Amyloidosis, FamilialPhase 3NCT03862807
Patisiran in Patients With Hereditary Transthyretin-mediated Amyloidosis (hATTR Amyloidosis) Disease Progression Post-Liver Transplant
A Phase 3 study testing Patisiran in people with Amyloidosis, Familial and Transthyretin Amyloidosis, run by Alnylam Pharmaceuticals at 9 sites in 7 countries.
Trial summary
The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics of patisiran in participants with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) with disease progression after liver transplant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyloidosis, Familial, Transthyretin Amyloidosis
- What is being tested?
- Patisiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 9 sitesin 7 countries
- Study dates
- 27 Mar 2019to 20 Oct 2020
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Received liver transplant for treatment of hATTR amyloidosis ≥12 months before study start
- Has increase in polyneuropathy disability (PND) score after liver transplant
- Has received stable immunosuppressive regimen with ≤10 mg/day of prednisone for at least 3 months before study start
- Has Karnofsky Performance Status (KPS) of ≥70%
- Has vitamin A level greater than or equal to lower limit of normal
Who cannot join
- Has previously received inotersen or patisiran
- Has clinically significant liver function test abnormalities
- Has known portal hypertension with ascites
- Has estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73 m^2
- Has known leptomeningeal amyloidosis
- Has infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
Show all 10Show fewer
- Has New York Heart Association heart failure classification of >2
- Is wheelchair bound or bedridden
- Has received organ transplants other than liver transplant
- Will be using another tetramer stabilizer during the study
Trial locations and contacts
9 sites in 7 countries.
9 sites in 7 countries
France2 sites
Clinical Trial Site
Créteil
Clinical Trial Site
Le Kremlin-Bicêtre
About this study
Official title: An Open-label Study to Evaluate Safety, Efficacy and Pharmacokinetics (PK) of Patisiran-LNP in Patients With Hereditary Transthyretin-mediated Amyloidosis (hATTR Amyloidosis) With Disease Progression Post-Orthotopic Liver Transplant
The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics of patisiran in participants with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) with disease progression after liver transplant.
- Conditions
- Amyloidosis, Familial, Transthyretin Amyloidosis
- Being tested
- Patisiran
- Medical subject headings
- Amyloidosis, Familial, Amyloidosis, Hereditary, Transthyretin-Related
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PatisiranDrug
Also called ALN-TTR02, ONPATTRO
Patisiran was administered via IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| Patisiran | Experimental | Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w. Receives: Drug: Patisiran |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average of Month 6 and Month 12 Percentage Reduction From Baseline in Serum Transthyretin (TTR)
Serum TTR was assessed using enzyme linked immunosorbent assay (ELISA). The average of the percentage reduction in serum TTR observed at Month 6 and at Month 12 is first calculated for each patient and then the median (95% CI) of these averaged values is summarized for the Safety Analysis Set.
Measured: Baseline, Months 6 and 12
Secondary outcomes (6)
Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 12
The NIS is a composite neurologic impairment score that assesses motor weakness (NIS-W), sensation (NIS-S) and reflexes (NIS-R) by physical exam. The minimum and maximum values are 0 and 244, respectively. A higher score indicates a worse outcome.
Measured: Baseline, Month 12
Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Score at Month 12
The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The minimum and maximum values are -4 and 136, respectively. A higher score indicates a worse outcome.
Measured: Baseline, Month 12
Change From Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 12
The R-ODS is comprised of a 24-item linearly weighted scale that specifically captures activity and social participation limitations. The minimum and maximum values are 0 and 48, respectively. A higher score indicates a better outcome.
Measured: Baseline, Month 12
Change From Baseline in the Composite Autonomic Symptom Score (COMPASS-31) at Month 12
The COMPASS-31 questionnaire is a measure of autonomic neuropathy symptoms. The questions evaluate 6 autonomic domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor). The minimum and maximum values are 0 and 100, respectively. A higher score indicates a worse outcome.
Measured: Baseline, Month 12
Change From Baseline in the Modified Body Mass Index (mBMI) at Month 12
Nutritional status of participants was evaluated using the mBMI, calculated as BMI (kg/m^2) multiplied by albumin (g/L). An increase from baseline in mBMI suggests improvement, and a decrease from baseline suggests worsening.
Measured: Baseline, Month 12
Percentage of Participants With Adverse Events
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: From baseline to end of study at Month 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2019
- Study start27 Mar 2019
- Primary completion6 Oct 2020
- Study completion20 Oct 2020
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 (3)Papers the sponsor has linked to this study.
- Other trials for Amyloidosis, FamilialStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 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
- NCT03862807
- Sponsor's protocol ID
- ALN-TTR02-008
- Other IDs
- 2018-003519-24, 2018
- Status last verified
- Nov 2021
- First submitted
- 28 Feb 2019
- Last updated
- 22 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- 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.
Publications
Badri P, Habtemariam B, Melch M, Clausen VA, Arum S, Li X, Jay PY, Vest J, Robbie GJ. Pharmacokinetics and Pharmacodynamics of Patisiran in Patients with hATTR Amyloidosis and with Polyneuropathy After Liver Transplantation. Clin Pharmacokinet. 2023 Oct;62(10):1509-1522. doi: 10.1007/s40262-023-01292-w. Epub 2023 Aug 28.
PubMed 37639169Schmidt HH, Wixner J, Plante-Bordeneuve V, Munoz-Beamud F, Llado L, Gillmore JD, Mazzeo A, Li X, Arum S, Jay PY, Adams D; Patisiran Post-LT Study Group. Patisiran treatment in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy after liver transplantation. Am J Transplant. 2022 Jun;22(6):1646-1657. doi: 10.1111/ajt.17009. Epub 2022 Mar 26.
PubMed 35213769Seibert K, Wlodarski R, Sarswat N, Appelbaum D, Issa NP, Soliven B, Rezania K. Progressive Multiple Mononeuropathy in a Patient With Familial Transthyretin Amyloidosis After Liver Transplantation. J Clin Neuromuscul Dis. 2022 Mar 1;23(3):143-147. doi: 10.1097/CND.0000000000000368.
PubMed 35188911
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
- An Open-label Study to Evaluate Safety, Efficacy and Pharmacokinetics (PK) of Patisiran-LNP in Patients With Hereditary Transthyretin-mediated Amyloidosis (hATTR Amyloidosis) With Disease Progression Post-Orthotopic Liver Transplant
- ClinicalTrials.gov ID
- NCT03862807
- Acronym / sponsor ID
- ALN-TTR02-008
- Conditions
- Amyloidosis, Familial, Transthyretin Amyloidosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 27 Mar 2019 (actual)
- Primary completion
- 6 Oct 2020 (actual)
- Study completion
- 20 Oct 2020 (actual)
- First posted
- 5 Mar 2019 (actual)
- Results
- Posted 21 Dec 2021
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 efficacy, safety and pharmacokinetics of patisiran in participants with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) with disease progression after liver transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patisiran | Experimental | Drug: PatisiranParticipants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Received liver transplant for treatment of hATTR amyloidosis ≥12 months before study start
- Has increase in polyneuropathy disability (PND) score after liver transplant
- Has received stable immunosuppressive regimen with ≤10 mg/day of prednisone for at least 3 months before study start
- Has Karnofsky Performance Status (KPS) of ≥70%
- Has vitamin A level greater than or equal to lower limit of normal
Key exclusion criteria (10 listed)
- Has previously received inotersen or patisiran
- Has clinically significant liver function test abnormalities
- Has known portal hypertension with ascites
- Has estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73 m^2
- Has known leptomeningeal amyloidosis
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 |
|---|---|---|
| PatisiranAlso: ALN-TTR02, ONPATTROPatisiran was administered via IV infusion. | Drug | Patisiran |
Primary outcome
Average of Month 6 and Month 12 Percentage Reduction From Baseline in Serum Transthyretin (TTR)
Time frame: Baseline, Months 6 and 12
Serum TTR was assessed using enzyme linked immunosorbent assay (ELISA). The average of the percentage reduction in serum TTR observed at Month 6 and at Month 12 is first calculated for each patient and then the median (95% CI) of these averaged values is summarized for the Safety Analysis Set.
6 secondary outcomes
Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 12
Time frame: Baseline, Month 12
Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Score at Month 12
Time frame: Baseline, Month 12
Change From Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 12
Time frame: Baseline, Month 12
Change From Baseline in the Composite Autonomic Symptom Score (COMPASS-31) at Month 12
Time frame: Baseline, Month 12
Change From Baseline in the Modified Body Mass Index (mBMI) at Month 12
Time frame: Baseline, Month 12
Percentage of Participants With Adverse Events
Time frame: From baseline to end of study at Month 13
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 37639169Badri P, Habtemariam B, Melch M, Clausen VA, Arum S, Li X, Jay PY, Vest J, Robbie GJ. Pharmacokinetics and Pharmacodynamics of Patisiran in Patients with hATTR Amyloidosis and with Polyneuropathy After Liver Transplantation. Clin Pharmacokinet. 2023 Oct;62(10):1509-1522. doi: 10.1007/s40262-023-01292-w. Epub 2023 Aug 28.
- Derived from this study: PubMed 35213769Schmidt HH, Wixner J, Plante-Bordeneuve V, Munoz-Beamud F, Llado L, Gillmore JD, Mazzeo A, Li X, Arum S, Jay PY, Adams D; Patisiran Post-LT Study Group. Patisiran treatment in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy after liver transplantation. Am J Transplant. 2022 Jun;22(6):1646-1657. doi: 10.1111/ajt.17009. Epub 2022 Mar 26.
- Derived from this study: PubMed 35188911Seibert K, Wlodarski R, Sarswat N, Appelbaum D, Issa NP, Soliven B, Rezania K. Progressive Multiple Mononeuropathy in a Patient With Familial Transthyretin Amyloidosis After Liver Transplantation. J Clin Neuromuscul Dis. 2022 Mar 1;23(3):143-147. doi: 10.1097/CND.0000000000000368.
- 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 Amyloidosis, Familial
RecruitingObservational study
Essen Amyloidosis Registry
Amyloidosis; Systemic, Amyloidosis Cardiac
Active, not recruitingPhase 3
A Phase 3 Study of NTLA-2001 in ATTRv-PN
Neuromuscular Disease, Neuromuscular Diseases (NMD)
RecruitingPhase 3
MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
RecruitingObservational study
Swiss Cardiac Amyloidosis REgistry (Swiss-CARE)
Amyloid Cardiomyopathy
Not yet recruitingObservational study
Southeastern ATTR Amyloidosis Consortium: SEATTRAC Family Registry
Amyloidosis, Hereditary
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 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Patisiran in people with Amyloidosis, Familial and Transthyretin Amyloidosis, run by Alnylam Pharmaceuticals at 9 sites in 7 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 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 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 9 sites in France, Spain, Germany, Italy, Portugal and 2 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. 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 21 Dec 2021). 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?
Average of Month 6 and Month 12 Percentage Reduction From Baseline in Serum Transthyretin (TTR) (time frame: Baseline, Months 6 and 12). 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 NCT03862807, which also lists 3 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.