Acute Intermittent PorphyriaPhase 1/2NCT02949830
A Study to Evaluate Long-term Safety and Clinical Activity of Givosiran (ALN-AS1) in Patient With Acute Intermittent Porphyria (AIP)
A Phase 1/2 study testing Givosiran in people with Acute Intermittent Porphyria, run by Alnylam Pharmaceuticals at 5 sites in 3 countries.
Trial summary
The purpose of this study is to determine the long-term safety, tolerability and pharmacokinetics of givosiran (ALN-AS1) in AIP patients who completed study ALN-AS1-001 (NCT02452372). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Intermittent Porphyria
- What is being tested?
- Givosiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 5 sitesin 3 countries
- Study dates
- Oct 2016to 5 Nov 2021
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Completed participation in Part C of study ALN-AS1-001 (NCT02452372)
- Not on a scheduled regimen of hemin
- Women of child bearing potential must have a negative serum pregnancy test, not be nursing, and use acceptable contraception
- Willing and able to comply with the study requirements and to provide written informed consent
Who cannot join
- Clinically significant abnormal laboratory results
- Received an investigational agent (other than ALN-AS1) within 90 days before the first dose of study drug or are in follow-up of another clinical study
- History of multiple drug allergies or intolerance to subcutaneous injection
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
United States3 sites
Clinical Trial Site
Galveston, Texas
Clinical Trial Site
New York, New York
Clinical Trial Site
San Francisco, California
About this study
Official title: A Multicenter, Open-label Extension Study to Evaluate the Long-term Safety and Clinical Activity of Subcutaneously Administered ALN-AS1 in Patients With Acute Intermittent Porphyria Who Have Completed a Previous Clinical Study With ALN-AS1
The purpose of this study is to determine the long-term safety, tolerability and pharmacokinetics of givosiran (ALN-AS1) in AIP patients who completed study ALN-AS1-001 (NCT02452372).
- Conditions
- Acute Intermittent Porphyria
- Being tested
- Givosiran
- Keywords
- RNAi therapeutic, Porphyria, AIP, Heme/Haem Arginate
- Medical subject headings
- Porphyria, Acute Intermittent, 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 subcutaneous (SC) injection.
| Study group | Role | What they receive |
|---|---|---|
| Givosiran | Experimental | At the beginning of this study, participants received either givosiran 2.5 mg/kg subcutaneous (SC) injection once monthly(QM), givosiran 5.0 mg/kg SC injection QM, or givosiran 5.0 mg/kg SC injection once every 3 months (Q3M). Within a year, all participants were transitioned to givosiran 2.5 mg/kg SC injection QM. Receives: Drug: Givosiran |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant or clinical investigational patient administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Measured: Through Month 49
Secondary outcomes (4)
The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) as Measured by Percent Decrease From Baseline
The PD effect of givosiran was evaluated by spot urine ALA levels normalized to spot urine creatinine levels.
Measured: Baseline; Month 48
The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) as Measured by Percent Decrease From Baseline
The PD effect of givosiran was evaluated by spot urine PBG levels normalized to spot urine creatinine levels.
Measured: Baseline; Month 48
Annualized Rate of Composite Porphyria Attacks
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. Composite porphyria attacks included porphyria attacks that required hospitalization, urgent healthcare visit, or intravenous (IV) hemin administration at home. The annualized attack rate (AAR) was calculated as the number of composite porphyria attacks/total person-years.
Measured: Through Month 48
Annualized Rate of Hemin Administration
The annualized rate of hemin administration was evaluated by annualized days of hemin use, which is calculated as the number of doses of hemin administered/total person-years.
Measured: Through Month 49
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2016 (estimated)
- Study startOct 2016
- Primary completion5 Nov 2021
- Study completion5 Nov 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 (1)Papers the sponsor has linked to this study.
- Other trials for Acute Intermittent 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 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
- NCT02949830
- Sponsor's protocol ID
- ALN-AS1-002
- Other IDs
- 2016-002638-54, 2016
- Status last verified
- Mar 2024
- First submitted
- 28 Oct 2016
- Last updated
- 12 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Sardh E, Balwani M, Rees DC, Anderson KE, Jia G, Sweetser MT, Wang B. Long-term follow-up of givosiran treatment in patients with acute intermittent porphyria from a phase 1/2, 48-month open-label extension study. Orphanet J Rare Dis. 2024 Oct 3;19(1):365. doi: 10.1186/s13023-024-03284-w.
PubMed 39363243
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label Extension Study to Evaluate the Long-term Safety and Clinical Activity of Subcutaneously Administered ALN-AS1 in Patients With Acute Intermittent Porphyria Who Have Completed a Previous Clinical Study With ALN-AS1
- ClinicalTrials.gov ID
- NCT02949830
- Acronym / sponsor ID
- ALN-AS1-002
- Conditions
- Acute Intermittent Porphyria
- Keywords
- RNAi therapeutic, Porphyria, AIP, Heme/Haem Arginate
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2016 (actual)
- Primary completion
- 5 Nov 2021 (actual)
- Study completion
- 5 Nov 2021 (actual)
- First posted
- 31 Oct 2016 (estimated)
- Results
- Posted 12 Mar 2024
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 determine the long-term safety, tolerability and pharmacokinetics of givosiran (ALN-AS1) in AIP patients who completed study ALN-AS1-001 (NCT02452372).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Givosiran | Experimental | Drug: GivosiranAt the beginning of this study, participants received either givosiran 2.5 mg/kg subcutaneous (SC) injection once monthly(QM), givosiran 5.0 mg/kg SC injection QM, or givosiran 5.0 mg/kg SC injection once every 3 months (Q3M). Within a year, all participants were transitioned to givosiran 2.5 mg/kg SC injection QM. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Completed participation in Part C of study ALN-AS1-001 (NCT02452372)
- Not on a scheduled regimen of hemin
- Women of child bearing potential must have a negative serum pregnancy test, not be nursing, and use acceptable contraception
- Willing and able to comply with the study requirements and to provide written informed consent
Key exclusion criteria (3 listed)
- Clinically significant abnormal laboratory results
- Received an investigational agent (other than ALN-AS1) within 90 days before the first dose of study drug or are in follow-up of another clinical study
- History of multiple drug allergies or intolerance to subcutaneous injection
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 subcutaneous (SC) injection. | Drug | Givosiran |
Primary outcome
Percentage of Participants With Adverse Events (AEs)
Time frame: Through Month 49
An AE is any untoward medical occurrence in a participant or clinical investigational patient administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
4 secondary outcomes
The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Delta-aminolevulinic Acid (ALA) as Measured by Percent Decrease From Baseline
Time frame: Baseline; Month 48
The Pharmacodynamic (PD) Effect of Givosiran on Urine Levels of Porphobilinogen (PBG) as Measured by Percent Decrease From Baseline
Time frame: Baseline; Month 48
Annualized Rate of Composite Porphyria Attacks
Time frame: Through Month 48
Annualized Rate of Hemin Administration
Time frame: Through Month 49
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39363243Sardh E, Balwani M, Rees DC, Anderson KE, Jia G, Sweetser MT, Wang B. Long-term follow-up of givosiran treatment in patients with acute intermittent porphyria from a phase 1/2, 48-month open-label extension study. Orphanet J Rare Dis. 2024 Oct 3;19(1):365. doi: 10.1186/s13023-024-03284-w.
- Individual participant dataSharing planned: Undecided
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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
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Givosiran in people with Acute Intermittent Porphyria, run by Alnylam Pharmaceuticals at 5 sites in 3 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 4 inclusion and 3 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 12 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Sweden, United Kingdom. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 12 Mar 2024). 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?
Percentage of Participants With Adverse Events (AEs) (time frame: Through Month 49). 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 NCT02949830, which also lists 1 linked publication.
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 12 Mar 2024.