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Nonalcoholic SteatohepatitisPhase 2NCT05824156

CM-101 in NASH Patients - The SPLASH Study

A Phase 2 study testing 5 mg/kg CM-101 in people with Nonalcoholic Steatohepatitis, run by ChemomAb Ltd. at 9 sites in Israel.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase 2a study is a multi-center, double-blind randomized, placebo-controlled study. The study is designed to determine the safety and tolerability of the anti-human CCL24 monoclonal antibody CM-101 in adult patients with non-cirrhotic nonalcoholic steatohepatitis (NASH) patients with stage 1c, 2 or 3 fibrosis. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Nonalcoholic Steatohepatitis
What is being tested?
5 mg/kg CM-101
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
23 participants
Where
9 sitesIsrael
Study dates
24 Feb 2021to 25 Aug 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histological confirmation of steatohepatitis and fibrosis without cirrhosis on a diagnostic liver biopsy obtained within the 18 months prior to the start of treatment, and/or during the screening period with:
  • NAS ≥ 4 with a score of at least 1 for each component (steatosis, ballooning degeneration and lobular inflammation) and b. Hepatic fibrosis stage F1c, 2 or 3 as defined by the NASH CRN scoring scale. F1c subjectspatients must have either: PRO-C3 >14 ng/ml or Liver stiffness value of >8.0 kPa measured by transient elastography
  • Patients with presence of greater than or equals to (≥) 10 percent (%) steatosis on MRI-derived proton-density fat-fraction (PDFF) performed as part of the screening procedure or within 12 weeks prior to randomization
  • Confirmation of disease status from time of biopsy by Transient Elastography performed during the screening period with liver stiffness value of 7-12 kPa.
  • Patients with presence of ≥1 of the following risk factors:
  • Obesity (BMI ≥30 kg/m2),
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  • Type 2 diabetes diagnosed per 2013 American Diabetes Association criteria,
  • HTN per 2017 AHA Guidelines for Hypertension,
  • ALT >1.5× upper limit of normal (ULN)
  • Patients with a stable body mass index (BMI) between 25- 45 kg/m², both inclusive. Body weight is required to be stable (i.e., not varying by > 5% for at least 12 weeks) prior to study entry;
  • Patients on chronic medication must be on a stable regimen for ≥ 12 weeks prior to Randomization and should attempt to maintain a stable dosing regimen during the study period;
  • Patients must have the following laboratory parameters at screening:
  • Total bilirubin < 1.5 mg/dL (26 micromol/L)
  • AST < 5 x ULN
  • INR < 1.3
  • Creatinine clearance ≥60 mL/min as calculated by Cockcroft Gault equation;
  • Alpha-fetoprotein in normal range (i.e. <20 ng/mL). If greater than normal, the patient requires a negative ultrasound for hepatocellular carcinoma within 12 weeks prior to randomization
  • Women of childbearing potential must agree to use an approved form of contraception (e.g. oral, transdermal patch, implanted contraceptives, intrauterine device, diaphragm, condom, abstinence or surgical sterility) prior to randomization and for the duration of study participation through to 60 days after the last dose of the study medication. Confirmation that female patients are not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for documented postmenopausal or surgically sterilized women;
  • Male patients must agree to use a barrier method of contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide) or abstinence for the duration of study participation through 60 days after the last dose of the study medication.
  • Patients able to understand and sign a written informed consent form (ICF), communicate with the investigator, and understand and comply with protocol requirements.

