Flag of the European Union

EU Clinical Trials Register

Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:

interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC

clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
Clinical Trials Information System (CTIS).

The EU Clinical Trials Register currently displays 43881 clinical trials with a EudraCT protocol, of which 7295 are clinical trials conducted with subjects less than 18 years old. The register also displays information on 18700 older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).

Examples: Cancer AND drug name. Pneumonia AND sponsor name.
How to search [pdf]

Advanced Search:

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

< Back to search results

Clinical Trial Results:
Evaluation of Efficacy, Safety and Tolerability of NGM282 (Aldafermin) in a Phase 2b, Randomized, Double-blind, Placebo-controlled, Multi-center Study in Subjects with Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (ALPINE 4)

Summary
EudraCT number	2019-002341-38
Trial protocol	GB DE FR BE PL
Global end of trial date	23 Feb 2023

Results information
Results version number	v1(current)
This version publication date	20 Mar 2024
First version publication date	20 Mar 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

282-CC-207

ISRCTN number

-

US NCT number

NCT04210245

WHO universal trial number (UTN)

-

Sponsor organisation name

NGM Biopharmaceuticals, Inc.

Sponsor organisation address

333 Oyster Point Boulevard, San Francisco, United States, CA 94080

Public contact

NGM Study Director, NGM Biopharmaceuticals, Inc., ngm282@ngmbio.com

Scientific contact

NGM Study Director, NGM Biopharmaceuticals, Inc., ngm282@ngmbio.com

Is trial part of an agreed paediatric investigation plan (PIP)

No

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Analysis stage

Final

Date of interim/final analysis

13 Sep 2023

Is this the analysis of the primary completion data?

Yes

Primary completion date

23 Feb 2023

Global end of trial reached?

Yes

Global end of trial date

23 Feb 2023

Was the trial ended prematurely?

No

Main objective of the trial

The primary objective of this study is to evaluate the efficacy and safety of aldafermin compared to placebo.

Protection of trial subjects

This study was conducted in accordance with the protocol and with the following: 1. Ethical principles for medical subjects involving human subjects derived from the Declaration of Helsinki. 2. Applicable ICH Good Clinical Practice Guidelines. 3. Applicable laws and regulations.

Background therapy

Not Applicable.

Evidence for comparator

Not Applicable.

Actual start date of recruitment

23 Dec 2019

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 121

Country: Number of subjects enrolled

Hong Kong: 5

Country: Number of subjects enrolled

Australia: 18

Country: Number of subjects enrolled

Poland: 2

Country: Number of subjects enrolled

United Kingdom: 3

Country: Number of subjects enrolled

Belgium: 1

Country: Number of subjects enrolled

France: 6

Country: Number of subjects enrolled

Germany: 4

Worldwide total number of subjects

160

EEA total number of subjects

13

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

111

From 65 to 84 years

49

85 years and over

0

Subject disposition

Top of page

Recruitment details

The study was conducted at 81 sites in the US (including Puerto Rico), Australia, Hong Kong, and Europe (including Belgium, France, Germany, Poland, Spain (screened the subjects, none enrolled), and the United Kingdom).

Screening details

In total 580 subjects were screened of which 420 patients failed (367 failed randomization criteria, 22 withdrew, 3 due to adverse events, 2 lost to follow-up, 2 due to Physician decision and 24 patients for other reasons). Total 160 patients were randomized. Note: A subject could have more than one screen-failure reason.

Period 1 title

Overall Study (Overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

-

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Placebo matched to aldafermin will be administered as per the schedule specified in the arm.

Aldafermin 0.3 mg

Arm description

-

Arm type

Experimental

Investigational medicinal product name

Aldafermin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Solution for injection

Dosage and administration details

Doses of 0.3 mg. For Sub-Cutaneous administration daily for 48 weeks.

Aldafermin 1 mg

Arm description

-

Arm type

Experimental

Investigational medicinal product name

Aldafermin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Solution for injection

Dosage and administration details

Doses of 1 mg. For Sub-Cutaneous administration daily for 48 weeks.

Aldafermin 3 mg

Arm description

-

Arm type

Experimental

Investigational medicinal product name

Aldafermin

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled syringe

Routes of administration

Solution for injection

Dosage and administration details

Doses of 3 mg. For Sub-Cutaneous administration daily for 48 weeks.

Number of subjects in period 1	Placebo	Aldafermin 0.3 mg	Aldafermin 1 mg	Aldafermin 3 mg
Started	56	7	42	55
Completed	49	7	37	44
Not completed	7	0	5	11
Consent withdrawn by subject	4	-	1	4
Adverse event, non-fatal	-	-	3	6
Other	2	-	-	-
Lost to follow-up	1	-	1	1

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

-

Reporting group title

Aldafermin 0.3 mg

Reporting group description

-

Reporting group title

Aldafermin 1 mg

Reporting group description

-

Reporting group title

Aldafermin 3 mg

Reporting group description

-

Reporting group values	Placebo	Aldafermin 0.3 mg	Aldafermin 1 mg	Aldafermin 3 mg	Total
Number of subjects	56	7	42	55	160
Age categorical
Units: Subjects
In utero	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0
Adults (18-64 years)	45	5	24	37	111
From 65-84 years	11	2	18	18	49
85 years and over	0	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	58.3 ± 8.11	59.7 ± 6.78	61.3 ± 7.57	59.6 ± 8.72	-
Gender categorical
Units: Subjects
Female	39	5	23	36	103
Male	17	2	19	19	57

Subject analysis set title

Safety Population

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects who received at least 1 dose (full or partial) of study drug were included in the Safety Analysis Set. All safety endpoints are summarized using the Safety Analysis Set and were based on the actual treatment received if it differed from the randomized treatment.

Subject analysis sets values	Safety Population
Number of subjects	160
Age categorical
Units: Subjects
In utero	0
Preterm newborn infants (gestational age < 37 wks)	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	111
From 65-84 years	49
85 years and over	0
Age continuous
Units: years
arithmetic mean (standard deviation)	59.6 ± 8.15
Gender categorical
Units: Subjects
Female	103
Male	57

End points

Top of page

Reporting group title

Placebo

Reporting group description

-

Reporting group title

Aldafermin 0.3 mg

Reporting group description

-

Reporting group title

Aldafermin 1 mg

Reporting group description

-

Reporting group title

Aldafermin 3 mg

Reporting group description

-

Subject analysis set title

Safety Population

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects who received at least 1 dose (full or partial) of study drug were included in the Safety Analysis Set. All safety endpoints are summarized using the Safety Analysis Set and were based on the actual treatment received if it differed from the randomized treatment.

Primary: The Change from Baseline in ELF at Week 48

Top of page

End point title

The Change from Baseline in ELF at Week 48 ^[1]

End point description

p-values were not reported for the Aldafermin 0.3 mg group versus placebo because the Aldafermin 0.3 mg treatment group was terminated during the study.

End point type

Primary

End point timeframe

Week 48

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The 0.3 mg Aldafermin was reported for safety and not for efficacy, since the 0.3 mg Aldafermin arm was discontinued and all the patients was merged with 1 mg Aldafermin.

End point values	Placebo	Aldafermin 1 mg	Aldafermin 3 mg
Number of subjects analysed	49	37	44
Units: ELF Score
arithmetic mean (standard deviation)	0.263 ± 0.5767	0.125 ± 0.6938	-0.213 ± 0.6145

Least Squares (LS) Placebo vs Aldafermin 1 mg

Comparison groups

Placebo v Aldafermin 1 mg

Number of subjects included in analysis

86

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3112

Method

t-test, 2-sided

Parameter type

Mean difference (final values)

Point estimate

-0.137

Confidence interval

level

95%

sides

2-sided

lower limit

-0.403

upper limit

0.129

Variability estimate

Standard error of the mean

Dispersion value

0.1347

Least Squares (LS) Placebo vs Aldafermin 3 mg

Comparison groups

Placebo v Aldafermin 3 mg

Number of subjects included in analysis

93

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0003

Method

t-test, 2-sided

Parameter type

Mean difference (final values)

Point estimate

-0.473

Confidence interval

level

95%

sides

2-sided

lower limit

-0.726

upper limit

-0.22

Variability estimate

Standard error of the mean

Dispersion value

0.128

Primary: Safety assessed by reported and observed adverse events

Top of page

End point title

Safety assessed by reported and observed adverse events ^[2]

End point description

End point type

Primary

End point timeframe

48 weeks

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was performed for this endpoint. The information has been introduced in the section "Adverse Events".

End point values	Safety Population
Number of subjects analysed	160
Units: number of adverse events	160

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Adverse event monitoring starts from the time the patient consents to the study until they complete the trial i.e., the screening period, the double-blind treatment period of 48 weeks, and the safety follow-up period of 6-10 weeks.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Placebo

Reporting group description

-

Reporting group title

Aldafermin 0.3 mg

Reporting group description

-

Reporting group title

Aldafermin 1 mg

Reporting group description

-

Reporting group title

Aldafermin 3 mg

Reporting group description

-

Serious adverse events	Placebo	Aldafermin 0.3 mg	Aldafermin 1 mg	Aldafermin 3 mg
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	11 / 42 (26.19%)	5 / 55 (9.09%)
number of deaths (all causes)	0	0	1	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	0 / 42 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rectal cancer
subjects affected / exposed	1 / 56 (1.79%)	0 / 7 (0.00%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of head and neck
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	0 / 42 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	0 / 42 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 56 (1.79%)	0 / 7 (0.00%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	0 / 42 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Angina pectoris
subjects affected / exposed	1 / 56 (1.79%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arteriosclerosis coronary artery
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Cardiac failure acute
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Haematemesis
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	0 / 42 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 56 (1.79%)	0 / 7 (0.00%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	0 / 42 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
COVID-19
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Soft tissue infection
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	1 / 56 (1.79%)	0 / 7 (0.00%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	Aldafermin 0.3 mg	Aldafermin 1 mg	Aldafermin 3 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	49 / 56 (87.50%)	5 / 7 (71.43%)	40 / 42 (95.24%)	52 / 55 (94.55%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	1	0	1
Vascular disorders
Haematoma
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	1	0	1
Hypertension
subjects affected / exposed	2 / 56 (3.57%)	1 / 7 (14.29%)	0 / 42 (0.00%)	4 / 55 (7.27%)
occurrences all number	2	1	0	4
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0
Fatigue
subjects affected / exposed	5 / 56 (8.93%)	0 / 7 (0.00%)	6 / 42 (14.29%)	7 / 55 (12.73%)
occurrences all number	5	0	6	7
Injection site bruising
subjects affected / exposed	6 / 56 (10.71%)	1 / 7 (14.29%)	1 / 42 (2.38%)	4 / 55 (7.27%)
occurrences all number	6	1	1	4
Injection site pain
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	2 / 42 (4.76%)	3 / 55 (5.45%)
occurrences all number	3	0	2	3
Oedema peripheral
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	2 / 42 (4.76%)	1 / 55 (1.82%)
occurrences all number	3	0	2	1
Pyrexia
subjects affected / exposed	2 / 56 (3.57%)	0 / 7 (0.00%)	4 / 42 (9.52%)	0 / 55 (0.00%)
occurrences all number	2	0	4	0
Injection site erythema
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	5 / 55 (9.09%)
occurrences all number	0	0	1	5
Injection site pruritus
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	3 / 55 (5.45%)
occurrences all number	0	0	1	3
Immune system disorders
Reaction to food additive
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	4 / 56 (7.14%)	1 / 7 (14.29%)	5 / 42 (11.90%)	2 / 55 (3.64%)
occurrences all number	4	1	5	2
Oropharyngeal pain
subjects affected / exposed	2 / 56 (3.57%)	0 / 7 (0.00%)	3 / 42 (7.14%)	0 / 55 (0.00%)
occurrences all number	2	0	3	0
Investigations
Blood calcium increased
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0
White blood cell count increased
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	0 / 42 (0.00%)	3 / 55 (5.45%)
occurrences all number	0	0	0	3
Fall
subjects affected / exposed	1 / 56 (1.79%)	0 / 7 (0.00%)	3 / 42 (7.14%)	2 / 55 (3.64%)
occurrences all number	1	0	3	2
Procedural pain
subjects affected / exposed	6 / 56 (10.71%)	0 / 7 (0.00%)	2 / 42 (4.76%)	4 / 55 (7.27%)
occurrences all number	6	0	2	4
Skin laceration
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0
Cardiac disorders
Tachycardia
subjects affected / exposed	1 / 56 (1.79%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	1	0	0
Nervous system disorders
Dizziness
subjects affected / exposed	4 / 56 (7.14%)	0 / 7 (0.00%)	2 / 42 (4.76%)	3 / 55 (5.45%)
occurrences all number	4	0	2	3
Headache
subjects affected / exposed	5 / 56 (8.93%)	0 / 7 (0.00%)	4 / 42 (9.52%)	8 / 55 (14.55%)
occurrences all number	5	0	4	8
Loss of consciousness
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0
Memory impairment
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	0 / 42 (0.00%)	1 / 55 (1.82%)
occurrences all number	3	0	0	1
Neuralgia
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	3	0	0	0
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	1 / 56 (1.79%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	1	0	0
Abdominal distension
subjects affected / exposed	5 / 56 (8.93%)	1 / 7 (14.29%)	3 / 42 (7.14%)	6 / 55 (10.91%)
occurrences all number	5	1	3	6
Abdominal pain
subjects affected / exposed	5 / 56 (8.93%)	0 / 7 (0.00%)	2 / 42 (4.76%)	6 / 55 (10.91%)
