Clinical trial NCT04880031: A Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) With an Extension
Official title: A Phase 2a, Randomized, Blinded, Placebo-controlled Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) With a Single Arm Open-label Extension
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Nonalcoholic Steatohepatitis (NASH)
Keywords: BOS-580
Safety
Tolerability
Pharmacokinetics
Efimosfermin
Lead sponsor: Boston Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-05-10
Enrollment: 231
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, blinded, placebo-controlled study of Efimosfermin in obese participants at risk for, or with biopsy-confirmed, nonalcoholic steatohepatitis (NASH), with a single arm open-label extension. It includes Parts A, B, C and D.


Eligibility criteria: Inclusion Criteria (Part A and Part B):

* Participant is either male or female and 18 to 75 years of age inclusive, at the time of signing the informed consent
* Obese participants with body mass index (BMI) of ≥ 27 kg/m\^2
* Hepatic fat fraction (HFF) measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) ≥8%
* Liver fibrosis assessment based on a vibration controlled transient elastography (VCTE) liver stiffness measurement (LSM) score of 7.0 to 9.9 kPa (Part A only) inclusive or 7.0 to 20.0 kPa (Part B only) inclusive and Liver injury assessment measured by aspartate aminotransferase (AST) \>25U/L. A qualifying historical biopsy (confirmed eligibility based on the central pathology read) supersedes the LSM, controlled attenuation parameter (CAP) score criteria and AST criteria.
* Histopathologically confirmed F2 or F3 stage NASH on a diagnostic liver biopsy performed during Screening or within 6 months prior to the first day of dosing for historical biopsies (Part B only).
* History or presence of at least 2 of 4 components of metabolic syndrome: obesity/overweight, dyslipidemia (high triglycerides and/or low high density lipoprotein \[HDL\]), type 2 diabetes with elevated glycated hemoglobin (HbA1c), and hypertension.

Inclusion Criteria (Part C):

* Participant must have completed the Part B of the study.
* Participant willing to undergo liver biopsy at Week 56
* NASH F stage \<F4 at 24 week assessment in Part B

Inclusion Criteria (Part D):

* BMI of ≥ 25 kg/m\^2
* Liver fibrosis based on assessments taken during screening visit
* Participant should be willing and able to undergo liver biopsy during Screening (if a historical biopsy within 12 months prior to Screening is not available) and per protocol as judged by the Investigator.
* Other inclusion criteria may apply

Exclusion Criteria (Part A and Part B):

* Documented clinical, laboratory or radiologic evidence of cirrhosis (compensated or decompensated)
* Triglycerides ≥ 500 mg/dL
* Change in body weight (more than 5% self-reported OR 5 kg self-reported change during the previous 3 months from Screening, whichever is smaller)
* History of type 1 diabetes, diabetic ketoacidosis, or positive glutamic acid decarboxylase (GAD) auto-antibodies (latent autoimmune diabetes in adults)
* Hemoglobin A1c \> 9.5%
* Participants with a condition that requires substantial anticoagulant medication may not be eligible for the study enrollment (e.g., deep vein thrombosis).

Exclusion Criteria (Part C):

• Participants that received their 24 week dose in Part B \> 10 weeks prior to enrollment into Part C

Exclusion Criteria (Part D):

* Other causes of chronic liver disease
* Documented evidence or history of decompensated liver cirrhosis.
* History of type 1 diabetes or poorly controlled type 2 diabetes.
* History of malignancy.
* Use of other investigational drugs.
* Other exclusion criteria may apply

Primary outcomes:
measure: Part A, Part B, Part C, and Part D: Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)
timeFrame: Until End of study/Early Termination (Day 393)
measure: Part A, Part B, Part C, and Part D: Changes from Baseline in systolic and diastolic blood pressure (BP)
timeFrame: Baseline, Week 12 (Day 85, Part A), Week 24 (Day 169, Part B), Week 56 (Day 393, Part C), and Weeks 36 (Day 253), and 48 (Day 337) (Part D)
measure: Part A, Part B, Part C, and Part D: Changes from Baseline in heart rate
timeFrame: Baseline, Week 12 (Day 85, Part A), Week 24 (Day 169, Part B), Week 56 (Day 393, Part C), and Weeks 36 (Day 253), and 48 (Day 337) (Part D)
measure: Part A, Part B, Part C, and Part D: Number of participants with Grade 3 and Grade 4 laboratory abnormalities
timeFrame: Baseline, Week 12 (Day 85, Part A), Week 24 (Day 169, Part B), Week 56 (Day 393, Part C), and Weeks 36 (Day 253), and 48 (Day 337) (Part D)
Secondary outcomes:
measure: Part A only: Efimosfermin serum concentration on Day 8 of the first dose
timeFrame: Day 8
measure: Part A only: Efimosfermin serum concentration at the end of the dosing interval (Ctrough)
timeFrame: Pre-dose at Days 15, 29, 43, 57, 71, 85 and 113 (End of study/Early termination) for bi-weekly schedule; pre-dose on Days 29, 57, 85 and 113 (End of study/Early termination) for the monthly schedule
measure: Part B only: Efimosfermin serum concentration on Day 7
timeFrame: Day 7
measure: Part B and Part C: Efimosfermin serum concentration at the end of the dosing interval (Ctrough)
timeFrame: Pre-dose at Days 29, 57, 85, 113, 141, 169, 225, 253, 281, 309, 316, 323, 330, 337, 365 and at Day 393 (End of study/Early Termination)
measure: Part B and Part C: Area under the serum concentration-time curve (AUC) for Efimosfermin for one dosing interval at steady state
timeFrame: At Days 121, 127, 134, 316, 323, 330 and pre-dose at Days 141 and 337
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Research Associates
state: Alabama
city: Chandler
country: United States
facility: Arizona Liver Health
state: Arizona
city: Peoria
country: United States
facility: Arizona Liver Health
state: Arizona
city: Tucson
country: United States
facility: Arizona Liver Health
state: Arizona
city: Tucson
country: United States
facility: Liver Institute PPLC
state: Arizona
city: Tucson
country: United States
facility: QLMC
state: Arizona
city: Canoga Park
country: United States
facility: Alliance Research Institute
state: California
city: Fountain Valley
country: United States
facility: Ark Clinical Research
state: California
city: Fresno
country: United States
facility: Fresno Clinical Research Center
state: California
city: Montclair
country: United States
facility: Catalina Research Institute
state: California
city: Orange
country: United States
facility: Knowledge Research Center
state: California
city: Oxnard
country: United States
facility: FOMAT Medical Research
state: California
city: Rialto
country: United States
facility: Inland Empire Clinical Trials
state: California
city: Fort Myers
country: United States
facility: Southwest General Healthcare Center
state: Florida
city: Fort Myers
country: United States
facility: Covenant Metabolic Specialists - Fort Myers
state: Florida
city: Hialeah Gardens
country: United States
facility: Evolution Clinical Trials
state: Florida
city: Kendall
country: United States
facility: Entrust Clinical Research Center
state: Florida
city: Lehigh Acres
country: United States
facility: Galenus Group
state: Florida
city: Miami Lakes
country: United States
facility: Panex Clinical Research
state: Florida
city: Miami
country: United States
facility: G+C Research Group
state: Florida
city: Miami
country: United States
facility: Miami Clinical Research
state: Florida
city: Miami
country: United States
facility: Advanced Clinical Research
state: Florida
city: Miami
country: United States
facility: Admed Research
state: Florida
city: Miami
country: United States
facility: Century Research
state: Florida
city: Orlando
country: United States
facility: Charter Research
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Sarasota
country: United States
facility: Covenant Metabolic Specialists - Sarasota
state: Florida
city: Marrero
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: Fayetteville
country: United States
facility: Coastal Research Institute, LLC
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research LLC
state: North Dakota
city: East Greenwich
country: United States
facility: Velocity Clinical Research
state: Rhode Island
city: Austin
country: United States
facility: Accelemed Research
state: Texas
city: Austin
country: United States
facility: Pinnacle Clinical Research - Austin
state: Texas
city: Austin
country: United States
facility: Texas Liver Institute - Austin
state: Texas
city: Bellaire
country: United States
facility: Apex Mobile Clinical Research
state: Texas
city: Brownsville
country: United States
facility: South Texas Research Institute-Brownsville
state: Texas
city: Edinburg
country: United States
facility: South Texas Research Institute-Edinburg
state: Texas
city: Georgetown
country: United States
facility: Pinnacle Clinical Research - Georgetown
state: Texas
city: Houston
country: United States
facility: Houston Research Institute
state: Texas
city: Pearland
country: United States
facility: LinQ Research, LLC
state: Texas
city: San Antonio
country: United States
facility: Quality Research, Inc
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation at Texas Liver Institute
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research - San Antonio
state: Texas
city: Waco
country: United States
facility: Velocity Clinical Research - Waco
state: Texas
city: Salt Lake City
country: United States
facility: Olympus Family Medicine
state: Utah
city: South Ogden
country: United States
facility: South Ogden Family Medicine
state: Utah
city: Seattle
country: United States
facility: Liver Institute NorthWest
state: Washington
Study officials:
References: