Phase 3
Completed N=94
ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)
Acute Hepatic Porphyria · Acute Intermittent Porphyria · Porphyria, Acute Intermittent · Acute Porphyria
Source: ClinicalTrials.gov NCT03338816 ↗
Enrolled (actual)
94
Serious AEs
31.2%
Results posted
Feb 2020
Primary outcomePrimary: Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP) — 12.52; 3.22 annualized attack rate — p=<0.0001
◆ Published Evidence
Highly cited
592citations · ~99 / year
Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria.
Summary
The purpose of this study is to evaluate the effect of subcutaneous givosiran (ALN-AS1), compared to placebo, on the rate of porphyria attacks in patients with Acute Hepatic Porphyrias (AHP).
Linked Publications (5)
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Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria.
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Efficacy and safety of givosiran for acute hepatic porphyria: Final results of the randomized phase III ENVISION trial.
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Disease burden in patients with acute hepatic porphyria: experience from the phase 3 ENVISION study.
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A randomized, placebo-controlled study of givosiran in patients with acute hepatic porphyrias (ENVISION): Final (36-month) analysis of the Taiwan Cohort.
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Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP) |
12.52; 3.22 | <0.0001 sig |
| SECONDARY The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP |
19.965; 1.756; 23.150; 4.013 | — |
| SECONDARY The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP |
49.110; 12.906 | — |
| SECONDARY Annualized Rate of Hemin Administration in Participants With AIP |
29.71; 6.77 | — |
| SECONDARY Annualized Rate of Porphyria Attacks in Participants With AHP |
12.26; 3.35 | — |
| SECONDARY Area Under the Curve (AUC) of the Change From Baseline in Weekly Mean Score of Daily Worst Pain as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Numeric Rating Scale (NRS) in Participants With AIP |
5.286; -11.514 | — |
| SECONDARY Average Change From Baseline in Weekly Mean Score of Daily Worst Pain as Measured by the Brief Pain Inventory-Short Form (BPI-SF) Numeric Rating Scale (NRS) in Participants With AIP |
0.245; -0.506 | — |
| SECONDARY AUC of the Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP |
-4.208; -11.148 | — |
| SECONDARY Average Change From Baseline in Weekly Mean Score of Daily Worst Fatigue Score as Measured by the Brief Fatigue Inventory-Short Form (BFI-SF) NRS in Participants With AIP |
-0.182; -0.502 | — |
| SECONDARY AUC of the Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP |
-4.011; 1.481 | — |
| SECONDARY Average Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP |
-0.181; 0.067 | — |
| SECONDARY Change From Baseline in the Physical Component Summary (PCS) of the 12-Item Short Form Survey (SF-12) in Participants With AIP |
1.431; 5.369 | — |
Eligibility Criteria
Inclusion Criteria
- ≥ 12 years of age
- Diagnosed with Acute Hepatic Porphyria (Acute Intermittent Porphyria, Hereditary Corproporhyria, Variegate Porphyria, aminolevulinic acid (ALA) dehydratase deficient porphyria)
- Elevated urinary or plasma porphobilinogen (PBG) or ALA values within the past year,
- Have active disease, with at least 2 documented porphyria attacks within the last 6 months
- Willing to discontinue or not initiate the use of prophylactic hemin throughout the study.
- Women of child bearing potential must have a negative serum pregnancy test, not be nursing, and use acceptable contraception
Exclusion Criteria
- Clinically significant abnormal laboratory results
- Anticipated liver transplantation
- History of multiple drug allergies or intolerance to subcutaneous injections
- Active HIV, hepatitis C virus, or hepatitis B virus infection(s)
- History of recurrent pancreatitis
Data sourced from ClinicalTrials.gov (NCT03338816) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.