Trial Outcomes & Findings for Study of Aldafermin (NGM282) in Subjects With Compensated Cirrhosis (ALPINE 4) (NCT NCT04210245)

Last Updated: 2025-03-26

Results Overview

Enhanced Liver Fibrosis (ELF) score is a non-invasive blood test derived from the measurement of hyaluronic acid (HA), amino terminal propeptide of type III procollagen (PIIINP), and tissue inhibitor of metalloprotease 1 (TIMP1) using a proprietary algorithm (Siemens). ELF score is a laboratory test, is unitless, and is used as a continuous variable. The minimal ELF score is zero, the maximal ELF score is unknown. The higher the ELF score, the worse the disease outcome. ELF is a score on a scale of severity assessment against biopsy-proven fibrosis. A score of \<7.7 is none to mild, \> 7.7-9.8 is moderate, \> 9.8 is severe.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

160 participants

Primary outcome timeframe

48 weeks

Results posted on

2025-03-26

Participant Flow

Participant milestones

Participant milestones
Measure	Daily 0.3 mg Dose Administered by subcutaneous injection daily for 48 weeks	Daily 1 mg Dose Administered by subcutaneous injection daily for 48 weeks	Daily 3 mg Dose Administered by subcutaneous injection daily for 48 weeks	Placebo Administered by subcutaneous injection daily for 48 weeks
Overall Study STARTED	7	42	55	56
Overall Study COMPLETED	7	37	44	49
Overall Study NOT COMPLETED	0	5	11	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Daily 1 mg Dose Administered by subcutaneous injection daily for 48 weeks	Daily 3 mg Dose Administered by subcutaneous injection daily for 48 weeks	Placebo Administered by subcutaneous injection daily for 48 weeks
Overall Study Adverse Event	3	6	0
Overall Study Withdrawal by Subject	1	4	4
Overall Study Lost to Follow-up	1	1	1
Overall Study 1 due to life stressors and injection site discomfort and 1 subject started prohibited medication	0	0	2

Baseline Characteristics

Study of Aldafermin (NGM282) in Subjects With Compensated Cirrhosis (ALPINE 4)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daily 0.3 mg Dose n=7 Participants Administered by subcutaneous injection daily for 48 weeks	Daily 1 mg Dose n=42 Participants Administered by subcutaneous injection daily for 48 weeks	Daily 3 mg Dose n=55 Participants Administered by subcutaneous injection daily for 48 weeks	Placebo n=56 Participants Administered by subcutaneous injection daily for 48 weeks	Total n=160 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	24 Participants n=7 Participants	37 Participants n=5 Participants	45 Participants n=4 Participants	111 Participants n=21 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	18 Participants n=7 Participants	18 Participants n=5 Participants	11 Participants n=4 Participants	49 Participants n=21 Participants
Age, Continuous	59.7 years STANDARD_DEVIATION 6.78 • n=5 Participants	61.3 years STANDARD_DEVIATION 7.57 • n=7 Participants	59.6 years STANDARD_DEVIATION 8.72 • n=5 Participants	58.3 years STANDARD_DEVIATION 8.11 • n=4 Participants	59.6 years STANDARD_DEVIATION 8.15 • n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	23 Participants n=7 Participants	36 Participants n=5 Participants	39 Participants n=4 Participants	103 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	19 Participants n=7 Participants	19 Participants n=5 Participants	17 Participants n=4 Participants	57 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants	18 Participants n=4 Participants	40 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	33 Participants n=7 Participants	43 Participants n=5 Participants	38 Participants n=4 Participants	118 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	10 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	38 Participants n=7 Participants	47 Participants n=5 Participants	46 Participants n=4 Participants	138 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	7 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Height	164.3 centimeter STANDARD_DEVIATION 11.35 • n=5 Participants	167.5 centimeter STANDARD_DEVIATION 11.23 • n=7 Participants	166.2 centimeter STANDARD_DEVIATION 10.02 • n=5 Participants	163.9 centimeter STANDARD_DEVIATION 8.89 • n=4 Participants	165.7 centimeter STANDARD_DEVIATION 10.05 • n=21 Participants
Weight	88.19 kilogram STANDARD_DEVIATION 9.680 • n=5 Participants	101.47 kilogram STANDARD_DEVIATION 22.240 • n=7 Participants	95.27 kilogram STANDARD_DEVIATION 22.407 • n=5 Participants	93.43 kilogram STANDARD_DEVIATION 19.906 • n=4 Participants	95.95 kilogram STANDARD_DEVIATION 21.255 • n=21 Participants
BMI	32.768 kg/m^2 STANDARD_DEVIATION 3.2236 • n=5 Participants	35.979 kg/m^2 STANDARD_DEVIATION 6.3231 • n=7 Participants	34.265 kg/m^2 STANDARD_DEVIATION 6.7146 • n=5 Participants	34.757 kg/m^2 STANDARD_DEVIATION 7.1164 • n=4 Participants	34.822 kg/m^2 STANDARD_DEVIATION 6.6468 • n=21 Participants

PRIMARY outcome

Timeframe: 48 weeks

Population: Enrollment to the 0.3 mg dose treatment arm was terminated during the study.

Outcome measures

Outcome measures
Measure	Daily 0.3 mg Dose n=7 Participants Administered by subcutaneous injection daily for 48 weeks.	Daily 1 mg Dose n=37 Participants Administered by subcutaneous injection daily for 48 weeks	Daily 3 mg Dose n=44 Participants Administered by subcutaneous injection daily for 48 weeks	Placebo n=49 Participants Administered by subcutaneous injection daily for 48 weeks
Change From Baseline in Enhanced Liver Fibrosis Score at Week 48	-0.071 score on a scale Standard Deviation 0.7214	0.125 score on a scale Standard Deviation 0.6938	-0.213 score on a scale Standard Deviation 0.6145	0.263 score on a scale Standard Deviation 0.5767

Adverse Events

Daily 0.3 mg Dose

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Daily 1 mg Dose

Serious events: 11 serious events

Other events: 40 other events

Deaths: 1 deaths

Daily 3 mg Dose

Serious events: 5 serious events

Other events: 52 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

VP, Clinical Operations

NGM Biopharmaceuticals

Phone: (650) 243-5555

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Daily 0.3 mg Dose n=7 participants at risk Administered by subcutaneous injection daily for 48 weeks	Daily 1 mg Dose n=42 participants at risk Administered by subcutaneous injection daily for 48 weeks	Daily 3 mg Dose n=55 participants at risk Administered by subcutaneous injection daily for 48 weeks	Placebo n=56 participants at risk Administered by subcutaneous injection daily for 48 weeks
Infections and infestations COVID-19	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Cardiac disorders Angina pectoris	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	1.8% 1/56 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)
Hepatobiliary disorders Cholecystitis acute	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/42 • Adverse event data were collected from consenting to the end of study (1 years)	1.8% 1/55 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Injury, poisoning and procedural complications Contusion	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/42 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	1.8% 1/56 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)
Infections and infestations Femur fracture	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Cardiac disorders Cardiac arrest	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Cardiac disorders Cardiac failure acute	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Cardiac disorders Myocardial infarction	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Gastrointestinal disorders Haematemesis	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/42 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	1.8% 1/56 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)
Renal and urinary disorders Acute kidney disorders	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/42 • Adverse event data were collected from consenting to the end of study (1 years)	1.8% 1/55 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Infections and infestations Lower respiratory tract infection	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Infections and infestations Osteomyelitis	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Infections and infestations Pyelonephritis acute	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Infections and infestations Soft tissue infection	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	2.4% 1/42 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/42 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	1.8% 1/56 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/42 • Adverse event data were collected from consenting to the end of study (1 years)	1.8% 1/55 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/42 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/55 • Adverse event data were collected from consenting to the end of study (1 years)	1.8% 1/56 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of head and neck	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/42 • Adverse event data were collected from consenting to the end of study (1 years)	1.8% 1/55 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/42 • Adverse event data were collected from consenting to the end of study (1 years)	1.8% 1/55 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)
Vascular disorders Hypertension	0.00% 0/7 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/42 • Adverse event data were collected from consenting to the end of study (1 years)	1.8% 1/55 • Number of events 1 • Adverse event data were collected from consenting to the end of study (1 years)	0.00% 0/56 • Adverse event data were collected from consenting to the end of study (1 years)