PH1Phase 2NCT03350451
An Extension Study of an Investigational Drug, Lumasiran (ALN-GO1), in Participants With Primary Hyperoxaluria Type 1
A Phase 2 study testing Lumasiran in people with PH1 and Primary Hyperoxaluria, run by Alnylam Pharmaceuticals at 9 sites in 5 countries.
Trial summary
The purpose of this study is to evaluate the long-term safety and tolerability of lumasiran in participants with Primary Hyperoxaluria Type 1. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- PH1, Primary Hyperoxaluria, RNAi Therapeutic
- What is being tested?
- Lumasiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 9 sitesin 5 countries
- Study dates
- 4 Apr 2018to 7 Feb 2023
- Phase
- Phase 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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Enrollment within 12 months of completion of Study ALN-GO1-001
- In the opinion of the investigator tolerated the study drug
- If taking Vitamin B6 (pyridoxine), willing to remain on a stable regimen for the study duration
- Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use a highly effective method of contraception
- Willing to provide written informed consent and to comply with study requirements
Who cannot join
- Clinically significant health concerns (with the exception of PH1)
- Clinically significant cardiovascular abnormality
- Abnormal for AST/ALT and any other clinical safety laboratory result considered clinically significant
- Requirement for chronic dialysis
Trial locations and contacts
9 sites in 5 countries.
9 sites in 5 countries
France3 sites
Clinical Trial Site
Bordeaux
Clinical Trial Site
Lyon
Clinical Trial Site
Paris
United Kingdom2 sites
Clinical Trial Site
Birmingham
Clinical Trial Site
London
About this study
Official title: A Phase 2, Multicenter, Open-Label, Extension Study to Evaluate the Long-Term Administration of ALN-GO1 in Patients With Primary Hyperoxaluria Type 1
The purpose of this study is to evaluate the long-term safety and tolerability of lumasiran in participants with Primary Hyperoxaluria Type 1.
- Conditions
- PH1, Primary Hyperoxaluria, RNAi Therapeutic, siRNA, AGT
- Being tested
- Lumasiran
- Keywords
- Hyperoxaluria, Primary, Hyperoxaluria, Kidney Diseases, Urologic Diseases, Metabolism, Inborn Errors, Genetic Diseases, Inborn, Metabolic Diseases
- Medical subject headings
- Hyperoxaluria, Primary, Hyperoxaluria, Kidney Diseases, Urologic Diseases, Metabolism, Inborn Errors, Genetic Diseases, Inborn, Metabolic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LumasiranDrug
Also called ALN-GO1
Multiple doses of lumasiran by SC injection
| Study group | Role | What they receive |
|---|---|---|
| Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M | Experimental | Participants enrolling from study 001B (NCT02706886), received lumasiran, subcutaneous (SC) injection, at a starting dose of 1.0 milligrams per kilograms (mg/kg) once monthly (QM) or 3.0 mg/kg once every 3 months [Q3M]) from Day 1 up to a maximum of Month 6. By Month 6, all participants were approved to change dose and/or dosing regimen to receive lumasiran, SC injection at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period.
All 3 participants who began treatment at 1 mg/kg QM transitioned to 3 mg/kg Q3M regimen by Month 6. As the cumulative dose administered over 6 months was the same for both 1 mg/kg QM \& 3 mg/kg Q3M, these participants were pooled into one arm as recommended by the Safety Review Committee (SRC). Receives: Drug: Lumasiran |
| Lumasiran (ALN-GO1): 3.0 mg/kg QM | Experimental | Participants enrolling from study 001B, received lumasiran, SC injection, at a starting dose of 3.0 mg/kg, QM, from Day 1 up to a maximum of Month 21. By Month 21, all participants were approved to change dosing regimen to receive lumasiran, SC injection, at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period. Receives: Drug: Lumasiran |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With at Least One Adverse Event (AE)
AE is any untoward medical occurrence in a participant or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Safety analysis set included all participants who received any amount of study drug.
Measured: Baseline (Day -1) up to 54 months
Secondary outcomes (3)
Change From Baseline in 24-hour Urinary Oxalate Corrected for Body Surface Area (BSA) at 54 Months
Oxalate produced by the liver is the key toxic metabolite that drives disease pathology in participants with primary hyperoxaluria type 1 (PH1). The risk of disease complications increase continuously as oxalate levels increase. 24-hour urinary oxalate (millimole [mmol]/ 24 hour [h]/1.73 meters squared [m^2]) corrected for BSA at each visit per participant was calculated as follows: [Urine oxalate concentration (micromole per liter [umol/L])/1000 (umol/mmol)]*[24hour urine volume (mL)/1000 (mL/L)]* [24 hours/actual collection hours]*1.73/(BSA). Baseline was the derived baseline value from the lumasiran treated period of Study ALN-GO1-001. A negative change from baseline indicated a favorable outcome. PD analysis set included all participants who received any amount of study drug and who had at least 1 post-dose urine sample for PD. Overall number of participants analyzed are the number of participants with data available for analysis.
Measured: Baseline (Day -1) up to 54 months
Change From Baseline in 24-hour Urinary Oxalate:Creatinine Ratio at 54 Months
Baseline is the derived baseline value from the lumasiran treated period of Study ALN-GO1-001. A negative change from baseline indicates a favorable outcome. PD analysis set included all participants who received any amount of study drug and who had at least 1 post-dose urine sample for PD.
Measured: Baseline (Day -1) up to 54 months
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at 54 Months
Baseline was defined as the last measurement prior to the first dose of lumasiran in the ALN-GO1-001 study. eGFR was calculated based on the Modification of Diet in Renal Disease (MDRD) formula for participants >=18 years of age at enrollment and the Schwartz Bedside formula for participants <18 years of age at enrollment. eGFR based on MDRD formula was calculated as follows: eGFR (mL/min/1.73 m^2) = 175 × (serum creatinine {SCr} [μmol/deciliter(dL)]/88.4)-1.154 × (age)-0.203 × (0.742, if female), or × (1.212, if African American) and based on Schwartz formula: eGFR (mL/min/1.73m2) = (36.2 × height [cm])/ SCr (μmol /dL). Safety analysis set included all participants who received any amount of study drug.
Measured: Baseline (Day -1) up to 54 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2017
- Study start4 Apr 2018
- Primary completion7 Feb 2023
- Study completion7 Feb 2023
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.
- Other trials for PH1Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 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
- NCT03350451
- Sponsor's protocol ID
- ALN-GO1-002
- Other IDs
- 2016-003134-24, 2016
- Status last verified
- Mar 2024
- First submitted
- 17 Nov 2017
- Last updated
- 25 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Multicenter, Open-Label, Extension Study to Evaluate the Long-Term Administration of ALN-GO1 in Patients With Primary Hyperoxaluria Type 1
- ClinicalTrials.gov ID
- NCT03350451
- Acronym / sponsor ID
- ALN-GO1-002
- Conditions
- PH1, Primary Hyperoxaluria, RNAi Therapeutic, siRNA, AGT
- Keywords
- Hyperoxaluria, Primary, Hyperoxaluria, Kidney Diseases, Urologic Diseases, Metabolism, Inborn Errors, Genetic Diseases, Inborn, Metabolic Diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 4 Apr 2018 (actual)
- Primary completion
- 7 Feb 2023 (actual)
- Study completion
- 7 Feb 2023 (actual)
- First posted
- 22 Nov 2017 (actual)
- Results
- Posted 25 Apr 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 evaluate the long-term safety and tolerability of lumasiran in participants with Primary Hyperoxaluria Type 1.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M | Experimental | Drug: LumasiranParticipants enrolling from study 001B (NCT02706886), received lumasiran, subcutaneous (SC) injection, at a starting dose of 1.0 milligrams per kilograms (mg/kg) once monthly (QM) or 3.0 mg/kg once every 3 months [Q3M]) from Day 1 up to a maximum of Month 6. By Month 6, all participants were approved to change dose and/or dosing regimen to receive lumasiran, SC injection at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period. All 3 participants who began treatment at 1 mg/kg QM transitioned to 3 mg/kg Q3M regimen by Month 6. As the cumulative dose administered over 6 months was the same for both 1 mg/kg QM \& 3 mg/kg Q3M, these participants were pooled into one arm as recommended by the Safety Review Committee (SRC). |
| Lumasiran (ALN-GO1): 3.0 mg/kg QM | Experimental | Drug: LumasiranParticipants enrolling from study 001B, received lumasiran, SC injection, at a starting dose of 3.0 mg/kg, QM, from Day 1 up to a maximum of Month 21. By Month 21, all participants were approved to change dosing regimen to receive lumasiran, SC injection, at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Enrollment within 12 months of completion of Study ALN-GO1-001
- In the opinion of the investigator tolerated the study drug
- If taking Vitamin B6 (pyridoxine), willing to remain on a stable regimen for the study duration
- Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use a highly effective method of contraception
- Willing to provide written informed consent and to comply with study requirements
Key exclusion criteria (4 listed)
- Clinically significant health concerns (with the exception of PH1)
- Clinically significant cardiovascular abnormality
- Abnormal for AST/ALT and any other clinical safety laboratory result considered clinically significant
- Requirement for chronic dialysis
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 |
|---|---|---|
| LumasiranAlso: ALN-GO1Multiple doses of lumasiran by SC injection | Drug | Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M, Lumasiran (ALN-GO1): 3.0 mg/kg QM |
Primary outcome
Number of Participants With at Least One Adverse Event (AE)
Time frame: Baseline (Day -1) up to 54 months
AE is any untoward medical occurrence in a participant or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Safety analysis set included all participants who received any amount of study drug.
3 secondary outcomes
Change From Baseline in 24-hour Urinary Oxalate Corrected for Body Surface Area (BSA) at 54 Months
Time frame: Baseline (Day -1) up to 54 months
Change From Baseline in 24-hour Urinary Oxalate:Creatinine Ratio at 54 Months
Time frame: Baseline (Day -1) up to 54 months
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at 54 Months
Time frame: Baseline (Day -1) up to 54 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Related trials for PH1
RecruitingPhase 1/2
Phase 1/2 Study of ABO-101 in Primary Hyperoxaluria Type 1 (redePHine)
Primary Hyperoxaluria Type 1 (PH1)
Enrolling by invitationObservational study
Follow-up of Pediatric Patients Affected by Primary Hyperoxaluria Type 1 (PH1) Treated With Lumasiran
Hyperoxaluria, Primary
RecruitingPhase 2
Study of YOLT-203 in Children and Adults With Primary Hyperoxaluria Type 1 (PH1)
Primary Hyperoxaluria Type 1, PH1
Active, not recruitingPhase 3
Long Term Extension Study in Patients With Primary Hyperoxaluria
Primary Hyperoxaluria Type 1 (PH1), Primary Hyperoxaluria Type 2 (PH2)
Active, not recruitingObservational study
BONAPH1DE, A Prospective Observational Study of Patients With Primary Hyperoxaluria Type 1 (PH1)
Primary Hyperoxaluria Type 1
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
9 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lumasiran in people with PH1 and Primary Hyperoxaluria, run by Alnylam Pharmaceuticals at 9 sites in 5 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 5 inclusion and 4 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 25 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 9 sites in France, Israel, United Kingdom, Germany, Netherlands. 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 phase mean?
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 25 Apr 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?
Number of Participants With at Least One Adverse Event (AE) (time frame: Baseline (Day -1) up to 54 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Apr 2024.