Leronlimab (PRO 140) in Patients With Nonalcoholic Steatohepatitis

NCT04521114 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CDI-NASH-01
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 7

Brief Summary

This is a phase II study of of Leronlimab (PRO 140)-Humanized monoclonal antibody to CCR5 in patients with Nonalcoholic Steatohepatitis (NASH).

Conditions

Nonalcoholic Steatohepatitis (NASH)

Keywords

NASH; PRO 140; Leronlimab

Outcome Measures

Primary Outcomes (1)

• MRI-PDFF Change From Baseline to Week 14

  Change in hepatic fat fraction from baseline assessed by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) at week 14

  Change from baseline (day one, first day of treatment) to EOT (day 92, 13 weeks of treatment)

Secondary Outcomes (20)

• MRI-cT1 Change From Baseline to Week 14

  Measured at baseline (day 1) and at EOT (day 92)

• Alkaline Phosphatase

  Measured at baseline (day 1) and at EOT (day 92)

• Alanine Aminotraferase (ALT)

  Measured at baseline (day 1) and at day 92

• Aspartate Aminotransferase (AST)

  Measured at baseline (day 1) and at EOT (day 92)

• GGT S

  Measured at baseline (day 1) and at EOT (day 92)

Study Arms (3)

Leronlimab 700 mg

EXPERIMENTAL

Leronlimab 700 mg SC weekly injection

Drug: leronlimab 700 mg

Leronlimab 350 mg

EXPERIMENTAL

Leronlimab 350 mg SC weekly injection

Drug: leronlimab 350 mg

Placebo

PLACEBO COMPARATOR

Placebo SC weekly injection

Drug: Placebo

Interventions

Placebo DRUG

Placebo will be administered subcutaneously every week for 13 weeks.

Placebo

leronlimab 700 mg DRUG

700 mg leronlimab will be administered subcutaneously every week for 13 weeks.

Also known as: PRO 140

Leronlimab 700 mg

leronlimab 350 mg DRUG

350 mg leronlimab will be administered subcutaneously every week for 13 weeks.

Also known as: PRO 140

Leronlimab 350 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is a male or female between 18 to 75 years of age inclusive.
• Evidence of nonalcoholic steatohepatitis (NASH) based on one of the following criteria:
• Criteria 1: Histologically-confirmed diagnosis of NASH on a liver biopsy, or
• Criteria 2: FibroScan or Shearwave US during screening (or within 6 months before screening) shows kPa ≥7 but \<14 and CAP ≥260.
• Subject shows presence of hepatic fat fraction as defined by ≥ 8% on MRI-PDFF and cT1 ≥ 800 ms at Screening.
• Has had a stable body weight (±5%) within 6 months prior to Screening.
• Body Mass Index (BMI) ≥ 28 kg/m2 at Screening
• Has clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator.
• Laboratory Screening results as indicated below:
• AST:ALT Ratio ≤ 1, if AST or ALT value is \> ULN
• Screening Liver enzymes (AST, ALT, and ALK PHOS) \< 5 x ULN.
• Total Bilirubin ≤ 1.3 mg/dL (except if Gilbert's Disease)
• Platelet count ≥ 150,000/mm3
• International normalized ratio (INR) \< 1.3
• Estimated Glomerular Filtration Rate (eGFR) ≥ 60/mL/min

You may not qualify if:

• Any concurrent clinically significant liver disease with an etiology other than NASH including autoimmune hepatitis, alcoholic hepatitis, hypoxic/ischemic hepatopathy, and biliary tract disease.
• History of alcohol consumption greater than 21/units/week (for males) and 14/units/week (for females) within the last 2 years prior to screening.
• Note: Use of online unit calculator for alcohol consumption is recommended (e.g., https://alcoholchange.org.uk/alcohol-facts/interactive-tools/unit-calculator)
• Any drug-induced steatohepatitis secondary to amiodarone, corticosteroids, estrogens, methotrexate, tetracycline, or other medications known to cause hepatic steatosis.
• Undergone major surgery, including liver surgery, within 6 months prior to screening deemed clinically significant by the investigator.
• Prior or pending liver transplantation.
• History or presence of cirrhosis or stage 4 fibrosis in historical liver biopsy and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding.
• Active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test), hepatitis C (defined as having a positive Anti-HCV test with detectable reflex HCV RNA; Note: Subject with positive Anti-HCV test and with undetectable HCV RNA would not be excluded), acute hepatitis A (defined as subjects with serum positive for hepatitis A IgM (HAV) antibody) or acute hepatitis E (defined as having anti-HEV IgM antibody).
• Any active infection requiring systemic therapy at the time of screening, which is considered clinically significant per the Investigator.
• Positive test for human immunodeficiency virus (HIV) or HIV infection.
• History of bleeding diathesis within 6 months of screening.
• Any malignancy within the past 5 years, excluding successfully treated basal cell carcinoma or squamous cell carcinoma without evidence of metastases.
• Seizure disorder requiring ongoing antiseizure therapy or with any condition that, in the judgment of the investigator, is likely to increase the risk of seizure (e.g. CNS malignancy)
• Clinically significant active cardiac disease which would interfere with study conduct or study results interpretation per the PI.
• Any known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Sponsors & Collaborators

• CytoDyn, Inc.: lead

Study Sites (7)

Southern California Research Center

Coronado, California, 92118, United States

Location

Meridien Research

Maitland, Florida, 32751, United States

Location

Floridian Clinical Research

Miami Lakes, Florida, 33016, United States

Location

Sensible Healthcare, LLC

Ocoee, Florida, 34761, United States

Location

Center for Advanced Research & Education

Gainesville, Georgia, 30501, United States

Location

Care United Research LLC

Forney, Texas, 75126, United States

Location

American Research Corporation

San Antonio, Texas, 78215, United States

Location

Related Publications (1)

• Munteanu M, Tiniakos D, Anstee Q, Charlotte F, Marchesini G, Bugianesi E, Trauner M, Romero Gomez M, Oliveira C, Day C, Dufour JF, Bellentani S, Ngo Y, Traussnig S, Perazzo H, Deckmyn O, Bedossa P, Ratziu V, Poynard T; FLIP Consortium and the FibroFrance Group. Diagnostic performance of FibroTest, SteatoTest and ActiTest in patients with NAFLD using the SAF score as histological reference. Aliment Pharmacol Ther. 2016 Oct;44(8):877-89. doi: 10.1111/apt.13770. Epub 2016 Aug 23.

  PMID: 27549244 BACKGROUND

Related Links

• Diagnostic performance of FibroTest

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

leronlimab

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Joseph Meidling, Senior Director - Clinical Operations
• Organization: CytoDyn Inc.

jmeidling@cytodyn.com

(360) 980-8524

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: August 20, 2020
• Study Start: December 1, 2020
• Primary Completion: December 29, 2021
• Study Completion: December 29, 2021
• Last Updated: March 1, 2023
• Results First Posted: March 1, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)