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: April 14, 2021
• 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 male subjects. The pharmacokinetics and pharmacodynamics will also be evaluated.

Condition or disease	Intervention/treatment	Phase
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Primary Immune Thrombocytopenia	Drug: PF-06755347 intravenous; Drug: Placebo intravenous; Drug: PF-06755347 subcutaneous; Drug: Placebo subcutaneous	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 112 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
• 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 TO HEALTHY ADULT MALE PARTICIPANTS
• Actual Study Start Date: July 17, 2017
• Estimated Primary Completion Date: June 3, 2022
• Estimated Study Completion Date: June 3, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: PF-06755347 intravenous; intravenous administration	Drug: PF-06755347 intravenous; Single doses of PF-06755347 will be administered intravenously dose levels 1, 2, 3, 4, 5, and 6.
Placebo Comparator: Placebo intravenous; intravenous administration	Drug: Placebo intravenous; Placebo comparator
Experimental: PF-06755347 subcutaneous; subcutaneous administration	Drug: PF-06755347 subcutaneous; single doses of PF-06755347 will be administered subcutaneously at dose levels of SC1, SC2, SC3, SC4, and SC5.
Placebo Comparator: Placebo subcutaneous; subcutaneous administration	Drug: Placebo subcutaneous; placebo comparator

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 1 - 5 ]
2. 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
3. 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
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 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.

Secondary Outcome Measures :

1. 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 ]
2. 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 ]
3. 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 ]
4. 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)
5. 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 ]
6. 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).
7. 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 ]
8. 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.
9. 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)
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. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: Yes

Criteria

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.

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

Christchurch Clinical Studies Trust Ltd; Recruiting

Christchurch, New Zealand, 8011

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: April 14, 2021
• Last Verified: April 2021

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