Trial · NCT03945292
Safety, Tolerability and Pharmacodynamic Effect of Fazirsiran (TAK-999, ARO-AAT)
NCT03945292, Phase 2, Completed, Arrowhead Pharmaceuticals; results first posted 2024-12-30
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Safety, Tolerability and Pharmacodynamic Effect of Fazirsiran (TAK-999, ARO-AAT). Trials, record NCT03945292. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03945292
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Safety, Tolerability and Pharmacodynamic Effect of Fazirsiran (TAK-999, ARO-AAT)
- NCT number
- NCT03945292
- Status
- Completed
- Phases
- Phase 2
- Enrollment
- 40 participants, actual
- Lead sponsor
- Arrowhead Pharmaceuticals
- Conditions
- Alpha 1-Antitrypsin Deficiency
- Interventions
- Fazisiran Injection, Placebo
- First posted
- 2019-05-10
- Last updated
- 2025-11-04
- Other registries' IDs
- eudract:2018-003385-14
- Results first posted
- 2024-12-30
Source ClinicalTrials.gov
Registered outcomes28
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16 | Baseline, Week 16 (+/- 2 weeks) | |
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase | 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. | 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. |
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase | From dose administration of the first dose of open-label phase fazirsiran through EOS or Early Termination (up to Week 196). | 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. |
| Secondary | Absolute Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96. |
| Secondary | Percent Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96. |
| Secondary | Absolute Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96. |
| Secondary | Percent Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96. |
| Secondary | Absolute Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96. |
| Secondary | Percent Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | Post-dose biopsy includes all post-dose biopsy collected at Week 48 or Week 72 or Week 96. |
| Secondary | Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS) | 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) | PDLB=post-dose liver biopsy |
1 to 10 of 28Source ClinicalTrials.gov
See all 28 registered outcomesOutcomes28
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16 | Baseline, Week 16 (+/- 2 weeks) | Full Analysis Set: All randomized participants who received at least one dose of study drug. | percentage change | LEAST_SQUARES_MEAN |
| SECONDARY | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase | 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. | Safety Analysis Set: All participants who receive at least one dose of study drug. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Phase | From dose administration of the first dose of open-label phase fazirsiran through EOS or Early Termination (up to Week 196). | Safety Analysis Set: All participants who receive at least one dose of study drug. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Absolute Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | 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. | nmol/g | MEAN |
| SECONDARY | Percent Change From Baseline in Total Liver Z-AAT (Insoluble + Soluble) Protein at Post-dose Biopsy for Participants With Fibrosis | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | 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. | percentage change | LEAST_SQUARES_MEAN |
| SECONDARY | Absolute Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | 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. | nmol/g | MEAN |
| SECONDARY | Percent Change From Baseline in Liver Z-AAT Soluble Protein at Post-dose Biopsy for Participants With Fibrosis | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | 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. | percentage change | LEAST_SQUARES_MEAN |
| SECONDARY | Absolute Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | 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. | nmol/g | MEAN |
| SECONDARY | Percent Change From Baseline in Liver Z-AAT Insoluble Protein at Post-dose Biopsy for Participants With Fibrosis | Baseline, Week 48 (+/- 2 weeks), or Week 72 (+/- 4 weeks), or Week 96 (+/- 4 weeks) | 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. | percentage change | LEAST_SQUARES_MEAN |
