Primary Sclerosing Cholangitis
Conditions
Brief summary
The purpose of this study is to determine the safety, tolerability, and activity of NGM282 in patients with Primary Sclerosing Cholangitis.
Interventions
BIOLOGICALNGM282
OTHERPlacebo
Sponsors
NGM Biopharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of PSC
Exclusion criteria
* Clinically significant acute or chronic liver disease of an etiology other than PSC * Secondary or IgG4 related sclerosing cholangitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in alkaline phosphatase levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Rate of Change in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess rate of change in alkaline phosphatase levels. Serum levels of alkaline phosphatase was measured in a central laboratory using standard enzymatic method. The unit of measure is U/L. |
| Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in aspartate aminotransferase and alanine aminotransferase levels. |
| Mean Percent Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in aspartate aminotransferase and alanine aminotransferase levels. |
| Mean Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in bilirubin (direct and total) levels. |
| Mean Percent Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in bilirubin (direct and total) levels. |
| Mean Change From Baseline in Gamma Glutamyl Transferase in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in gamma glutamyl transferase levels. |
| Mean Percent Change From Baseline in Gamma Glutamyl Transferase in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in gamma glutamyl transferase levels. |
| Mean Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in cholesterol levels. |
| Mean Percent Change From Baseline in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in alkaline phosphatase levels. |
| Mean Change From Baseline in 25-Hydroxyvitamin D in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in 25-Hydroxyvitamin D levels. |
| Mean Percent Change From Baseline in 25-Hydroxyvitamin D in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in 25-Hydroxyvitamin D levels. |
| Mean Change From Baseline in Prothrombin International Normalized Ratio in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in Prothrombin levels. |
| Mean Percent Change From Baseline in Prothrombin International Normalized Ratio in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in Prothrombin levels. |
| Mean Change From Baseline in Calprotectin in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in Calprotectin levels. |
| Mean Change From Baseline in Enhanced Liver Fibrosis Score in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | 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. |
| Severity of Inflammatory Bowel Disease-Associated Intestinal Symptoms in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Severity of inflammatory bowel disease (IBD)-associated symptoms and acute cholangitis are summarized with number and percentage. The partial Mayo IBD scale assesses stool frequency, rectal bleeding, and there is a Physician's global assessment. Each section is summed and remission is defined as a total score of 0-1, mild disease 2-4, moderate disease 5-6, and severe disease 7-9. Higher total scores indicate more severe disease. The number of participants are being presented based on the severity of their IBD symptoms. |
| Mean Percent Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Baseline to Week 12 | Blood samples were collected to assess changes in cholesterol levels. |
Countries
France, Netherlands, United Kingdom, United States
Participant flow
Recruitment details
A total of 62 participants who met all inclusion criteria and no exclusion criteria were randomized to receive treatment over a 12-week treatment period at 24 clinic sites in the United States, 5 sites in the United Kingdom, 5 sites in the Netherlands, and 1 site in France.
Participants by arm
| Arm | Count |
|---|---|
| NGM282 1.0 mg Participants who were randomized to NGM282 1.0 mg self-administered NGM282 as an subcutaneous (SC) injection to the abdomen daily, at approximately the same time each morning, over the 12-week treatment period. | 21 |
| NGM282 3.0 mg Participants who were randomized to NGM282 3.0 mg self-administered NGM282 as an subcutaneous (SC) injection to the abdomen daily, at approximately the same time each morning, over the 12-week treatment period. | 21 |
| Placebo Participants who were randomized to placebo self-administered placebo as an subcutaneous (SC) injection to the abdomen daily, at approximately the same time each morning, over the 12-week treatment period. | 20 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 |
| Overall Study | Noncompliance with study drug | 1 | 1 | 0 |
| Overall Study | Other | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | NGM282 1.0 mg | NGM282 3.0 mg |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 1 Participants | 5 Participants | 4 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 56 Participants | 17 Participants | 20 Participants |
| Age, Continuous | 43.4 years STANDARD_DEVIATION 12.4 | 43.2 years STANDARD_DEVIATION 13.8 | 46.0 years STANDARD_DEVIATION 15.9 | 40.2 years STANDARD_DEVIATION 13 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 7 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 16 Participants | 52 Participants | 18 Participants | 18 Participants |
| Sex: Female, Male Female | 8 Participants | 24 Participants | 7 Participants | 9 Participants |
| Sex: Female, Male Male | 12 Participants | 38 Participants | 14 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 21 | 0 / 20 |
| other Total, other adverse events | 17 / 21 | 20 / 21 | 18 / 20 |
| serious Total, serious adverse events | 1 / 21 | 2 / 21 | 0 / 20 |
Outcome results
Primary
Mean Change From Baseline in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in alkaline phosphatase levels.
