Clinical Trials Register

Summary
EudraCT Number:	2018-004258-77
Sponsor's Protocol Code Number:	CM-101-PSC-001
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-11-26
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2018-004258-77

A.3

Full title of the trial

A Phase 2, Open Label, Multiple Center Study to Evaluate the Safety, Tolerability, and Efficacy of CM-101 Administered for 12 Weeks in Adult Subjects with Primary Sclerosing Cholangitis.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A phase 2 study being run in multiple centres to evaluate the safety, tolerability and efficacy of a study drug (called CM-101) which will be given to patients with primary sclerosing cholangitis for 12 weeks.

A.3.2

Name or abbreviated title of the trial where available

The SPRING Study

A.4.1

Sponsor's protocol code number

CM-101-PSC-001

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ChemomAb Ltd.
B.1.3.4	Country	Israel
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ChemomAb Ltd.
B.5.2	Functional name of contact point	Adi Mor
B.5.3	Address:
B.5.3.1	Street Address	Kiryat Atidim, building 7, entrance B,
B.5.3.2	Town/ city	Tel Aviv
B.5.3.3	Post code	58288
B.5.3.4	Country	Israel
B.5.4	Telephone number	+972- 773310158
B.5.6	E-mail	adimor@chemomab.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	CM-101
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Treatment of Primary Sclerosing Cholangitis

E.1.1.1

Medical condition in easily understood language

Chronic Liver Disease

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10036732
E.1.2	Term	Primary sclerosing cholangitis
E.1.2	System Organ Class	100000004871

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to determine the activity of the anti-human CCL24 monoclonal antibody CM-101, administered over 12 weeks, in male and female adult subjects with primary sclerosing cholangitis, as measured by a decrease in alkaline phosphatase (ALP) levels.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects must meet all inclusion criteria to be eligible for the study:
1. Males and females, Age 18 Years to 75 Years, both inclusive
2. Subjects with diagnosis of large duct PSC (intrahepatic and/or extrahepatic), of more than 6 months duration, based on the EASL 2009 cholestatic guidelines definition (cholestatic liver function tests with consistent magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) showing sclerosing cholangitis, +/- a liver biopsy consistent with PSC once secondary causes of sclerosing cholangitis have been excluded).
Note: Subjects must have cholangiographic changes showing sclerosing cholangitis in order to be eligible for the study.
3. Subjects must have a recent (within 12 months of Day 0) imaging surveillance that is interpreted by the investigator as low risk for cholangiocarcinoma. The minimum imaging requirement is a transabdominal ultrasound however other imaging modalities such as CT or MR are also accepted.
Note: Subjects that do not have such imaging will have a transabdominal ultrasound done as part of the screening procedures.
4. Subjects with serum ALP greater than 1.5 × upper limit of normal (ULN) as determined by the mean of the Screening and Baseline values
5. Subjects receiving Ursodeoxycholic acid (UDCA), must have been stable for ≥3 months prior to, and including, Day 0 and must not have exceeded 20 mg/kg/day during this time.
6. For subjects with concomitant IBD:
a. Colonoscopy or other appropriate endoscopic procedure within 12-18 months of Day 0 confirming no dysplasia or colorectal cancer
b. Subjects with Crohn’s Disease (CD) must be in remission as defined by a Crohn’s Disease Activity Index (CDAI) <150
c. Subjects with ulcerative colitis (UC) must either be in remission or have mild disease. Remission is defined as a partial Mayo score of ≤2 with no individual sub-score exceeding 1. Mild disease is defined as a partial Mayo score ≤3 with no individual sub-score exceeding 1 point.
7. Subjects receiving concomitant medications need to be on stable therapy for > 3 months prior to study Day 0
8. Female subjects of childbearing potential must have a negative serum/urine pregnancy test prior to starting study treatment. Sexually active women of childbearing potential must agree to use an effective method of contraception from the Screening Visit throughout the study period including the 15 weeks post last dose follow-up period.
Effective methods of contraception are considered to be those listed below:
• Barrier method, i.e., (a) condom (male or female) with spermicide or (b) diaphragm with spermicide; or
• Intrauterine device; or
• Vasectomy (partner), or
• Hormonal (e.g., contraceptive pill, patch, intramuscular implant or injection)
• Abstinence, if in line with the preferred and usual lifestyle of the subject [where abstinence is defined as refraining from heterosexual intercourse during the trial duration (from first administration of investigational product until the end of the 15 weeks post last dose follow-up period)]
9. Male subjects, if not vasectomized, must agree to use barrier contraception (condom plus spermicide) during heterosexual intercourse from screening through to study completion and for 60 days from the last dose of study investigational medicinal product.
10. Subjects able to understand and sign a written informed consent form (ICF)

E.4

Principal exclusion criteria

Subjects must not meet any exclusion criteria to be eligible for the study:
1. Subjects with presence of documented secondary sclerosing cholangitis on prior clinical investigations.
2. Subjects with presence of competing etiology of liver disease including, but not limited to, viral hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis etc.
3. Subjects with evidence of autoimmune immunoglobin (Ig) IgG4-associated cholangitis,
4. Subjects with small duct cholangitis in the absence of large duct disease.
5. Subjects with percutaneous biliary drain or bile duct stent
6. Subjects that have undergone prior biliary surgery (laparoscopic or open surgery) other than those who at the time of screening are more than 6 weeks after cholecystectomy without surgical complications
7. Subjects with evidence of cirrhosis, as determined by local transient elastography taken within 6 months of study screening.
8. History of cirrhosis and/or hepatic impairment (Child-Pugh classes A, B and C) and/or hepatic decompensation including ascites, encephalopathy or variceal bleeding
9. Subjects who have undergone or are planned for liver transplantation or current model of end stage liver disease
10. Subjects with Aspartate aminotransferase (AST) and alanine aminotransferase (ALT); above the allowed cut-offs,
11. Subjects with Total Bilirubin > 2 x ULN
12. Subjects with International Normalized Ratio (INR) > 1.3 in the absence of anticoagulants
13. Subjects with serum creatinine >1.4 mg/dL (123 μmol/L) and/or platelet count <50 x 109/L
14. Subjects with history of cholangiocarcinoma or a high suspicion of cholangiocarcinoma, as indicated by clinical judgment, a functional dominant stricture (Bilirubin <2x ULN) or an elevated Ca 19-9 value (>129 U/mL) at screening.
15. Subjects with a prior dominant biliary stricture necessitating biliary intervention should have been stable (Bilirubin <2x ULN) for the previous 6 months without intervention and a low level of clinic suspicion of cholangiocarcinoma.
16. Subjects with active malignancy (within 3 years of diagnosis), other than:
a) adequately treated nonmetastatic basal cell skin cancer;
b) squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to first study treatment; and
17. history of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to first study treatment. Subjects that lost > 10% of their body weight during the 6 months prior to screening
18. Subjects that consume alcohol greater than 21 units/week for males or 14 units/week for females
19. Subjects experiencing cholangitis within last 90 days or ongoing need for prophylactic antibiotics
20. Subjects experiencing flare in colitis activity within 90 days of screening requiring intensification of therapy beyond baseline maintenance treatment
21. Subjects treated with the following medications ≤6 months of study Day 0 and throughout the trial: fenofibrate or other fibrates and potentially hepatotoxic medications
22. Subjects with known chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or that has positive hepatitis B core antibody (anti-HBc) at screening
23. Subjects with evidence of an active infection during the Screening Period
24. Subjects with any identified congenital or acquired immune-deficiency
25. Subjects who went through major surgical procedure within 30 days of screening or prior organ transplantation
26. Subjects which have received a live vaccine within 30 days of planned start of study therapy.
27. Females subjects who are pregnant or breastfeeding
28. Subjects that have participated in an investigational trial of a drug or device either within 60 days of screening or 5 half-life’s of the last dose of investigational drug, where the study drug half-life is greater than 12 days
29. Subjects 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

E.5 End points

E.5.1

Primary end point(s)

The Study primary objective is to determine the activity of the anti-human CCL24 monoclonal antibody CM-101, administered over 12 weeks, in male and female adult subjects with primary sclerosing cholangitis, as measured by a decrease in alkaline phosphatase (ALP) levels.

1. Percent change from baseline through Week 15 in serum alkaline phosphatase

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 15

E.5.2

Secondary end point(s)

To evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodinamic (PD) profiles, ADA development, biochemical response (liver enzyme levels) and a panel of biomarkers to monitor disease progression in PSC.

Incidence and characteristics of adverse events (AEs) occurring following repeated administrations of CM-101
2. Elucidate the Serum PK profile of repeated administrations of CM-101. The following parameters and others will be calculated:
- Maximum CM-101 plasma concentration (Cmax)
- Time to Cmax (tmax)
- Area under the curve (AUC) to the final concentration  limit of quantitation (LOQ), AUC(0-t) and to infinity AUCinf
- Terminal elimination rate constant (λz)
- Terminal elimination half-life (T½)
Additional parameters may be also calculated as deemed necessary
2. Evaluation of the development of anti-drug antibodies (ADA) following repeated administrations of CM-101
3. Percent change from baseline over time in liver enzymes (ALT, AST and GGT)
4. Change from baseline through Week 15 in markers of liver fibrosis- such as ELF™ Blood Test, PRO-C3 and PRO-C5

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 27

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Israel

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1