Nonalcoholic Steatohepatitis (NASH)
Conditions
Keywords
BOS-580, Safety, Tolerability, Pharmacokinetics, Efimosfermin
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.
Interventions
DRUGEfimosfermin
Efimosfermin will be administered by subcutaneous injection
DRUGPlacebo
Placebo will be administered by subcutaneous injection
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Part C - Open Label; Part D - Open Label
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Until End of study/Early Termination (Day 393) | The effects of Efimosfermin on safety and tolerability will be assessed. |
| Part A, Part B, Part C, and Part D: Changes from Baseline in systolic and diastolic blood pressure (BP) | 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) | The effects of Efimosfermin on safety and tolerability will be assessed. |
| Part A, Part B, Part C, and Part D: Changes from Baseline in heart rate | 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) | The effects of Efimosfermin on safety and tolerability will be assessed. |
| Part A, Part B, Part C, and Part D: Number of participants with Grade 3 and Grade 4 laboratory abnormalities | 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) | The effects of Efimosfermin on safety and tolerability will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A only: Efimosfermin serum concentration on Day 8 of the first dose | Day 8 | The pharmacokinetics (PK) of Efimosfermin will be assessed. |
| Part A only: Efimosfermin serum concentration at the end of the dosing interval (Ctrough) | 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 | The PK of Efimosfermin will be assessed. |
| Part B only: Efimosfermin serum concentration on Day 7 | Day 7 | The PK of Efimosfermin will be assessed. |
| Part B and Part C: Efimosfermin serum concentration at the end of the dosing interval (Ctrough) | 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) | The PK of Efimosfermin will be assessed. |
| Part B and Part C: Area under the serum concentration-time curve (AUC) for Efimosfermin for one dosing interval at steady state | At Days 121, 127, 134, 316, 323, 330 and pre-dose at Days 141 and 337 | The PK of Efimosfermin will be assessed. |
Countries
United States
Outcome results
None listed