Clinical trial NCT03275740: A First in HumanTrial to Evaluate The Safety, Tolerability, And Pharmacokinetics Of PF-06755347
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Healthy
Primary Immune Thrombocytopenia
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-09-08
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: single ascending dose study
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs
timeFrame: Baseline (Study Day -2) through study completion (Study Day 36 for IV treatment cohorts, and Study Day 71 SC treatment cohorts).
measure: Number of Participants With Laboratory Test Abnormalities
timeFrame: 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.
measure: Number of Participants With Vital Signs Meeting Categorical Criteria
timeFrame: 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.
measure: Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria
timeFrame: 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:
measure: Maximum Plasma Concentration (Cmax) of PF-06755347 Following Single IV Dose
timeFrame: 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.
measure: Cmax of PF-06755347 Following Single SC Dose
timeFrame: Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
measure: Dose Normalized Cmax (Cmax(dn)) of PF-06755347 Following Single IV Dose
timeFrame: 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.
measure: Cmax(dn) of PF-06755347 Following Single SC Dose
timeFrame: Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
measure: Time for Cmax (Tmax) of PF-06755347 Following Single IV Dose
timeFrame: 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.
measure: Tmax of PF-06755347 Following Single SC Dose
timeFrame: Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
measure: Area Under the Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-06755347 Following Single IV Dose
timeFrame: 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.
measure: AUClast of PF-06755347 Following Single SC Dose
timeFrame: Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
measure: Dose Normalized AUClast (AUClast(dn)) of PF-06755347 Following Single IV Dose
timeFrame: 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.
measure: AUClast(dn) of PF-06755347 Following Single SC Dose
timeFrame: Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
measure: Area Under the Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06755347 Following Single IV Dose
timeFrame: 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.
measure: AUCinf of PF-06755347 Following Single SC Dose
timeFrame: Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
measure: Dose Normalized AUCinf (AUCinf(dn)) of PF-06755347 Following Single IV Dose
timeFrame: 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.
measure: AUCinf(dn) of PF-06755347 Following Single SC Dose
timeFrame: Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
measure: Terminal Half-life (t½) of PF-06755347 Following Single IV Dose
timeFrame: 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.
measure: t½ of PF-06755347 Following Single SC Dose
timeFrame: Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
measure: Clearance (CL) of PF-06755347 Following Single IV Dose
timeFrame: 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.
measure: Apparent Clearance (CL/F) of PF-06755347 Following Single SC Dose
timeFrame: Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
measure: Number of Participants With Positive Anti-Drug Antibody to PF-06755347
timeFrame: Baseline, Study Days 8, 15, and 36 for all treatment cohorts plus Day 71 for SC treatment cohorts
measure: Change From Baseline in Interferon Gamma (IFN-γ ) at Scheduled Timepoints
timeFrame: Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.
measure: Change From Baseline in Tumor Necrosis Factor Alpha (TNFα) at Scheduled Timepoints
timeFrame: Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.
measure: Change From Baseline in Interleukin 6 (IL-6) at Scheduled Timepoints
timeFrame: Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.
measure: Change From Baseline in Complement 3a (C3a) at Scheduled Timepoints
timeFrame: Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.
measure: Change From Baseline in Complement 5a (C5a) at Scheduled Timepoints
timeFrame: Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.
measure: Change From Baseline in Activated Factor B (Bb) at Scheduled Timepoints
timeFrame: Day -1, hours 0, 5, 12, 24, 48, 72 for all treatment cohorts. Hours 1 (or end of infusion), 8, and 120 and Days 11 and 29 for IV treatment cohorts; Days 5, 8, 15, 36 and 71 for SC treatment cohorts.
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Pfizer New Haven Clinical Research Unit
state: Connecticut
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit
city: Christchurch
country: New Zealand
facility: NZCR (New Zealand Clinical Research) OPCO Limited
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: London
country: United Kingdom
facility: Hammersmith Medicines Research (HMR)
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: