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

Phase 1TerminatedNCT03275740

Pfizer58 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Healthy Primary Immune Thrombocytopenia Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Interventions

PF-06755347 intravenous healthy participantDRUG

Single doses of PF-06755347 will be administered intravenously dose levels 1, 2, 3, 4, 5, and 6.

Placebo intravenous healthy participantDRUG

Placebo comparator

PF-06755347 subcutaneous healthy participantDRUG

single doses of PF-06755347 will be administered subcutaneously at dose levels of SC1, SC2, SC3, SC4, and SC5.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (6)

Pfizer New Haven Clinical Research Unit

New Haven, Connecticut, United States

Pfizer Clinical Research Unit

Brussels, Belgium

NZCR (New Zealand Clinical Research) OPCO Limited

Christchurch, New Zealand

Hospital Universitario La Paz

Madrid, Spain

Outcomes

Primary Outcomes

Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs

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.

Time frame: Baseline (Study Day -2) through study completion (Study Day 36 for IV treatment cohorts, and Study Day 71 SC treatment cohorts).

Number of Participants With Laboratory Test Abnormalities

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.

Time frame: 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.

Number of Participants With Vital Signs Meeting Categorical Criteria

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.

Data from ClinicalTrials.gov

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