Clinical trial NCT04832139: A Study of Marstacimab to Compare Prefilled Pen (PFP) Device to Prefilled Syringe (PFS) Device
Official title: A PHASE 1, OPEN-LABEL, RANDOMIZED, 4-PERIOD, 2-SEQUENCE, CROSSOVER STUDY TO EVALUATE THE BIOEQUIVALENCE OF MARSTACIMAB (PF-06741086) PREFILLED SYRINGE DEVICE AND PREFILLED PEN DEVICE FOLLOWING SUBCUTANEOUS ADMINISTRATION IN HEALTHY ADULT MALE PARTICIPANTS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Bioequivalence
Phase 1
Prefilled Pen
Prefilled syringe
pharmacokinetic
subcutaneous
hemophilia
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-04-05
Enrollment: 22
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The goal in this study is to show that there are not significant differences in biologic activity of the study drug when administered using either the prefilled pen and prefilled syringe.


Eligibility criteria: Inclusion Criteria:

* Male participants who are overtly healthy as determined by medical evaluation
* Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
* BMI of 17.5 to 30.5 kg/m2; and a total body weight ≥ 50 kg (110 lb).
* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria:

* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, dermatological, or allergic disease
* Any condition possibly affecting drug absorption (eg, conditions affecting SC administration)
* Previous or current treatment for and/or history of coronary artery diseases, venous or arterial thrombosis, or ischemic disease.
* History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, HBcAb or HCVAb
* Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior, laboratory abnormality or COVID-19 related condition that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study
* 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
* 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).
* A positive urine drug test at screening and/or admission
* Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic)
* Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
* Participants with ANY of the following abnormalities in clinical laboratory tests at screening:

  * AST or ALT level ≥1.5 × ULN;
  * Total bilirubin level ≥1.5 × ULN.
* An estimated glomerular filtration rate (eGFR) of \<60 mL/min/1.73m2 based on the CKD-EPI equation.
* Resistance to activated protein C (or Factor V Leiden mutation), prothrombin 20210 mutation, antithrombin III deficiency, protein C deficiency, or protein S deficiency.
* Presence of Lupus anticoagulant anti-cardiolipin antibodies (IgG, IgM or IgA)
* High sensitivity C-reactive protein (hsCRP) above the upper limits of normal
* Abnormal hematology values as defined by the following laboratory tests at Screening and/or admission:

  * Platelet count \<100,000/uL
  * Hemoglobin level \<10 g/dL
* A positive COVID-19 test.
* History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening
* Use of tobacco/nicotine containing products in excess of the equivalent of 5 cigarettes/day
* Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
* Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of the protocol
* 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: Area Under the plasma concentraiton time Curve from time zero extrapolated to infinite time (AUCinf)
timeFrame: Day 1 Hour 0, 1, 2, 4, 8, 12, 24, 48, 72; Day 7; Day 14; Day 21 after each dose
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Day 1 Hour 0, 1, 2, 4, 8, 12, 24, 48, 72; Day 7; Day 14; Day 21 after each dose
Secondary outcomes:
measure: Area under the concentration time curve from time 0 to time of last quatifiable concenteration
timeFrame: Day 1 Hour 0, 1, 2, 4, 8, 12, 24, 48, 72; Day 7; Day 14; Day 21 after each dose
measure: Time for Cmax
timeFrame: Day 1 Hour 0, 1, 2, 4, 8, 12, 24, 48, 72; Day 7; Day 14; Day 21 after each dose
measure: Apparent clearance after subcutaneous dose
timeFrame: Day 1 Hour 0, 1, 2, 4, 8, 12, 24, 48, 72; Day 7; Day 14; Day 21 after each dose
measure: Apparent volume of distribution after subcutaneous dose
timeFrame: Day 1 Hour 0, 1, 2, 4, 8, 12, 24, 48, 72; Day 7; Day 14; Day 21 after each dose
measure: Terminal half-life after subcutaneous dose
timeFrame: Day 1 Hour 0, 1, 2, 4, 8, 12, 24, 48, 72; Day 7; Day 14; Day 21 after each dose
measure: Incidence of clinically significant laboratory value abnormalities
timeFrame: Baseline through the end of study, approximately 161 days
measure: Incidence of anti-drug antibody against marstacimab
timeFrame: From Day 1, Period 1 through Day 21, Period 4 over a total of 84 days
measure: Incidence of Adverse Events
timeFrame: Baseline through the end of study, approximately 161 days
measure: Incidence of neutralizing antibody against marstacimab
timeFrame: From Day 1, Period 1 through Day 21, Period 4 over a total of 84 days
measure: Incidence of Serious Adverse Events
timeFrame: Baseline through the end of study, approximately 161 days
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Brussels Clinical Research Unit
state: Bruxelles-capitale, Région DE
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: