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

• ClinicalTrials.gov Identifier: NCT03275740
• Recruitment Status: Recruiting
• First Posted: September 8, 2017
• Last Update Posted: January 3, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

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

Study Design

• 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: May 24, 2024
• Estimated Study Completion Date: May 24, 2024

Arms and Interventions

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

Outcome Measures

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. ]

Eligibility Criteria

• 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

Contacts and Locations

Contacts

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

Locations

United States, Connecticut

Pfizer New Haven Clinical Research Unit; Terminated

New Haven, Connecticut, United States, 06511

Belgium

Pfizer Clinical Research Unit; Active, not recruiting

Brussels, Belgium, B-1070

New Zealand

NZCR (New Zealand Clinical Research) OPCO Limited; Active, not recruiting

Christchurch, New Zealand, 8011

Spain

Hospital Universitario La Paz; Recruiting

Madrid, Spain, 28046

Hospital Universitario Virgen del Rocío; Recruiting

Sevilla, Spain, 41013

United Kingdom

Hammersmith Medicines Research (HMR); Active, not recruiting

London, United Kingdom, NW10 7EW

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03275740
• Other Study ID Numbers: B7801001; 2018-003315-21 ( EudraCT Number )
• First Posted: September 8, 2017
• Last Update Posted: January 3, 2023
• Last Verified: December 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Polyradiculoneuropathy; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic; Blood Platelet Disorders; Hematologic Diseases; Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Thrombotic Microangiopathies; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Skin Manifestations; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases