CM-101 in PSC Patients -The SPRING Study

NCT04595825 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: CM-101-PSC-101
• Study Type: interventional
• Target: 68
• Locations: 5 countries
• Sites: 33

Brief Summary

This study is designed to assess the safety, tolerability and activity of the anti-human CCL24 monoclonal antibody CM-101 in adult subjects with Primary Sclerosing Cholangitis (PSC). At least 68 subjects at approximately 50 sites will be randomized to receive either CM-101 at doses of 10 mg/kg or 20 mg/kg or matching placebo.

Conditions

Primary Sclerosing Cholangitis

Keywords

Anti-fibrotic

Outcome Measures

Primary Outcomes (1)

• Safety-related endpoints - number of participants with treatment-emergent adverse events (TEAEs)

  Frequency and severity of treatment-emergent adverse events (TEAEs), including vital sign changes, changes in clinical safety laboratories and evaluation of infusion site reactions.

  15 week double-blind (DB) treatment period

Secondary Outcomes (23)

• Safety-related endpoints - number of participants with abnormal vital sign changes

  48 week double-blind (DB) and open-label (OL) treatment periods

• Safety-related endpoints - number of participants with abnormal changes in clinical safety laboratory test results

  48 week double-blind (DB) and open-label (OL) treatment periods

• Safety-related endpoints - number of participants with infusion site reactions

  48 week double-blind (DB) and open-label (OL) treatment periods

• Alkaline phosphate (ALP) levels

  Change from baseline through Week 15

• Enhanced Liver Fibrosis (ELF) score value

  Change from baseline through Week 15

Study Arms (2)

Anti-human CCL24 monoclonal antibody (CM-101)

EXPERIMENTAL

Anti-human CCL24 monoclonal antibody CM-101 Intravenous Infusion over 60 minutes (±5 minutes)

Biological: Anti-human CCL24 monoclonal antibody (CM-101)

Placebo

PLACEBO COMPARATOR

Placebo - intravenous infusion

Other: Placebo

Interventions

Anti-human CCL24 monoclonal antibody (CM-101) BIOLOGICAL

Anti-human CCL24 monoclonal antibody (CM-101) 100 mg Intravenous Infusion over 60 minutes (±5 minutes)

Anti-human CCL24 monoclonal antibody (CM-101)

Placebo OTHER

Placebo - intravenous infusion

Placebo

Eligibility Criteria

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

You may qualify if:

• Subjects with diagnosis of large duct PSC of more than 24 weeks' duration
• Subjects that have no significant clinical concern for cholangiocarcinoma based on clinical, laboratory or imaging findings
• Subjects with serum Alkaline phosphatase (ALP) greater than 1.5 × Upper limit of normal (ULN) in Screening blood tests.
• Subjects receiving Ursodeoxycholic acid (UDCA) must receive a stable dose for ≥12 weeks prior to Screening
• Subjects with concomitant inflammatory bowel disease (IBD) is allowed but not required, and must meet the following stability criteria.
• Subjects with ulcerative colitis: Must be either in remission or have mild disease. Must have recent colonoscopy with biopsy confirming no dysplasia or colorectal cancer or history of colectomy.
• Subjects with Crohn's Disease must be in remission as defined by a Crohn's Disease Activity Index (CDAI) \< 150.
• Subjects receiving concomitant medication for IBD, dose must be stable ≥12 weeks prior to screening and dose should remain stable during DB portion of the study
• Subjects receiving concomitant medication for their PSC must be on stable therapy ≥12 weeks prior to randomization and plan to remain on that stable dose during the DB portion of the study
• Female subjects of childbearing potential, must have a negative serum pregnancy test prior to starting study treatment and must have agree to highly effective method of contraception from the Screening Visit throughout the study period including 18 weeks post last dose
• Male subjects, if not vasectomized, must agree to use barrier contraception from screening through to study completion and for 90 days from the last dose of study drug

You may not qualify if:

• Subjects with presence of documented secondary sclerosing cholangitis on prior clinical investigations
• Subjects with presence of competing etiology of liver disease.
• Subjects with possible overlap syndrome with autoimmune hepatitis are excluded if the Investigator considers autoimmune hepatitis as the predominant liver injury
• Subjects with small duct PSC in the absence of large duct disease
• Subjects with percutaneous biliary drain or bile duct stent or subjects who had required biliary drainage within 12 weeks of Screening
• Subjects that have undergone prior biliary surgery other than those who at the time of screening are more than 6 weeks after cholecystectomy without surgical complications
• Subjects with evidence of liver cirrhosis, as determined by local transient elastography values of ≥ 14.4 kPa obtained during the Screening period. In case of a fibrosis staging discrepancy between a recent (≤ 12 months) liver biopsy staging and the transient elastography results, eligibility will be based on the liver biopsy staging.
• History of cirrhosis and/or hepatic impairment (Child-Pugh classes A, B and C), and/or hepatic decompensation including ascites, encephalopathy, or variceal bleeding
• Subjects who have undergone or are planned for liver transplantation or with current model of end stage liver disease
• Subjects with Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) values \> 5 × ULN as determined at Screening
• Subjects who show 'clinically significant' lab changes at Screening
• Subjects with serum total bilirubin values \> 3 × ULN at Screening
• Subjects with known Gilbert's syndrome or a history of elevations in unconjugated (indirect) bilirubin \>ULN
• Subjects with international normalized ratio (INR) \>1.5 which does not correct on vitamin K replacement, in the absence of anticoagulants
• Subjects with serum creatinine \> 1.4 mg/dL (123 μmol/L) and/or a platelet count \< 100 × 109 /L

Sponsors & Collaborators

• ChemomAb Ltd.: lead

Study Sites (33)

Scripps Clinic Torrey Pines - site P83

La Jolla, California, 92037, United States

Location

UC Davis Health System - Midtown Ambulatory Care Center - site P79

Sacramento, California, 95816-5202, United States

Location

Northwestern University - site P77

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital - site P95

Boston, Massachusetts, 02114, United States

Location

Harvard Medical School - Beth Israel Deaconess Medical Center (BIDMC) - Liver Center - site P81

Boston, Massachusetts, 02215, United States

Location

Gastro One - GI Diagnostic and Therapeutic Endoscopy Center - 1310 Wolf Park - site P82

Germantown, Tennessee, 38138-1741, United States

Location

Methodist Dallas Medical Center - site P72

Dallas, Texas, 75203, United States

Location

Virginia Commonwealth - site P94

Richmond, Virginia, 23284, United States

Location

Klinikum der Johann Wolfgang Goethe-Universitaet - site P42

Frankfurt am Main, Germany

Location

Universitätsklinikum Hamburg-Eppendorf (UKE) - site P47

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover (MHH) - site P41

Hanover, Germany

Location

Soroka MC - site P23

Beersheba, Israel

Location

Shamir Medical Center (Assaf Harofeh) - site P28

Be’er Ya‘aqov, Israel

Location

Carmel - site P27

Haifa, Israel

Location

Rambam MC - site P22

Haifa, Israel

Location

Hadassah Ein Kereme - site P21

Jerusalem, 91120, Israel

Location

Shaarei Tszedek Medical Center - site P29

Jerusalem, Israel

Location

Galilee Medical Center - site P24

Nahariya, Israel

Location

EMMS Holy Family Nazareth Hospital - site P26

Nazareth, Israel

Location

Assuta Medical Center - site P31

Tel Aviv, Israel

Location

Tel-Aviv Sourasky Medical Center - site P30

Tel Aviv, Israel

Location

Hospital Clínic de Barcelona - site P67

Barcelona, 8036, Spain

Location

Hospital Universitario Ramón y Cajal - site P61

Madrid, 28034, Spain

Location

Hospital Universitari i Politècnic La Fe - site P64

Valencia, 46026, Spain

Location

Hospital Universitario Miguel Servet - site P65

Zaragoza, 50009, Spain

Location

Leeds Teaching Hospitals NHS Trust - site P08

Leeds, WYK, LS9 7TF, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust - site P05

Birmingham, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust - Addenbrookes Hospital - site P09

Cambridge, United Kingdom

Location

NHS Greater Glasgow and Clyde - site P03

Glasgow, United Kingdom

Location

King's College Hospital NHS Foundation Trust - site P04

London, United Kingdom

Location

The Royal Free Hospital - site P01

London, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust- site P11

Oxford, United Kingdom

Location

Plymouth Hospitals NHS Trust - Derriford Hospital - site P07

Plymouth, United Kingdom

Location

MeSH Terms

Conditions

Cholangitis, Sclerosing

Interventions

streptococcal polysaccharide type III group B

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Study Officials

• Matthew Frankel, MD

  ChemomAb Ltd.

  STUDY DIRECTOR

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: October 7, 2020
• First Posted: October 22, 2020
• Study Start: October 1, 2020
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2025
• Last Updated: January 9, 2024

Record last verified: 2024-01

Locations

US (8); IL (10); ES (4); DE (3); GB (8)