FIH Study to Evaluate the Tolerability of PF-07832837 in Healthy Adults and Patients
- Conditions
- Interventions
- Registration Number
- NCT06564389
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics (PK) 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 (PD) of PF-07832837 in participants with moderate to severe AD, including p...
- 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.
...
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 143
-
Part 1 only: Adult participants between 18 to 55 years of age, inclusive, at the time of signing the Informed Consent Document (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:
- 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 (Section 10.9 Appendix 9: Diagnostic Criteria for Atopic Dermatitis).
- 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 (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%, Investigator's Global Assessment (IGA) ≥3, and EASI ≥12 at both the screening and baseline visits).
- 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. Note: Controlled comorbid diseases (ie, controlled diabetes not requiring insulin, controlled hypertension), are acceptable, so long as they do not require administration of prohibited medications.
Mild or moderate asthma that is well-controlled (not requiring high dose inhaled corticosteroids, systemic [oral or parenteral] corticosteroids, or biologic asthma treatments).
-
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:
- A positive QuantiFERON-TB Gold In-tube or equivalent test.
- 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 (eg, psoriasis, seborrheic dermatitis, lupus) 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. NOTE: potential participants may be rescreened after infection resolves.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description placebo Placebo single or multiple doses of placebo PF-07832837 PF-07832837 single or multiple doses of PF-07832837 at ascending dose levels
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) and serious adverse events (SAEs) Following single ascending doses (SAD) Baseline up to Day 35 An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitaliza...
Number of Participants with Clinically significant Laboratory Abnormalities Following SAD Baseline up to Day 35 Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.
Number of Participants with Change from Baseline in Electrocardiogram (ECG) Findings Following SAD Baseline up to Day 35 Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, corrected QT (QTc) intervals and QRS complex. Clinically significant findings were determined by the investigator.
Number of Participants with Clinically Significant Change from Baseline in Vital Signs Following SAD Baseline up to Day 35 Vital signs included blood pressure, pulse rate, respiratory rate, oxygen saturation and oral temperature. Clinically significant findings were determined by the investigator.
Number of Participants with Clinically Significant Change from Baseline in Cardiac Telemetry Findings Following SAD Day 1 Cardiac telemetry was collected in Part 1 SAD cohorts only. Number of participants with any cardiac telemetry abnormalities were reported in this outcome measure.
Number of Participants With Treatment Emergent Treatment-Related AEs and SAEs Following multiple ascending doses (MAD) Baseline up to Day 50 An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitaliza...
Number of Participants with Clinically significant Laboratory Abnormalities Following MAD Baseline up to Day 50 Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.
Number of Participants with Change from Baseline in Electrocardiogram (ECG) Findings Following MAD Baseline up to Day 50 Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, corrected QT (QTc) intervals and QRS complex. Clinically significant findings were determined by the investigator.
Number of Participants With Treatment Emergent Treatment-Related AEs and SAEs in participants with atopic dermatitis (AD) Baseline up to Day 78 An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitaliza...
Number of Participants with Clinically significant Laboratory Abnormalities in participants with AD Baseline up to Day 78 Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.
Number of Participants with Change from Baseline in Electrocardiogram (ECG) Findings in participants with AD Baseline up to Day 78 Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, corrected QT (QTc) intervals and QRS complex. Clinically significant findings were determined by the investigator.
Number of Participants with Clinically Significant Change from Baseline in Vital Signs in participants with AD Baseline up to Day 78 Vital signs included blood pressure, pulse rate, respiratory rate, oxygen saturation and oral temperature. Clinically significant findings were determined by the investigator.
- Secondary Outcome Measures
Name Time Method Area Under the Curve From Time Zero to Last (AUClast) of PF-07832837 following SAD Day 1 to Day 35 estimated by Linear/Log trapezoidal method
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07832837 following SAD Day 1 to Day 35 AUClast + (Clast\*/kel), where Clast\* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis
Maximum Observed Serum Concentration (Cmax) of PF-07832837 following SAD Day 1 to Day 35 Observed directly from data
Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-07832837 following SAD Day 1 to Day 35 Observed directly from data as time of first occurrence
Terminal serum elimination half life (t1/2) of PF-07832837 following SAD Day 1 to Day 35 Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the loglinear concentration time curve. Only those data points judged to describe the terminal log-linear decline will be used in the regression
Area Under the Serum Concentration-Time Curve Over the Dosing Interval (AUCtau) of PF-07832837 following MAD Day 1 to Day 22 Linear/log trapezoidal method
Maximum Observed Serum Concentration (Cmax) of PF-07832837 following MAD Day 1 to Day 22 Observed directly from data
Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-07832837 following MAD Day 1 to Day 22 Observed directly from data as the time of first occurrence
Percent change from baseline in Eczema Area and Severity Index (EASI) total score at Week 8 Baseline, Week 8 EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and...
Trial Locations
- Locations (1)
Anaheim Clinical Trials, LLC
🇺🇸Anaheim, California, United States