Acute Hepatic PorphyriaPhase 3NCT03338816
ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)
A Phase 3 study testing Givosiran in people with Acute Hepatic Porphyria and Acute Intermittent Porphyria, run by Alnylam Pharmaceuticals at 36 sites in 18 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Acute Hepatic Porphyria, Acute Intermittent Porphyria, Porphyria, Acute Intermittent
- What is being tested?
- Givosiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 94 participants
- Where
- 36 sitesin 18 countries
- Study dates
- 16 Nov 2017to 31 May 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- ≥ 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
Who cannot join
- 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
Trial locations and contacts
36 sites in 18 countries.
36 sites in 18 countries
United States10 sites
Clinical Trial Site
Ann Arbor, Michigan, 48109
Clinical Trial Site
Boston, Massachusetts, 02114
Clinical Trial Site
Galveston, Texas, 77555
Clinical Trial Site
Little Rock, Arkansas, 72205
Clinical Trial Site
New York, New York, 10029
Clinical Trial Site
Philadelphia, Pennsylvania, 19107
Clinical Trial Site
Salt Lake City, Utah, 84112
Clinical Trial Site
San Francisco, California, 94143
Clinical Trial Site
Seattle, Washington, 98195
Clinical Trial Site
Winston-Salem, North Carolina, 27157
Australia3 sites
Clinical Trial Site
Auchenflower, 4066
Clinical Trial Site
Camperdown, 2050
Clinical Trial Site
Parkville, Victoria, 3050
Japan3 sites
Clinical Trial Site
Hamamatsu, 430-0929
Clinical Trial Site
Iizuka, 820-8505
Clinical Trial Site
Tokyo, 108-0073
Spain3 sites
Clinical Trial Site
Barcelona, 08036
Clinical Trial Site
El Palmar, 30120
Clinical Trial Site
Pamplona, 31008
Taiwan3 sites
Clinical Trial Site
Taichung, 40705
Clinical Trial Site
Taipei, 10002
Clinical Trial Site
Taoyuan City, 33305
Germany2 sites
Clinical Trial Site
Chemnitz, 09116
Clinical Trial Site
Munich, 80331
About this study
Official title: ENVISION: A Phase 3 Randomized, Double-blind, Placebo-Controlled Multicenter Study With an Open-label Extension to Evaluate the Efficacy and Safety of Givosiran in Patients With Acute Hepatic Porphyrias
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).
- Conditions
- Acute Hepatic Porphyria, Acute Intermittent Porphyria, Porphyria, Acute Intermittent, Acute Porphyria, Hereditary Coproporphyria (HCP), Variegate Porphyria (VP)
- Being tested
- Givosiran, Placebo
- Keywords
- Acute Intermittent Porphyria (AIP), Acute Hepatic Porphyria (AHP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), ALA dehydratase deficient porphyria (ADP) (ALAD), RNAi therapeutic, Porphyria
- Medical subject headings
- Coproporphyria, Hereditary, Porphyria, Acute Intermittent, Porphyria, Variegate, Porphyrias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GivosiranDrug
Also called ALN-AS1, GIVLAARI
Givosiran by SC
PlaceboDrug
Matching placebo (normal saline [0.9% NaCl]) by SC
| Study group | Role | What they receive |
|---|---|---|
| Givosiran/Givosiran | Experimental | Givosiran 2.5 mg/kg administered subcutaneously (SC), monthly (QM), for 6 months during the 6-Month Double-blind (DB) Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the Open-label Extension (OLE) Period. Receives: Drug: Givosiran; Drug: Placebo |
| Placebo/Givosiran | Placebo comparator | Matching placebo (normal saline [0.9% NaCl]) was administered SC, QM, for 6 months during the 6-Month DB Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the OLE period. Receives: Drug: Givosiran; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)
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.
Measured: 6 months
Secondary outcomes (11)
The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP
The PD effect of givosiran was evaluated by spot urine ALA levels normalized to spot urine creatinine levels.
Measured: 3 and 6 months
The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP
The PD effect of givosiran was evaluated by spot urine PBG levels normalized to spot urine creatinine levels.
Measured: 6 months
Annualized Rate of Hemin Administration in Participants With AIP
Annualized rate of hemin doses was evaluated as annualized days of hemin use.
Measured: 6 months
Annualized Rate of Porphyria Attacks in Participants With AHP
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.
Measured: 6 months
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
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.
Measured: Baseline and 6 months
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
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.
Measured: Baseline and 6 months
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
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.
Measured: Baseline and 6 months
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
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.
Measured: Baseline and 6 months
AUC of the Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP
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.
Measured: Baseline and 6 months
Average Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP
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.
Measured: Baseline and 6 months
Change From Baseline in the Physical Component Summary (PCS) of the 12-Item Short Form Survey (SF-12) in Participants With AIP
The SF-12 is a survey designed for use in patients with multiple chronic conditions. This 12-item scale can be used to assess the physical and mental health of respondents. 10 of the 12 questions are answered on a 5 point likert scale and 2 are answered on a 3 point likert scale. The questions are then scored and weighted into 2 subscales, physical health and mental health. Respondents can have a score that ranges from 0-100 with 100 being the best score and indicating high physical or mental health. A 3 point change in SF-12 score reflects a meaningful difference. A higher score indicates improvement.
Measured: Baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2017
- Study start16 Nov 2017
- Primary completion31 Jan 2019
- Study completion31 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Acute Hepatic PorphyriaStudies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03338816
- Sponsor's protocol ID
- ALN-AS1-003
- Status last verified
- May 2022
- First submitted
- 7 Nov 2017
- Last updated
- 22 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.
- Expanded access
- Available
Publications
Badri P, Kolachana K, Duong A, Lasko M, Nandi T, Mehrotra N, Robbie GJ. Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules. Clin Pharmacokinet. 2026 Feb;65(2):293-311. doi: 10.1007/s40262-025-01606-0. Epub 2025 Dec 12.
PubMed 41388232Lee MJ, Kuo HC, Chou LN, Sweetser MT, Wang JD. A randomized, placebo-controlled study of givosiran in patients with acute hepatic porphyrias (ENVISION): Final (36-month) analysis of the Taiwan Cohort. J Formos Med Assoc. 2024 Jun;123(6):679-686. doi: 10.1016/j.jfma.2023.10.016. Epub 2023 Dec 2.
PubMed 38044204Kuter DJ, Bonkovsky HL, Monroy S, Ross G, Guillen-Navarro E, Cappellini MD, Minder AE, Hother-Nielsen O, Ventura P, Jia G, Sweetser MT, Thapar M; ENVISION Investigators. Efficacy and safety of givosiran for acute hepatic porphyria: Final results of the randomized phase III ENVISION trial. J Hepatol. 2023 Nov;79(5):1150-1158. doi: 10.1016/j.jhep.2023.06.013. Epub 2023 Jul 20.
PubMed 37479139Wang B, Ventura P, Takase KI, Thapar M, Cassiman D, Kubisch I, Liu S, Sweetser MT, Balwani M. Disease burden in patients with acute hepatic porphyria: experience from the phase 3 ENVISION study. Orphanet J Rare Dis. 2022 Aug 26;17(1):327. doi: 10.1186/s13023-022-02463-x.
PubMed 36028858Balwani M, Sardh E, Ventura P, Peiro PA, Rees DC, Stolzel U, Bissell DM, Bonkovsky HL, Windyga J, Anderson KE, Parker C, Silver SM, Keel SB, Wang JD, Stein PE, Harper P, Vassiliou D, Wang B, Phillips J, Ivanova A, Langendonk JG, Kauppinen R, Minder E, Horie Y, Penz C, Chen J, Liu S, Ko JJ, Sweetser MT, Garg P, Vaishnaw A, Kim JB, Simon AR, Gouya L; ENVISION Investigators. Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria. N Engl J Med. 2020 Jun 11;382(24):2289-2301. doi: 10.1056/NEJMoa1913147.
PubMed 32521132
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ENVISION: A Phase 3 Randomized, Double-blind, Placebo-Controlled Multicenter Study With an Open-label Extension to Evaluate the Efficacy and Safety of Givosiran in Patients With Acute Hepatic Porphyrias
- ClinicalTrials.gov ID
- NCT03338816
- Acronym / sponsor ID
- ALN-AS1-003
- Conditions
- Acute Hepatic Porphyria, Acute Intermittent Porphyria, Porphyria, Acute Intermittent, Acute Porphyria, Hereditary Coproporphyria (HCP), Variegate Porphyria (VP)
- Keywords
- Acute Intermittent Porphyria (AIP), Acute Hepatic Porphyria (AHP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), ALA dehydratase deficient porphyria (ADP) (ALAD), RNAi therapeutic, Porphyria
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 16 Nov 2017 (actual)
- Primary completion
- 31 Jan 2019 (actual)
- Study completion
- 31 May 2021 (actual)
- First posted
- 9 Nov 2017 (actual)
- Results
- Posted 11 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Givosiran/Givosiran | Experimental | Drug: Givosiran, Drug: PlaceboGivosiran 2.5 mg/kg administered subcutaneously (SC), monthly (QM), for 6 months during the 6-Month Double-blind (DB) Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the Open-label Extension (OLE) Period. |
| Placebo/Givosiran | Placebo comparator | Drug: Givosiran, Drug: PlaceboMatching placebo (normal saline [0.9% NaCl]) was administered SC, QM, for 6 months during the 6-Month DB Period, followed by givosiran 2.5 mg/kg or 1.25 mg/kg SC, QM for 29 months during the OLE period. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- ≥ 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GivosiranAlso: ALN-AS1, GIVLAARIGivosiran by SC | Drug | Givosiran/Givosiran, Placebo/Givosiran |
| PlaceboMatching placebo (normal saline [0.9% NaCl]) by SC | Drug | Givosiran/Givosiran, Placebo/Givosiran |
Primary outcome
Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP)
Time frame: 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.
11 secondary outcomes
The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) in Participants With AIP
Time frame: 3 and 6 months
The PD Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) in Participants With AIP
Time frame: 6 months
Annualized Rate of Hemin Administration in Participants With AIP
Time frame: 6 months
Annualized Rate of Porphyria Attacks in Participants With AHP
Time frame: 6 months
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
Time frame: Baseline and 6 months
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
Time frame: Baseline and 6 months
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
Time frame: Baseline and 6 months
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
Time frame: Baseline and 6 months
AUC of the Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP
Time frame: Baseline and 6 months
Average Change From Baseline in Weekly Mean Score Daily Worst Nausea Score as Measured by NRS in Participants With AIP
Time frame: Baseline and 6 months
Change From Baseline in the Physical Component Summary (PCS) of the 12-Item Short Form Survey (SF-12) in Participants With AIP
Time frame: Baseline and 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41388232Badri P, Kolachana K, Duong A, Lasko M, Nandi T, Mehrotra N, Robbie GJ. Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules. Clin Pharmacokinet. 2026 Feb;65(2):293-311. doi: 10.1007/s40262-025-01606-0. Epub 2025 Dec 12.
- Derived from this study: PubMed 38044204Lee MJ, Kuo HC, Chou LN, Sweetser MT, Wang JD. A randomized, placebo-controlled study of givosiran in patients with acute hepatic porphyrias (ENVISION): Final (36-month) analysis of the Taiwan Cohort. J Formos Med Assoc. 2024 Jun;123(6):679-686. doi: 10.1016/j.jfma.2023.10.016. Epub 2023 Dec 2.
- Derived from this study: PubMed 37479139Kuter DJ, Bonkovsky HL, Monroy S, Ross G, Guillen-Navarro E, Cappellini MD, Minder AE, Hother-Nielsen O, Ventura P, Jia G, Sweetser MT, Thapar M; ENVISION Investigators. Efficacy and safety of givosiran for acute hepatic porphyria: Final results of the randomized phase III ENVISION trial. J Hepatol. 2023 Nov;79(5):1150-1158. doi: 10.1016/j.jhep.2023.06.013. Epub 2023 Jul 20.
- Derived from this study: PubMed 36028858Wang B, Ventura P, Takase KI, Thapar M, Cassiman D, Kubisch I, Liu S, Sweetser MT, Balwani M. Disease burden in patients with acute hepatic porphyria: experience from the phase 3 ENVISION study. Orphanet J Rare Dis. 2022 Aug 26;17(1):327. doi: 10.1186/s13023-022-02463-x.
- Derived from this study: PubMed 32521132Balwani M, Sardh E, Ventura P, Peiro PA, Rees DC, Stolzel U, Bissell DM, Bonkovsky HL, Windyga J, Anderson KE, Parker C, Silver SM, Keel SB, Wang JD, Stein PE, Harper P, Vassiliou D, Wang B, Phillips J, Ivanova A, Langendonk JG, Kauppinen R, Minder E, Horie Y, Penz C, Chen J, Liu S, Ko JJ, Sweetser MT, Garg P, Vaishnaw A, Kim JB, Simon AR, Gouya L; ENVISION Investigators. Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria. N Engl J Med. 2020 Jun 11;382(24):2289-2301. doi: 10.1056/NEJMoa1913147.
- Individual participant dataSharing planned: Yes. Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Alnylam Pharmaceuticals
36 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Givosiran in people with Acute Hepatic Porphyria and Acute Intermittent Porphyria, run by Alnylam Pharmaceuticals at 36 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States, Australia, Japan, Spain, Taiwan and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annualized Rate of Porphyria Attacks in Participants With Acute Intermittent Porphyria (AIP) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03338816, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2024.