7).
measure: Number of Participants With Permanent Discontinuation Due to TEAEs in Part 1
timeFrame: From Study Day 1 (baseline) up to Day 421 (Cohort 1 and 2), Day 601 (Cohort 3), Day 691 (Cohort 4), Day 781 (Cohort 5), and Day 511 (Cohort 7).
measure: Number of Participants With All-Causality TEAEs and SAEs in Part 2
timeFrame: From Study Day 1 (baseline) up to Day 691.
measure: Number of Participants With Treatment-Related TEAEs and SAEs in Part 2
timeFrame: From Study Day 1 (baseline) up to Day 691.
measure: Number of All-Causality TEAEs According to Severity in Part 2
timeFrame: From Study Day 1 (baseline) up to Day 691.
measure: Number of Participants With Permanent Discontinuation Due to TEAEs in Part 2
timeFrame: From Study Day 1 (baseline) up to Day 691.
measure: Number of Participants With All-Causality TEAEs and SAEs in Part 3
timeFrame: From Study Day 1 (baseline) up to Day 1105.
measure: Number of Participants With Treatment-Related TEAEs and SAEs in Part 3
timeFrame: From Study Day 1 (baseline) up to Day 1105.
measure: Number of All-Causality TEAEs According to Severity in Part 3
timeFrame: From Study Day 1 (baseline) up to Day 1105.
measure: Number of Participants With Permanent Discontinuation Due to TEAEs in Part 3
timeFrame: From Study Day 1 (baseline) up to Day 1105.
measure: Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 1
timeFrame: Part 1 single-dose cohorts: from Study Day 1 (baseline) up to Day 211. Part 1 multiple-dose cohorts: from Study Day 1 (baseline) up to Day 241.
measure: Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 2
timeFrame: Part 2: from Study Day 1 (baseline) up to Day 211.
measure: Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis in Part 3
timeFrame: Part 3: from Study Day 1 (baseline) up to Day 966.
measure: Number of Participants With Vital Sign Abnormalities in Part 1
timeFrame: Study Day 1 (baseline) up to end of study (Study Day 211 for Part 1 SD cohorts, and Study Day 241 for Part 1 MD cohorts).
measure: Number of Participants With Vital Sign Abnormalities in Part 2
timeFrame: Study Day 1 (baseline) up to end of study (Study Day 211).
measure: Number of Participants With Vital Sign Abnormalities in Part 3
timeFrame: Study Day 1 (baseline) up to end of study (Study Day 337).
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities in Part 1
timeFrame: Study Day 1 (baseline) up to end of study (Study Day 211 for Part 1 SD cohorts, and Study Day 241 for Part 1 MD cohorts).
measure: Number of Participants With ECG Abnormalities in Part 2
timeFrame: Study Day 1 (baseline) up to end of study (Study Day 211).
measure: Number of Participants With ECG Abnormalities in Part 3
timeFrame: Study Day 1 (baseline) up to end of study (Study Day 337).
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of PF-06817024 Following Single Dose in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose).
measure: Cmax of PF-06817024 Following Multiple Doses in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
measure: Cmax of PF-06817024 in Part 2
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose).
measure: Cmax of PF-06817024 in Part 3
timeFrame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
measure: Dose Normalized Maximum Observed Serum Concentration (Cmax[dn]) of PF-06817024 Following Single Dose in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose).
measure: Cmax(dn) of PF-06817024 Following Multiple Doses in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
measure: Cmax(dn) of PF-06817024 in Part 2
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose).
measure: Cmax(dn) of PF-06817024 in Part 3
timeFrame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06817024 Following Single Dose in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose).
measure: Tmax of PF-06817024 Following Multiple Doses in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
measure: Tmax of PF-06817024 in Part 2
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose).
measure: Tmax of PF-06817024 in Part 3
timeFrame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
measure: Area Under the Curve From Time Zero to Infinity Concentration (AUCinf) of PF-06817024 Following Single Dose in Part 1 and 2
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to 780 days for Part 1 and 690 days for Part 2). For Part 1 only: at post-dose 48 and 72 hour, Days 46 and 151.
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06817024 Following Single Dose in Part 1 and 2
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to 780 days for Part 1 and 690 days for Part 2). For Part 1 only: at post-dose 48 and 72 hour, Days 46 and 151.
measure: Area Under the Curve Within Dosing Interval (AUCtau) of PF-06817024 Following Multiple Doses in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
measure: AUCtau of PF-06817024 in Part 3
timeFrame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
measure: Dose Normalized Area Under the Curve Within Dosing Interval (AUCtau[dn]) of PF-06817024 Following Multiple Doses in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
measure: AUCtau(dn) of PF-06817024 Following Multiple Doses in Part 3
timeFrame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
measure: Average Concentration Over Dosing Interval (Cav) of PF-06817024 Following Multiple Doses in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
measure: Cav of PF-06817024 Following Multiple Doses in Part 3
timeFrame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
measure: Terminal Elimination Half Life (t1/2) of PF-06817024 Following Single Dose in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose).
