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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03275740
Recruitment Status : Recruiting
First Posted : September 8, 2017
Last Update Posted : April 14, 2021
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE July 6, 2017
First Posted Date  ICMJE September 8, 2017
Last Update Posted Date April 14, 2021
Actual Study Start Date  ICMJE July 17, 2017
Estimated Primary Completion Date June 3, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 11, 2021)
  • Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) [ Time Frame: Baseline (study day -2) through study completion (study day 36 for intravenous dose cohorts 1 - 6, and study day 71 for subcutaneous dose cohorts 1 - 5 ]
  • Number of Participants With Clinical Laboratory Abnormalities [ Time Frame: Baseline, study days 2, 4, 6, 8, 11, 15, 22, 29 and 36 for i.v. dose cohorts 1 - 6, and Baseline, study days 2, 3, 4, 6, 8, 11, 15, 22, 29, 36, 50 and day 71 for subcutaneous dose cohorts 1 - 5. ]
    Safety laboratory includes Hematology, Chemistry, Urinalysis, prothrombin time/international normalized ratio, partial thromboplastin time, D dimer, and fibrinogen
  • Number of Participants With Categorical Vital Signs Data [ Time Frame: Baseline, study days 1, 2, 3, 4, 6, 8, 11, 15, 22, and day 36 for i.v. dose cohorts 1 - 6 and Baseline, study days 1, 2, 3, 4, 6, 8, 11, 15, 22, 29, 36, 50 and day 71 for subcutaneous dose cohorts 1 - 3. ]
    Vital signs include blood pressure, pulse rate, and oral body temperature. Number of participants with maximum increase from Baseline in sitting SBP and DBP of greater than or equal to 30 mmHg will be reported
  • Number of Participants With Abnormal Electrocardiogram (ECG) [ Time Frame: Baseline (study day 1, pre-dose), study days 1 (post dose), 2, 4, 6, 8, 11, 22, 36 (end of study visit for intravenous dose cohorts 1 - 6, and end of study visit day 71 for subcutaneous dose cohorts 1 - 5 ]
    Criteria for ECG abnormalities: maximum PR interval >=300 milliseconds (msec) and maximum increase PR interval increase from baseline (IFB): percent change (Pctchg) >=25 percent (%) for baseline value of >200 msec and Pctchg>=50% for baseline value of <=200 msec for PR interval, maximum QRS interval >=140 msec and a maximum IFB: Pctchg>=50%, maximum QTCF interval (Fridericia's Correction) of 450 msec to <480 msec, 480 msec to <500 msec or >=500 msec and a maximum change of <=30change<60 or >=60 msec from baseline.
Original Primary Outcome Measures  ICMJE
 (submitted: September 5, 2017)
  • Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) [ Time Frame: Baseline (study day -1) through study completion (study day 36 for dose cohorts <=1mg/kg, and study day 71 for dose cohorts >1mg/kg) ]
  • Number of Participants With Clinical Laboratory Abnormalities [ Time Frame: Baseline (study day -1), study days 2, 4, 6, 8, and final study visit (study day 36 for dose cohorts <=1mg/kg, and study day 71 for dose cohorts >1mg/kg) ]
    Safety laboratory includes Hematology, Chemistry, Urinalysis, prothrombin time/international normalized ratio, partial thromboplastin time, D dimer, and fibrinogen
  • Number of Participants With Categorical Vital Signs Data [ Time Frame: Baseline (study day 1, pre-dose), study days 1 (post dose), 2, 3, 4, 6, 8, 15, 22, and end of study visit (study day 36 for dose cohorts <=1mg/kg, and study day 71 for dose cohorts >1mg/kg) ]
    Vital signs include blood pressure, pulse rate, and oral body temperature. Number of participants with maximum increase from Baseline in sitting SBP and DBP of greater than or equal to 30 mmHg will be reported
  • Number of Participants With Abnormal Electrocardiogram (ECG) [ Time Frame: Baseline (study day 1, pre-dose), study days 1 (post dose), 2, 4, 6, 8, 22, and end of study visit (study day 36 for dose cohorts <=1mg/kg, and study day 71 for dose cohorts >1mg/kg) ]
    Criteria for ECG abnormalities: maximum PR interval >=300 milliseconds (msec) and maximum increase PR interval increase from baseline (IFB): percent change (Pctchg) >=25 percent (%) for baseline value of >200 msec and Pctchg>=50% for baseline value of <=200 msec for PR interval, maximum QRS interval >=140 msec and a maximum IFB: Pctchg>=50%, maximum QTCF interval (Fridericia's Correction) of 450 msec to <480 msec, 480 msec to <500 msec or >=500 msec and a maximum change of <=30change<60 or >=60 msec from baseline.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 11, 2021)
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Baseline, 1, 3, 4, 5, 6, 8, 12 & 24 hours post dose for i.v. cohorts and baseline, 6 & 12 hours for subcutaneous cohorts. Study days 3, 4, 6, and 8 for i.v. dose cohorts 1-2, plus days 15, 22, 29, 36, 50 and 71 for i.v. cohorts 3 - 6 and subcu cohorts ]
  • Dose Normalized Maximum Observed Plasma Concentration Cmax [ Time Frame: Baseline, 1, 3, 4, 5, 6, 8, 12 & 24 hours post dose for i.v. cohorts and baseline, 6 & 12 hours for subcu cohorts. Study days 3, 4, 6, and 8 for i.v. dose cohorts 1-2, plus days 15, 22, 29, 36, 50 and 71 for i.v. cohorts 3 - 6 and subcu cohorts ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Baseline, 1, 3, 4, 5, 6, 8, 12 & 24 hours post dose for i.v. cohorts and baseline, 6 & 12 hours for subcutaneous cohorts. Study days 3, 4, 6, and 8 for i.v. dose cohorts 1-2, plus days 15, 22, 29, 36, 50 and 71 for i.v. cohorts 3 - 6 and subcu cohorts ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: Baseline, 1, 3, 4, 5, 6, 8, 12 & 24 hours post dose for i.v. cohorts and baseline, 6 & 12 hours for subcutaneous cohorts. Study days 3, 4, 6, and 8 for i.v. dose cohorts 1-2, plus days 15, 22, 29, 36, 50 and 71 for i.v. cohorts 3 - 6 and subcu cohorts ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
  • Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: Baseline, 1, 3, 4, 5, 6, 8, 12 & 24 hours post dose for i.v. cohorts and baseline, 6 & 12 hours for subcu cohorts. Study days 3, 4, 6, and 8 for i.v. dose cohorts 1-2, plus days 15, 22, 29, 36, 50 and 71 for i.v. cohorts 3 - 6 and subcu cohorts ]
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) [ Time Frame: Baseline, 1, 3, 4, 5, 6, 8, 12 & 24 hours post dose for i.v. cohorts and baseline, 6 & 12 hours for subcu cohorts. Study days 3, 4, 6, and 8 for i.v. dose cohorts 1-2, plus days 15, 22, 29, 36, 50 and 71 for i.v. cohorts 3 - 6 and subcu cohorts ]
    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).
  • Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) [ Time Frame: Baseline, 1, 3, 4, 5, 6, 8, 12 & 24 hours post dose for i.v. cohorts and baseline, 6 & 12 hours for subcu cohorts. Study days 3, 4, 6, and 8 for i.v. dose cohorts 1-2, plus days 15, 22, 29, 36, 50 and 71 for i.v. cohorts 3 - 6 and subcu cohorts ]
  • Plasma Decay Half-Life (t1/2) [ Time Frame: Baseline, 1, 3, 4, 5, 6, 8, 12 & 24 hours post dose for i.v. cohorts and baseline, 6 & 12 hours for subcu cohorts. Study days 3, 4, 6, and 8 for i.v. dose cohorts 1-2, plus days 15, 22, 29, 36, 50 and 71 for i.v. cohorts 3 - 6 and subcu cohorts ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Apparent Clearance (CL) [ Time Frame: Baseline, 1, 3, 4, 5, 6, 8, 12 & 24 hours post dose for i.v. cohorts and baseline, 6 & 12 hours for subcu cohorts. Study days 3, 4, 6, and 8 for i.v. dose cohorts 1-2, plus days 15, 22, 29, 36, 50 and 71 for i.v. cohorts 3 - 6 and subcu cohorts ]
    Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of study drug (R0/Css)
  • Incidence of Anti-Drug Antibody (ADA) [ Time Frame: Baseline, study days 8, 15, and 36 for all dose cohorts plus day 71 for subcu cohorts ]
  • Characterisation of biomarker changes [ Time Frame: Baseline (study day 1, pre-dose), 1, 3, 5, 8, and 24 hours post dose, study days 3, 4, 8, 15, and day 36 for i.v. cohorts and study day 71 for sub cu dose cohorts ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 5, 2017)
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Baseline (study day 1, pre-dose), 0.5, 1, 3, 5, 8, 12 and 24 hours post dose study day 1, study days 3, 4, 6, 8, 15, 22, 29, and end of study visit (study day 36 for dose cohorts <=1mg/kg, and study day 71 for dose cohorts >1mg/kg) ]
  • Dose Normalized Maximum Observed Plasma Concentration Cmax [ Time Frame: Baseline (study day 1, pre-dose), 0.5, 1, 3, 5, 8, 12 and 24 hours post dose study day 1, study days 3, 4, 6, 8, 15, 22, 29, and end of study visit (study day 36 for dose cohorts <=1mg/kg, and study day 71 for dose cohorts >1mg/kg) ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Baseline (study day 1, pre-dose), 0.5, 1, 3, 5, 8, 12 and 24 hours post dose study day 1, study days 3, 4, 6, 8, 15, 22, 29, and end of study visit (study day 36 for dose cohorts <=1mg/kg, and study day 71 for dose cohorts >1mg/kg) ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: Baseline (study day 1, pre-dose), 0.5, 1, 3, 5, 8, 12 and 24 hours post dose study day 1, study days 3, 4, 6, 8, 15, 22, 29, and end of study visit (study day 36 for dose cohorts <=1mg/kg, and study day 71 for dose cohorts >1mg/kg) ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
  • Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: Baseline (study day 1, pre-dose), 0.5, 1, 3, 5, 8, 12 and 24 hours post dose study day 1, study days 3, 4, 6, 8, 15, 22, 29, and end of study visit (study day 36 for dose cohorts <=1mg/kg, and study day 71 for dose cohorts >1mg/kg) ]
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) [ Time Frame: Baseline (study day 1, pre-dose), 0.5, 1, 3, 5, 8, 12 and 24 hours post dose study day 1, study days 3, 4, 6, 8, 15, 22, 29, and end of study visit (study day 36 for dose cohorts <=1mg/kg, and study day 71 for dose cohorts >1mg/kg) ]
    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).
  • Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) [ Time Frame: Baseline (study day 1, pre-dose), 0.5, 1, 3, 5, 8, 12 and 24 hours post dose study day 1, study days 3, 4, 6, 8, 15, 22, 29, and end of study visit (study day 36 for dose cohorts <=1mg/kg, and study day 71 for dose cohorts >1mg/kg) ]
  • Plasma Decay Half-Life (t1/2) [ Time Frame: Baseline (study day 1, pre-dose), 0.5, 1, 3, 5, 8, 12 and 24 hours post dose study day 1, study days 3, 4, 6, 8, 15, 22, 29, and end of study visit (study day 36 for dose cohorts <=1mg/kg, and study day 71 for dose cohorts >1mg/kg) ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
  • Apparent Clearance (CL) [ Time Frame: Baseline (study day 1, pre-dose), 0.5, 1, 3, 5, 8, 12 and 24 hours post dose study day 1, study days 3, 4, 6, 8, 15, 22, 29, and end of study visit ]
    Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of study drug (R0/Css)
  • Incidence of Anti-Drug Antibody (ADA) [ Time Frame: Baseline, study days 15, 22, 29, and end of study visit (study day 36 for dose cohorts <=1mg/kg, and study day 71 for dose cohorts >1mg/kg) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A First in HumanTrial to Evaluate The Safety, Tolerability, And Pharmacokinetics Of PF-06755347
Official Title  ICMJE A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, FIRST-IN-HUMAN TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF PF-06755347 AFTER SINGLE ASCENDING INTRAVENOUS AND SUBCUTANEOUS DOSING TO HEALTHY ADULT MALE PARTICIPANTS
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 male subjects. The pharmacokinetics and pharmacodynamics will also be evaluated.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
single ascending dose study
Masking: Double (Participant, Investigator)
Masking Description:
Double blind (investigator and subject), sponsor open
Primary Purpose: Treatment
Condition  ICMJE
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
  • Primary Immune Thrombocytopenia
Intervention  ICMJE
  • Drug: PF-06755347 intravenous
    Single doses of PF-06755347 will be administered intravenously dose levels 1, 2, 3, 4, 5, and 6.
  • Drug: Placebo intravenous
    Placebo comparator
  • Drug: PF-06755347 subcutaneous
    single doses of PF-06755347 will be administered subcutaneously at dose levels of SC1, SC2, SC3, SC4, and SC5.
  • Drug: Placebo subcutaneous
    placebo comparator
Study Arms  ICMJE
  • Experimental: PF-06755347 intravenous
    intravenous administration
    Intervention: Drug: PF-06755347 intravenous
  • Placebo Comparator: Placebo intravenous
    intravenous administration
    Intervention: Drug: Placebo intravenous
  • Experimental: PF-06755347 subcutaneous
    subcutaneous administration
    Intervention: Drug: PF-06755347 subcutaneous
  • Placebo Comparator: Placebo subcutaneous
    subcutaneous administration
    Intervention: Drug: Placebo subcutaneous
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 11, 2021)
112
Original Estimated Enrollment  ICMJE
 (submitted: September 5, 2017)
73
Estimated Study Completion Date  ICMJE June 3, 2022
Estimated Primary Completion Date June 3, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Healthy male participants 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 oral temperature, blood pressure (BP) and pulse rate measurement, pulse oximetry, 12 lead ECG or clinical laboratory tests.
  • Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
  • Chest X ray with no evidence of current, active tuberculosis (TB) or previous inactive TB, general infections, heart failure, malignancy, or other clinically significant abnormalities taken at Screening or within 3 months prior to Screening and read by a qualified radiologist.

Exclusion Criteria:

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
  • Participants with a history of autoimmune disorders and other conditions that compromise or impair the immune system (including but not limited to: Crohns Disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Graves disease, and asthma) or have a current positive result for the following; rheumatoid factor, anti-nuclear antibody, or abnormal free triiodothyronine (T3), free thyroxine (T4), thyroid stimulating hormone (TSH), or thyroid stimulating antibody (TSAb) suggestive of thyroid disease.

Subjects with a history of allergic or anaphylactic reaction to any drug including immunoglobulin.

  • History of active infections within 28 days prior to the screening visit.
  • Subjects with a history of or current positive results for any of the following serological tests: Hepatitis B surface antigen (HepBsAg), Hepatitis B core antibody (HepBcAb), Hepatitis C antibody (HCVAb) or human immunodeficiency virus (HIV).
  • Subjects with a history of thromboembolic events or current positive result for anti-cardiolipin antibody.
  • History of TB or active, latent or inadequately treated TB infection. All positive TB test result(s) are exclusionary
  • Male subjects with partners currently pregnant; male subjects able to father children who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com
Listed Location Countries  ICMJE Belgium,   New Zealand,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03275740
Other Study ID Numbers  ICMJE B7801001
2018-003315-21 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP