Trial · NCT03338816

ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)

NCT03338816, Phase 3, Completed, Alnylam Pharmaceuticals; results first posted 2020-02-11

3 sourcestrials-2026-11-12-0.5.0

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ConductScience Library. ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP). Trials, record NCT03338816. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03338816

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)
NCT number: NCT03338816
Status: Completed
Phases: Phase 3
Enrollment: 94 participants, actual
Lead sponsor: Alnylam Pharmaceuticals
Conditions: Acute Hepatic Porphyria, Acute Intermittent Porphyria, Porphyria, Acute Intermittent, Acute Porphyria, Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), ALA Dehydratase Deficient Porphyria (ADP)
Interventions: Givosiran, Placebo
First posted: 2017-11-09
Last updated: 2024-04-22
Results first posted: 2020-02-11

Source ClinicalTrials.gov

Registered outcomes12

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)	6 months	Porphyria attacks were defined as meeting all of the following criteria: an acute episode of neurovisceral pain in the abdomen, back, chest, extremities and/or limbs, no other medically determined cause, and required treatment with intravenous (IV) dextrose or hemin, carbohydrates, or analgesics, or other medications such as antiemetics at a dose or frequency beyond the participant's usual daily porphyria management. The annualized rate of porphyria attacks is a composite endpoint which included porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home.
Secondary	The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP	3 and 6 months	The PD effect of givosiran was evaluated by spot urine ALA levels normalized to spot urine creatinine levels.
Secondary	The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP	6 months	The PD effect of givosiran was evaluated by spot urine PBG levels normalized to spot urine creatinine levels.
Secondary	Annualized Rate of Hemin Administration in Participants With AIP	6 months	Annualized rate of hemin doses was evaluated as annualized days of hemin use.
Secondary	Annualized Rate of Porphyria Attacks in Participants With AHP	6 months	Porphyria attacks were defined as meeting all of the following criteria: an acute episode of neurovisceral pain in the abdomen, back, chest, extremities and/or limbs, no other medically determined cause, and required treatment with intravenous (IV) dextrose or hemin, carbohydrates, or analgesics, or other medications such as antiemetics at a dose or frequency beyond the participant's usual daily porphyria management. The annualized rate of porphyria attacks is a composite endpoint which included porphyria attacks requiring hospitalization, urgent healthcare visit, or IV hemin administration at home.
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	Baseline and 6 months	Participants rated worst daily pain score in an eDiary using the 11-point BPI-SF NRS, in which 0=no pain and 10=worst pain. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the post baseline weekly mean score minus the baseline score. Lower scores indicate an improvement. The 6-month AUC was calculated based on change from baseline in weekly mean scores.
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	Baseline and 6 months	Participants rated worst daily pain score in an eDiary using the 11-point BPI-SF NRS, in which 0=no pain and 10=worst pain. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score. Lower scores indicate an improvement.
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	Baseline and 6 months	Participants rated daily worst fatigue score in an eDiary using the 11-point BFI-SF NRS, in which 0=no fatigue and 10=worst fatigue. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the post baseline weekly mean score minus the baseline score. Lower scores indicate an improvement. The 6-month AUC was calculated based on change from baseline in weekly mean scores.
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	Baseline and 6 months	Participants rated daily worst fatigue score in an eDiary using the 11-point BFI-SF NRS, in which 0=no fatigue and 10=worst fatigue. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score. Lower scores indicate an improvement.
Secondary	AUC of the Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP	Baseline and 6 months	Participants rated worst daily nausea score in an eDiary using an 11-point NRS, in which 0=no nausea and 10=worst nausea. Daily eDiary entries were averaged into a weekly (i.e. 7 day) score. The change from baseline in weekly mean scores is defined as the postbaseline weekly mean score minus the baseline score. Lower scores indicate an improvement. The 6-month AUC was calculated based on change from baseline in weekly mean scores.

1 to 10 of 12Source ClinicalTrials.gov

See all 12 registered outcomes

Outcomes12

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)	6 months	AIP participants in the Full Analysis Set (FASAIP): All randomized AIP participants (with identified mutation in the hydroxymethylbilane synthase \[HMBS\] gene) who received at least one dose of study drug.	annualized attack rate	MEAN
SECONDARY	The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP	3 and 6 months	FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.	mmol/mol creatinine (Cr)	LEAST_SQUARES_MEAN
SECONDARY	The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP	6 months	FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.	mmol/mol Cr	LEAST_SQUARES_MEAN
SECONDARY	Annualized Rate of Hemin Administration in Participants With AIP	6 months	FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.	annualized rate of use	MEAN
SECONDARY	Annualized Rate of Porphyria Attacks in Participants With AHP	6 months	Full Analysis Set (FAS): All randomized patients who received at least one dose of study drug.	annualized attack rate	MEAN
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	Baseline and 6 months	FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.	score on a scale*week	MEDIAN
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	Baseline and 6 months	FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.	score on a scale	MEDIAN
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	Baseline and 6 months	FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.	score on a scale*week	LEAST_SQUARES_MEAN
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	Baseline and 6 months	FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.	score on a scale	LEAST_SQUARES_MEAN
SECONDARY	AUC of the Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP	Baseline and 6 months	FASAIP: All randomized AIP participants (with identified mutation in the HMBS gene) who received at least one dose of study drug.	score on a scale	LEAST_SQUARES_MEAN

