A First in HumanTrial to Evaluate The Safety, Tolerability, And Pharmacokinetics Of PF-06755347

Phase 1

Terminated

Conditions: Healthy
Primary Immune Thrombocytopenia
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Interventions: Drug: PF-06755347 intravenous healthy participant
Drug: Placebo intravenous healthy participant
Drug: PF-06755347 subcutaneous healthy participant
Drug: Placebo subcutaneous healthy participant
Drug: PF-06755347 subcutaneous ITP

Registration Number: NCT03275740

Lead Sponsor: Pfizer

Brief Summary: This phase 1 single ascending dose study will provide a first in human assessment of safety and tolerability of PF-06755347 in healthy adult males as well as adult males and females with Immune Thrombocytopenia (ITP). Pharmacokinetics and pharmacodynamics will also be evaluated.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 58

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
PF-06755347 intravenous healthy participant	PF-06755347 intravenous healthy participant	intravenous administration
Placebo intravenous healthy participant	Placebo intravenous healthy participant	intravenous administration
PF-06755347 subcutaneous healthy participant	PF-06755347 subcutaneous healthy participant	subcutaneous administration
Placebo subcutaneous healthy participant	Placebo subcutaneous healthy participant	subcutaneous administration
PF-06755347 subcutaneous ITP	PF-06755347 subcutaneous ITP	subcutaneous

Primary Outcome Measures

Name	Time	Method
Number of Participants With Vital Signs Meeting Categorical Criteria	Baseline, Study Days 1, 2, 4, 6, 8, 11, 15, 22, 29 and 36 for IV treatment cohorts, and Baseline, Study Days 1, 2, 3, 4, 6, 8, 11, 15, 22, 29, 36, 50 and 71 for SC treatment cohorts.	Supine blood pressure and pulse rate were measured. Categorical classes for vital signs of potential clinical concerns were defined as followed: systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); diastolic blood pressure (DBP) \<50 mmHg; pulse rate \<40 beats per minute (bpm); pulse rate \>120 bpm, and increase from baseline in SBP ≥30 mmHg; decrease from baseline in SBP ≥30 mmHg; increase from baseline in DBP ≥20 mmHg; decrease from baseline in DBP ≥20 mmHg. Baseline was defined as the mean of the replicated predose (0 hour) measurement on Day 1.
Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs	Baseline (Study Day -2) through study completion (Study Day 36 for IV treatment cohorts, and Study Day 71 SC treatment cohorts).	Adverse event (AE) was any untoward medical occurrence in the participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Serious AE was any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or was considered to be an important medical event. Any events occurring following start of treatment or increasing in severity were counted as treatment-emergent. AEs included both serious and non-serious AEs.
Number of Participants With Laboratory Test Abnormalities	Baseline, Study Days 1, 2, 4, 6, 8, 11, 15, 22, 29 and 36 for IV treatment cohorts, and Baseline, Study Days 1, 2, 3, 4, 6, 8, 11, 15, 22, 29, 36, 50 and 71 for SC treatment cohorts.	Laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, absolute and percent total neutrophils, eosinophils, monocytes, basophils and lymphocytes),chemistry (blood urea nitrogen/urea and creatinine, fasting glucose, calcium, sodium, potassium, chloride, total carbon dioxide, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin and total protein),urinalysis(pH, qualitative glucose, qualitative protein, qualitative blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy, urinary albumin to creatinine ratio and urinary protein to creatinine ratio) and other tests. Abnormality was determined by the investigator. Only lab abnormalities with at least 1 occurrence in participants are reported.
Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria	Baseline (Study Day 1, predose), Study Days 1 (postdose), 2, 4, 6, 8, 11, 22, 36 (end of study visit for IV treatment cohorts) and 71 (end of study visit for SC treatment cohorts).	Number of participants with ECG findings meeting the following criteria: time between the onset of atrial depolarization and onset of ventricular depolarization (PR interval) ≥300 msec; time from ECG Q-wave to the end of the S wave corresponding to ventricular depolarization (QRS duration) ≥140 msec; correct time from ECG Q-wave to the end of the T wave corresponding to electrical systole for heart rate using Fridericia's formula (QTcF interval): ≥450 to \<480 msec; QTcF interval ≥480 to \<500 msec; QTcF interval: ≥500 msec; PR interval percent change from baseline (≥25/50%): ≥25% if baseline \>200 msec or ≥ 50% if baseline ≤200 msec; QRS duration percent change from baseline ≥50%; QTcF interval change from baseline: \>30 to ≤60 msec; QTcF interval change from baseline \>60 msec. Baseline was defined as the average of the triplicate predose recordings collected at 0 hour on Day 1.

Secondary Outcome Measures

Name	Time	Method
AUClast of PF-06755347 Following Single SC Dose	Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.	AUClast was determined using linear/Log trapezoidal method
Maximum Plasma Concentration (Cmax) of PF-06755347 Following Single IV Dose	Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.	Cmax was the highest concentration observed directly from data
Cmax of PF-06755347 Following Single SC Dose	Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.	Cmax was the highest concentration observed directly from data
Cmax(dn) of PF-06755347 Following Single SC Dose	Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.	Cmax(dn) = Cmax/Dose
Tmax of PF-06755347 Following Single SC Dose	Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.	Tmax was the time to reach maximum observed plasma concentration, which was observed directly from data as time of first occurrence.
Area Under the Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06755347 Following Single IV Dose	Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.	AUClast + (Clast\/kel), where Clast\ was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Area Under the Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06755347 Following Single IV Dose	Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.	AUClast was determined using linear/Log trapezoidal method
AUClast(dn) of PF-06755347 Following Single SC Dose	Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.	AUClast(dn) = AUClast/Dose
Dose Normalized Cmax (Cmax(dn)) of PF-06755347 Following Single IV Dose	Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.	Cmax(dn) = Cmax/Dose
Time for Cmax (Tmax) of PF-06755347 Following Single IV Dose	Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.	Tmax was the time to reach maximum observed plasma concentration, which was observed directly from data as time of first occurrence.
Dose Normalized AUClast (AUClast(dn)) of PF-06755347 Following Single IV Dose	Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.	AUClast(dn) = AUClast/Dose
AUCinf of PF-06755347 Following Single SC Dose	Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.	AUClast + (Clast\/kel), where Clast\ was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Dose Normalized AUCinf (AUCinf(dn)) of PF-06755347 Following Single IV Dose	Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.	AUCinf(dn) = AUCinf/Dose
AUCinf(dn) of PF-06755347 Following Single SC Dose	Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.	AUCinf(dn) = AUCinf/Dose
Terminal Half-life (t½) of PF-06755347 Following Single IV Dose	Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. t½ = Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
t½ of PF-06755347 Following Single SC Dose	Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. t½ = Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Clearance (CL) of PF-06755347 Following Single IV Dose	Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.	CL = Dose/AUCinf Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of study drug.
Apparent Clearance (CL/F) of PF-06755347 Following Single SC Dose	Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.	CL/F = Dose/AUCinf Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Number of Participants With Positive Anti-Drug Antibody to PF-06755347	Baseline, Study Days 8, 15, and 36 for all treatment cohorts plus Day 71 for SC treatment cohorts	Human serum samples were analyzed for the presence or absence of anti-PF-06755347 antibodies (ADA) following a tiered approach of screening, confirmation and titer determination, using an electrochemiluminescent (ECL) immunoassay. Baseline was the measurement on Day -1.
Change From Baseline in Interferon Gamma (IFN-γ ) at Scheduled Timepoints	Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.	IFN-γ was one of the 3 cytokine biomarkers explored in the study. Baseline was defined as the average of measurement on Day -1 and pre-dose (0 hours) measurement on Day 1.
Change From Baseline in Tumor Necrosis Factor Alpha (TNFα) at Scheduled Timepoints	Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.	TNFα was one of the 3 cytokine biomarkers explored in the study. Baseline was defined as the average of measurement on Day -1 and pre-dose (0 hours) measurement on Day 1.
Change From Baseline in Interleukin 6 (IL-6) at Scheduled Timepoints	Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.	IL-6 was one of the 3 cytokine biomarkers explored in the study. Baseline was defined as the average of measurement on Day -1 and pre-dose (0 hours) measurement on Day 1.
Change From Baseline in Complement 3a (C3a) at Scheduled Timepoints	Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.	C3a was one of the 3 complement components/biomarkers explored in the study. Baseline was defined as the average of measurement on Day -1 and pre-dose (0 hours) measurement on Day 1.
Change From Baseline in Complement 5a (C5a) at Scheduled Timepoints	Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.	C5a was one of the 3 complement components/biomarkers explored in the study. Baseline was defined as the average of measurement on Day -1 and pre-dose (0 hours) measurement on Day 1.
Change From Baseline in Activated Factor B (Bb) at Scheduled Timepoints	Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.	Bb was one of the complement components/biomarkers explored in the study. Baseline was defined as the average of measurement on Day -1 and pre-dose (0 hours) measurement on Day 1.

Trial Locations

Locations (6): Hospital Universitario Virgen del Rocío
🇪🇸
Sevilla, Spain
Pfizer Clinical Research Unit
🇧🇪
Brussels, Belgium
Hospital Universitario La Paz
🇪🇸
Madrid, Spain
Hammersmith Medicines Research (HMR)
🇬🇧
London, United Kingdom
NZCR (New Zealand Clinical Research) OPCO Limited
🇳🇿
Christchurch, New Zealand
Pfizer New Haven Clinical Research Unit
🇺🇸
New Haven, Connecticut, United States