TTR-mediated AmyloidosisPhase 2NCT01961921
The Study of ALN-TTR02 (Patisiran) for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis in Patients Who Have Already Been Treated With ALN-TTR02 (Patisiran)
A Phase 2 study testing ALN-TTR02 (patisiran) administered by intravenous (IV) infusion in people with TTR-mediated Amyloidosis, run by Alnylam Pharmaceuticals at 9 sites in 7 countries.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of long-term dosing with ALN-TTR02 (patisiran) in patients with transthyretin (TTR) mediated amyloidosis (ATTR). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- TTR-mediated Amyloidosis
- What is being tested?
- ALN-TTR02 (patisiran) administered by intravenous (IV) infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 9 sitesin 7 countries
- Study dates
- Oct 2013to Aug 2016
- 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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Previously received and tolerated ALN-TTR02 (patisiran) in Study ALN-TTR02-002.
- Adequate Karnofsky performance status, liver function, and renal function.
Who cannot join
- Pregnant or nursing.
- Has had a liver transplant.
- Has a New York Heart Association heart failure classification >2.
- Has unstable angina.
- Has uncontrolled clinically significant cardiac arrhythmia.
Trial locations and contacts
9 sites in 7 countries.
9 sites in 7 countries
France2 sites
Clinical Trial Site
Le Kremlin-Bicêtre
Clinical Trial Site
Marseille
About this study
Official title: A Phase 2, Multicenter, Open-Label, Extension Study to Evaluate the Long-Term Safety, Clinical Activity, and Pharmacokinetics of ALN-TTR02 in Patients With Familial Amyloidotic Polyneuropathy Who Have Previously Received ALN-TTR02
The purpose of this study is to evaluate the safety and tolerability of long-term dosing with ALN-TTR02 (patisiran) in patients with transthyretin (TTR) mediated amyloidosis (ATTR).
- Conditions
- TTR-mediated Amyloidosis
- Being tested
- ALN-TTR02 (patisiran) administered by intravenous (IV) infusion
- Keywords
- RNAi therapeutic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALN-TTR02 (patisiran) administered by intravenous (IV) infusionDrug
| Study group | Role | What they receive |
|---|---|---|
| ALN-TTR02 (patisiran) | Experimental | Not described Receives: Drug: ALN-TTR02 (patisiran) administered by intravenous (IV) infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Participants Experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation
An AE is any untoward medical occurrence in a patient or clinical investigational patient administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Measured: From Baseline up to 56 days post last dose
Secondary outcomes (6)
Percentage Change From Baseline in Serum TTR Levels
TTR levels, measured using the enzyme-linked immunosorbent assay (ELISA) method.
Measured: From Baseline up to 56 days post last dose
Change From Baseline in the Modified Neuropathy Impairment Score +7 (mNIS+7)
The mNIS+7 assessment is a composite measure of neurologic impairment that provides a comprehensive measure of large and small fiber function that encompasses the totality of the motor, sensory, and autonomic deficits seen in hereditary transthyretin-mediated amyloidosis (hATTR) patients with polyneuropathy. The minimum and maximum values are 0 and 304, respectively. A higher score indicates a worse outcome.
Measured: Baseline, Month 24
Change From Baseline in Quality of Life and Disability as Assessed by the EuroQoL (Quality of Life)-5 Dimensions (EQ-5D), EuroQoL Visual Analog Scale (EQ-VAS) Questionnaires and Rasch-built Overall Disability Scale (R-ODS)
The overall EQ-5D is measured on a scale from 0 to 1, with 0 being worst and 1 best. The EQ-VAS is measured on a scale of 0-100, with 0 being the worst and 100 the best. The R-ODS captures activity and social participation limitations in patients. The R-ODS score ranges from 0 (most severe activity and social participation limitations) to 100 (no activity and social participation limitations).
Measured: Baseline, Month 24
Change in Gait Speed With 10-meter Walk Test
The 10-meter walk test measures the time (in seconds) that it takes a patient to walk 10 meters.
Measured: Baseline, Month 24
Mean Change From Baseline in Hand Grip Strength
The mean (SEM) hand grip strength change from baseline at 24 months between patients who used patisiran with or without a concomitant TTR stabilizer.
Measured: Baseline, Month 24
Change From Baseline in Nutritional Status (Modified Body Mass Index, mBMI)
Nutritional status of patients 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 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2013 (estimated)
- Study startOct 2013
- Primary completionJul 2016
- Study completionAug 2016
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 TTR-mediated AmyloidosisStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jared Gollob, MD, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01961921
- Sponsor's protocol ID
- ALN-TTR02-003
- Other IDs
- 2013-001644-65
- Status last verified
- Nov 2018
- First submitted
- 9 Oct 2013
- Last updated
- 19 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- 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
Coelho T, Adams D, Conceicao I, Waddington-Cruz M, Schmidt HH, Buades J, Campistol J, Berk JL, Polydefkis M, Wang JJ, Chen J, Sweetser MT, Gollob J, Suhr OB. A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis. Orphanet J Rare Dis. 2020 Jul 8;15(1):179. doi: 10.1186/s13023-020-01399-4.
PubMed 32641071
Study at a glance
From the registry record, last updated by the sponsor on 19 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 Safety, Clinical Activity, and Pharmacokinetics of ALN-TTR02 in Patients With Familial Amyloidotic Polyneuropathy Who Have Previously Received ALN-TTR02
- ClinicalTrials.gov ID
- NCT01961921
- Acronym / sponsor ID
- ALN-TTR02-003
- Conditions
- TTR-mediated Amyloidosis
- Keywords
- RNAi therapeutic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2013
- Primary completion
- Jul 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 14 Oct 2013 (estimated)
- Results
- Posted 30 Oct 2018
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 long-term dosing with ALN-TTR02 (patisiran) in patients with transthyretin (TTR) mediated amyloidosis (ATTR).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ALN-TTR02 (patisiran) | Experimental | Drug: ALN-TTR02 (patisiran) administered by intravenous (IV) infusion |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Previously received and tolerated ALN-TTR02 (patisiran) in Study ALN-TTR02-002.
- Adequate Karnofsky performance status, liver function, and renal function.
Key exclusion criteria (5 listed)
- Pregnant or nursing.
- Has had a liver transplant.
- Has a New York Heart Association heart failure classification >2.
- Has unstable angina.
- Has uncontrolled clinically significant cardiac arrhythmia.
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 |
|---|---|---|
| ALN-TTR02 (patisiran) administered by intravenous (IV) infusion | Drug | ALN-TTR02 (patisiran) |
Primary outcome
The Number of Participants Experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation
Time frame: From Baseline up to 56 days post last dose
An AE is any untoward medical occurrence in a patient or clinical investigational patient administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
6 secondary outcomes
Percentage Change From Baseline in Serum TTR Levels
Time frame: From Baseline up to 56 days post last dose
Change From Baseline in the Modified Neuropathy Impairment Score +7 (mNIS+7)
Time frame: Baseline, Month 24
Change From Baseline in Quality of Life and Disability as Assessed by the EuroQoL (Quality of Life)-5 Dimensions (EQ-5D), EuroQoL Visual Analog Scale (EQ-VAS) Questionnaires and Rasch-built Overall Disability Scale (R-ODS)
Time frame: Baseline, Month 24
Change in Gait Speed With 10-meter Walk Test
Time frame: Baseline, Month 24
Mean Change From Baseline in Hand Grip Strength
Time frame: Baseline, Month 24
Change From Baseline in Nutritional Status (Modified Body Mass Index, mBMI)
Time frame: Baseline, Month 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32641071Coelho T, Adams D, Conceicao I, Waddington-Cruz M, Schmidt HH, Buades J, Campistol J, Berk JL, Polydefkis M, Wang JJ, Chen J, Sweetser MT, Gollob J, Suhr OB. A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis. Orphanet J Rare Dis. 2020 Jul 8;15(1):179. doi: 10.1186/s13023-020-01399-4.
- 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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HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
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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.
Jared Gollob, MD 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 2 study testing ALN-TTR02 (patisiran) administered by intravenous (IV) infusion in people with TTR-mediated 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 2 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 19 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, Portugal, United States, Brazil, Germany 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 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 30 Oct 2018). 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?
The Number of Participants Experiencing Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation (time frame: From Baseline up to 56 days post last dose). 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 NCT01961921, 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 19 Apr 2024.