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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03248882




Registration number
NCT03248882
Ethics application status
Date submitted
10/08/2017
Date registered
14/08/2017
Date last updated
10/03/2020

Titles & IDs
Public title
Phase 2a, Dose-ranging Study With PF-05221304 in Nonalcoholic Fatty Liver Disease (NAFLD)
Scientific title
A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING, PARALLEL GROUP STUDY TO EVALUATE SAFETY, TOLERABILITY, AND PHARMACODYNAMICS OF PF-05221304 ADMINISTERED DAILY FOR 16-WEEKS TO ADULT SUBJECTS WITH NONALCOHOLIC FATTY LIVER DISEASE
Secondary ID [1] 0 0
2017-001156-55
Secondary ID [2] 0 0
C1171002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nonalcoholic Fatty Liver Disease 0 0
Nonalcoholic Steatohepatitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Liver
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Diet and Nutrition 0 0 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - PF-05221304

Placebo Comparator: Placebo - Double-Blind, PF-05221304-matching Placebo

Active Comparator: PF-05221304 - 2 mg - PF-05221304 - 2 mg, once-daily

Active Comparator: PF-05221304 - 10 mg - PF-05221304 - 10 mg, once-daily

Active Comparator: PF-05221304 - 25 mg - PF-05221304 - 25 mg, once-daily

Active Comparator: PF-05221304 - 50 mg - PF-05221304 - 50 mg, once-daily


Treatment: Drugs: Placebo
Placebo

Treatment: Drugs: PF-05221304
PF-05221304, Experimental Drug

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

Outcomes
Primary outcome [1] 0 0
Percent Change From Baseline in Liver Fat by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI- PDFF) at Week 16 - MRI-PDFF utilized a gradient echo sequence with low flip angle (FA) to minimize T1 bias, corrected T2* decay (due to iron overload) via modeling of the fat signal as a superposition of multiple frequency components from 5 different lipid types, and was applied in each of the 9 Couinaud segments. This technique improved fat quantification accuracy for the entire liver permitting quantification of small differences/changes following pharmacological intervention.
Timepoint [1] 0 0
Baseline (between Day -14 and Day 1), Week 16
Secondary outcome [1] 0 0
Percent Change From Baseline in Alanine Aminotransferase at Week 16 - Potential improvement in liver function was denoted by reduction in alanine transaminase (ALT)
Timepoint [1] 0 0
Baseline (Day 1 pre-dose), Week 16
Secondary outcome [2] 0 0
Number of Participants With Treatment-Emergent Adverse Events - An AE was any untoward medical occurrence in a study subject administered a product or medical device. A serious AE (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Any such events with initial onset or increasing in severity after the first dose of study treatment were counted as treatment-emergent.
Timepoint [2] 0 0
From first dose of study treatment (Day 1) up to Week 20
Secondary outcome [3] 0 0
Number of Participants With Laboratory Abnormalities - Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, reticulocytes, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, prothrombin time [PT], PT/international normalized ratio, reticulocytes); chemistry (indirect bilirubin, direct bilirubin, protein, albumin, blood urea nitrogen, creatinine, creatine kinase, urate, calcium, sodium, potassium, chloride, bicarbonate, urine urobilinogen); urinalysis (pH, urine glucose, urine ketones, urine protein, urine hemoglobin, nitrites, leukocyte esterase, urine erythrocytes, urine leukocytes, urine hyaline casts, urine bilirubin, granular casts).
Timepoint [3] 0 0
From first dose of study treatment (Day 1) up to Week 20
Secondary outcome [4] 0 0
Number of Participants With Vital Signs Data Meeting Predefined Criteria - Vital signs categorical summarization criteria: 1) sitting systolic blood pressure (SBP) <90 or >180 millimeters of mercury (mmHg); 2) sitting diastolic blood pressure (DBP) <50 mmHg or >110 mmHg; 3) sitting pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in sitting DBP greater than or equal to (>=) 20 mmHg; 5) change from baseline (increase or decrease) in sitting SBP >=30 mmHg.
Timepoint [4] 0 0
From first dose of study treatment (Day 1) up to Week 18
Secondary outcome [5] 0 0
Number of Participants With 12-Lead Electrocardiogram (ECG) Data Meeting Predefined Criteria - ECG categorical summarization criteria: 1) QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization) >=140 milliseconds (msec); 2) QRS interval >=50% change from baseline; 3) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization) >=300 msec; 4) PR interval >=25% change when baseline is >200 msec or >=50% change when baseline is <=200 msec; 5) QT interval (time from ECG Q wave to the end of the T wave corresponding to electrical systole): absolute value of >=500 msec; 6) QTcF interval (QT corrected for heart rate using Fridericia's formula) absolute value of 450 to <480 msec; 7) QTcF interval: absolute value of 480 to <500 msec; 8) QTcF interval: absolute value >=500 msec; 9) QTcF interval: a change from baseline of 30 to <60 msec; 10) QTcF interval: a change from baseline >=60 msec.
Timepoint [5] 0 0
From first dose of study treatment (Day 1) up to Week 18

Eligibility
Key inclusion criteria
- Body Mass Index >= 25 kg/m2

- Body Weight > 50 kg

- Liver fat (assessed via MRI-PDFF) >= 8%

- Biopsy-proven NASH - diagnosed in previous 24-months

- Presumed NASH - per Sponsor's definition

- NAFLD with minimal inflammation/fibrosis

- Features of Metabolic Syndrome
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Alcohol-induced steatohepatitis or other forms of chronic liver disease

- Positive for Hepatitis B, Hepatitis C, or Human Deficiency Virus

- Severe Renal Impairment

- Contraindications for MRI

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
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Australian Clinical Research Network - Maroubra
Recruitment hospital [2] 0 0
Spectrum Medical Imaging - Randwick
Recruitment hospital [3] 0 0
Castlereagh Imaging - Westmead
Recruitment hospital [4] 0 0
Storr Liver Centre, Westmead Hospital - Westmead
Recruitment hospital [5] 0 0
Dr. Jones & Partners Medical Imaging - Adelaide
Recruitment hospital [6] 0 0
Royal Adelaide Hospital, Department of Gastroenterology and Hepatology - Adelaide
Recruitment hospital [7] 0 0
Flinders Medical Centre/Department of Gastroenterology & Hepatology - Adelaide
Recruitment hospital [8] 0 0
Radiology SA - Adelaide
Recruitment hospital [9] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2035 - Maroubra
Recruitment postcode(s) [2] 0 0
2013 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
5042 - Adelaide
Recruitment postcode(s) [6] 0 0
5067 - Adelaide
Recruitment postcode(s) [7] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
State/province [2] 0 0
Colorado
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United States of America
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Florida
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United States of America
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Hawaii
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United States of America
State/province [5] 0 0
Indiana
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United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
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Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
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United States of America
State/province [9] 0 0
Michigan
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Minnesota
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Mississippi
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New York
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North Carolina
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Ohio
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Tennessee
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Texas
Country [17] 0 0
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Utah
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
United States of America
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Washington
Country [20] 0 0
Canada
State/province [20] 0 0
British Columbia
Country [21] 0 0
Canada
State/province [21] 0 0
Nova Scotia
Country [22] 0 0
Canada
State/province [22] 0 0
Ontario
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Canada
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Quebec
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Israel
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Hadera
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Nahariya
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Israel
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Nazareth
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Israel
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Petah Tikva
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Israel
State/province [30] 0 0
Ramat-Gan
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Israel
State/province [31] 0 0
Tel-Aviv
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Poland
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Bialystok
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Gdansk
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Poland
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Gdynia
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Jaworze
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Poland
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Katowice
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Krakow
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Lodz
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Poznan
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Rzeszow
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Warszawa
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Poland
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Wroclaw
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Taiwan
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Changhua County
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Taiwan
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Kaohsiung
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Taiwan
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Tainan
Country [46] 0 0
Taiwan
State/province [46] 0 0
Taipei

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

Ethics approval
Ethics application status

Summary
Brief summary
Phase 2a, dose-ranging Study with PF-05221304 in Nonalcoholic Fatty Liver Disease (NAFLD)
Trial website
https://clinicaltrials.gov/show/NCT03248882
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

Summary results
Other publications