Clinical Trials Register

Summary
EudraCT Number:	2019-000440-10
Sponsor's Protocol Code Number:	CADPT02A12001
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-01-13
Trial results	View 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

Germany - BfArM

A.2

EudraCT number

2019-000440-10

A.3

Full title of the trial

NASH EXploratory Single and COmbination Treatment (NEXSCOT): An open label, multicenter, platform study to evaluate the safety, tolerability, pharmacokinetics and efficacy of various single and combination treatments in patients with non-alcoholic fatty liver disease (NAFLD) who manifest a non-alcoholic steatohepatitis (NASH)-like biomarker phenotype

A.3.1

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

Study of safety, pharmacokinetics (PK), and efficacy of various single and combination treatments in patients with non-alcoholic fatty liver disease (NAFLD) who have characteristics of non-alcoholic steatohepatitis (NASH)

A.3.2

Name or abbreviated title of the trial where available

NEXSCOT

A.4.1

Sponsor's protocol code number

CADPT02A12001

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04147195

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	Novartis Pharma AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma GmbH
B.5.2	Functional name of contact point	Medizinischer Infoservice (MCC)
B.5.3	Address:
B.5.3.1	Street Address	Roonstrasse 25
B.5.3.2	Town/ city	Nürnberg
B.5.3.3	Post code	90429
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49911273-12100
B.5.5	Fax number	+4991127312160
B.5.6	E-mail	infoservice.novartis@novartis.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	LYS006
D.3.2	Product code	LYS006
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not established
D.3.9.2	Current sponsor code	LYS006
D.3.9.3	Other descriptive name	LYS006
D.3.9.4	EV Substance Code	SUB182365
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
D.IMP: 2
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	Tropifexor
D.3.2	Product code	LJN452
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TROPIFEXOR
D.3.9.2	Current sponsor code	LJN452
D.3.9.4	EV Substance Code	SUB190922
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

non-alcoholic fatty liver disease (NAFLD)

E.1.1.1

Medical condition in easily understood language

Liver disease

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	24.1
E.1.2	Level	PT
E.1.2	Classification code	10053219
E.1.2	Term	Non-alcoholic steatohepatitis
E.1.2	System Organ Class	10019805 - Hepatobiliary disorders

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 and tolerability of single or combination therapy during 12 weeks of treatment by monitoring safety endpoints (including vital signs, physical examination, laboratory measurements, electrocardiogram [ECG]) and adverse events.

E.2.2

Secondary objectives of the trial

Objectives 1-4: To determine the effect of twelve weeks of single or combination therapy on
1: Circulating markers of ongoing liver fibrosis as measured by the Enhanced Liver Fibrosis (ELF) Test
2: Intrahepatic lipid content (percent liver fat) by measuring Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)
3: Cardiometabolic risk parameters by measuring body weight, waist and hip circumference, waist-to-hip ratio, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), hemoglobin A1C (HbA1c), fasting glucose, fasting insulin, and fasting lipid profile
4: Circulating markers of liver and/or systemic inflammation by measuring liver function tests (ALT) and high-sensitivity C-reactive Protein (hsCRP)
And
Objective 5: To evaluate the PK of each individual agent when administered as a single or combination therapy by collecting and analyzing blood samples to obtain plasma concentrations over 12 weeks of treatment.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

In line with the CTFG Recommendation paper (2019), Cohort 1 of the study can be defined as a sub-study. Further cohorts (sub-studies) will be added to the protocol via a protocol amendment and will be submitted to Health Authorities as substantial amendment applications. There is no specific title, date, version or objectives for Cohort 1, as all the cohorts will be conducted under the same protocol and will have the same objectives. Cohort 1 includes two arms: LYS006 treatment arm and LYS006 and tropifexor combination treatment arm.

E.3

Principal inclusion criteria

•Phenotypic diagnosis of NASH based on the presence of all of the
following:
•ALT ≥ 43 IU/L (males) or ≥ 28 IU/L (females) at screening
•BMI ≥ 27 kg/m2 (in participants with a self-identified race other than
Asian) or ≥ 23 kg/m2 (in participants with a self-identified Asian race)
•History of Type 2 diabetes mellitus with HbA1c ≤ 9% at baseline
•ELF Test score ≥ 8.5 and ≤ 10.5 at either screening or baseline
•Liver fat ≥ 8%
•Participants must weigh at least 40 kg (88 lbs.) and no more than 150
kg (330 lbs.)

E.4

Principal exclusion criteria

•Use of other investigational drugs within 5 half-lives of randomization, or within 3 months, whichever is longer
•Use of obeticholic acid (OCA) or pharmacologically-active weight loss drugs within 1 month of randomization.
•Use of strong CYP3A4/5 inhibitors or strong CYP3A4 inducers within 5 half-lives or 7 days of randomization, whichever is longer.
•History or presence of other concomitant liver diseases
•History or current diagnosis of ECG abnormalities
•Patients with contraindications to MRI imaging
•Current or history of significant alcohol consumption
•Clinical evidence of hepatic decompensation or severe liver impairment
•Women of child bearing potential (unless on highly effective methods of contraception)
•Presence of liver cirrhosis
•For cohort 1, use of OAT3 inhibitors or BRCP inhibitors within 5 half-lives or 7 days of randomization, whichever is longer

E.5 End points

E.5.1

Primary end point(s)

Safety endpoints (including vital signs, physical examination, laboratory measurements, ECG); Adverse events

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 21 weeks after first dose

E.5.2

Secondary end point(s)

Enhanced Liver Fibrosis (ELF) Test
Percent (%) liver fat as measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)
Body weight, waist and hip circumferences, waist-to-hip ratio,
Homeostasis Model Assessment of Insulin Resistance (HOMA-IR),
hemoglobin A1c (HbA1c), fasting glucose, fasting insulin, fasting lipid
profile
Liver function tests (ALT), high-sensitivity C-reactive Protein (hsCRP)
Plasma concentrations

E.5.2.1

Timepoint(s) of evaluation of this end point

Up to 21 weeks after first dose

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

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability and biomarker efficacy

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

Yes

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

Yes

E.8.2.3.1

Comparator description

Platform study

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

Argentina

Germany

United States

E.8.7

Trial has a data monitoring committee

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.1.1.1

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:

200

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

250

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)

None

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

2020-02-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-02-20

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-01-06

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