Clinical trial NCT04668066: Study to Evaluate Safety and Tolerability of PF-07242813 in Healthy Participants and Participants With Atopic Dermatitis
Official title: A PHASE 1 FIRST IN HUMAN, RANDOMIZED, DOUBLE BLIND, SPONSOR OPEN, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE DOSE ESCALATION, PARALLEL GROUP STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF PF 07242813 IN HEALTHY PARTICIPANTS AND PARTICIPANTS WITH ATOPIC DERMATITIS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atopic Dermatitis
Keywords: Atopic Dermatitis
inflammatory skin disease
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-12-16
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: This is the first time PF-07242813 will be given to humans. The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics of escalating single and repeat doses of PF-07242813 in healthy participants and in participants with moderate to severe atopic dermatitis. An additional goal is to assess the pharmacodynamics of PF-07242813 in participants with moderate to severe AD, including potential effects on clinical signs and symptoms.


Eligibility criteria: Inclusion Criteria Part 1 (Healthy Volunteer Cohorts):

* BMI of 17.5 to 30.5 kg/m2; and BW\>50 kg (110 lbs)
* Overtly healthy as determined by medical evaluation including medical history, physical examination, vital sign assessments, temperature, 12-lead ECGs, laboratory tests
* Japanese cohort: healthy adults of Japanese descent, where parents and grandparents are Japanese
* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol

Inclusion Criteria Part 2 (Atopic Dermatitis Cohort):

* Have a clinical diagnosis of chronic atopic dermatitis (also known as atopic eczema) for approximately 1 year prior to Day 1 and have the diagnosis of AD confirmed (Hanifin and Rajka criteria of AD).
* Either have had an inadequate response to treatment with topical medications (for at least 4 consecutive weeks within 1 year of the first dose of the study drug) OR Have a documented reason why topical treatments are considered medically inappropriate (eg, because of important side effects or safety risks) within the last year.
* Have moderate to severe AD (defined as having an affected BSA (captured as part of EASI) ≥10%, IGA ≥3, and EASI ≥12 at both the screening and baseline visits).
* Generally healthy adult, with no significant comorbidities.
* Mild or moderate asthma that is well-controlled (not requiring high dose inhaled corticosteroids, systemic \[oral or parenteral\] corticosteroids, or biologic asthma treatments).
* BMI of 17.5 to 40 kg/m2; and a total body weight \>50 kg (110 lbs).

Exclusion Criteria Part 1 (Healthy Volunteer Cohorts):

* Evidence of active, latent, or inadequately treated infection with TB; History of HIV, hepatitis B or C infection; positive testing for HIV, HepB, HepC except HepB vaccination
* Medical or psychiatric condition that may increase the risk of study participation, or inappropriate for the study in investigator's judgement
* History of any lymphoproliferative disorder, evidence or history of clinically significant diseases
* History of systemic infection requiring hospitalization, parenteral antimicrobial therapy, or judged clinically significant by the investigator within 6 months
* Known history of or evidence of current endocrine disease
* Exposure to live or attenuated vaccines within 28 days of screening.
* Have any malignancies or a history of malignancies except adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ.
* Allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
* Have undergone significant trauma or major surgery within 1 month of 1st dose of study drug.
* Use of prescription or nonprescription drugs, dietary or herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to 1st dose of study drug.
* Females taking hormone replacement therapy may be eligible to participate in this study if they are willing to discontinue therapy at least 28 days prior to the first dose of study treatment and remain off hormonal therapy for the duration of the study.
* Positive urine drug test, alcohol intake more than 14 units per week or use of tobacco/nicotine containing products more than 5 cigarettes per day.
* Treatment with an investigational drug within 28 days or 5 half-lives preceding the first dose of study treatment (whichever is longer).
* Abnormal BP, ECG and lab tests including AST/ALT, total bilirubin and anterior pituitary hormones, at screenings and/or baseline, based on pre-specified criteria per protocol.
* Unwilling or unable to comply with the Lifestyle guidance specified in this protocol (Lifestyle Considerations section).

Exclusion Criteria Part 2 (Atopic Dermatitis Cohort):

* Evidence of active, latent, or inadequately treated TB.
* History of or positive result for HIV or hepatitis infection. Positive Covid-19 test (if collected).
* Significant medical or psychiatric condition, including suicidal ideation (C-SSRS screening assessment noting suicidal ideation in prior 6 months is not eligible).
* H/o or current endocrine disease.
* History of systemic infection requiring hospitalization, parenteral antimicrobial treatment or considered significant by Investigator.
* History of or current malignancy, with the exception of non-metastatic BCC, squamous cell skin or cervical in situ.
* Currently have active forms of other inflammatory skin diseases.
* Have history of or current evidence of skin disease at the time of Day 1 that would interfere with evaluation of atopic dermatitis or response to treatment.
* Have active chronic or acute skin infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks prior to Day 1, or superficial skin infections within 1 week prior to Day 1.
* Score of \>5 on the Fitzpatrick Skin Type Assessment.
* History of anaphylaxis with the exception of participants with sensitivity and/or anaphylaxis only to a single, avoidable allergen.

Primary outcomes:
measure: Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: From start of study treatment on Day 1 to Day 71
measure: Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs
timeFrame: From start of study treatment on Day 1 to Day 99
measure: Part 2: Number of Participants With TEAEs and TESAEs
timeFrame: From start of study treatment on Day 1 to Week 16
measure: Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs
timeFrame: From initiation of treatment to day 71
measure: Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs
timeFrame: From start of study treatment on Day 1 to Day 99
measure: Part 2: Number of Participants With Clinically Significant Findings in Vital Signs
timeFrame: From start of study treatment on Day 1 to Week 16
measure: Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities
timeFrame: Baseline (last pre-dose measurement) to Day 71
measure: Part 1: MAD Cohorts: Number of Participants With Laboratory Test Abnormalities
timeFrame: Baseline (last pre-dose measurement) to Day 99
measure: Part 2: Number of Participants With Laboratory Test Abnormalities
timeFrame: Baseline (last pre-dose measurement) to Week 16
measure: Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities
timeFrame: From pre-dose up to 6 hours post dose on Day 1
measure: Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG)
timeFrame: From pre-dose on Day 1 up to Day 71
measure: Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in ECG
timeFrame: From pre-dose on Day 1 up to Day 99
measure: Part 2: Number of Participants With Clinically Significant Findings in ECG
timeFrame: From pre-dose on week 1 to week 16
Secondary outcomes:
measure: Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for PF-07242813
timeFrame: Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV
measure: Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-07242813
timeFrame: Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV
measure: Part 1: SAD Cohorts: Maximum Serum Concentration (Cmax) for PF-07242813
timeFrame: Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV
measure: Part 1: SAD Cohorts: Time to Reach Maximum Concentration (Tmax) for PF-07242813
timeFrame: Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV
measure: Part 1: SAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813
timeFrame: Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV
measure: Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813
timeFrame: Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose)
measure: Part 1: MAD Cohorts: Cmax for PF-07242813
timeFrame: Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose)
measure: Part 1: MAD Cohorts: Tmax for PF-07242813
timeFrame: Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose)
measure: Part 1: MAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813
timeFrame: Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose)
measure: Part 2: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 6
timeFrame: Baseline, Week 6
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Fountain Valley
country: United States
facility: First OC Dermatology
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine of USC
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute, PC
state: Oklahoma
city: Orem
country: United States
facility: Aspen Clinical Research
state: Utah
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: