Clinical trial NCT05206604: A First-in-human Study of Multiple Doses of Topically Administered PF-07295324 and PF-07259955
Official title: A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, VEHICLE-CONTROLLED, FIRST-IN-HUMAN, MULTIPLE-DOSE STUDY, TO INVESTIGATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS, OF TOPICALLY ADMINISTERED PF-07295324 AND PF-07259955, IN HEALTHY ADULT PARTICIPANTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-01-25
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the safety, (local and systemic) tolerability, and pharmacokinetics following multiple doses of topically applied, maximum feasible formulations of PF-07295324 (0.12% w/w) or PF-07259955 (2% w/w), on approximately 20% body surface area (BSA), in healthy adult participants.


Eligibility criteria: Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

Age and Sex:

1. Healthy (except obese) female participants of non-childbearing potential and/or male participants, at the time of screening, must be 18 to 60 years of age, inclusive, at the time of signing the informed consent document (ICD).
2. Male and female of non-child bearing potential participants, who are healthy as determined by medical evaluation including medical history, physical examination, vital assessments, 12 lead ECGs, and laboratory tests.
3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

   Weight:
4. Body mass index (BMI) of 17.5 to 35 kg/m2; and a total body weight \>50 kg (110 lb).
5. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICD and the protocol.

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, immunological/rheumatological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
2. Participants who have any visible skin damage or skin condition (eg sunburn, excessively deep tans, uneven skin tones, tattoos, scars, excessive hair, numerous freckles, or other disfigurations) in or around the application site which, in the opinion of the investigative personnel, will interfere with the evaluation of the test site reaction.
3. Participants who have a history of or have active AD/eczema/urticaria.
4. Evidence of active or 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 (QFT).
   * History of either untreated or inadequately treated latent or active TB infection, or current treatment for the same.
5. History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed. As an exception a positive HBsAb test due to hepatitis B vaccination is permissible.
6. Have a history of systemic infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator within 6 months prior to Day 1.
7. A history (single episode) of disseminated herpes zoster or disseminated herpes simplex, or a recurrent (more than one episode of) localized, dermatomal herpes zoster.
8. Acute disease state (unstable medical condition such as nausea, vomiting, fever or diarrhea, etc) within 7 days of Day 1.
9. Have any malignancies or have a history of malignancies with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin.
10. Have a first-degree relative with hereditary immunodeficiency.
11. A history of any lymphoproliferative disorder (such as Epstein Barr Virus \[EBV\] -related lymphoproliferative disorder), history of lymphoma, leukemia, malignancies or signs and symptoms suggestive of current lymphatic disease.
12. Have undergone significant trauma or major surgery within 4 weeks of screening.
13. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to COVID-19 pandemic (eg. Contact with positive case, residence, or travel to an area with high incidence) that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

    Prior/Concomitant Therapy:
14. Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study intervention. (Refer to Section 6.8 Concomitant Therapy for additional details).
15. Participants who are vaccinated with vaccines that have live components (or live attenuated vaccines) within the 6 weeks prior to the first dose of PF-07295324/vehicle or PF-07259955/vehicle or who are expected to be vaccinated during treatment or during follow-up period.

    NOTE regarding COVID vaccines with authorization or approval for emergency use:

    There is no requirement for washout of COVID vaccines prior to the first dose of PF-07295324/vehicle or PF-07259955/vehicle if the vaccine is not live attenuated (eg, mRNA, utilizing a viral vector,inactivated virus).There is no protocol-specified requirement for the interruption of IP dosing prior to or after vaccination if the COVID vaccine is not live attenuated.
16. Participants in any cohort of this study can only be randomized and receive the IP in only 1 cohort of this study.

    Prior/Concurrent Clinical Study Experience:
17. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer).

    Diagnostic Assessments:
18. A positive urine drug test.
19. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
20. Baseline 12 lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline corrected QT (QTc) interval \>450 msec, complete left bundle branch block \[LBBB\], signs of an acute or indeterminate age myocardial infarction, ST T interval changes suggestive of myocardial ischemia, second or third degree atrioventricular \[AV\] block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is \>450 msec, this interval should be rate corrected using the Fridericia method and the resulting QTcF should be used for decision making and reporting. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the participant's eligibility. Computer interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants.
21. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary:

    * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥1.5 × upper limit of normal (ULN);
    * Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.

    Other Exclusions:
22. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine).
23. Use of tobacco/nicotine containing products more than 5 cigarettes/day.
24. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
25. History of serious adverse reactions or hypersensitivity to any topical drug; or known allergy to any of the test product(s) or any components in the test product(s) or history of hypersensitivity; or allergic reactions to any of the study preparations as described in the PF-07295324 IB and PF-07259955 IB.
26. Not willing to refrain from shaving, the use of depilatories or other hair-removal activities, antiperspirants, lotions, skin creams, fragrances or perfumes, or body oils (eg, baby oil; coconut oil), use of hair products, hair gels, and hair oil in the treatment areas for 48 hours prior to admission to the CRU and for the duration of the stay in the CRU.
27. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
28. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to the end of follow up (ie, up to 44 days)
measure: Number of Participants With Laboratory Abnormalities
timeFrame: At screening, admission (Day -1), on Days 5, 7, 10, at discharge (Day 12), and at early termination if applicable
measure: Number of Participants With Vital Signs Abnormalities
timeFrame: At screening, on Days 1, 2, 5, 7, 10, 11, at discharge (Day 12), and at early termination if applicable
measure: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings
timeFrame: At screening, on Days 1, 2, 5, 7, 10, 11, at discharge (Day 12), and at early termination if applicable
measure: Skin Irritation Assessments Using Draize Scoring
timeFrame: Screening up to Day 12 or early termination if applicable
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of PF-07295324 on Days 1 and 10
timeFrame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07295324 on Days 1 and 10
timeFrame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: Area Under the Concentration-Time Profile From Time Zero to the Dosing Interval Tau (AUCtau) of PF-07295324 on Days 1 and 10
timeFrame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: Average Plasma Concentration (Cavg) of PF-07295324 on Days 1 and 10
timeFrame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: Pre-Dose Concentration (Ctrough) of PF-07295324 on Days 1 and 10
timeFrame: Pre-dose on Days 1 and 10
measure: Observed Accumulation Ratio for Cmax (Rac[Cmax]) of PF-07295324 on Day 10
timeFrame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: Observed Accumulation Ratio for AUCtau (Rac[AUCtau]) of PF-07295324 on Day 10
timeFrame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: Terminal Half-Life (t1/2) of PF-07295324 on Day 10
timeFrame: On Days 1, 2, 5, 7, 10, 11, 12, and early termination (if applicable) at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: Apparent Clearance (CL/F) of PF-07295324 on Day 10
timeFrame: On Days 1, 2, 5, 7, 10, 11, 12, and early termination (if applicable) at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: Apparent Volume of Distribution (Vz/F) of PF-07295324 on Day 10
timeFrame: On Days 1, 2, 5, 7, 10, 11, 12, and early termination (if applicable) at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: Cmax of PF-07259955 on Days 1 and 10
timeFrame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: Tmax of PF-07259955 on Days 1 and 10
timeFrame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: AUCtau of PF-07259955 on Days 1 and 10
timeFrame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: Cavg of PF-07259955 on Days 1 and 10
timeFrame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: Ctrough of PF-07259955 on Days 1 and 10
timeFrame: Pre-dose on Days 1 and 10
measure: Rac(Cmax) of PF-07259955 on Day 10
timeFrame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: Rac(AUCtau) of PF-07259955 on Day 10
timeFrame: On Days 1 and 10 at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: t½ of PF-07259955 on Day 10
timeFrame: On Days 1, 2, 5, 7, 10, 11, 12, and early termination (if applicable) at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: CL/F of PF-07259955 on Day 10
timeFrame: On Days 1, 2, 5, 7, 10, 11, 12, and early termination (if applicable) at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
measure: Vz/F of PF-07259955 on Day 10
timeFrame: On Days 1, 2, 5, 7, 10, 11, 12, and early termination (if applicable) at pre-dose, 1, 2, 4, 6, 8, 12, and 24 hours after application
Other outcomes:
Locations:
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: