A STUDY TO ASSESS EFFICACY AND SAFETY OF PF-06865571 ALONE AND WHEN COADMINISTERED WITH PF-05221304 IN ADULT PARTICIPANTS WITH BIOPSY CONFIRMED NONALCOHOLIC STEATOHEPATITIS AND FIBROSIS STAGE 2 OR 3

Phase 1

• Conditions: BIOPSY-CONFIRMED NONALCOHOLIC STEATOHEPATITIS WITH FIBROSIS STAGE 2 OR 3; MedDRA version: 24.1Level: PTClassification code 10053219Term: Non-alcoholic steatohepatitisSystem Organ Class: 10019805 - Hepatobiliary disorders; MedDRA version: 20.0Level: PTClassification code 10019668Term: Hepatic fibrosisSystem Organ Class: 10019805 - Hepatobiliary disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2019-004775-39-SK
• Lead Sponsor: Pfizer Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-06-01
• Last Update Posted: 18 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

1. Male or female participants between the ages of 18 (or the minimum country-specific age of consent if >18) and 75 years, inclusive, at PreQ (Prequalification visit) and SCR1 (Screen 1 / Visit 1);
2. At PreQ and SCR1, meet = 2 of the following criteria [for laboratory parameters, results must be as assessed by the sponsor-identified central laboratory, with a single repeat permitted to assess eligibility, at each of these 2 visits, if needed] –
- FPG = 100 mg/dL (5.6 mmol/L), or on pharmacological agents with explicit purpose of improving glycemic control;
- Fasting serum HDL-C <40 mg/dL (1 mmol/L) for males and <50 mg/dL (1.3 mmol/L) for females, or on pharmacological agents with explicit purpose to increase HDL-C;
- Fasting serum TG =150 mg/dL (1.7 mmol/L), or on pharmacological agents with explicit purpose to decrease TG;
- Seated BP =130 / 85 mm Hg, or on pharmacological agents with explicit purpose for BP control;
- Waist circumference =40 inches (102 cm) for males and =35 inches (89 cm) for females.
3.Meet the following criteria, based on an evaluable FibroScan® as defined in Section 8.1.2.1 (±AST as assessed by sponsor-identified central laboratory); with a single repeat assessment permitted to assess eligibility, if needed, at each of these 2 visits;
•At PreQ and SCR1, FASTTM score =0.30, derived using sponsor provided NASH tool;
OR
•At PreQ and SCR1, meet a combination of
•CAPTM =280 dB/m plus
•VCTETM between 8.0 and 20.0 kPa, inclusive;
•Eligibility using this non-invasive assessment must occur prior to conduct of screening/baseline liver biopsy at SCR2.
4. At SCR2, ultrasound-guided (and in limited cases, other imaging technique(s) as outlined in Section 8.1.1), percutaneous, liver biopsy meeting the NASH CRN definition14 as determined by sponsor identified central pathologist(s) as follows –
•A total NAS score of =4 (and up to total score of 8) comprising of steatosis grade =1, plus inflammation grade of =1, plus ballooning grade of =1;
•Along with fibrosis of F2 or F3;
NOTE: A historical biopsy may be accepted if performed =12 weeks prior to SCR2 and tissue slides are accessible to the sponsor identified central in such cases,
•Eligibility based on inclusion criterion 3 at PreQ and SCR1 is not required;
•SCR2 date reflects date of shipment of historical tissue sample to sponsor identified central laboratory after confirmation of eligibility based on assessments performed at PreQ and SCR1 visits;
•In all cases, date of procedure of the liver biopsy used to determine
eligibility (and serve as baseline) must be =24 weeks prior to Day 1.
5. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures –
-Including following completion of screening/baseline liver biopsy, participants must confirm willingness to undergo the 2nd biopsy, while in study.
Weight:
6. BMI =25.0 kg/m2 (for sites in Africa, Europe, North/South America) or =22.5kg/m2 (for sites in Asia) with upper limit of 45 kg/m2 (including rounding to a maximum of 45.1 kg/m2, calculated using sponsor-provided NASH tool) at PreQ and SCR1 with a single repeat assessment of body weight and/or BMI permitted on a different day to assess eligibility, if needed, at each of these 2 visits;
•In all cases, eligibility must conform to ability to ascertain evaluable FibroScan® (Section 8.1.2.1) and conduct of percutaneous liver biopsy (Section 8.1.1).
7. Body

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:

1. Current significant alcohol consumption at either PreQ and SCR1 defined as any one of these parameters – with a single repeat assessment of laboratory-related parameters permitted using sponsor-identified central laboratory, to assess eligibility, if needed, at each of these 2 visits:
•>14 drinks/week (men) and >7 drinks/week (women) where 1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor
•%CDT=1.5x ULN
•Total score of =8 on the AUDIT questionnaire
2. Evidence of other causes of liver disease at either PreQ and SCR1
3. History of pancreatitis, at PreQ
4. Any condition possibly affecting drug absorption at PreQ
•Participants who have undergone cholecystectomy and/or appendectomy are eligible for this study so long as the surgery occurred >6 months prior to PreQ
5. Diagnosis of T2DM which requires management with >3 medications within 12 weeks prior to SCR1 or management with excluded agents for glycemic control
6. Dyslipidemia which requires management with >3 lipid-modifying agents within 12 weeks prior to SCR1 or use of excluded agents for lipid management –
•Specific restrictions need to be satisfied at SCR1 in order to progress
•Those on gemfibrozil or lovastatin will need to agree to be switched to another agent once deemed eligible and for duration of study;
•Those on statins will be permitted based on review of the total daily dose
7. At PreQ or SCR1, those with severe hypertension defined as seated systolic BP=180 mmHg and diastolic BP =105 mm Hg, or both with a single repeat permitted, if needed, to assess eligibility at each of these 2 visits; and/or managed with >3 agents to control BP within 12 weeks prior to SCR1
•BP must be assessed using a blood pressure cuff size available at individual sites and compatible with the arm circumference of the participant
•Participants with seated BP =160/100 mmHg at PreQ or SCR1 must use the Run-In period to revise/adjust medications to improve BP control with BP-related randomization criteria met before dosing on Day 1/Visit 5
8. Cardiovascular event within 12 months prior to PreQ
9. Recent systemically administered treatments for malignancy including the use of chemotherapy, radiotherapy, or immunotherapy;
•Or any other active malignancy, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
10. Other medical or psychiatric condition including recent or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified