Evaluation Of Safety, Tolerability And Pharmacokinetics Of Single And Multiple Doses Of PF-06730512

A Phase 1, Randomized, Double Blind, Sponsor-open, Placebo-controlled, First-in-human Trial To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Pf-06730512 After Single And Multiple Ascending Intravenous Infusion Or Subcutaneous Administration To Healthy Adult Subjects And An Open-label Evaluation In Healthy Japanese Subjects

The purpose of this study is to determine the safety, tolerability and pharmacokinetics of escalating single and multiple intravenous (IV) infusions and subcutaneous (SC) injections of PF-06730512 in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Biological: PF-06730512; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, B-1070
    • Pfizer Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy female subjects of nonchildbearing potential and/or male subjects who, at the time of screening, are between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure (BP) and pulse rate (PR) measurement, 12-lead electrocardiogram (ECG), or clinical laboratory tests.
• Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

Exclusion Criteria:

- History of allergic reactions to diagnostic or therapeutic protein. History of recurrent infections or active infection within 28 days of screening.

Exposure to live vaccines within 28 days of screening.

- History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody (HepBcAb), or hepatitis C antibody (HCVAb). As an exception, a positive hepatitis B surface antibody (HBsAb) finding as a result of subject vaccination is permissible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PF-06730512; Study Drug being used in the study	Biological: PF-06730512; Comparison of different dosages of PF-06730512 to Placebo
PLACEBO_COMPARATOR: Placebo; Placebo for IV/SC administration	Drug: Placebo; Comparison of Placebo to different doses of PF-06730512

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Treatment Emergent Treatment-Related Adverse Event(s)	Number of Subjects With Treatment Emergent Treatment-Related Adverse Event(s)	Dosing through approximately Day 71 (single dose) or Day 113 (multiple dose)
Number of subjects with injection site reaction(s)	Number of subjects with injection site reaction(s)	Dosing through approximately Day 71 (single dose) or Day 113 (multiple dose)
Number of subjects with laboratory test findings of potential clinical importance	Number of subjects with laboratory test findings of potential clinical importance	Dosing through approximately Day 71 (single dose) or Day 113 (multiple dose)
Number of subjects with vital signs findings of potential clinical importance	Number of subjects with vital signs findings of potential clinical importance	Dosing through approximately Day 71 (single dose) or Day 113 (multiple dose)
Number of subjects with ECG findings of potential clinical importance	Number of subjects with ECG findings of potential clinical importance	Dosing through approximately Day 71 (single dose) or Day 113 (multiple dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of PF-06730512	Maximum Observed Plasma Concentration (Cmax) of PF-06730512	Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose)
Time to Reach Maximum Observed Concentration (Tmax) of PF-06730512	Time to Reach Maximum Observed Concentration (Tmax) of PF-06730512	Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose)
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06730512	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06730512	Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose)
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0- infinity)] of PF-06730512, as permitted	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0- infinity)] of PF-06730512, as permitted	Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose)
Clearance (CL) or Apparent Clearance (CL/F) of PF-06730512, as permitted	Clearance (CL) or Apparent Clearance (CL/F) of PF-06730512, as permitted	Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose)
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06730512	Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06730512	Day 1 to approximately Day 113
Apparent Volume of Distribution of PF-06730512, as permitted	Apparent Volume of Distribution of PF-06730512, as permitted	Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose)
Terminal half-life, as permitted	Terminal half-life, as permitted	Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose)
Accumulation ratio (Rac), as permitted	Accumulation ratio (Rac), as permitted	Day 1 to approximately Day 113
Minimum observed concentration during the dosing interval (Cmin)	Minimum observed concentration during the dosing interval (Cmin)	Day 1 to approximately Day 113
Incidence of the development of anti-drug antibody (ADA) and neutralizing antibody (NAb)	Incidence of the development of anti-drug antibody (ADA) and neutralizing antibody (NAb)	Day 1 to approximately Day 71 (single dose) or Day 113 (multiple dose)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Lim CN, Kantaridis C, Huyghe I, Gorman D, Berasi S, Sonnenberg GE. A Phase 1 first-in-human study of the safety, tolerability, and pharmacokinetics of the ROBO2 fusion protein PF-06730512 in healthy participants. Pharmacol Res Perspect. 2021 Aug;9(4):e00813. doi: 10.1002/prp2.813.

Helpful Links

• To obtain contact information for a study center near you, click here.
• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 10, 2017
• Primary Completion (ACTUAL): May 3, 2018
• Study Completion (ACTUAL): May 3, 2018

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 5, 2017
• First Posted (ACTUAL): May 9, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 22, 2018
• Last Update Submitted That Met QC Criteria: May 18, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: C0221001; 2016-004493-18 (EUDRACT_NUMBER); FIH SAD/MAD (OTHER: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No