Status:
COMPLETED
Leronlimab (PRO 140) in Patients With Nonalcoholic Steatohepatitis
Lead Sponsor:
CytoDyn, Inc.
Conditions:
Nonalcoholic Steatohepatitis (NASH)
Eligibility:
All Genders
18-75 years
Phase:
PHASE2
Brief Summary
This is a phase II study of of Leronlimab (PRO 140)-Humanized monoclonal antibody to CCR5 in patients with Nonalcoholic Steatohepatitis (NASH).
Detailed Description
This is an exploratory phase II, multi-center, two-part study (Part 1: randomized, placebo-controlled, two-arm with 60 patients; Part 2: non-randomized, single-arm, open-label with 30 patients) design...
Eligibility Criteria
Inclusion
- Subjects are required to meet ALL of the following criteria for enrollment into the study:
- 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
- Glycosylated hemoglobin (HbA1c) \< 9%.
- Thyroid-Stimulating Hormone (TSH) within normal reference range. Note: Any subject with a non-clinically significant TSH value outside of the normal range may be enrolled if their T3 and free T4 values are within the normal range.
- Subjects with pre-diabetes or type 2 diabetes will be allowed to participate if the following criteria is met:
- Subjects who are taking anti-diabetic medications should be on a stable dose for a period of at least 3 months prior to Screening and do not anticipate clinically significant dose adjustments during the course of study.
- Subjects must be on a stable diet/lifestyle regimen for at least 3 months prior to screening and do not anticipate a clinically significant change during the course of study.
- Subjects who are taking Vitamin E should be on a stable dose of Vitamin E (if ≥ 400 IU) for a period of at least 4 weeks prior to Screening and do not anticipate dose adjustments for the duration of the study.
- Both male and female patients and their partners of childbearing potential must agree to use two medically accepted methods of contraception (e.g., barrier contraceptives \[male condom, female condom, or diaphragm with a spermicidal gel\], hormonal contraceptives \[implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings\], or one of the following methods of birth control (intrauterine devices, tubal sterilization or vasectomy) or must practice complete abstinence from intercourse of reproductive potential from study entry to 6 months after the last day of treatment (excluding women who are not of childbearing potential and men who have been sterilized).
- Females of child-bearing potential must have a negative serum pregnancy test at Screening Visit and negative urine pregnancy test prior to receiving the first dose of study drug; and Male participants must agree to use contraception and refrain from donating sperm for at least 90 days after the last dose of study intervention.
- Subject is willing and able to give informed consent prior to any study specific procedures being performed.
- Subject is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures and study restrictions
Exclusion
- Subjects meeting ANY of the following criteria will be excluded from enrollment:
- 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.
- Prior therapy with Leronlimab or any other CCR5 antagonist (e.g. maraviroc) within 6 months prior to screening.
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to humanized monoclonal antibodies.
- Any condition requiring continuous systemic treatment with immunosuppressive (such as corticosteroids) or immunomodulatory medications.
- Note: Inhaled or topical steroids of up to 5 mg daily prednisone equivalent dose are permitted in the bsence of active autoimmune disease.
- History of administration of a live, attenuated vaccine within four weeks prior to start of PRO 140 treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study.
- Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed. However intranasal influenza vaccines (e.g., Flu-Mist ®) are live attenuated vaccines, and are not allowed.
- Currently participating in an investigational study or received an investigational drug within 28 days or 5 half-lives (whichever is longer) prior to study drug administration
Key Trial Info
Start Date :
December 1 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 29 2021
Estimated Enrollment :
87 Patients enrolled
Trial Details
Trial ID
NCT04521114
Start Date
December 1 2020
End Date
December 29 2021
Last Update
March 1 2023
Active Locations (7)
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1
Southern California Research Center
Coronado, California, United States, 92118
2
Meridien Research
Maitland, Florida, United States, 32751
3
Floridian Clinical Research
Miami Lakes, Florida, United States, 33016
4
Sensible Healthcare, LLC
Ocoee, Florida, United States, 34761