1 to 10 of 12Source ClinicalTrials.gov

See all 12 outcomes

Results by group26

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Spread	Units
Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)	Placebo		12.52	95% Confidence Interval 9.35 to 16.76	annualized attack rate
Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)	Givosiran 2.5 mg/kg		3.22	95% Confidence Interval 2.25 to 4.59	annualized attack rate
The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP	Placebo	Month 3	19.965	Standard Error 1.475	mmol/mol creatinine (Cr)
The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP	Givosiran 2.5 mg/kg	Month 3	1.756	Standard Error 1.413	mmol/mol creatinine (Cr)
The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP	Placebo	Month 6	23.150	Standard Error 2.534	mmol/mol creatinine (Cr)
The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP	Givosiran 2.5 mg/kg	Month 6	4.013	Standard Error 2.352	mmol/mol creatinine (Cr)
The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP	Placebo		49.110	Standard Error 4.959	mmol/mol Cr
The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP	Givosiran 2.5 mg/kg		12.906	Standard Error 4.642	mmol/mol Cr
Annualized Rate of Hemin Administration in Participants With AIP	Placebo		29.71	95% Confidence Interval 18.41 to 47.94	annualized rate of use
Annualized Rate of Hemin Administration in Participants With AIP	Givosiran 2.5 mg/kg		6.77	95% Confidence Interval 4.20 to 10.92	annualized rate of use

1 to 10 of 26Source ClinicalTrials.gov

See all 26 results by group

Participant flow24

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
6-Month Double-blind Period	STARTED	Placebo 6-Month DB	46
6-Month Double-blind Period	STARTED	Givosiran 2.5 mg/kg 6-Month DB	48
6-Month Double-blind Period	STARTED	Placebo/Givosiran	0
6-Month Double-blind Period	STARTED	Givosiran/Givosiran	0
6-Month Double-blind Period	COMPLETED	Placebo 6-Month DB	46
6-Month Double-blind Period	COMPLETED	Givosiran 2.5 mg/kg 6-Month DB	48
6-Month Double-blind Period	COMPLETED	Placebo/Givosiran	0
6-Month Double-blind Period	COMPLETED	Givosiran/Givosiran	0
6-Month Double-blind Period	NOT COMPLETED	Placebo 6-Month DB	0
6-Month Double-blind Period	NOT COMPLETED	Givosiran 2.5 mg/kg 6-Month DB	0

1 to 10 of 24Source ClinicalTrials.gov

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Adverse events860

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
other	Abdominal pain	Gastrointestinal disorders	Placebo 6-Month DB	3	46
other	Abdominal pain	Gastrointestinal disorders	Givosiran 2.5 mg/kg 6-Month DB	4	48
other	Abdominal pain	Gastrointestinal disorders	Placebo/Givosiran	0	46
other	Abdominal pain	Gastrointestinal disorders	Givosiran/Givosiran	0	48
other	Abdominal pain	Gastrointestinal disorders	All Givosiran	0	94
other	Constipation	Gastrointestinal disorders	Placebo 6-Month DB	0	46
other	Constipation	Gastrointestinal disorders	Givosiran 2.5 mg/kg 6-Month DB	3	48
other	Constipation	Gastrointestinal disorders	Placebo/Givosiran	0	46
other	Constipation	Gastrointestinal disorders	Givosiran/Givosiran	0	48
other	Constipation	Gastrointestinal disorders	All Givosiran	0	94

1 to 10 of 860Source ClinicalTrials.gov

See all 860 adverse events

Adverse event totals15

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Placebo 6-Month DB	0	46
Total, all-cause mortality	Givosiran 2.5 mg/kg 6-Month DB	0	48
Total, all-cause mortality	Placebo/Givosiran	0	46
Total, all-cause mortality	Givosiran/Givosiran	1	48
Total, all-cause mortality	All Givosiran	1	94
Total, other adverse events	Placebo 6-Month DB	37	46
Total, other adverse events	Givosiran 2.5 mg/kg 6-Month DB	43	48
Total, other adverse events	Placebo/Givosiran	44	46
Total, other adverse events	Givosiran/Givosiran	47	48
Total, other adverse events	All Givosiran	91	94

1 to 10 of 15Source ClinicalTrials.gov

See all 15 adverse event totals

Papers5

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
32521132	DERIVED	PubMed
36028858	DERIVED	PubMed
37479139	DERIVED	PubMed
38044204	DERIVED	PubMed
41388232	DERIVED	PubMed

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.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

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.

For software

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The record and each of its lists are JSON, twenty rows a page. No key.

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