| SECONDARY | Absolute Change From Baseline in Liver Function Tests: Alanine Aminotransferase (ALT) at Week 16 and Over Time Through End of Study (EOS) | 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) | Safety Analysis Set: all participants who received at least one dose of study drug; participants with an assessment at given time point. | U/L | MEAN |
1 to 10 of 28Source ClinicalTrials.gov
See all 28 outcomesResults by group1,216
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16 | Fazirsiran 25 mg | -62.17 | Standard Error 4.279 | percentage change | |
| Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16 | Fazirsiran 100 mg | -85.39 | Standard Error 4.634 | percentage change | |
| Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16 | Fazirsiran 200 mg | -92.93 | Standard Error 4.341 | percentage change | |
| Percent Change From Baseline in Serum Z-Alpha-1 Antitrypsin (Z-AAT) at Week 16 | Placebo | 4.64 | Standard Error 3.211 | percentage change | |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase | Fazirsiran 25 mg | TEAEs | 9 | Participants | |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase | Fazirsiran 100 mg | TEAEs | 8 | Participants | |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase | Fazirsiran 200 mg | TEAEs | 9 | Participants | |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase | Placebo | TEAEs | 14 | Participants | |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase | Fazirsiran 25 mg | TESAEs | 0 | Participants | |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Phase | Fazirsiran 100 mg | TESAEs | 0 | Participants |
1 to 10 of 1,216Source ClinicalTrials.gov
See all 1,216 results by groupParticipant flow48
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Double-Blind (DB) Period: Weeks 0 to 48 | STARTED | Fazirsiran 25 mg | 9 | |
| Double-Blind (DB) Period: Weeks 0 to 48 | STARTED | Fazirsiran 100 mg | 8 | |
| Double-Blind (DB) Period: Weeks 0 to 48 | STARTED | Fazirsiran 200 mg | 9 | |
| Double-Blind (DB) Period: Weeks 0 to 48 | STARTED | Placebo | 14 | |
| Double-Blind (DB) Period: Weeks 0 to 48 | STARTED | Fazirsiran 25 mg DB/200 mg OL | 0 | |
| Double-Blind (DB) Period: Weeks 0 to 48 | STARTED | Fazirsiran 100 mg DB/200 mg OL | 0 | |
| Double-Blind (DB) Period: Weeks 0 to 48 | STARTED | Fazirsiran 200 mg DB/200 mg OL | 0 | |
| Double-Blind (DB) Period: Weeks 0 to 48 | STARTED | Placebo DB / Fazirsiran 200 mg OL | 0 | |
| Double-Blind (DB) Period: Weeks 0 to 48 | COMPLETED | Fazirsiran 25 mg | 8 | |
| Double-Blind (DB) Period: Weeks 0 to 48 | COMPLETED | Fazirsiran 100 mg | 8 |
1 to 10 of 48Source ClinicalTrials.gov
See all 48 participant flowAdverse events1,704
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Eosinophilia | Blood and lymphatic system disorders | Fazirsiran 25 mg | 0 | 9 | |
| other | Eosinophilia | Blood and lymphatic system disorders | Fazirsiran 100 mg | 1 | 8 | |
| other | Eosinophilia | Blood and lymphatic system disorders | Fazirsiran 200 mg | 0 | 9 | |
| other | Eosinophilia | Blood and lymphatic system disorders | Placebo | 0 | 14 | |
| other | Eosinophilia | Blood and lymphatic system disorders | Fazirsiran 25 mg DB/200 mg OL | 0 | 4 | |
| other | Eosinophilia | Blood and lymphatic system disorders | Fazirsiran 100 mg DB/200 mg OL | 0 | 5 | |
| other | Eosinophilia | Blood and lymphatic system disorders | Fazirsiran 200 mg DB/200 mg OL | 0 | 5 | |
| other | Eosinophilia | Blood and lymphatic system disorders | Placebo DB / Fazirsiran 200 mg OL | 0 | 9 | |
| other | Lymph node pain | Blood and lymphatic system disorders | Fazirsiran 25 mg | 0 | 9 | |
| other | Lymph node pain | Blood and lymphatic system disorders | Fazirsiran 100 mg | 1 | 8 |
1 to 10 of 1,704Source ClinicalTrials.gov
See all 1,704 adverse eventsAdverse event totals24
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Fazirsiran 25 mg | 0 | 9 |
| Total, all-cause mortality | Fazirsiran 100 mg | 0 | 8 |
| Total, all-cause mortality | Fazirsiran 200 mg | 0 | 9 |
| Total, all-cause mortality | Placebo | 0 | 14 |
| Total, all-cause mortality | Fazirsiran 25 mg DB/200 mg OL | 0 | 4 |
| Total, all-cause mortality | Fazirsiran 100 mg DB/200 mg OL | 0 | 5 |
| Total, all-cause mortality | Fazirsiran 200 mg DB/200 mg OL | 0 | 5 |
| Total, all-cause mortality | Placebo DB / Fazirsiran 200 mg OL | 0 | 9 |
| Total, other adverse events | Fazirsiran 25 mg | 9 | 9 |
| Total, other adverse events | Fazirsiran 100 mg | 8 | 8 |
1 to 10 of 24Source ClinicalTrials.gov
See all 24 adverse event totalsPapers2
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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