measure: t1/2 of PF-06817024 Following Multiple Doses in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
measure: t1/2 of PF-06817024 in Part 2
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to a maximum of 690 days/16560 hours post dose).
measure: t1/2 of PF-06817024 in Part 3
timeFrame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
measure: Apparent Volume of Distribution (Vz/F) of PF-06817024 for the Subcutaneous Cohort in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose).
measure: Apparent Clearance (CL/F) of PF-06817024 for the Subcutaneous Cohort in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, 96 hours post dose on Day 1, and on Follow-up Days 8, 15, 32, 46, 61, 91, 121, 151, 181, 211, and at Extended Follow-Up visits (up to a maximum of 780 days/18720 hours post dose).
measure: Volume of Distribution at Steady State (Vss) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, and 96 hour post dose on Day 1, and Days 8, 15, 32, 61, 91, 121, 181, 211, and at Extended Follow-Up visits (up to 780 days for Part 1 and 690 days for Part 2). For Part 1 only: at post-dose 48 and 72 hour, Days 46 and 151.
measure: Clearance (CL) of PF-06817024 Following Single Intravenous Dose in Part 1 and Part 2
timeFrame: On Day 1 at pre-dose, post-dose 1, 2, 4, 8, 12, 24, 96 hour, Day 8, 15, 32, 61, 91, 121,181, 211, 241, 331, and 421. For Part 1 only: at post-dose 48 and 72 hour, Day 46 and 151. For Part 2 only: on Day 511, 601, and 691.
measure: Trough Serum Concentration (Cmin) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1
timeFrame: At pre-dose on Day 31 or Day 46.
measure: Cmin of PF-06817024 Post Last Dose Following Multiple Doses in Part 3
timeFrame: At pre dose (0 hour) on Day 85.
measure: Accumulation Ratio for Cmax (Rac, Cmax) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
measure: Rac, Cmax of PF-06817024 Post Last Dose Following Multiple Doses in Part 3
timeFrame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
measure: Accumulation Ratio for AUCtau (Rac) of PF-06817024 Post Second Dose Following Multiple Doses in Part 1
timeFrame: Pre-dose, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hr post dose on Day 1, Days 8 and 15, Day 31/46 (at pre-dose, 1, 2, 4, 8, 12, 24, 48 hr), Days 61, 91, 121, 151, 181, 211, 241, at Extended Follow-Up visits (up to a maximum of 645 days/15480 hr post dose).
measure: Rac of PF-06817024 Post Last Dose Following Multiple Doses in Part 3
timeFrame: On Day 1 (at pre-dose, 1.5, 4, and 168 hours post dose), and Days 29, 57, and 85 (at pre-dose, 1.5 and 4 hours post dose), and on Days 113, 253, 337, and Extended Follow-Up visits (up to a maximum of 882 days/21168 hours post dose on Day 85).
measure: Number of Participants With Treatment-Induced Anti-Drug Antibody (ADA) Against PF-06817024 in Part 1, 2, and 3
timeFrame: Part 1 SD cohorts: baseline up to Day 780; Part 1 MD cohort: baseline up to Day 693; Part 2: baseline up to Day 692, Part 3: baseline up to Day 964.
measure: Number of Participants With Treatment-Induced Neutralizing Antibodies (NAbs) Against PF-06817024 in Part 1, 2, and 3
timeFrame: Part 1 SD cohorts: baseline up to Day 780; Part 1 MD cohort: baseline up to Day 693; Part 2: baseline up to Day 692, Part 3: baseline up to Day 964.
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis Dermatology
state: California
city: Sacramento
country: United States
facility: UC Davis CTSC Clinical Research Center
state: California
city: Sacramento
country: United States
facility: UC Davis Health
state: California
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
city: Shelton
country: United States
facility: Dermatology Physicians of Connecticut
state: Connecticut
city: Tampa
country: United States
facility: ForCare Clinical Research
state: Florida
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research Group, LLC
state: Indiana
city: Indianapolis
country: United States
facility: Dawes Fretzin Dermatology Group, LLC
state: Indiana
city: Plainfield
country: United States
facility: The Indiana Clinical Trials Center
state: Indiana
city: Edina
country: United States
facility: Academic Dermatology
state: Minnesota
city: Minneapolis
country: United States
facility: Clinical Research Institute, Inc.
state: Minnesota
city: Minneapolis
country: United States
facility: Ear, Nose & Throat Specialty Care of Minnesota, P.A.
state: Minnesota
city: Saint Paul
country: United States
facility: Prism Research, LLC
state: Minnesota
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Raleigh
country: United States
facility: Carolina Phase 1 Research, LLC
state: North Carolina
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute, PC
state: Oklahoma
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: San Antonio
country: United States
facility: Lee Medical Associates, PA
state: Texas
city: San Antonio
country: United States
facility: Progressive Clinical Research, PA
state: Texas
city: Norfolk
country: United States
facility: Virginia Clinical Research, Inc.
state: Virginia
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: