Study in Healthy Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-06687234

A Phase 1, Double Blind, Third-Party Open, Randomized, Placebo Controlled, Single And Multiple Dose, Parallel Group Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of PF-06687234 In Healthy Subjects

This Phase 1 study will be a double blind, third party open (ie, subject blind, investigator blind and Sponsor open), randomized, placebo controlled, single and multiple dose escalation study in healthy subjects, females of non childbearing potential and males between the ages of 18 and 55 years, inclusive. There may be up to 11 Cohorts in the study. Approximately 7 cohorts are anticipated in the Single Dose (SD) portion of the study and up to 4 cohorts are anticipated in the Multiple Dose (MD) portion of the study.

Following the last subject Day 28 visit from the first two single dose cohorts (Cohorts 1 and 2), all available data inclusive of Day 28 will be evaluated for PK, immunogenicity, safety and tolerability. FDA review and agreement to move forward will take place before the remaining single dose cohorts and the multiple dose phase (Cohorts 3 to 11) can be initiated.

A total of up to approximately 82 subjects are anticipated to be enrolled in the study. The duration of dosing in the multiple dose cohorts would be 4 weeks and the regimen may include weekly (total of 5 doses), every 2 weeks (total of 3 doses) or monthly dosing (total of two doses).

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-06687234; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 10
• 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 females of non childbearing potential and healthy males
• No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB)
• Ability to personally sign and date the informed consent document and able to comply with schedule of activities
• For Single Dose Cohort 7 only, Japanese subjects must have four biological Japanese grandparents born in Japan.

EXCLUSION CRITERIA

• Evidence or history of clinically significant health concerns
• Treatment with an investigational drug within 30 days
• Exposure to any live vaccines within 28 days prior to investigational product administration.
• History of drug and/ or alcohol abuse and tobacco use equivalent of 5 cigarettes per day.
• Known history of infection with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus
• Pregnant female subjects
• History of sensitivity to heparin
• Unwilling or unable to comply with the Lifestyle Guidelines as stated in the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Cohort 1; Subjects will receive 2mg of PF 06687234 or placebo via the SC route	Drug: PF-06687234; PF-06687234 will be administered via the SC or the IV route and in either single dose or multiple doses; Other Names: Dekavil; Drug: Placebo; In Cohorts 1 and 2, up to 1 subject will receive placebo. In all other Cohorts (Cohorts 3 to 11), up to 2 subjects will receive placebo.
OTHER: Cohort 2; Subjects will receive 20mg PF 06687234 or placebo via the SC route	Drug: PF-06687234; PF-06687234 will be administered via the SC or the IV route and in either single dose or multiple doses; Other Names: Dekavil; Drug: Placebo; In Cohorts 1 and 2, up to 1 subject will receive placebo. In all other Cohorts (Cohorts 3 to 11), up to 2 subjects will receive placebo.
OTHER: Cohort 3; This is an optional cohort that may be added anytime during the study. In this cohort, subjects will receive PF 06687234 or placebo via the SC route	Drug: PF-06687234; PF-06687234 will be administered via the SC or the IV route and in either single dose or multiple doses; Other Names: Dekavil; Drug: Placebo; In Cohorts 1 and 2, up to 1 subject will receive placebo. In all other Cohorts (Cohorts 3 to 11), up to 2 subjects will receive placebo.
OTHER: Cohort 4; Subjects will receive 40mg of PF 06687234 or placebo via the SC route	Drug: PF-06687234; PF-06687234 will be administered via the SC or the IV route and in either single dose or multiple doses; Other Names: Dekavil; Drug: Placebo; In Cohorts 1 and 2, up to 1 subject will receive placebo. In all other Cohorts (Cohorts 3 to 11), up to 2 subjects will receive placebo.
OTHER: Cohort 5; Subjects will receive 80mg of PF 06687234 or placebo via the SC route	Drug: PF-06687234; PF-06687234 will be administered via the SC or the IV route and in either single dose or multiple doses; Other Names: Dekavil; Drug: Placebo; In Cohorts 1 and 2, up to 1 subject will receive placebo. In all other Cohorts (Cohorts 3 to 11), up to 2 subjects will receive placebo.
OTHER: Cohort 6; Subjects receive a single dose of PF 06687234 or placebo via the IV route	Drug: PF-06687234; PF-06687234 will be administered via the SC or the IV route and in either single dose or multiple doses; Other Names: Dekavil; Drug: Placebo; In Cohorts 1 and 2, up to 1 subject will receive placebo. In all other Cohorts (Cohorts 3 to 11), up to 2 subjects will receive placebo.
OTHER: Cohort 7; This is an optional cohort where Japanese subjects will receive PF 06687234 or placebo via the SC route	Drug: PF-06687234; PF-06687234 will be administered via the SC or the IV route and in either single dose or multiple doses; Other Names: Dekavil; Drug: Placebo; In Cohorts 1 and 2, up to 1 subject will receive placebo. In all other Cohorts (Cohorts 3 to 11), up to 2 subjects will receive placebo.
OTHER: Cohort 8; Subjects in this cohort may receive 20 mg of PF 06687234 or placebo via the SC route every week with a total of 5 doses	Drug: PF-06687234; PF-06687234 will be administered via the SC or the IV route and in either single dose or multiple doses; Other Names: Dekavil; Drug: Placebo; In Cohorts 1 and 2, up to 1 subject will receive placebo. In all other Cohorts (Cohorts 3 to 11), up to 2 subjects will receive placebo.
OTHER: Cohort 9; Subjects in this cohort may receive 40 mg of PF 06687234 or placebo via the SC route every two weeks with a total of 3 doses	Drug: PF-06687234; PF-06687234 will be administered via the SC or the IV route and in either single dose or multiple doses; Other Names: Dekavil; Drug: Placebo; In Cohorts 1 and 2, up to 1 subject will receive placebo. In all other Cohorts (Cohorts 3 to 11), up to 2 subjects will receive placebo.
OTHER: Cohort 10; This is an optional cohort. The maximum dose tested in the multiple dose cohort will not exceed the highest dose tested in the single dose cohorts	Drug: PF-06687234; PF-06687234 will be administered via the SC or the IV route and in either single dose or multiple doses; Other Names: Dekavil; Drug: Placebo; In Cohorts 1 and 2, up to 1 subject will receive placebo. In all other Cohorts (Cohorts 3 to 11), up to 2 subjects will receive placebo.
OTHER: Cohort 11; This is an optional cohort. The maximum dose tested in the multiple dose cohort will not exceed the highest dose tested in the single dose cohorts	Drug: PF-06687234; PF-06687234 will be administered via the SC or the IV route and in either single dose or multiple doses; Other Names: Dekavil; Drug: Placebo; In Cohorts 1 and 2, up to 1 subject will receive placebo. In all other Cohorts (Cohorts 3 to 11), up to 2 subjects will receive placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs)	To determine the safety and tolerability of PF 06687234 by assessing averse events, vital signs measurements, 12 lead ECGs, physical examination findings, blood and urine safety tests including ferritin, transferrin, serum iron, reticulocytes, hemoglobin, platelets and any abnormal laboratory results.	4 weeks in the single dose portion and 8 weeks in the multiple dose portion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of PF 06687234 (IV and SC single doses)		Day 1 prior to 0 hr & 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post dose and 8 and 11 days post dose along with early termination or follow up visit.
Maximum Observed Plasma Concentration (Cmax) of PF 06687234 (SC multiple doses)		Day 1 and Day 29 prior to 0 hr & 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post dose. Pre-dose samples on Day 8, 15, 22, 36, 39 and 43 along with early termination or follow up visit.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF 06687234 (IV and SC single doses)		Day 1 prior to 0 hr & 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post dose and 8 and 11 days post dose along with early termination or follow up visit.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF 06687234 (SC multiple doses)		Day 1 and Day 29 prior to 0 hr & 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post dose. Pre-dose samples on Day 8, 15, 22, 36, 39 and 43 along with early termination or follow up visit.
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF 06687234 (IV and SC single doses)	AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).	Day 1 prior to 0 hr & 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post dose and 8 and 11 days post dose along with early termination or follow up visit.
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF 06687234 (SC multiple doses)	AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf).	Day 1 and Day 29 prior to 0 hr & 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post dose. Pre-dose samples on Day 8, 15, 22, 36, 39 and 43 along with early termination or follow up visit.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF 06687234 (IV and SC single doses)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	Day 1 prior to 0 hr & 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post dose and 8 and 11 days post dose along with early termination or follow up visit.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF 06687234 (SC multiple doses)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast	Day 1 and Day 29 prior to 0 hr & 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post dose. Pre-dose samples on Day 8, 15, 22, 36, 39 and 43 along with early termination or follow up visit.
Plasma Decay Half-Life (t1/2) of PF 06687234 (IV and SC single doses)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Day 1 prior to 0 hr & 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post dose and 8 and 11 days post dose along with early termination or follow up visit.
Plasma Decay Half-Life (t1/2) of PF 06687234 (SC multiple doses)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Day 1 and Day 29 prior to 0 hr & 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 96 hours post dose. Pre-dose samples on Day 8, 15, 22, 36, 39 and 43 along with early termination or follow up visit.
Incidence of development of anti-drug antibody (ADA)		up to 2 months
Incidence of development of neutralizing antibody (NAb)		up to 2 months

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Principal Investigator: Laure Mendes da Costa, Pfizer Clinical Research Unit

Publications and helpful links

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: February 1, 2016
• Primary Completion (ACTUAL): August 1, 2016
• Study Completion (ACTUAL): August 1, 2016

Study Registration Dates

• First Submitted: January 8, 2016
• First Submitted That Met QC Criteria: March 12, 2016
• First Posted (ESTIMATE): March 17, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): November 6, 2016
• Last Update Submitted That Met QC Criteria: November 4, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Healthy Subjects
• Other Study ID Numbers: B7581001; 2015-000710-22 (EUDRACT_NUMBER); DEKAVIL (OTHER: Alias Study Number)