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

NCT03275740 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: B78010012018-003315-21
• Study Type: interventional
• Target: 58
• Locations: 5 countries
• Sites: 6

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.

Conditions

Healthy; Primary Immune Thrombocytopenia; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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 Electrocardiograms (ECGs) Meeting Categorical Criteria

  Number of participants with ECG findings meeting the following criteria: time between the onset of atrial depolarization and onset of ventricular depolarization (PR interval) ≥300 msec; time from ECG Q-wave to the end of the S wave corresponding to ventricular depolarization (QRS duration) ≥140 msec; correct time from ECG Q-wave to the end of the T wave corresponding to electrical systole for heart rate using Fridericia's formula (QTcF interval): ≥450 to \<480 msec; QTcF interval ≥480 to \<500 msec; QTcF interval: ≥500 msec; PR interval percent change from baseline (≥25/50%): ≥25% if baseline \>200 msec or ≥ 50% if baseline ≤200 msec; QRS duration percent change from baseline ≥50%; QTcF interval change from baseline: \>30 to ≤60 msec; QTcF interval change from baseline \>60 msec. Baseline was defined as the average of the triplicate predose recordings collected at 0 hour on Day 1.

  Baseline (Study Day 1, predose), Study Days 1 (postdose), 2, 4, 6, 8, 11, 22, 36 (end of study visit for IV treatment cohorts) and 71 (end of study visit for SC treatment cohorts).

Secondary Outcomes (25)

• Maximum Plasma Concentration (Cmax) of PF-06755347 Following Single IV Dose

  Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.

• Cmax of PF-06755347 Following Single SC Dose

  Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.

• Dose Normalized Cmax (Cmax(dn)) of PF-06755347 Following Single IV Dose

  Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.

• Cmax(dn) of PF-06755347 Following Single SC Dose

  Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.

• Time for Cmax (Tmax) of PF-06755347 Following Single IV Dose

  Hours 0, 1, 3, 5, 8, 12, 24, 48, 72, 120, and 168 for every cohort, hour 36 for Cohorts 1 and 2, Days 15, 22, 29, and 36 for Cohorts 3-6, hours 3.5, 4, and 6 for Cohorts 5 and 6.

Study Arms (5)

PF-06755347 intravenous healthy participant

EXPERIMENTAL

intravenous administration

Drug: PF-06755347 intravenous healthy participant

Placebo intravenous healthy participant

PLACEBO COMPARATOR

intravenous administration

Drug: Placebo intravenous healthy participant

PF-06755347 subcutaneous healthy participant

EXPERIMENTAL

subcutaneous administration

Drug: PF-06755347 subcutaneous healthy participant

Placebo subcutaneous healthy participant

PLACEBO COMPARATOR

subcutaneous administration

Drug: Placebo subcutaneous healthy participant

PF-06755347 subcutaneous ITP

EXPERIMENTAL

subcutaneous

Drug: PF-06755347 subcutaneous ITP

Interventions

PF-06755347 intravenous healthy participant DRUG

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

PF-06755347 intravenous healthy participant

Placebo intravenous healthy participant DRUG

Placebo comparator

Placebo intravenous healthy participant

PF-06755347 subcutaneous healthy participant DRUG

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

PF-06755347 subcutaneous healthy participant

Placebo subcutaneous healthy participant DRUG

placebo comparator

Placebo subcutaneous healthy participant

PF-06755347 subcutaneous ITP DRUG

single doses of PF-06755347 will be administered subcutaneously at 2 dose levels tested in healthy participants

PF-06755347 subcutaneous ITP

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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).
• 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).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (6)

Pfizer New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Pfizer Clinical Research Unit

Brussels, B-1070, Belgium

Location

NZCR (New Zealand Clinical Research) OPCO Limited

Christchurch, 8011, New Zealand

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hammersmith Medicines Research (HMR)

London, NW10 7EW, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Polyradiculoneuropathy; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes

Limitations and Caveats

The study was terminated due to sponsor's business decision.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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).
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: single ascending dose study

Study Record Dates

• First Submitted: July 6, 2017
• First Posted: September 8, 2017
• Study Start: July 17, 2017
• Primary Completion: January 6, 2023
• Study Completion: January 6, 2023
• Last Updated: July 5, 2024
• Results First Posted: July 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); BE (1); GB (1); US (1); NZ (1)