Time frame: Baseline to Week 12
Population: Mean change from baseline in ALP was assessed in participants with available data in the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NGM282 1.0 mg | Mean Change From Baseline in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis | 25.6 International units/Liter | Standard Error 100.3 |
| NGM282 3.0 mg | Mean Change From Baseline in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis | -9.8 International units/Liter | Standard Error 101.3 |
| Placebo | Mean Change From Baseline in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis | -0.6 International units/Liter | Standard Error 79.5 |
p-value: 0.43495% CI: [-68, 28]Wilcoxon (Mann-Whitney)
p-value: 0.64695% CI: [-41, 71]Wilcoxon (Mann-Whitney)
Secondary
Mean Change From Baseline in 25-Hydroxyvitamin D in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in 25-Hydroxyvitamin D levels.
Time frame: Baseline to Week 12
Population: Mean change from baseline in 25-Hydroxyvitamin D was assessed in the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NGM282 1.0 mg | Mean Change From Baseline in 25-Hydroxyvitamin D in Patients With Primary Sclerosing Cholangitis | 6.4 nmol/Liter | Standard Error 33.9 |
| NGM282 3.0 mg | Mean Change From Baseline in 25-Hydroxyvitamin D in Patients With Primary Sclerosing Cholangitis | 1.1 nmol/Liter | Standard Error 30.6 |
| Placebo | Mean Change From Baseline in 25-Hydroxyvitamin D in Patients With Primary Sclerosing Cholangitis | 0.7 nmol/Liter | Standard Error 21.7 |
Secondary
Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in aspartate aminotransferase and alanine aminotransferase levels.
Time frame: Baseline to Week 12
Population: Mean changes from baseline in aspartate aminotransferase and alanine aminotransferase were assessed in participants with available data in the Full Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NGM282 1.0 mg | Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis | Aspartate aminotransferase | -0.2 units/liter | Standard Error 7 |
| NGM282 1.0 mg | Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis | Alanine aminotransferase | 8.5 units/liter | Standard Error 10.2 |
| NGM282 3.0 mg | Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis | Aspartate aminotransferase | -30.9 units/liter | Standard Error 7 |
| NGM282 3.0 mg | Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis | Alanine aminotransferase | -45.1 units/liter | Standard Error 10.4 |
| Placebo | Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis | Aspartate aminotransferase | -13.3 units/liter | Standard Error 7.1 |
| Placebo | Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis | Alanine aminotransferase | -12.1 units/liter | Standard Error 10.5 |
Secondary
Mean Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in bilirubin (direct and total) levels.
Time frame: Baseline to Week 12
Population: Mean change from baseline in bilirubin (total and direct) was assessed in participants with available data in the Full Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NGM282 1.0 mg | Mean Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis | Direct bilirubin | 9.14 micromole/liter | Standard Error 5.19 |
| NGM282 1.0 mg | Mean Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis | Total bilirubin | 9.78 micromole/liter | Standard Error 5.88 |
| NGM282 3.0 mg | Mean Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis | Direct bilirubin | 0.54 micromole/liter | Standard Error 5.3 |
| NGM282 3.0 mg | Mean Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis | Total bilirubin | 0.04 micromole/liter | Standard Error 6.01 |
| Placebo | Mean Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis | Direct bilirubin | 0.55 micromole/liter | Standard Error 5.2 |
| Placebo | Mean Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis | Total bilirubin | 0.83 micromole/liter | Standard Error 6.02 |
Secondary
Mean Change From Baseline in Calprotectin in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in Calprotectin levels.
Time frame: Baseline to Week 12
Population: Mean change from baseline in Calprotectin was assessed in participants with available data in the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NGM282 1.0 mg | Mean Change From Baseline in Calprotectin in Patients With Primary Sclerosing Cholangitis | 353.4 microgram/gram | Standard Deviation 839.8 |
| NGM282 3.0 mg | Mean Change From Baseline in Calprotectin in Patients With Primary Sclerosing Cholangitis | 211.8 microgram/gram | Standard Deviation 585.8 |
| Placebo | Mean Change From Baseline in Calprotectin in Patients With Primary Sclerosing Cholangitis | -10.3 microgram/gram | Standard Deviation 457.9 |
Secondary
Mean Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in cholesterol levels.
Time frame: Baseline to Week 12
Population: Mean change from baseline in cholesterol levels were assessed in participants with available data in the Full Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NGM282 1.0 mg | Mean Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Total cholesterol | 0.14 millimole/liter | Standard Deviation 1.01 |
| NGM282 1.0 mg | Mean Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | High-density lipoprotein | 0.04 millimole/liter | Standard Deviation 0.46 |
| NGM282 1.0 mg | Mean Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Low-density lipoprotein | 0.07 millimole/liter | Standard Deviation 0.85 |
| NGM282 1.0 mg | Mean Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Triglycerides | 0.01 millimole/liter | Standard Deviation 0.59 |
| NGM282 3.0 mg | Mean Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Triglycerides | -0.08 millimole/liter | Standard Deviation 0.37 |
| NGM282 3.0 mg | Mean Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Total cholesterol | 0.26 millimole/liter | Standard Deviation 1.1 |
| NGM282 3.0 mg | Mean Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Low-density lipoprotein | 0.30 millimole/liter | Standard Deviation 0.71 |
| NGM282 3.0 mg | Mean Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | High-density lipoprotein | -0.05 millimole/liter | Standard Deviation 0.5 |
| Placebo | Mean Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Triglycerides | 0.10 millimole/liter | Standard Deviation 0.34 |
| Placebo | Mean Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | High-density lipoprotein | -0.06 millimole/liter | Standard Deviation 0.19 |
| Placebo | Mean Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Low-density lipoprotein | 0.12 millimole/liter | Standard Deviation 0.54 |
| Placebo | Mean Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Total cholesterol | 0.15 millimole/liter | Standard Deviation 0.69 |
Secondary
Mean Change From Baseline in Enhanced Liver Fibrosis Score in Patients With Primary Sclerosing Cholangitis
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.
Time frame: Baseline to Week 12
Population: Mean change from baseline in Enhanced Liver Fibrosis Score was assessed in the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NGM282 1.0 mg | Mean Change From Baseline in Enhanced Liver Fibrosis Score in Patients With Primary Sclerosing Cholangitis | -0.22 units on a scale | Standard Deviation 0.64 |
| NGM282 3.0 mg | Mean Change From Baseline in Enhanced Liver Fibrosis Score in Patients With Primary Sclerosing Cholangitis | -0.26 units on a scale | Standard Deviation 0.66 |
| Placebo | Mean Change From Baseline in Enhanced Liver Fibrosis Score in Patients With Primary Sclerosing Cholangitis | 0.05 units on a scale | Standard Deviation 0.52 |
Secondary
Mean Change From Baseline in Gamma Glutamyl Transferase in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in gamma glutamyl transferase levels.
Time frame: Baseline to Week 12
Population: Mean change from baseline in gamma glutamyl transferase was assessed in participants with available data in the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NGM282 1.0 mg | Mean Change From Baseline in Gamma Glutamyl Transferase in Patients With Primary Sclerosing Cholangitis | 156.6 units/liter | Standard Error 45.7 |
| NGM282 3.0 mg | Mean Change From Baseline in Gamma Glutamyl Transferase in Patients With Primary Sclerosing Cholangitis | -20.3 units/liter | Standard Error 46.3 |
| Placebo | Mean Change From Baseline in Gamma Glutamyl Transferase in Patients With Primary Sclerosing Cholangitis | 4.6 units/liter | Standard Error 46.5 |
Secondary
Mean Change From Baseline in Prothrombin International Normalized Ratio in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in Prothrombin levels.
Time frame: Baseline to Week 12
Population: Mean change from baseline in Prothrombin was assessed in participants with available data in the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NGM282 1.0 mg | Mean Change From Baseline in Prothrombin International Normalized Ratio in Patients With Primary Sclerosing Cholangitis | 0.03 International normalized ratio | Standard Deviation 0.09 |
| NGM282 3.0 mg | Mean Change From Baseline in Prothrombin International Normalized Ratio in Patients With Primary Sclerosing Cholangitis | 0.01 International normalized ratio | Standard Deviation 0.07 |
| Placebo | Mean Change From Baseline in Prothrombin International Normalized Ratio in Patients With Primary Sclerosing Cholangitis | 0.00 International normalized ratio | Standard Deviation 0.08 |
Secondary
Mean Percent Change From Baseline in 25-Hydroxyvitamin D in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in 25-Hydroxyvitamin D levels.
Time frame: Baseline to Week 12
Population: Mean percent change from baseline in 25-Hydroxyvitamin D was assessed in the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NGM282 1.0 mg | Mean Percent Change From Baseline in 25-Hydroxyvitamin D in Patients With Primary Sclerosing Cholangitis | 30.5 percent change | Standard Error 97.3 |
| NGM282 3.0 mg | Mean Percent Change From Baseline in 25-Hydroxyvitamin D in Patients With Primary Sclerosing Cholangitis | 17.0 percent change | Standard Error 64.8 |
| Placebo | Mean Percent Change From Baseline in 25-Hydroxyvitamin D in Patients With Primary Sclerosing Cholangitis | 4.4 percent change | Standard Error 41.6 |
Secondary
Mean Percent Change From Baseline in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in alkaline phosphatase levels.
Time frame: Baseline to Week 12
Population: Mean percent change from baseline in ALP was assessed in participants with available data in the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NGM282 1.0 mg | Mean Percent Change From Baseline in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis | 7.1 percent change | Standard Error 5.8 |
| NGM282 3.0 mg | Mean Percent Change From Baseline in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis | -4.2 percent change | Standard Error 5.9 |
| Placebo | Mean Percent Change From Baseline in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis | -3.4 percent change | Standard Error 6 |
Secondary
Mean Percent Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in aspartate aminotransferase and alanine aminotransferase levels.
Time frame: Baseline to Week 12
Population: Mean percent changes from baseline in aspartate aminotransferase and alanine aminotransferase were assessed in participants with available data in the Full Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NGM282 1.0 mg | Mean Percent Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis | Aspartate aminotransferase | 2.6 percent change | Standard Error 7.8 |
| NGM282 1.0 mg | Mean Percent Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis | Alanine aminotransferase | 7.2 percent change | Standard Error 8.1 |
| NGM282 3.0 mg | Mean Percent Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis | Aspartate aminotransferase | -25.5 percent change | Standard Error 7.9 |
| NGM282 3.0 mg | Mean Percent Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis | Alanine aminotransferase | -29.2 percent change | Standard Error 8.2 |
| Placebo | Mean Percent Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis | Aspartate aminotransferase | -7.2 percent change | Standard Error 8 |
| Placebo | Mean Percent Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase in Patients With Primary Sclerosing Cholangitis | Alanine aminotransferase | -6.1 percent change | Standard Error 8.3 |
Secondary
Mean Percent Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in bilirubin (direct and total) levels.
