Assessment of the Safety of Foralumab, an Oral Anti-CD3 Antibody, in Patients With NASH and T2DM

NCT03291249 | Withdrawn Phase 2

• 1 other identifier: TZLS-0401-001
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized, placebo-controlled, four-arm, double-blind study. Subjects will be randomized (1:1:1:1) to receive either a daily oral placebo solution or a daily oral dose of 0.5 mg, 2.5 mg or 5.0 mg Foralumab Solution for 30 consecutive days. Subjects will record adverse events and daily administration of study medication in a subject diary. This will serve as a measure of compliance and record of safety and tolerability. Subjects will be followed up for 30 days following completion of treatment. Study visits performed on Days 14, 30 and 60 of the study, will monitor metabolic parameters (body mass index \[BMI\] and waist circumference), serum lipid profiles, immunological markers (c-reactive protein \[CRP\] and an array of cytokines), hepatic enzymes and functions (13C-methacetin breath test \[MBT\]) and liver steatosis/fibrosis, which will be compared to baseline levels (Day 1). The safety and tolerability of the treatment regimen will be determined by monitoring vital signs, laboratory values, adverse events and physical findings throughout the study. In addition, its efficacy will be established upon either reduced Day 30 serum alanine aminotransferase (ALT) levels, reduced hemoglobin A1c (HbA1c) or improved homeostasis model assessment (HOMA) or HOMA of insulin resistance (HOMA-IR) scores as compared to baseline (Day 1). In addition, to assess the efficacy of the tested Foralumab Solution regimen in improving overall subject status, a battery of exploratory metabolic, immunologic and hepatic markers will be evaluated on Days 30 and 60.

Conditions

NASH - Nonalcoholic Steatohepatitis; NAFLD; T2DM (Type 2 Diabetes Mellitus)

Outcome Measures

Primary Outcomes (3)

• severity and duration for all adverse events

  Incidence, severity, and duration for all adverse events (AEs), and abnormal laboratory and physical findings up until 30 days after last dose

  30 days after last dose

• Abnormal laboratory findings

  Incidence, severity, and duration for all adverse events (AEs), and abnormal laboratory and physical findings up until 30 days after last dose

  30 days after last dose

• Abnormal physical findings

  Incidence, severity, and duration for all adverse events (AEs), and abnormal laboratory and physical findings up until 30 days after last dose

  30 days after last dose

Secondary Outcomes (3)

• Change ALT levels

  Day 30 versus Day 1 serum ALT levels

• Change in HbA1c levels

  Day 30 versus Day 1

• change in HOMA/HOMA-IR scores

  Day 30 versus Day 1

Other Outcomes (11)

• Body mass index (BMI)

  Day 1 versus day 30 and 60

• Change in Immunological markers

  Day 1 versus day 30 and 60

• Cytokine levels

  Day 1 versus day 30 and 60

Study Arms (4)

Group A

PLACEBO COMPARATOR

Group A will receive placebo solution for 30 consecutive days

Other: placebo; Drug: Omeprazole 20mg

Group B

EXPERIMENTAL

Group B will receive 0.5 mg Foralumab Solution daily for 30 consecutive days

Drug: Foralumab; Drug: Omeprazole 20mg

Group C

EXPERIMENTAL

Group B will receive 2.5 mg Foralumab Solution daily for 30 consecutive days

Drug: Foralumab; Drug: Omeprazole 20mg

Group D

EXPERIMENTAL

Group B will receive 5.0 mg Foralumab Solution daily for 30 consecutive days

Drug: Foralumab; Drug: Omeprazole 20mg

Interventions

Foralumab DRUG

Anti CD3 mAb

Also known as: Anti CD3

Group B; Group C; Group D

placebo OTHER

Placebo oral solution

Group A

Omeprazole 20mg DRUG

Omeprazole is a proton pump inhibitor used to neutralize stomach PH

Group A; Group B; Group C; Group D

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Provision of written informed consent
• Diagnosis of T2DM
• HbA1c \< 9.0 while on standard of care
• Historical histology-based confirmation of NASH within 12 months prior to screening OR
• Diagnosis of NAFLD based on all the following:
• Presentation of at least one other parameter of the metabolic syndrome from the following list of three:
• (i) hypertension \[≥130/85 mmHg or regularly taking an antihypertensive\], (ii) dyslipidemia with high serum triglycerides \[≥150 mg/dL or regularly taking medicines to lower high triglyceride levels\] or low serum HDL \[\<50 mg/dL for women and \<40 mg/dL for men\], (iii) obesity (BMI \> 30 kg/m2) or central obesity \[waistline measurement ≥ 89 cm for women and ≥ 102 cm for men\])
• ALT \> 40 IU
• Fat fraction \>10% in MRI performed during screening or up to 3 months prior to screening.
• Agree to the use of effective contraceptive measures, as defined in the protocol, if either male or female with child-bearing potential.

You may not qualify if:

• Subject with cirrhosis per biopsy (fibrosis staging score \>= 4) or Fibroscan® \>14 kPa within 12 months of screening.
• Presence of vascular liver disease
• Any history or evidence of decompensated liver disease such as recurrent variceal bleeding, refractory ascites or hepatic encephalopathy
• Known history of chronic alcoholic liver disease, chronic hepatitis B or C infection, drug-induced liver injury (DILI), hemochromatosis, Wilson's disease, 1-antitrypsin deficiency, primary biliary cirrhosis or secondary sclerosing cholangitis, autoimmune hepatitis
• Known HIV antibody-positive
• History of liver transplantation
• BMI \<25kg/m2
• Clinically significant alcohol use
• Score of ≥ 2 on the CAGE questionnaire, OR
• Any subject with current significant alcohol consumption or a history of significant alcohol consumption for a period of more than 3 consecutive months any time within 1 year prior to screening, as determined by medical history (medical chart review and/or interview). Significant alcohol consumption is defined as: females: \>20 g/day; males: \>30 g/day, with a standard drink in the US averaging 14 g alcohol.
• Type 1 diabetes
• Bariatric surgery within the last 5 years
• Weight loss or gain of ≥5 kg in the past 6 months or \>10% change in bodyweight in the past 12 months
• Inadequate vascular access on physical examination
• Lactating/breastfeeding/pregnant at screening

Sponsors & Collaborators

• Tiziana Life Sciences LTD: lead

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2

Interventions

foralumab; Muromonab-CD3; Omeprazole

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Immunoglobulin G; Immunoglobulin Isotypes; Serum Globulins; Globulins; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

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

Study Record Dates

• First Submitted: August 21, 2017
• First Posted: September 25, 2017
• Study Start: December 1, 2017
• Primary Completion: December 1, 2018
• Study Completion: June 1, 2019
• Last Updated: September 12, 2019

Record last verified: 2017-08