Study to Evaluate Safety and Tolerability of PF-07242813 in Healthy Participants and Participants With Atopic Dermatitis

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04668066

Collaborator

(none)

145

Enrollment

Locations

Arms

Anticipated Duration (Months)

20.7

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis	Drug: PF-07242813 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

145 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Basic Science

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

Actual Study Start Date :

Dec 10, 2020

Anticipated Primary Completion Date :

Dec 9, 2022

Anticipated Study Completion Date :

Dec 9, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single ascending doses of PF-07242813 or placebo in healthy participants Participants will receive a single intravenous dose of either PF-07242813 or placebo	Drug: PF-07242813 PF-07242813 given intravenously or subcutaneous Drug: Placebo Placebo given intravenously or subcutaneous
Experimental: Multiple ascending doses of PF-07242813 or placebo in healthy participants Participants will receive multiple subcutaneous doses PF-07242813 or placebo	Drug: PF-07242813 PF-07242813 given intravenously or subcutaneous Drug: Placebo Placebo given intravenously or subcutaneous
Experimental: Single dose of PF-07242813 or placebo in participants with moderate to severe atopic dermatitis Participants will receive a single intravenous dose of either PF-07242813 or placebo	Drug: PF-07242813 PF-07242813 given intravenously or subcutaneous Drug: Placebo Placebo given intravenously or subcutaneous

Arm

Intervention/Treatment

Experimental: Single ascending doses of PF-07242813 or placebo in healthy participants

Participants will receive a single intravenous dose of either PF-07242813 or placebo

Drug: PF-07242813

PF-07242813 given intravenously or subcutaneous

Drug: Placebo

Placebo given intravenously or subcutaneous

Experimental: Multiple ascending doses of PF-07242813 or placebo in healthy participants

Participants will receive multiple subcutaneous doses PF-07242813 or placebo

Drug: PF-07242813

PF-07242813 given intravenously or subcutaneous

Drug: Placebo

Placebo given intravenously or subcutaneous

Experimental: Single dose of PF-07242813 or placebo in participants with moderate to severe atopic dermatitis

Participants will receive a single intravenous dose of either PF-07242813 or placebo

Drug: PF-07242813

PF-07242813 given intravenously or subcutaneous

Drug: Placebo

Placebo given intravenously or subcutaneous

Outcome Measures

Primary Outcome Measures

Incidence of treatment-emergent adverse events (AEs and SAEs). [Baseline up to Week 16]
Number of Participants With Clinically Significant Change From Baseline in Safety Laboratory Tests [Baseline up to Week 16]
Number of Participants With Clinically Significant Change From Baseline in ECG [Baseline up to Week 16]
Number of Participants With Clinically Significant Change From Baseline in Vital Signs [Baseline up to Week 16]
Number of Participants With Clinically Significant Change From Baseline in Cardiac telemetry (SAD only) [Baseline up to Day 71]

Secondary Outcome Measures

Single Dose: AUC from time zero to time of last measurable concentration (AUClast) in the Dose Escalation and Dose Finding Arms [0, 2, 6, 12, 24, 48, 72, 96 hours post-dose and Days 15, 29, 43, 57, and 71]
Pharmacokinetic (PK) assessments for PF-07242813
Single Dose: AUC from time zero to time to infinity (AUCinf) in the Dose Escalation and Dose Finding Arms [0, 2, 6, 12, 24, 48, 72, 96 hours post-dose and Days 15, 29, 43, 57, and 71]
PK assessments for PF-07242813
Single Dose: Maximum Observed Concentration (Cmax) in the Dose Escalation and Dose Finding Arms [0, 2, 6, 12, 24, 48, 72, 96, hours post-dose and Days 8, 15, 29, 43, 57, and 71]
PK assessments for PF-07242813
Single Dose: Tmax time to reach maximum concentration (Tmax) in the Dose Escalation and Dose Finding Arms [0, 2, 6, 12, 24, 48, 72, 96 hours post-dose and Days 15, 29, 43, 57, and 71]
PK assessments for PF-07242813
Single Dose: Terminal Elimination half-life (t1/2) in the Dose Escalation and Dose Finding Arms [0, 2, 6, 12, 24, 48, 72, 96 hours post-dose and Days 15, 29, 43, 57, and 71]
PK assessments for PF-07242813
Repeat Dose: AUC from time zero to time curve within dosing interval (AUCtau) in the Dose Escalation and Dose Finding Arms [Day 1 - 0, 2, 6, 12, 24, 48, 72, 96 hours post-dose; Days 15 and 29 - 0, 2, 6, 8, 12, 24, 48 and 96 hours post-dose; and Days 43, 57, 71, 85 and 99]
PK assessments for PF-07242813
Repeat Dose: Cmax in the Dose Escalation and Dose Finding Arms [Day 1 - 0, 2, 6, 12, 24, 48, 72, 96 hours post-dose; Days 15 and 29 - 0, 2, 6, 8, 12, 24, 48 and 96 hours post-dose; and Days 43, 57, 71, 85 and 99]
PK assessments for PF-07242813
Repeat Dose: Tmax in the Dose Escalation and Dose Finding Arms [Day 1 - 0, 2, 6, 12, 24, 48, 72, 96 hours post-dose; Days 15 and 29 - 0, 2, 6, 8, 12, 24, 48 and 96 hours post-dose; and Days 43, 57, 71, 85 and 99]
PK assessments for PF-07248144
Repeat dose: t1/2 in the Dose Escalation and Dose Finding Arms [Day 1 - 0, 2, 6, 12, 24, 48, 72, 96 hours post-dose; Days 15 and 29 - 0, 2, 6, 8, 12, 24, 48 and 96 hours post-dose; and Days 43, 57, 71, 85 and 99]
PK assessments for PF-07242813
Percent change from baseline in Eczema Area and Severity Index (EASI) total score at Week 6 [Baseline to Week 6]
Efficacy evaluation for atopic dermatitis cohort.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anaheim Clinical Trials, LLC	Anaheim	California	United States	92801
2	First OC Dermatology	Fountain Valley	California	United States	92708
3	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
4	Orange County Research Center	Tustin	California	United States	92780
5	Carolina Phase I Research, LLC	Raleigh	North Carolina	United States	27612
6	Vital Prospects Clinical Research Institute, PC	Tulsa	Oklahoma	United States	74136
7	Aspen Clinical Research	Orem	Utah	United States	84058