Time frame: Baseline to Week 12
Population: Mean percent changes from baseline in bilirubin (total and direct) were assessed in participants with available data in the Full Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NGM282 1.0 mg | Mean Percent Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis | Direct bilirubin | 36.5 percent change | Standard Error 16.7 |
| NGM282 1.0 mg | Mean Percent Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis | Total bilirubin | 27.2 percent change | Standard Error 17.9 |
| NGM282 3.0 mg | Mean Percent Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis | Direct bilirubin | 5.7 percent change | Standard Error 17.1 |
| NGM282 3.0 mg | Mean Percent Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis | Total bilirubin | -3.6 percent change | Standard Error 18.2 |
| Placebo | Mean Percent Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis | Direct bilirubin | 9.2 percent change | Standard Error 17.1 |
| Placebo | Mean Percent Change From Baseline in Bilirubin (Direct and Total) in Patients With Primary Sclerosing Cholangitis | Total bilirubin | 6.8 percent change | Standard Error 18.2 |
Secondary
Mean Percent Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in cholesterol levels.
Time frame: Baseline to Week 12
Population: Mean percent change from baseline in cholesterol levels were assessed in the Full Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NGM282 1.0 mg | Mean Percent Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Total cholesterol | 1.81 percent change | Standard Deviation 16.45 |
| NGM282 1.0 mg | Mean Percent Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | High-density lipoprotein | 0.47 percent change | Standard Deviation 28.94 |
| NGM282 1.0 mg | Mean Percent Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Low-density lipoprotein | 1.36 percent change | Standard Deviation 27.56 |
| NGM282 1.0 mg | Mean Percent Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Triglycerides | 3.47 percent change | Standard Deviation 45.71 |
| NGM282 3.0 mg | Mean Percent Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Triglycerides | -5.81 percent change | Standard Deviation 27.22 |
| NGM282 3.0 mg | Mean Percent Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Total cholesterol | 5.67 percent change | Standard Deviation 16.31 |
| NGM282 3.0 mg | Mean Percent Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Low-density lipoprotein | 10.63 percent change | Standard Deviation 19.62 |
| NGM282 3.0 mg | Mean Percent Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | High-density lipoprotein | -0.36 percent change | Standard Deviation 23.87 |
| Placebo | Mean Percent Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Triglycerides | 11.61 percent change | Standard Deviation 33.32 |
| Placebo | Mean Percent Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | High-density lipoprotein | -3.09 percent change | Standard Deviation 10.42 |
| Placebo | Mean Percent Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Low-density lipoprotein | 6.18 percent change | Standard Deviation 19.15 |
| Placebo | Mean Percent Change From Baseline in Cholesterol Levels in Patients With Primary Sclerosing Cholangitis | Total cholesterol | 3.89 percent change | Standard Deviation 12.17 |
Secondary
Mean Percent Change From Baseline in Gamma Glutamyl Transferase in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in gamma glutamyl transferase levels.
Time frame: Baseline to Week 12
Population: Mean percent change from baseline in gamma glutamyl transferase was assessed in participants with available data in the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NGM282 1.0 mg | Mean Percent Change From Baseline in Gamma Glutamyl Transferase in Patients With Primary Sclerosing Cholangitis | 20.9 percent change | Standard Error 10.5 |
| NGM282 3.0 mg | Mean Percent Change From Baseline in Gamma Glutamyl Transferase in Patients With Primary Sclerosing Cholangitis | 6.6 percent change | Standard Error 10.6 |
| Placebo | Mean Percent Change From Baseline in Gamma Glutamyl Transferase in Patients With Primary Sclerosing Cholangitis | 7.5 percent change | Standard Error 10.6 |
Secondary
Mean Percent Change From Baseline in Prothrombin International Normalized Ratio in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess changes in Prothrombin levels.
Time frame: Baseline to Week 12
Population: Mean percent change from baseline in Prothrombin was assessed in participants with available data in the Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NGM282 1.0 mg | Mean Percent Change From Baseline in Prothrombin International Normalized Ratio in Patients With Primary Sclerosing Cholangitis | 3.39 percent change | Standard Deviation 8.02 |
| NGM282 3.0 mg | Mean Percent Change From Baseline in Prothrombin International Normalized Ratio in Patients With Primary Sclerosing Cholangitis | 0.65 percent change | Standard Deviation 6.67 |
| Placebo | Mean Percent Change From Baseline in Prothrombin International Normalized Ratio in Patients With Primary Sclerosing Cholangitis | 0.47 percent change | Standard Deviation 6.75 |
Secondary
Mean Rate of Change in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis
Blood samples were collected to assess rate of change in alkaline phosphatase levels. Serum levels of alkaline phosphatase was measured in a central laboratory using standard enzymatic method. The unit of measure is U/L.
Time frame: Baseline to Week 12
Population: Mean rate of change in ALP was assessed in participants with available data in the Full Analysis Set .
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NGM282 1.0 mg | Mean Rate of Change in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis | Weeks 1 through 4 | -17.7 U/L/Week | Standard Error 6.4 |
| NGM282 1.0 mg | Mean Rate of Change in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis | Weeks 5 through 12 | 11.9 U/L/Week | Standard Error 4.5 |
| NGM282 3.0 mg | Mean Rate of Change in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis | Weeks 1 through 4 | -2.2 U/L/Week | Standard Error 6.1 |
| NGM282 3.0 mg | Mean Rate of Change in Alkaline Phosphatase in Patients With Primary Sclerosing Cholangitis | Weeks 5 through 12 | -0.2 U/L/Week | Standard Error 2.2 |
Secondary
Severity of Inflammatory Bowel Disease-Associated Intestinal Symptoms in Patients With Primary Sclerosing Cholangitis
Severity of inflammatory bowel disease (IBD)-associated symptoms and acute cholangitis are summarized with number and percentage. The partial Mayo IBD scale assesses stool frequency, rectal bleeding, and there is a Physician's global assessment. Each section is summed and remission is defined as a total score of 0-1, mild disease 2-4, moderate disease 5-6, and severe disease 7-9. Higher total scores indicate more severe disease. The number of participants are being presented based on the severity of their IBD symptoms.
Time frame: Baseline to Week 12
Population: Severity of inflammatory bowel disease-associated intestinal symptoms were assessed in the Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NGM282 1.0 mg | Severity of Inflammatory Bowel Disease-Associated Intestinal Symptoms in Patients With Primary Sclerosing Cholangitis | Remission | 12 Participants |
| NGM282 1.0 mg | Severity of Inflammatory Bowel Disease-Associated Intestinal Symptoms in Patients With Primary Sclerosing Cholangitis | Mild disease | 8 Participants |
| NGM282 1.0 mg | Severity of Inflammatory Bowel Disease-Associated Intestinal Symptoms in Patients With Primary Sclerosing Cholangitis | Moderate disease | 1 Participants |
| NGM282 1.0 mg | Severity of Inflammatory Bowel Disease-Associated Intestinal Symptoms in Patients With Primary Sclerosing Cholangitis | Severe disease | 0 Participants |
| NGM282 3.0 mg | Severity of Inflammatory Bowel Disease-Associated Intestinal Symptoms in Patients With Primary Sclerosing Cholangitis | Severe disease | 0 Participants |
| NGM282 3.0 mg | Severity of Inflammatory Bowel Disease-Associated Intestinal Symptoms in Patients With Primary Sclerosing Cholangitis | Remission | 13 Participants |
| NGM282 3.0 mg | Severity of Inflammatory Bowel Disease-Associated Intestinal Symptoms in Patients With Primary Sclerosing Cholangitis | Moderate disease | 0 Participants |
| NGM282 3.0 mg | Severity of Inflammatory Bowel Disease-Associated Intestinal Symptoms in Patients With Primary Sclerosing Cholangitis | Mild disease | 8 Participants |
| Placebo | Severity of Inflammatory Bowel Disease-Associated Intestinal Symptoms in Patients With Primary Sclerosing Cholangitis | Severe disease | 0 Participants |
| Placebo | Severity of Inflammatory Bowel Disease-Associated Intestinal Symptoms in Patients With Primary Sclerosing Cholangitis | Mild disease | 3 Participants |
| Placebo | Severity of Inflammatory Bowel Disease-Associated Intestinal Symptoms in Patients With Primary Sclerosing Cholangitis | Moderate disease | 0 Participants |
| Placebo | Severity of Inflammatory Bowel Disease-Associated Intestinal Symptoms in Patients With Primary Sclerosing Cholangitis | Remission | 17 Participants |