Clinical trial NCT06564389: FIH Study to Evaluate the Tolerability of PF-07832837 in Healthy Adults and Patients
Official title: A PHASE 1, FIRST IN HUMAN, RANDOMIZED, DOUBLE-BLIND, SPONSOROPEN, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE DOSE ESCALATION, PARALLEL GROUP STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF PF-07832837 IN HEALTHY PARTICIPANTS AND PARTICIPANTS WITH MODERATE TO SEVERE ATOPIC DERMATITIS
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Participants
Atopic Dermatitis
Keywords: healthy
atopic dermatitis
first in human
monoclonal antibody
anti-inflammatory
pharmacokinetics
pharmacodynamics
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2024-08-21
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics of escalating single and repeat doses of PF-07832837 in healthy participants and in participants with moderate to severe atopic dermatitis. An additional goal is to assess the pharmacodynamics of PF-07832837 in participants with moderate to severe AD, including potential effects on clinical signs and symptoms

Detailed description: This is a first-in-human (FIH) study of PF-07832837 that will be conducted in 2 parts: Part 1 will be conducted in healthy adult participants and Part 2 will be conducted in adult participants with moderate to severe AD.

Part 1 is within-cohort randomized, participant- and investigator-blind, sponsor-open, placebo-controlled investigation of the safety, tolerability, PK, and immunogenicity following single and multiple ascending doses of PF-07832837 in healthy participants. Part 1 may also include a cohort of Japanese healthy adult participants to provide safety, tolerability, and PK data in Japanese population to enable the inclusion of Japanese participants in future clinical trials.

Part 2 is a randomized, participant- and investigator-blind, sponsor-open, placebo-controlled study to investigate the safety, tolerability, PK, and pharmacodynamics (including clinical effects) of PF-07832837 in participants with moderate to severe AD. Part 2 will consist of cohorts of participants with moderate to severe AD. A total of approximately 28 participants will receive either active PF-07832837 or placebo.

Eligibility criteria: Inclusion Criteria:

* Part 1 only: Adult participants between 18 to 55 years of age, inclusive, at the time of signing the ICD
* Part 2 only: Adult participants, who at the time of screening, are between the ages of 18 and 70 years, inclusive. Participants above 65 years need to be discussed with the sponsor.
* Part 1 only: Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, vital sign assessments, temperature, 12-lead ECGs, laboratory tests
* BMI of 17.5 to 40 kg/m2; and a total body weight \>50 kg (110 lbs)
* Part 2 only: Must meet the following AD criteria:

  1. Have a clinical diagnosis of chronic AD (also known as atopic eczema) for approximately 1 year prior to Day 1 and have the diagnosis of AD confirmed.
  2. 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 intervention). OR Have a documented reason why topical treatments are considered medically inappropriate within the last year.
  3. 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).
  4. Have an otherwise healthy medical evaluation (other than signs and symptoms of AD) including medical history, physical examination, vital sign assessments, temperature, 12-lead ECGs, laboratory tests.

Mild or moderate asthma that is well-controlled (not requiring high dose inhaled corticosteroids, systemic \[oral or parenteral\] corticosteroids, or biologic asthma treatments).

Exclusion Criteria:

* Have a history of systemic infection requiring hospitalization and parenteral antimicrobial therapy, any lymphoproliferative disorder, malignancies.
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, immunological/rheumatological disorder.
* Have undergone significant trauma or major surgery within 1 month of the first dose of study intervention.
* Evidence of active, latent, or inadequately treated infection with Mycobacterium tuberculosis (TB) as defined by both of the following:

  1. A positive QuantiFERON-TB Gold In-tube or equivalent test.
  2. History of either untreated or inadequately treated latent or active TB infection, or current treatment for the same.

Part 2 Only

* Currently have active forms of other inflammatory skin diseases
* Have history of or current evidence of skin conditions 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 following exceptions: participants with sensitivity and/or anaphylaxis only to a single, avoidable allergen (eg, aspirin, penicillin, sulfa drugs, nonsteroidal anti-inflammatory drugs \[NSAIDs\], peanuts) may be enrolled, if in the opinion of the investigator, the participant is aware of the hypersensitivity and avoids the problematic allergen. Participants must carry appropriate treatment for anaphylaxis and must know how to manage anaphylactic reactions.
* Any investigational or experimental therapy taken or procedure performed for AD, psoriasis, psoriatic arthritis, rheumatoid arthritis or other inflammatory diseases in the previous 1 year should be discussed with the Pfizer Medical Monitor (or designee).

Primary outcomes:
measure: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) and serious adverse events (SAEs) Following single ascending doses (SAD)
timeFrame: Baseline up to Day 35
measure: Number of Participants with Clinically significant Laboratory Abnormalities Following SAD
timeFrame: Baseline up to Day 35
measure: Number of Participants with Change from Baseline in Electrocardiogram (ECG) Findings Following SAD
timeFrame: Baseline up to Day 35
measure: Number of Participants with Clinically Significant Change from Baseline in Vital Signs Following SAD
timeFrame: Baseline up to Day 35
measure: Number of Participants with Clinically Significant Change from Baseline in Cardiac Telemetry Findings Following SAD
timeFrame: Day 1
measure: Number of Participants With Treatment Emergent Treatment-Related AEs and SAEs Following multiple ascending doses (MAD)
timeFrame: Baseline up to Day 50
measure: Number of Participants with Clinically significant Laboratory Abnormalities Following MAD
timeFrame: Baseline up to Day 50
measure: Number of Participants with Change from Baseline in Electrocardiogram (ECG) Findings Following MAD
timeFrame: Baseline up to Day 50
measure: Number of Participants With Treatment Emergent Treatment-Related AEs and SAEs in participants with atopic dermatitis (AD)
timeFrame: Baseline up to Day 78
measure: Number of Participants with Clinically significant Laboratory Abnormalities in participants with AD
timeFrame: Baseline up to Day 78
measure: Number of Participants with Change from Baseline in Electrocardiogram (ECG) Findings in participants with AD
timeFrame: Baseline up to Day 78
measure: Number of Participants with Clinically Significant Change from Baseline in Vital Signs in participants with AD
timeFrame: Baseline up to Day 78
Secondary outcomes:
measure: Area Under the Curve From Time Zero to Last (AUClast) of PF-07832837 following SAD
timeFrame: Day 1 to Day 35
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07832837 following SAD
timeFrame: Day 1 to Day 35
measure: Maximum Observed Serum Concentration (Cmax) of PF-07832837 following SAD
timeFrame: Day 1 to Day 35
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-07832837 following SAD
timeFrame: Day 1 to Day 35
measure: Terminal serum elimination half life (t1/2) of PF-07832837 following SAD
timeFrame: Day 1 to Day 35
measure: Area Under the Serum Concentration-Time Curve Over the Dosing Interval (AUCtau) of PF-07832837 following MAD
timeFrame: Day 1 to Day 22
measure: Maximum Observed Serum Concentration (Cmax) of PF-07832837 following MAD
timeFrame: Day 1 to Day 22
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-07832837 following MAD
timeFrame: Day 1 to Day 22
measure: Percent change from baseline in Eczema Area and Severity Index (EASI) total score at Week 8
timeFrame: Baseline, Week 8
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: