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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03275740




Registration number
NCT03275740
Ethics application status
Date submitted
6/07/2017
Date registered
8/09/2017

Titles & IDs
Public title
A First in HumanTrial to Evaluate The Safety, Tolerability, And Pharmacokinetics Of PF-06755347
Scientific 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
Secondary ID [1] 0 0
2018-003315-21
Secondary ID [2] 0 0
B7801001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy 0 0
Primary Immune Thrombocytopenia 0 0
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Neurological 0 0 0 0
Neurodegenerative diseases
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PF-06755347 intravenous healthy participant
Treatment: Drugs - Placebo intravenous healthy participant
Treatment: Drugs - PF-06755347 subcutaneous healthy participant
Treatment: Drugs - Placebo subcutaneous healthy participant
Treatment: Drugs - PF-06755347 subcutaneous ITP

Experimental: PF-06755347 intravenous healthy participant - intravenous administration

Placebo comparator: Placebo intravenous healthy participant - intravenous administration

Experimental: PF-06755347 subcutaneous healthy participant - subcutaneous administration

Placebo comparator: Placebo subcutaneous healthy participant - subcutaneous administration

Experimental: PF-06755347 subcutaneous ITP - subcutaneous


Treatment: Drugs: PF-06755347 intravenous healthy participant
Single doses of PF-06755347 will be administered intravenously dose levels 1, 2, 3, 4, 5, and 6.

Treatment: Drugs: Placebo intravenous healthy participant
Placebo comparator

Treatment: Drugs: PF-06755347 subcutaneous healthy participant
single doses of PF-06755347 will be administered subcutaneously at dose levels of SC1, SC2, SC3, SC4, and SC5.

Treatment: Drugs: Placebo subcutaneous healthy participant
placebo comparator

Treatment: Drugs: PF-06755347 subcutaneous ITP
single doses of PF-06755347 will be administered subcutaneously at 2 dose levels tested in healthy participants

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With All-causality Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-related TEAEs, and Discontinuations From Study Due to TEAEs
Timepoint [1] 0 0
Baseline (Study Day -2) through study completion (Study Day 36 for IV treatment cohorts, and Study Day 71 SC treatment cohorts).
Primary outcome [2] 0 0
Number of Participants With Laboratory Test Abnormalities
Timepoint [2] 0 0
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.
Primary outcome [3] 0 0
Number of Participants With Vital Signs Meeting Categorical Criteria
Timepoint [3] 0 0
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.
Primary outcome [4] 0 0
Number of Participants With Electrocardiograms (ECGs) Meeting Categorical Criteria
Timepoint [4] 0 0
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 outcome [1] 0 0
Maximum Plasma Concentration (Cmax) of PF-06755347 Following Single IV Dose
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
Cmax of PF-06755347 Following Single SC Dose
Timepoint [2] 0 0
Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
Secondary outcome [3] 0 0
Dose Normalized Cmax (Cmax(dn)) of PF-06755347 Following Single IV Dose
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
Cmax(dn) of PF-06755347 Following Single SC Dose
Timepoint [4] 0 0
Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
Secondary outcome [5] 0 0
Time for Cmax (Tmax) of PF-06755347 Following Single IV Dose
Timepoint [5] 0 0
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.
Secondary outcome [6] 0 0
Tmax of PF-06755347 Following Single SC Dose
Timepoint [6] 0 0
Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
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.
Secondary outcome [8] 0 0
AUClast of PF-06755347 Following Single SC Dose
Timepoint [8] 0 0
Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
Secondary outcome [9] 0 0
Dose Normalized AUClast (AUClast(dn)) of PF-06755347 Following Single IV Dose
Timepoint [9] 0 0
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.
Secondary outcome [10] 0 0
AUClast(dn) of PF-06755347 Following Single SC Dose
Timepoint [10] 0 0
Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
Secondary outcome [11] 0 0
Area Under the Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06755347 Following Single IV Dose
Timepoint [11] 0 0
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.
Secondary outcome [12] 0 0
AUCinf of PF-06755347 Following Single SC Dose
Timepoint [12] 0 0
Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
Secondary outcome [13] 0 0
Dose Normalized AUCinf (AUCinf(dn)) of PF-06755347 Following Single IV Dose
Timepoint [13] 0 0
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.
Secondary outcome [14] 0 0
AUCinf(dn) of PF-06755347 Following Single SC Dose
Timepoint [14] 0 0
Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
Secondary outcome [15] 0 0
Terminal Half-life (t½) of PF-06755347 Following Single IV Dose
Timepoint [15] 0 0
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.
Secondary outcome [16] 0 0
t½ of PF-06755347 Following Single SC Dose
Timepoint [16] 0 0
Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
Secondary outcome [17] 0 0
Clearance (CL) of PF-06755347 Following Single IV Dose
Timepoint [17] 0 0
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.
Secondary outcome [18] 0 0
Apparent Clearance (CL/F) of PF-06755347 Following Single SC Dose
Timepoint [18] 0 0
Hours 0, 12, 24, 48, 72, 120, and 168, and Days 5, 11, 15, 22, 29, 36, 50 and 71.
Secondary outcome [19] 0 0
Number of Participants With Positive Anti-Drug Antibody to PF-06755347
Timepoint [19] 0 0
Baseline, Study Days 8, 15, and 36 for all treatment cohorts plus Day 71 for SC treatment cohorts
Secondary outcome [20] 0 0
Change From Baseline in Interferon Gamma (IFN-? ) at Scheduled Timepoints
Timepoint [20] 0 0
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.
Secondary outcome [21] 0 0
Change From Baseline in Tumor Necrosis Factor Alpha (TNFa) at Scheduled Timepoints
Timepoint [21] 0 0
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.
Secondary outcome [22] 0 0
Change From Baseline in Interleukin 6 (IL-6) at Scheduled Timepoints
Timepoint [22] 0 0
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.
Secondary outcome [23] 0 0
Change From Baseline in Complement 3a (C3a) at Scheduled Timepoints
Timepoint [23] 0 0
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.
Secondary outcome [24] 0 0
Change From Baseline in Complement 5a (C5a) at Scheduled Timepoints
Timepoint [24] 0 0
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.
Secondary outcome [25] 0 0
Change From Baseline in Activated Factor B (Bb) at Scheduled Timepoints
Timepoint [25] 0 0
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.

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Connecticut
Country [2] 0 0
Belgium
State/province [2] 0 0
Brussels
Country [3] 0 0
New Zealand
State/province [3] 0 0
Christchurch
Country [4] 0 0
Spain
State/province [4] 0 0
Madrid
Country [5] 0 0
Spain
State/province [5] 0 0
Sevilla
Country [6] 0 0
United Kingdom
State/province [6] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
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.


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.