Clinical Trials Register

Summary
EudraCT Number:	2019-002945-39
Sponsor's Protocol Code Number:	CM-101-PSC-101
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2019-11-14
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

2019-002945-39

A.3

Full title of the trial

A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Clinical Trial Evaluating the Safety and Efficacy of CM-101 in Subjects with Primary Sclerosing Cholangitis

A.3.1

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

A study to look at how well study drug CM-101 works in people with disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts

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-101

A.7

Trial is part of a Paediatric Investigation Plan

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	ChemomAb Ltd
B.4.2	Country	Israel
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	-
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	P.O. 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.3.2	Product code	CM-101
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TBC
D.3.9.2	Current sponsor code	CM-101
D.3.9.3	Other descriptive name	Humanised IgG1 monoclonal antibody against human eotaxin-2
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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	No
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	No
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	Yes
D.3.11.13.1	Other medicinal product type	monoclonal antibody

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

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

To determine the safety, tolerability and activity of the anti-human CCL24 monoclonal antibody CM-101, over 15 weeks, in male and female adult subjects with primary sclerosing cholangitis, as measured by a decrease in alkaline phosphatase (ALP) levels and reduction in ELF score (two primary end-points).

E.2.2

Secondary objectives of the trial

To evaluate the CM-101 pharmacokinetic (PK) and pharmacodynamic (PD) profiles, anti-drug antibodies (ADA) development, biochemical response to treatment (liver enzyme levels) and a panel of biomarkers to monitor disease progression in PSC.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males and females, age 18 to 75 years, both inclusive.

2. Subjects with diagnosis of large duct PSC (intrahepatic and/or extrahepatic), of more than 24 weeks’ duration (defined as cholestatic serum liver tests with consistent magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) showing sclerosing cholangitis once secondary causes of sclerosing cholangitis have been excluded).

3. Subjects that have had no significant clinical concern for cholangiocarcinoma based on clinical, laboratory or imaging findings in the 12 months preceding Randomization.

4. Subjects with serum ALP greater than 1.5 × upper limit of normal (ULN) in both Screening and Baseline blood tests (taken at least 5 days apart).

5. Subjects receiving Ursodeoxycholic Acid (UDCA), must recieve a stable dose for ≥12 weeks prior to, Randomization and must not exceed 23 mg/kg/day during this time.

6. Subjects with concomitant IBD:
a. Subjects with ulcerative colitis (UC) must have undergone colonoscopy with biopsy confirming no dysplasia or colorectal cancer within 18 months of Randomization;
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 point. Mild disease is defined as a Partial Mayo score of ≤3 with no individual sub-score exceeding 1 point.

7. Subjects receiving concomitant medications must be on stable therapy for > 12 weeks prior to Randomization.

8. Female subjects of childbearing potential (defined as sexually mature women who have not undergone surgical sterilization or who have not been naturally post-menopausal for at least 24 consecutive months for women ≤55 years; for women >55 years 12 consecutive months) must have a negative serum 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 18 weeks post last dose. 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 18 weeks post last dose)].

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 90 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

1. Subjects with presence of documented secondary sclerosing cholangitis (such as ischemic cholangitis, recurrent pancreatitis, intraductal stone disease, severe bacterial cholangitis, surgical or blunt abdominal trauma, recurrent pyogenic cholangitis, choledocholithiasis, toxic sclerosing cholangitis due to chemical agents, or any other cause of 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, (Ig) G4-associated cholangitis, primary biliary cholangitis etc.) are excluded from the study. Subjects with possible overlap syndrome with autoimmune hepatitis are excluded if the Investigator considers autoimmune hepatitis as the predominant liver injury.

3. Subjects with small duct PSC in the absence of large duct disease.

4. Subjects with percutaneous biliary drain or bile duct stent or subjects who had required biliary drainage within 12 weeks of screening.

5. 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.

6. Subjects with evidence of cirrhosis, as determined by local transient elastography (TE, preferably FibroscanTM) values of >/= 14.4 kPa obtained during the screening period.

7. History of cirrhosis and/or hepatic impairment (Child-Pugh classes A, B and C), and/or hepatic decompensation including ascites, encephalopathy or variceal bleeding.

8. Subjects who have undergone or are planned for liver transplantation or with current model of end stage liver disease (MELD) score ≥12.

9. Subjects with Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values > 5 x ULN as determined at Screening and/or Randomization blood tests (taken at least 5 days apart).

10. Subjects who show ‘clinically significant changes’ (as judged by the investigator) in liver transaminase levels on repeated measure will be excluded.

11. Subjects with serum Total Bilirubin values > 2 x ULN at Screening and/or at Randomization (taken at least 5 days apart). Subjects who show evidence of ‘clinically significant worsening’ (as judged by the investigator) of bilirubin between screening and Randomization will be excluded.

12. Subjects with known Gilbert's syndrome or a history of elevations in unconjugated (indirect) bilirubin >ULN.

13. Subjects with International Normalized Ratio (INR) >1.3 which does not correct on vitamin k replacement, in the absence of anticoagulants.

14. Subjects with serum creatinine >1.4 mg/dL (123 μmol/L) and/or a platelet count <100 x 109/L

15. Subjects with history of cholangiocarcinoma or a high clinical suspicion of cholangiocarcinoma, as indicated by clinical presentation, laboratory tests or imaging of a functional dominant stricture.

16. Subjects with elevated Ca 19-9 value (>129 U/mL) within 12 months prior to at Screening, unless Ca 19-9 levels have been stable and clinical evaluation & repeated MRI imaging within the same time period has not provided evidence of cholangiocarcinoma.

17. Subjects with a prior biliary stricture necessitating intervention should be stable for ≥24 weeks prior to Randomization without intervention, or episode of cholangitis, and should show a low level of clinical suspicion of cholangiocarcinoma.

18. Subjects with current known portal hypertension with complications, including known gastric or large esophageal varices, poorly controlled or diuretic resistant ascites, history of variceal bleeds, or related therapeutic or prophylactic interventions (e.g., beta blockers, insertion of variceal bands or transjugular intrahepatic portosystemic shunt [TIPS]).

19. Subjects with active malignancy (diagnosed and/or treated within 3 years of Randomization), other than:
a) adequately treated non-metastatic 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 Randomization;
c) history of cervical carcinoma in situ that has been adequately treated and that has not recurred;

20. Subjects with a ‘clinically significant’ (as judged by the Investigator) unexplained weight loss during the 24 weeks prior to Randomization.

E.5 End points

E.5.1

Primary end point(s)

1. Change from baseline through to Week 15 in serum alkaline phosphatase levels by treatment cohort

2. Change from baseline through to Week 15 in Enhanced Liver Fibrosis (ELF) score by treatment cohort

E.5.1.1

Timepoint(s) of evaluation of this end point

1) and 2) from baseline through to Week 15

E.5.2

Secondary end point(s)

1. Analyses of ALP response rates, defined as reduction of ALP to 1.3 x ULN, or a combination of ALP reduction to 1.5-1.3 x ULN with an at least 40% reduction from baseline

2. Percent change from baseline over time in liver enzymes (ALT, AST and GGT)

3. Change from baseline through to Week 15 in liver fibrosis markers - such as PRO-C3 and PRO-C5

4. Evaluation of the incidence and characteristics of treatment emergent adverse events (TEAEs) occurring following repeated administrations of CM-101

5. Elucidation of the Serum PK profile of repeated administrations of CM-101

6. Evaluation of the development of anti-drug antibodies (ADA) following repeated administrations of CM-101

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Refer to schedule of events

2) Change from baseline over time

3) Baseline through to Week 15

4) Duration of study

5) Refer to schedule of events

6) Refer to schedule of events

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in 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

When the last subject is followed for 105 days after the last study drug is administered

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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Standard of care

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-12-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-15

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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