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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 : February 1, 2022
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Healthy Primary Immune Thrombocytopenia Polyradiculoneuropathy, Chronic Inflammatory Demyelinating 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 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 67 participants
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 in healthy male participants. Masking will not be applied for participants with ITP (all ITP participants will receive PF-06755347).
Primary Purpose: Treatment
Official Title: 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 IN HEALTHY ADULT MALE PARTICIPANTS AND OPEN-LABEL AFTER SINGLE SUBCUTANEOUS DOSING IN MALE AND FEMALE PARTICIPANTS WITH PERSISTENT OR CHRONIC PRIMARY IMMUNE THROMBOCYTOPENIA
Actual Study Start Date : July 17, 2017
Estimated Primary Completion Date : June 2, 2023
Estimated Study Completion Date : June 2, 2023


Arm Intervention/treatment
Experimental: PF-06755347 intravenous healthy participant
intravenous administration
Drug: PF-06755347 intravenous healthy participant
Single doses of PF-06755347 will be administered intravenously dose levels 1, 2, 3, 4, 5, and 6.

Placebo Comparator: Placebo intravenous healthy participant
intravenous administration
Drug: Placebo intravenous healthy participant
Placebo comparator

Experimental: PF-06755347 subcutaneous healthy participant
subcutaneous administration
Drug: PF-06755347 subcutaneous healthy participant
single doses of PF-06755347 will be administered subcutaneously at dose levels of SC1, SC2, SC3, SC4, and SC5.

Placebo Comparator: Placebo subcutaneous healthy participant
subcutaneous administration
Drug: Placebo subcutaneous healthy participant
placebo comparator

Experimental: PF-06755347 subcutaneous ITP
subcutaneous
Drug: PF-06755347 subcutaneous ITP
single doses of PF-06755347 will be administered subcutaneously at 2 dose levels tested in healthy participants




Primary Outcome Measures :
  1. 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. ]
  2. Number of Participants With Clinical Laboratory Abnormalities [ Time Frame: Baseline, study days 1, 2, 4, 6, 8, 11, 15, 22, 29 and 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. ]
    Safety laboratory includes Hematology, Chemistry, Urinalysis, prothrombin time/international normalized ratio, partial thromboplastin time, D dimer, and fibrinogen

  3. Number of Participants With Categorical Vital Signs Data [ Time Frame: Baseline, study days 1, 2, 3, 4, 6, 8, 11, 15, 22, 29, 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. ]
    Vital signs include blood pressure, pulse rate, and 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

  4. 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. ]
    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.


Secondary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Hours 0, 12, 24, 48, 72, 120, 168 for all cohorts. Hours 1, 3, 5, & 8 for all i.v. cohorts. Hour 36 for i.v. cohorts 1-2. Days 15, 22, 29, and 36 for subcutaneous and i.v. cohorts 5 exp & 6. Days 5, 11, 50 & 71 for subcutaneous cohorts ]
  2. Dose Normalized Maximum Observed Plasma Concentration Cmax [ Time Frame: Hours 0, 12, 24, 48, 72, 120, 168 for all cohorts. Hours 1, 3, 5, & 8 for all i.v. cohorts. Hour 36 for i.v. cohorts 1-2. Days 15, 22, 29, and 36 for subcutaneous and i.v. cohorts 5 exp & 6. Days 5, 11, 50 & 71 for subcutaneous cohorts ]
  3. Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Hours 0, 12, 24, 48, 72, 120, 168 for all cohorts. Hours 1, 3, 5, & 8 for all i.v. cohorts. Hour 36 for i.v. cohorts 1-2. Days 15, 22, 29, and 36 for subcutaneous and i.v. cohorts 5 exp & 6. Days 5, 11, 50 & 71 for subcutaneous cohorts ]
  4. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: Hours 0, 12, 24, 48, 72, 120, 168 for all cohorts. Hours 1, 3, 5, & 8 for all i.v. cohorts. Hour 36 for i.v. cohorts 1-2. Days 15, 22, 29, and 36 for subcutaneous and i.v. cohorts 5 exp & 6. Days 5, 11, 50 & 71 for subcutaneous cohorts ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  5. Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: Hours 0, 12, 24, 48, 72, 120, 168 for all cohorts. Hours 1, 3, 5, & 8 for all i.v. cohorts. Hour 36 for i.v. cohorts 1-2. Days 15, 22, 29, and 36 for subcutaneous and i.v. cohorts 5 exp & 6. Days 5, 11, 50 & 71 for subcutaneous cohorts ]
  6. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) [ Time Frame: Hours 0, 12, 24, 48, 72, 120, 168 for all cohorts. Hours 1, 3, 5, & 8 for all i.v. cohorts. Hour 36 for i.v. cohorts 1-2. Days 15, 22, 29, and 36 for subcutaneous and i.v. cohorts 5 exp & 6. Days 5, 11, 50 & 71 for subcutaneous 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).

  7. Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) [ Time Frame: Hours 0, 12, 24, 48, 72, 120, 168 for all cohorts. Hours 1, 3, 5, & 8 for all i.v. cohorts. Hour 36 for i.v. cohorts 1-2. Days 15, 22, 29, and 36 for subcutaneous and i.v. cohorts 5 exp & 6. Days 5, 11, 50 & 71 for subcutaneous cohorts ]
  8. Plasma Decay Half-Life (t1/2) [ Time Frame: Hours 0, 12, 24, 48, 72, 120, 168 for all cohorts. Hours 1, 3, 5, & 8 for all i.v. cohorts. Hour 36 for i.v. cohorts 1-2. Days 15, 22, 29, and 36 for subcutaneous and i.v. cohorts 5 exp & 6. Days 5, 11, 50 & 71 for subcutaneous cohorts ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  9. Apparent Clearance (CL) [ Time Frame: Hours 0, 12, 24, 48, 72, 120, 168 for all cohorts. Hours 1, 3, 5, & 8 for all i.v. cohorts. Hour 36 for i.v. cohorts 1-2. Days 15, 22, 29, and 36 for subcutaneous and i.v. cohorts 5 exp & 6. Days 5, 11, 50 & 71 for subcutaneous cohorts ]
    Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of study drug (R0/Css)

  10. 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 ]
  11. Characterization of biomarker changes [ Time Frame: Day -1, hours 0, 5, 12, 24, 48, 72 for all cohorts. Hours 1 (or end of infusion, 8, 120 and days 11 & 29 for i.v. cohorts Days 5, 8, 15, 36 & 71 for subcutaneous cohorts. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria Healthy male participants:

  • 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 for Healthy male participants:

  • 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.
  • 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.
  • Inclusion Criteria for ITP participants:

Female participants may be of childbearing potential or non-childbearing potential.

-Diagnosis of Primary ITP. ITP must be diagnosed in accordance with established guidelines. ITP duration-Persistent (>3 months and ≤12 months) OR Chronic (>12 months).

AND

  • Platelet count 30-75 x 10E9/L (inclusive) with criteria achieved on 2 qualifying counts at least 5 days apart and within approx. 10 days of dosing
  • Participants must have received and responded to IVIg or corticosteroids as treatment for ITP (response is defined as achievement of platelet count >50 x 109/L and doubling of platelet count from baseline).

    --Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

  • BMI of 17.5 to 30.5 kg/m2 and a total body weight >40 kg (88 lbs).

Exclusion Criteria for ITP participants

  • History of clinically significant hematological (other than ITP), renal, endocrine, metabolic, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
  • Chest X-ray with evidence of current, active TB, previous inactive TB, general infections, heart failure, malignancy, or other clinically significant abnormalities.

Chest x-ray must be taken at Screening or within 3 months prior to Screening and read by a qualified radiologist.

  • Any bleeding event requiring medical evaluation or treatment in the 4 weeks prior to screening or current bleeding event that requires treatment.
  • Scheduled or anticipated invasive procedures (eg, surgery, dental procedures) within 28 days following PF-06755347 dosing.
  • Splenectomy within ≤180 days prior to PF-06755347 dosing or splenectomy planned during the period of the study.
  • History of any active autoimmune disorder (other than ITP) or other conditions that may compromise or impair the immune system (including but not limited to: Crohn's Disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Graves' disease, and asthma).
  • History of allergic or anaphylactic reaction to any drug including immunoglobulin.
  • History of active infections within 28 days prior to the screening visit.
  • History of Hepatitis B, Hepatitis C or HIV or current positive results for any of the following serological tests - HBsAg, HBcAb, HCVAb or HIV.
  • History of thromboembolic events
  • Hemoglobin <9 g/dL.
  • Positive Direct Coombs test

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03275740


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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United States, Connecticut
Pfizer New Haven Clinical Research Unit Terminated
New Haven, Connecticut, United States, 06511
Belgium
Pfizer Clinical Research Unit Recruiting
Brussels, Belgium, B-1070
New Zealand
NZCR (New Zealand Clinical Research) OPCO Limited Recruiting
Christchurch, New Zealand, 8011
United Kingdom
Hammersmith Medicines Research (HMR) Recruiting
London, United Kingdom, NW10 7EW
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03275740    
Other Study ID Numbers: B7801001
2018-003315-21 ( EudraCT Number )
First Posted: September 8, 2017    Key Record Dates
Last Update Posted: February 1, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Thrombocytopenia
Immune System Diseases
Polyradiculoneuropathy
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Purpura, Thrombocytopenic, Idiopathic
Blood Platelet Disorders
Hematologic Diseases
Purpura, Thrombocytopenic
Purpura
Blood Coagulation Disorders
Thrombotic Microangiopathies
Hemorrhagic Disorders
Autoimmune Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Polyneuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases