Clinical trial

Nonalcoholic Steatohepatitis (NASH)

Nonalcoholic fatty liver disease (NAFLD) is a medical condition that is characterized by the build-up of fat (called fatty infiltration) in the liver. There are two types of NAFLD:

  • Nonalcoholic fatty liver (NAFL), a generally benign condition in which there is fatty infiltration but no inflammation. It is now the most common cause of liver disorder in the western industrialized countries, affecting approximately 25% of the population, as weight gain and obesity have become more common. Many patients with NAFL never develop inflammation (NASH), although some do.
  • Nonalcoholic steatohepatitis (NASH), in which there is fatty infiltration along with liver inflammation and accumulation of scar tissue. The exact cause of NASH is unknown. However, it is seen more frequently in people with certain medical conditions such as diabetes, obesity, insulin resistance and hypertension. This combination of disorders is often called the "metabolic syndrome". It is not clear how many people have NASH because most of them have no symptoms but it is estimated that approximately 20 to 25% of NAFLD patients will develop NASH in the long term. There is no approved treatment for NASH. NASH can, in turn, deteriorate in cirrhosis and liver failure, for which the only therapeutic option is liver transplantation.

To be diagnosed with either form of NAFLD, a person must not have a history of heavy alcohol use or another problem that might be causing the liver condition (such as hepatitis C). There is no approved therapy for NASH

Chemomab is Testing the Novel Biologic Drug, CM-101, Which it has Developed for Treating NAFLD:

  • CM-101 targets the soluble protein CCL24, which was found to play a pivotal role in promoting fibrotic and inflammatory activities in the liver through its receptor, CCR3
  • Chemomab has demonstrated that CCL24 is strongly expressed in NASH patients’ liver samples (biopsies), while its levels in the blood correlate with the state of liver fibrosis

Chemomab conducted pre-clinical tests of CM-101 in NASH animal models, and found that CM-101 was effective and significantly attenuated disease severity.

Chemomab also tested CM-101 in healthy volunteers and patients with non-alcoholic fatty liver disease (NAFLD) and found CM-101 to be safe and well tolerated in all tested doses. The SPLASH study will test CM-101 activity, safety and tolerability in adult NASH patients.

This is a phase 2a study, administering 8 subcutaneous (SC) injections once every 2 weeks over 14 weeks of either the tested drug (CM-101) or placebo.

  • Key eligibility criteria

  • Males and females, 18 to 75 years of age

  • Liver biopsy from the last 12 months confirming the diagnosis of NASH, (with NAS score ≥ 4 and at least a score of 1 for each component) and fibrosis stage 2 or 3

  • Patients with at least one active risk factor from the below list:

    a. Obesity (BMI ≥30 kg/m2)

    b. Non-insulin-dependent Type 2 diabetes

    c. Hypertension

    d. ALT >1.5× upper limit of normal (ULN)

  • Patients with alcohol or drug-induced fatty liver disease are not eligible

  • Patients with other chronic liver diseases are not eligible

  • Patients taking weight loss medications are not eligible

  • Patients with other active non-liver diseases (such as cardiac, autoimmune, renal or neurological diseases) are not eligible

  • Patients’ concomitant medications must be stable for at least 12 weeks

The SPLASH study procedures

  • Screening

    4 weeks

  • Treatment period

    14 weeks: Subcutaneous drug
    administration once
    every 2 weeks, for a total of 8 treatments

  • Safety Follow-Up

    6 weeks after last treatment

Participants will sign an informed consent form and will be screened to make sure they are eligible to join the study.

If eligible, participants will be randomly assigned to receive SC injections of the study drug or a placebo. Participants will visit the study site once every 2 weeks for 14 weeks of treatment. After the last treatment participants will enter 6 weeks of study follow up. This study does not involve liver biopsies.

In total, each study participant will visit the testing site 11 times over 4 to 5 months.

This study is open for recruitment.

Israeli MoH number: MOH_2020-03-30_008503

Locations

  • Hadassah Medical Center

    Kiryat Hadassah, Ein Kerem, Jerusalem

  • Rabin Medical Center

    39 Jabotinski St., Petah Tikva 49100

  • Soroka Medical Center

    Ben Gurion Avenue, Beer-Sheva

  • Rambam Medical Center

    HaAliya HaShniya St 8, Haifa

  • EMMS Nazareth Hospital

    Nazareth

  • Carmel Medical Center

    Horev 2 st. Haifa

  • Galilee Medical Center

    Nahariya 22100