Who cannot join

  • Patients with medical/surgical history of bariatric surgery procedures or bariatric device insertion or patients that are planned for such interventions;
  • Patients taking weight loss medications;
  • Evidence of drug induced steatohepatitis secondary to amiodarone, corticosteroids, estrogens, methotrexate, tetracycline, or other medications known to cause hepatic steatosis;
  • History or presence of cirrhosis (compensated or decompensated) determined by histology or relevant medical complications and laboratory parameters;
  • Model for End-stage Liver Disease (MELD) score >12;
  • History of liver transplant, or current evaluation for or placement on a liver transplant waiting list;
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  • Abnormal laboratory screening values:
  • Hemoglobin < 12.0 g/dL in males and < 11.0 g/dL in females
  • Platelet count < 140,000/mm3
  • Total white blood cells (WBC) < 3,000 cells/mm3
  • Absolute neutrophil count (ANC) < 1,500 cells/mm3
  • Serum albumin < 3.5 g/dL
  • Screening ECG demonstrating prolongation of QT interval corrected by Fredericia Correction Formula (QTcF) of > 500 msec, or a history of clinically significant arrythmias
  • History of other chronic liver diseases including:
  • Alcoholic liver disease
  • Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg)
  • Hepatitis C as defined by presence of hepatitis C virus antibody (HCV-Ab) even if successfully treated with an antiviral regimen or positive HCV RNA (if necessary)
  • History or evidence of well documented autoimmune hepatitis (i.e. specific autoantibodies, hypergammaglobulinemia, consistent histologic changes)
  • History or evidence of primary biliary cholangitis (PBC)
  • History or evidence of primary sclerosing cholangitis (PSC)
  • History or evidence of Wilson's disease
  • History or evidence of alpha-1-antitrypsin deficiency
  • History or evidence of hemochromatosis
  • History or evidence of drug-induced liver disease, as defined on the basis of typical exposure and history
  • Known bile duct obstruction or a history of prior biliary tract diversion
  • Suspected or proven liver cancer;
  • History of human immunodeficiency virus (HIV) infection (positive HIV Ab);
  • Patients with diabetes mellitus type 1;
  • Patients with decompensated diabetes mellitus type 2 defined as either a HbA1c ≥ 9.5% at the time of screening or patients who are insulin dependent;
  • Patients under evaluation for a suspected malignancy, with any history of hepatocellular carcinoma (HCC), or a history of other malignancy diagnosed or treated within 2 years prior to Randomization (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to Screening);
  • Patients showing deleterious effects of alcohol abuse (as assessed by the investigator) or that consume excessive amounts of alcohol (>14 units/week for both females and males; for the purposes of this study one unit of alcohol is considered to be equal to 8 gr);
  • Patients treated with chronic medication including but not limited to anti-retrovirals, tamoxifen, methotrexate, cyclophosphamide, isotretinoin, bile acid binding resins, obeticholic acid, ursodeoxycholic acid or pharmacologic doses of oral glucocorticoids (≥ 10 mg of prednisone per day or equivalent) within 12 weeks of Randomization
  • Significant systemic or major illness other than liver disease including:
  • Acute coronary syndrome, unstable angina, congestive heart failure, or cerebrovascular event within 24 weeks prior to Randomization
  • Major surgery within 12 weeks prior to Randomization
  • CNS disorders including Alzheimer's disease or other forms of dementia, seizure disorders and Parkinson's disease
  • Autoimmune disease that has required systemic treatment in the 2 years preceding the study screening (i.e., with the use of disease-modifying agents, corticosteroids or immunosuppressive drugs)
  • Uncontrolled thyroid disease
  • Clinically significant renal dysfunction (estimated GFR < 60 ml/min (CKD equation))
  • A history of any clinically significant medical disorder that, in the judgement of the investigator, would interfere with patient treatment, assessment, or compliance with the protocol;
  • Known severe allergic or anaphylactic reactions to recombinant therapeutic proteins, fusion proteins, or chimeric, human, or humanized antibodies;
  • Patients with any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing and protocol requirements.
  • Participation in a study of another investigational agent within 28 days or five half-lives of the drug (whichever is longer) prior to screening;
  • Prior treatment with CM-101 antibody

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Israel9 sites

  • Soroka Medical Center - site 203

    Beersheba

  • Carmel Medical Center - site 207

    Haifa

  • Rambam Medical Center - site 202

    Haifa

  • Hadassah Ein Kereme - site 201

    Jerusalem, 91120

  • Shaare Zedek Medical Center - site 208

    Jerusalem

  • Galilee Medical Center - site 204

    Nahariya

  • Holy Family Nazareth Hospital - site 206

    Nazareth

  • Rabin Medical Center - site 205

    Petah Tikva

  • The Haim Sheba Medical Center - site 209

    Ramat Gan

Other trials in Israel

About this study

Official title: Phase 2A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study of CM-101 in Patients With Non-Alcoholic Steatohepatitis (NASH)

This phase 2a study is a multi-center, double-blind randomized, placebo-controlled study. The study is designed to determine the safety and tolerability of the anti-human CCL24 monoclonal antibody CM-101 in adult patients with non-cirrhotic nonalcoholic steatohepatitis (NASH) patients with stage 1c, 2 or 3 fibrosis. The patients will be randomized to 1 of 2 treatment groups: 5 mg/kg CM-101 or placebo.

Read the detailed description

This study will consist of screening period, treatment period and follow-up period. Adults with NASH will be included. Each subject will undergo screening procedures within up to 42 days prior to Randomization, to assess eligibility to participate in the study. After randomization patients will receive a dose of investigational product once every 2 weeks for a total of 8 administrations. This will result in a total coverage of 16 weeks. Study participation will last for up to approximately 26 weeks (up to 6 weeks for screening followed by 14 weeks treatment and 6 weeks follow-up).