occurrences all number	5	0	2	6
Abdominal pain lower
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	0 / 42 (0.00%)	2 / 55 (3.64%)
occurrences all number	3	0	0	2
Abdominal pain upper
subjects affected / exposed	10 / 56 (17.86%)	0 / 7 (0.00%)	3 / 42 (7.14%)	7 / 55 (12.73%)
occurrences all number	10	0	3	7
Constipation
subjects affected / exposed	7 / 56 (12.50%)	1 / 7 (14.29%)	5 / 42 (11.90%)	8 / 55 (14.55%)
occurrences all number	7	1	5	8
Diarrhoea
subjects affected / exposed	10 / 56 (17.86%)	1 / 7 (14.29%)	11 / 42 (26.19%)	22 / 55 (40.00%)
occurrences all number	10	1	11	22
Diverticulum
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	1	0	1
Dry mouth
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	3	0	0	0
Faeces discoloured
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	2 / 42 (4.76%)	3 / 55 (5.45%)
occurrences all number	0	0	2	3
Frequent bowel movements
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	4 / 42 (9.52%)	3 / 55 (5.45%)
occurrences all number	0	0	4	3
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 56 (1.79%)	0 / 7 (0.00%)	3 / 42 (7.14%)	2 / 55 (3.64%)
occurrences all number	1	0	3	2
Nausea
subjects affected / exposed	5 / 56 (8.93%)	2 / 7 (28.57%)	12 / 42 (28.57%)	18 / 55 (32.73%)
occurrences all number	5	2	12	18
Varices oesophageal
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0
Vomiting
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	2 / 42 (4.76%)	5 / 55 (9.09%)
occurrences all number	3	0	2	5
Hepatobiliary disorders
Portal hypertension
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0
Skin and subcutaneous tissue disorders
Dry skin
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0
Photosensitivity reaction
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0
Pruritus
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	1 / 42 (2.38%)	6 / 55 (10.91%)
occurrences all number	3	0	1	6
Rash
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	2 / 42 (4.76%)	5 / 55 (9.09%)
occurrences all number	3	0	2	5
Renal and urinary disorders
Dysuria
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	0 / 42 (0.00%)	1 / 55 (1.82%)
occurrences all number	3	0	0	1
Nephrolithiasis
subjects affected / exposed	2 / 56 (3.57%)	1 / 7 (14.29%)	3 / 42 (7.14%)	1 / 55 (1.82%)
occurrences all number	2	1	3	1
Proteinuria
subjects affected / exposed	1 / 56 (1.79%)	0 / 7 (0.00%)	0 / 42 (0.00%)	4 / 55 (7.27%)
occurrences all number	1	0	0	4
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	6 / 56 (10.71%)	0 / 7 (0.00%)	5 / 42 (11.90%)	7 / 55 (12.73%)
occurrences all number	6	0	5	7
Back pain
subjects affected / exposed	4 / 56 (7.14%)	1 / 7 (14.29%)	2 / 42 (4.76%)	2 / 55 (3.64%)
occurrences all number	4	1	2	2
Flank pain
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences all number	3	0	1	0
Muscle spasms
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	1 / 42 (2.38%)	2 / 55 (3.64%)
occurrences all number	3	0	1	2
Muscular weakness
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	0 / 42 (0.00%)	3 / 55 (5.45%)
occurrences all number	0	0	0	3
Musculoskeletal pain
subjects affected / exposed	4 / 56 (7.14%)	1 / 7 (14.29%)	0 / 42 (0.00%)	2 / 55 (3.64%)
occurrences all number	4	1	0	2
Neck pain
subjects affected / exposed	1 / 56 (1.79%)	1 / 7 (14.29%)	0 / 42 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	1	0	1
Osteoarthritis
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0
Pain in extremity
subjects affected / exposed	1 / 56 (1.79%)	0 / 7 (0.00%)	2 / 42 (4.76%)	3 / 55 (5.45%)
occurrences all number	1	0	2	3
Infections and infestations
COVID-19
subjects affected / exposed	17 / 56 (30.36%)	1 / 7 (14.29%)	13 / 42 (30.95%)	13 / 55 (23.64%)
occurrences all number	17	1	13	13
Lower respiratory tract infection
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0
Nasopharyngitis
subjects affected / exposed	5 / 56 (8.93%)	0 / 7 (0.00%)	2 / 42 (4.76%)	2 / 55 (3.64%)
occurrences all number	5	0	2	2
Sinusitis
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	2 / 42 (4.76%)	3 / 55 (5.45%)
occurrences all number	3	0	2	3
Skin bacterial infection
subjects affected / exposed	0 / 56 (0.00%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0
Upper respiratory tract infection
subjects affected / exposed	1 / 56 (1.79%)	1 / 7 (14.29%)	1 / 42 (2.38%)	2 / 55 (3.64%)
occurrences all number	1	1	1	2
Urinary tract infection
subjects affected / exposed	9 / 56 (16.07%)	2 / 7 (28.57%)	4 / 42 (9.52%)	4 / 55 (7.27%)
occurrences all number	9	2	4	4
Vulvovaginal candidiasis
subjects affected / exposed	1 / 56 (1.79%)	1 / 7 (14.29%)	0 / 42 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	1	0	0
Cellulitis
subjects affected / exposed	1 / 56 (1.79%)	1 / 7 (14.29%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences all number	1	1	1	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	3 / 56 (5.36%)	0 / 7 (0.00%)	1 / 42 (2.38%)	2 / 55 (3.64%)
occurrences all number	3	0	1	2
Diabetes mellitus
subjects affected / exposed	3 / 56 (5.36%)	1 / 7 (14.29%)	1 / 42 (2.38%)	1 / 55 (1.82%)
occurrences all number	3	1	1	1
Hypoglycaemia
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	1 / 42 (2.38%)	3 / 55 (5.45%)
occurrences all number	0	0	1	3
Increased appetite
subjects affected / exposed	0 / 56 (0.00%)	0 / 7 (0.00%)	2 / 42 (4.76%)	8 / 55 (14.55%)
occurrences all number	0	0	2	8
Type 2 diabetes mellitus
subjects affected / exposed	2 / 56 (3.57%)	0 / 7 (0.00%)	3 / 42 (7.14%)	0 / 55 (0.00%)
occurrences all number	2	0	3	0
Vitamin D deficiency
subjects affected / exposed	2 / 56 (3.57%)	1 / 7 (14.29%)	1 / 42 (2.38%)	0 / 55 (0.00%)
occurrences all number	2	1	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

28 Oct 2019

The changes implemented with this amendment are: - to provide clarifications and details on how liver biopsy will be performed; - to clarify when statin use will commence for participating subjects.

29 Jan 2020

The changes implemented with this amendment are: - to primarily provide clarifications on lipid lowering algorithm; - to correct description of how subjects will be provided rosuvastatin upon LDL-C testing, i.e., appropriate doses will be shipped to subjects via a courier service instead of being picked up by the subjects on the study visit; - to correct description of how independent adjudication for adverse events of interest will be conducted; - to adjust certain criteria for selection of subjects.

24 Sep 2020

The changes implemented with this amendment are: - to update the NASH cirrhosis diagnosis based on recent guidelines; - to refine the population with respect to platelet count; - to include updates included in country-specific protocol amendments based on health authority feedback.

16 Mar 2021

The changes implemented with this amendment are: - to discontinue randomization of subjects to the aldafermin 0.3 mg dose level; - remove the total liver fat content requirement as measured by MRI-PDFF; - clarify inclusion criterion #4; - move FibroScan® from Day -42 to Day -56; - update exclusion #10 from total bilirubin within ULN to ≤1.3 mg/dL; - update EGD requirements to include application of the Baveno VI criteria (to no more than 30% of the remaining population); - allow non-statin lipid lowering agents until Day 1 of Screening (rather than 3 months); - allowed an increased screening window with Medical Monitor approval.

11 Nov 2021

The changes implemented with this amendment are: - to change the primary efficacy endpoint from histologic response in NASH CRN fibrosis score to change in ELF score based on recent literature supporting correlation of ELF with clinical outcomes and consistent with FDA Guidance on NASH with compensated cirrhosis (FDA 2019); - to clarify eligibility criteria; - to update statistical methods to account for the change in primary efficacy endpoint; - to make editorial and typographical changes.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

For support, Contact us.

The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

European Medicines Agency © 1995-Sat May 18 06:19:20 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands