Acute Intermittent PorphyriaPhase 1NCT02452372
A Phase 1 Study of Givosiran (ALN-AS1) in Patients With Acute Intermittent Porphyria (AIP)
A Phase 1 study testing givosiran (ALN-AS1) and Sterile Normal Saline (0.9% NaCl) in people with Acute Intermittent Porphyria, run by Alnylam Pharmaceuticals at 6 sites in 3 countries.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of givosiran (ALN-AS1) in AIP patients as well as to characterize pharmacokinetics (PK) and pharmacodynamics (PD) of ALN-AS1 in AIP patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Intermittent Porphyria
- What is being tested?
- givosiran (ALN-AS1) and Sterile Normal Saline (0.9% NaCl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 6 May 2015to 6 Sep 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of AIP
- Urine PBG at Screening indicating patient is a high excreter
- No clinically significant health concerns
- Women of child bearing potential must have a negative pregnancy test, not be nursing, and use effective contraception
- Willing to provide written informed consent and willing to comply with study requirements.
- Diagnosis of AIP
Show all 10Show fewer
- Patient experienced a porphyria attack or was taking medication to prevent attacks recently
- No clinically significant health concerns
- Women of child bearing potential must have a negative pregnancy test, not be nursing, and use effective contraception
- Willing to provide written informed consent and willing to comply with study requirements.
Who cannot join
- Porphyria attack within 6 months of screening
- Started a new prescription medication within 3 months of screening
- Clinically significant abnormal laboratory results
- Received an investigational agent 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
- Part C
Show all 10Show fewer
- Stared a new prescription medication within 3 months of screening
- Clinically significant abnormal laboratory results
- Received an investigational agent 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
6 sites in 3 countries.
6 sites in 3 countries
United States4 sites
Clinical Trial Site
Birmingham, Alabama
Clinical Trial Site
Galveston, Texas
Clinical Trial Site
New York, New York
Clinical Trial Site
San Francisco, California
About this study
Official title: A Phase 1, Single-ascending Dose, Multiple-ascending Dose, and Multi-dose Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN AS1 in Patients With Acute Intermittent Porphyria (AIP)
The purpose of this study is to evaluate the safety and tolerability of givosiran (ALN-AS1) in AIP patients as well as to characterize pharmacokinetics (PK) and pharmacodynamics (PD) of ALN-AS1 in AIP patients.
- Conditions
- Acute Intermittent Porphyria
- Being tested
- givosiran (ALN-AS1), Sterile Normal Saline (0.9% NaCl)
- Keywords
- RNAi therapeutic, Porphyria, AIP
- 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.
givosiran (ALN-AS1)Drug
Single or multiple doses of ALN-AS1 by subcutaneous (sc) injection
Sterile Normal Saline (0.9% NaCl)Drug
calculated volume to match active comparator
| Study group | Role | What they receive |
|---|---|---|
| givosiran (ALN-AS1) | Active comparator | Not described Receives: Drug: givosiran (ALN-AS1) |
| Sterile Normal Saline (0.9% NaCl) | Placebo comparator | Not described Receives: Drug: Sterile Normal Saline (0.9% NaCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety of givosiran evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation
Measured: Part A (SAD phase): through day 42; Part B (MAD) phase: through Day 70; Part C (MD) phase: through Day 168
Secondary outcomes (6)
Profile of Pharmacokinetics (PK) of givosiran
Cmax
Measured: Part A (SAD) phase: predose - 42 days post-dose; Part B (MAD) phase: predose - 70 days post-dose; Part C (MD) phase: predose - 168 days post-dose
Profile of Pharmacokinetics (PK) of givosiran
tmax
Measured: Part A (SAD) phase: predose - 42 days post-dose; Part B (MAD) phase: predose - 70 days post-dose; Part C (MD) phase: predose - 168 days post-dose
Profile of Pharmacokinetics (PK) of givosiran
AUC
Measured: Part A (SAD) phase: predose - 42 days post-dose; Part B (MAD) phase: predose - 70 days post-dose; Part C (MD) phase: predose - 168 days post-dose
Profile of Pharmacokinetics (PK) of givosiran
t1/2
Measured: Part A (SAD) phase: predose - 42 days post-dose; Part B (MAD) phase: predose - 70 days post-dose; Part C (MD) phase: predose - 168 days post-dose
The change in delta-aminolevulinic acid (ALA) from baseline
Measured: Part A (SAD) phase: screening - 42 days post-dose; Part B (MAD) phase: screening - 70 days post-dose; Part C (MD) phase: screening - 168 days post-dose
The change in Porphobilinogen (PBG) from baseline
Measured: Part A (SAD) phase: screening - 42 days post-dose; Part B (MAD) phase: screening - 70 days post-dose; Part C (MD) phase: screening - 168 days post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2015 (estimated)
- Study start6 May 2015
- Primary completion6 Sep 2017
- Study completion6 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Amy Simon, MD, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02452372
- Sponsor's protocol ID
- ALN-AS1-001
- Status last verified
- Jun 2018
- First submitted
- 19 May 2015
- Last updated
- 14 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
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 39363243Sardh E, Harper P, Balwani M, Stein P, Rees D, Bissell DM, Desnick R, Parker C, Phillips J, Bonkovsky HL, Vassiliou D, Penz C, Chan-Daniels A, He Q, Querbes W, Fitzgerald K, Kim JB, Garg P, Vaishnaw A, Simon AR, Anderson KE. Phase 1 Trial of an RNA Interference Therapy for Acute Intermittent Porphyria. N Engl J Med. 2019 Feb 7;380(6):549-558. doi: 10.1056/NEJMoa1807838.
PubMed 30726693
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Single-ascending Dose, Multiple-ascending Dose, and Multi-dose Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN AS1 in Patients With Acute Intermittent Porphyria (AIP)
- ClinicalTrials.gov ID
- NCT02452372
- Acronym / sponsor ID
- ALN-AS1-001
- Conditions
- Acute Intermittent Porphyria
- Keywords
- RNAi therapeutic, Porphyria, AIP
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 6 May 2015 (actual)
- Primary completion
- 6 Sep 2017 (actual)
- Study completion
- 6 Sep 2017 (actual)
- First posted
- 22 May 2015 (estimated)
- Results
- Not posted in the source record
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 safety and tolerability of givosiran (ALN-AS1) in AIP patients as well as to characterize pharmacokinetics (PK) and pharmacodynamics (PD) of ALN-AS1 in AIP patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| givosiran (ALN-AS1) | Active comparator | Drug: givosiran (ALN-AS1) |
| Sterile Normal Saline (0.9% NaCl) | Placebo comparator | Drug: Sterile Normal Saline (0.9% NaCl) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Diagnosis of AIP
- Urine PBG at Screening indicating patient is a high excreter
- No clinically significant health concerns
- Women of child bearing potential must have a negative pregnancy test, not be nursing, and use effective contraception
- Willing to provide written informed consent and willing to comply with study requirements.
Key exclusion criteria (10 listed)
- Porphyria attack within 6 months of screening
- Started a new prescription medication within 3 months of screening
- Clinically significant abnormal laboratory results
- Received an investigational agent 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 |
|---|---|---|
| givosiran (ALN-AS1)Single or multiple doses of ALN-AS1 by subcutaneous (sc) injection | Drug | givosiran (ALN-AS1) |
| Sterile Normal Saline (0.9% NaCl)calculated volume to match active comparator | Drug | Sterile Normal Saline (0.9% NaCl) |
Primary outcome
The safety of givosiran evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation
Time frame: Part A (SAD phase): through day 42; Part B (MAD) phase: through Day 70; Part C (MD) phase: through Day 168
6 secondary outcomes
Profile of Pharmacokinetics (PK) of givosiran
Time frame: Part A (SAD) phase: predose - 42 days post-dose; Part B (MAD) phase: predose - 70 days post-dose; Part C (MD) phase: predose - 168 days post-dose
Profile of Pharmacokinetics (PK) of givosiran
Time frame: Part A (SAD) phase: predose - 42 days post-dose; Part B (MAD) phase: predose - 70 days post-dose; Part C (MD) phase: predose - 168 days post-dose
Profile of Pharmacokinetics (PK) of givosiran
Time frame: Part A (SAD) phase: predose - 42 days post-dose; Part B (MAD) phase: predose - 70 days post-dose; Part C (MD) phase: predose - 168 days post-dose
Profile of Pharmacokinetics (PK) of givosiran
Time frame: Part A (SAD) phase: predose - 42 days post-dose; Part B (MAD) phase: predose - 70 days post-dose; Part C (MD) phase: predose - 168 days post-dose
The change in delta-aminolevulinic acid (ALA) from baseline
Time frame: Part A (SAD) phase: screening - 42 days post-dose; Part B (MAD) phase: screening - 70 days post-dose; Part C (MD) phase: screening - 168 days post-dose
The change in Porphobilinogen (PBG) from baseline
Time frame: Part A (SAD) phase: screening - 42 days post-dose; Part B (MAD) phase: screening - 70 days post-dose; Part C (MD) phase: screening - 168 days post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2018.
- 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.
- Derived from this study: PubMed 30726693Sardh E, Harper P, Balwani M, Stein P, Rees D, Bissell DM, Desnick R, Parker C, Phillips J, Bonkovsky HL, Vassiliou D, Penz C, Chan-Daniels A, He Q, Querbes W, Fitzgerald K, Kim JB, Garg P, Vaishnaw A, Simon AR, Anderson KE. Phase 1 Trial of an RNA Interference Therapy for Acute Intermittent Porphyria. N Engl J Med. 2019 Feb 7;380(6):549-558. doi: 10.1056/NEJMoa1807838.
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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.
Amy Simon, MD study director
Alnylam Pharmaceuticals
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing givosiran (ALN-AS1) and Sterile Normal Saline (0.9% NaCl) in people with Acute Intermittent Porphyria, run by Alnylam Pharmaceuticals at 6 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 10 inclusion and 10 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 14 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The safety of givosiran evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation (time frame: Part A (SAD phase): through day 42; Part B (MAD) phase: through Day 70; Part C (MD) phase: through Day 168). 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 NCT02452372, which also lists 2 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 14 Jun 2018.