Being tested
5 mg/kg CM-101, Placebo
Keywords
Anti-fibrotic
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 5 mg/kg CM-101Biological

    CM-101, Monoclonal Ab blocking CCL24

  • PlaceboOther

    Placebo

Study groups in NCT05824156
Study groupRoleWhat they receive
5 mg/kg CM-101ExperimentalSubcutaneous injection CM-101 every 2 weeks
Receives: Biological: 5 mg/kg CM-101
PlaceboPlacebo comparatorSubcutaneous Injection Placebo every 2 weeks
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety-related endpoints - Treatment emergent adverse events (TEAEs)

    The safety and tolerability will be assessed by monitoring treatment emergent adverse events (TEAEs)

    Measured: 14-week treatment period

Secondary outcomes (20)

  1. Serum biomarkers for pharmacodynamic parameters - Enhanced liver function (ELF™) Blood Test

    Change in serum biomarkers for Enhanced liver function (ELF™) Blood Test

    Measured: Change from baseline to week 16

  2. Serum biomarkers for pharmacodynamic parameters - Pro-C3

    Change in serum biomarkers for Pro-C3

    Measured: Change from baseline to week 16

  3. Serum biomarkers for pharmacodynamic parameters - PRO-C4

    Change in serum biomarkers for PRO-C4

    Measured: Change from baseline to week 16

  4. Serum biomarkers for pharmacodynamic parameters - C3M

    Change in serum biomarkers for C3M

    Measured: Change from baseline to week 16

  5. Serum biomarkers for pharmacodynamic parameters - Cytokeratin-18 (cCK-18) (full length and fragments; M65, M30)

    Change in serum biomarkers for Cytokeratin-18 (cCK-18) (full length and fragments; M65, M30)

    Measured: Change from baseline to week 16

  6. Serum inflammatory markers - Fibrinogen

    Change over time in serum inflammatory markers - Fibrinogen

    Measured: From baseline over time

  7. Serum inflammatory markers - C-reactive protein (CRP)

    Change over time in serum inflammatory markers - C-reactive protein (CRP)

    Measured: From baseline over time

  8. Change in liver enzymes

    Absolute and percentage changes from Baseline over time through to week 16 as well as the percentage of normalization of ALT, AST, ALP, GGT, total bilirubin (TB) triglycerides and lipid profile (total cholesterol, HDL C, LDL C)

    Measured: From baseline over time

  9. Immune cell sub populations evaluation

    Whole Blood sampling for immune cell sub populations evaluation

    Measured: 16 weeks

  10. Change in Liver Stiffness

    Change from Baseline to week 8 and 16 in liver stiffness using Transient Elastography

    Measured: Change from Baseline to week 16

  11. Change in Liver Fat Content

    Change from Baseline to week 8 and 16 in LFC (Liver fat content) assessed by MRI-PDFF

    Measured: Change from Baseline to week 16

  12. Change in liver fibrosis - Fibrosis-4 (FIB-4) score

    Change from baseline to week 16 in: fibrosis-4 (FIB-4) score

    Measured: 16 weeks

  13. Change in liver fibrosis - AST/ALT ratio

    Change from baseline to week 16 in: AST/ALT ratio

    Measured: 16 weeks

  14. Change in liver fibrosis -APRI (AST to platelet ratio index)

    Change from baseline to week 16 in: APRI (AST to platelet ratio index)

    Measured: 16 weeks

  15. Change in liver fibrosis -the Nonalcoholic fatty liver disease (NAFLD) Fibrosis Score

    Change from baseline to week 16 in: the Nonalcoholic fatty liver disease (NAFLD) Fibrosis Score

    Measured: 16 weeks

  16. Pharmacokinetics (PK) profile - Cmax

    Elucidate CM-101 Serum PK profile - Observed maximum plasma concentration

    Measured: 14 weeks

  17. Pharmacokinetics (PK) profile - Tmax

    Elucidate CM-101 Serum PK profile - Time to reach the observed maximum plasma concentration (Cmax)

    Measured: 14 weeks

  18. Pharmacokinetics (PK) profile - AUC∞

    Elucidate CM-101 Serum PK profile - Area under the plasma concentration-time curve extrapolated to infinity, calculated as: AUC∞ = AUClast + Clast/λz, where AUClast is the last measurable concentration.

    Measured: 14 weeks

  19. Pharmacokinetics (PK) profile - t½

    Elucidate CM-101 Serum PK profile - Terminal elimination half-life, defined as 0.693/λz

    Measured: 14 weeks

  20. Anti-Drug Antibodies

    Evaluation of the development of anti-drug antibodies (ADA) following 14 weeks repeated administration

    Measured: 14 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Apr 2023
  2. Study start24 Feb 2021
  3. Primary completion15 Aug 2022
  4. Study completion25 Aug 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05824156
Sponsor's protocol ID
CM-101-NASH-201
Status last verified
Apr 2023
First submitted
6 Dec 2021
Last updated
21 Apr 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 5 mg/kg CM-101 in people with Nonalcoholic Steatohepatitis, run by ChemomAb Ltd. at 9 sites in Israel.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety-related endpoints - Treatment emergent adverse events (TEAEs) (time frame: 14-week treatment period). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05824156.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2023; AzTrials last refreshed its copy on 3 Nov 2026.

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