| Primary | Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16 | | Full Analysis Set: All randomized participants who received at least one dose of study drug. | Posted | | Least Squares Mean | Standard Error | percentage change | | Baseline, Week 16 (+/- 2 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG003 | Placebo | Participants with no fibrosis: Placebo administered on Day 1 and Week 4. Participants with fibrosis: Placebo administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
| | | Title | Denominators | Categories |
|---|
| | | Title | Measurements |
|---|
| - OG000-62.17± 4.279
- OG001-85.39± 4.634
- OG002-92.93± 4.341
- OG003
|
|
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| | Mixed model repeated measures (MMRM) | NAFLD=non-alcoholic fatty liver disease; NSH=non-alcoholic steatohepatitis | < 0.0001 | From a mixed model with repeated measures, including fixed effects for treatment, week, treatment-by-week interaction, presence of metabolic syndrome, presence of NAFLD or NASH, baseline serum Z-AAT as covariate, and subject as a random effect. | Difference | -66.81 | Standard Error of the Mean | 5.107 | 2-Sided | 95 | -77.18 | -56.45 | | | | | Superiority | | |
|
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase | An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with this treatment. A serious adverse event (SAE) is an AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction. TEAEs/TESAEs are defined as those AEs that first occurred or worsened in severity following dose administration through end of study (EOS) or Early Termination or first dose of open-label phase fazirsiran. | Safety Analysis Set: All participants who receive at least one dose of study drug. | Posted | | Count of Participants | | Participants | No | Double Blind Phase (up to Week 48): dose administration through end of study (EOS) or Early Termination or first dose of open-label phase fazirsiran. | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase | An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with this treatment. A serious adverse event (SAE) is an AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction. TEAEs/TESAEs are defined as those AEs that first occurred or worsened in severity following dose administration through end of study (EOS) or Early Termination or first dose of open-label phase fazirsiran. | Safety Analysis Set: All participants who receive at least one dose of study drug. | Posted | | Count of Participants | | Participants | No | From dose administration of the first dose of open-label phase fazirsiran through EOS or Early Termination (up to Week 196). | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Absolute Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis | Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96. | Biopsy Analysis Set: All randomized participants who received at least one dose of study drug and had at least one central read histology biopsy result. | Posted | | Mean | Standard Deviation | nmol/g | | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Percent Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis | Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96. | Biopsy Analysis Set: All randomized participants who received at least one dose of study drug and had at least one central read histology biopsy result. | Posted | | Least Squares Mean | Standard Error | percentage change | | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Absolute Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis | Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96. | Biopsy Analysis Set: All randomized participants who received at least one dose of study drug and had at least one central read histology biopsy result. | Posted | | Mean | Standard Deviation | nmol/g | | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Percent Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis | Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96. | Biopsy Analysis Set: All randomized participants who received at least one dose of study drug and had at least one central read histology biopsy result. | Posted | | Least Squares Mean | Standard Error | percentage change | | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Absolute Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis | Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96. | Biopsy Analysis Set: All randomized participants who received at least one dose of study drug and had at least one central read histology biopsy result. | Posted | | Mean | Standard Deviation | nmol/g | | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Percent Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis | Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96. | Biopsy Analysis Set: All randomized participants who received at least one dose of study drug and had at least one central read histology biopsy result. | Posted | | Least Squares Mean | Standard Error | percentage change | | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS) | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | U/L | | Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Percent Change From Baseline in Liver Function Tests: ALT at Week 16 and Over Time Through EOS | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | percentage change | | Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Absolute Change From Baseline in Liver Function Tests: Aspartate Aminotransferase (AST) at Week 16 and Over Time Through EOS | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | U/L | | Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Percent Change From Baseline in Liver Function Tests: AST at Week 16 and Over Time Through EOS | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | percentage change | | Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Absolute Change From Baseline in Liver Function Tests: Alkaline Phosphatase (ALP) at Week 16 and Over Time Through EOS | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | U/L | | Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Percent Change From Baseline in Liver Function Tests: ALP at Week 16 and Over Time Through EOS | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | percentage change | | Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Absolute Change From Baseline in Liver Function Tests: Gamma Glutamyl Transferase (GGT) at Week 16 and Over Time Through EOS | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | U/L | | Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124,136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Percent Change From Baseline in Liver Function Tests: GGT at Week 16 and Over Time Through EOS | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | percentage change | | Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Absolute Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | mg/dL | | Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124,136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Percent Change From Baseline in Liver Function Tests: Total Bilirubin at Week 16 and Over Time Through EOS | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | percentage change | | Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Absolute Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | mg/dL | | Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Percent Change From Baseline in Liver Function Tests: Direct Bilirubin at Week 16 and Over Time Through EOS | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | percentage change | | Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Absolute Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | ratio | | Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
|
| Secondary | Percent Change From Baseline in Liver Function Tests: Prothrombin International Normalized Ratio at Week 16 and Over Time Through EOS | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | percentage change | | Baseline, Week 16, Week 16 + 24 hours (H), Weeks 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
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| Secondary | Absolute Change in Serum Z-AAT Over Time Through EOS | PDLB=post-dose liver biopsy | Full Analysis Set: All randomized participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | μg/mL | | Baseline, Weeks 2, 4, 6, 16, 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
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| Secondary | Percent Change in Serum Z-AAT Over Time Through EOS | PDLB=post-dose liver biopsy | Full Analysis Set: All randomized participants who received at least one dose of study drug; participants with an assessment at given time point. | Posted | | Mean | Standard Deviation | percentage change | | Baseline, Weeks 2, 4, 6, 16, 28, 40, 48, 52, 64, 72, 76, 88, 96, 100, 112, 124, 136, 148, 160, Early Termination (up to 196 weeks), EOS (up to 208 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
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| Secondary | Pharmacokinetics (PK): ARO-AAT Plasma Concentration Summary for the Double-Blind Phase | | PK Population: all Full Analysis Set participants who have at least 1 measurable plasma concentration data; participants with an assessment at given time point. Data not collected Week 16 for participants with no fibrosis per protocol. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | Fazirsiran participants without fibrosis: Pre-dose, 1 hour, 2 hour, 24 hours post-dose on Day 1 (+/- 1 day). Fazirsiran participants with fibrosis: Pre-dose, 1 hour, 2 hours, 24 hours post-dose on Day 1 and Week 16 (+/- 1 day). | | | | ID | Title | Description |
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| OG000 | Fazirsiran 25 mg: Participants With No Fibrosis | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. | | OG001 | Fazirsiran 25 mg: Participants With Fibrosis | Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 100 mg: Participants With No Fibrosis | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. | | OG003 |
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| Secondary | Number of Participants Positive for Anti-Drug Antibodies to Fazirsiran | PDLB=post-dose liver biopsy | Safety Analysis Set: all participants who received at least one dose of fazirsiran; participants with an assessment at given time point | Posted | | Count of Participants | | Participants | No | Baseline, Weeks 4, 16, 28, 40, 48, 52, 64, 76, 88, 96, 100, 112, 124, 136, 148 or Early Termination (up to 148 weeks) | | | | ID | Title | Description |
|---|
| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG002 | Fazirsiran 200 mg | Participants with no fibrosis: Fazirsiran 200 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 200 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
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| Secondary | Percentage of Participants With Shifts From Baseline in METAVIR Fibrosis Stage at Post-Dose Biopsy for Participants With Fibrosis | The METAVIR scoring system is a system used to assess the extent of inflammation and fibrosis by histopathological evaluation in a liver biopsy. The stage represents the amount of fibrosis or scarring: 0= no fibrosis; 1=portal fibrosis without septa; 2=portal fibrosis with few septa; 3=numerous septa without cirrhosis; 4=cirrhosis. A higher score indicates a worse condition. | Biopsy Analysis Set: All randomized participants who received at least one dose of study drug and had at least one central read histology biopsy result; participants eligible to meet the defined criteria. (For example, participants with baseline METAVIR fibrosis score 0 are not eligible for improvement; participants with baseline METAVIR fibrosis score 4 are not eligible for worsening.) | Posted | | Number | | percentage of participants | | Baseline, Post-dose at Weeks 48 (+/- 2 weeks) or Week 72 (+/- 4 weeks) or Week 96 (+/- 4 weeks) | | | | ID | Title | Description |
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| OG000 | Fazirsiran 25 mg | Participants with no fibrosis: Fazirsiran 25 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 25 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. | | OG001 | Fazirsiran 100 mg | Participants with no fibrosis: Fazirsiran 100 mg administered on Day 1 and Week 4. Participants with fibrosis: Fazirsiran 100 mg administered on Day 1, Week 4, and Week 16, then every 12 weeks up to 18 total doses. |
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