Transthyretin (TTR)-Mediated AmyloidosisPhase 2NCT02595983
The Study of an Investigational Drug, Revusiran (ALN-TTRSC), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis in Patients Whose Disease Has Continued to Worsen Following Liver Transplant
A Phase 2 study testing Revusiran in people with Transthyretin (TTR)-Mediated Amyloidosis and Familial Amyloidotic Polyneuropathy (FAP), run by Alnylam Pharmaceuticals at 6 sites in 6 countries.
Trial summary
The purpose of this study was to evaluate the safety and effectiveness of revusiran (ALN-TTRSC) in adults with transthyretin-mediated amyloidosis (ATTR), whose disease has continued to worsen after liver transplantation. Dosing has been discontinued; patients are being followed-up for safety. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transthyretin (TTR)-Mediated Amyloidosis, Familial Amyloidotic Polyneuropathy (FAP), ATTR Amyloidosis
- What is being tested?
- Revusiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 6 sitesin 6 countries
- Study dates
- Oct 2015to 6 Feb 2017
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of FAP (familial amyloidotic polyneuropathy) with documented TTR mutation
- Received an orthotopic liver transplant ≥12 months before the date of informed consent
- An increase in polyneuropathy disability (PND) score post-transplant
- Polyneuropathy Disability score of ≤3b
Who cannot join
- New York Heart Association (NYHA) classification of >2
- Other known causes of sensorimotor or autonomic neuropathy (eg, autoimmune disease)
Trial locations and contacts
6 sites in 6 countries.
6 sites in 6 countries
About this study
Official title: An Open-label Study to Evaluate the Efficacy and Safety of Revusiran in Patients With Transthyretin-mediated Familial Amyloidotic Polyneuropathy With Disease Progression Post-Orthotopic Liver Transplant
The purpose of this study was to evaluate the safety and effectiveness of revusiran (ALN-TTRSC) in adults with transthyretin-mediated amyloidosis (ATTR), whose disease has continued to worsen after liver transplantation. Dosing has been discontinued; patients are being followed-up for safety.
- Conditions
- Transthyretin (TTR)-Mediated Amyloidosis, Familial Amyloidotic Polyneuropathy (FAP), ATTR Amyloidosis, Familial Amyloid Neuropathies
- Being tested
- Revusiran
- Keywords
- FAP, Familial Amyloidotic Polyneuropathy, ATTR Amyloidosis, Orthotopic Liver Transplant, RNAi therapeutic
- Medical subject headings
- Amyloid Neuropathies, Familial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RevusiranDrug
Also called ALN-TTRSC
500mg Revusiran by subcutaneous (sc) injection
| Study group | Role | What they receive |
|---|---|---|
| All Patients | Experimental | All patients who received at least 1 dose of revusiran (ALN-TTRSC) Receives: Drug: Revusiran |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Change From Baseline in Serum TTR at Month 6
A negative percentage change from baseline at Month 6 indicates a reduction in serum TTR level.
Measured: Month 6
Secondary outcomes (4)
Percentage Change From Baseline in Serum TTR Over 18 Months
A negative percentage change from baseline indicates a reduction in serum TTR level.
Measured: Weeks 3, 7, 12, 18, 24, 26 (Month 6), 39 (Month 9), 52 (Month 12), 57, 78 (Month 18)
Change From Baseline in Modified Neurological Impairment Score (mNIS +7) Composite Score Over 18 Months
The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness, electrophysiologic measurement of small and large nerve fiber function, sensory testing and postural blood pressure. The minimum and maximum values are 0 and 304, respectively. A higher score indicates a worse outcome. A negative change from baseline indicates an improvement.
Measured: Baseline, Months 6, 12, 18
Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) Questionnaire Score
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, Months 6, 12, 18
Number of Participants in Each Polyneuropathy Disability (PND) Stage Based on Worst Post-Baseline Score
PND Scores: Stage 0: No symptoms, Stage 1: Sensory disturbances but preserved walking capabilities, Stage 2: Impaired walking capacity, but ability to walk without a stick or crutches, Stage 3A/B: Walking with help of 1 or 2 sticks or crutches, Stage 4: confined to wheel chair. For each stage (0-4) at baseline, the number of participants is presented at their worst post-baseline score for each stage (0-4) post-baseline. Worst post-baseline is defined the highest PND classification for a participant recorded after the first dose of study drug.
Measured: Baseline, Months 6, 12, 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2015 (estimated)
- Study startOct 2015
- Primary completion6 Feb 2017
- Study completion6 Feb 2017
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 Transthyretin (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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John Vest, MD, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02595983
- Sponsor's protocol ID
- ALN-TTRSC-005
- Status last verified
- Mar 2019
- First submitted
- 30 Oct 2015
- Last updated
- 28 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study to Evaluate the Efficacy and Safety of Revusiran in Patients With Transthyretin-mediated Familial Amyloidotic Polyneuropathy With Disease Progression Post-Orthotopic Liver Transplant
- ClinicalTrials.gov ID
- NCT02595983
- Acronym / sponsor ID
- ALN-TTRSC-005
- Conditions
- Transthyretin (TTR)-Mediated Amyloidosis, Familial Amyloidotic Polyneuropathy (FAP), ATTR Amyloidosis, Familial Amyloid Neuropathies
- Keywords
- FAP, Familial Amyloidotic Polyneuropathy, ATTR Amyloidosis, Orthotopic Liver Transplant, RNAi therapeutic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2015
- Primary completion
- 6 Feb 2017 (actual)
- Study completion
- 6 Feb 2017 (actual)
- First posted
- 4 Nov 2015 (estimated)
- Results
- Posted 28 Mar 2019
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 was to evaluate the safety and effectiveness of revusiran (ALN-TTRSC) in adults with transthyretin-mediated amyloidosis (ATTR), whose disease has continued to worsen after liver transplantation. Dosing has been discontinued; patients are being followed-up for safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All Patients | Experimental | Drug: RevusiranAll patients who received at least 1 dose of revusiran (ALN-TTRSC) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of FAP (familial amyloidotic polyneuropathy) with documented TTR mutation
- Received an orthotopic liver transplant ≥12 months before the date of informed consent
- An increase in polyneuropathy disability (PND) score post-transplant
- Polyneuropathy Disability score of ≤3b
Key exclusion criteria (2 listed)
- New York Heart Association (NYHA) classification of >2
- Other known causes of sensorimotor or autonomic neuropathy (eg, autoimmune disease)
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 |
|---|---|---|
| RevusiranAlso: ALN-TTRSC500mg Revusiran by subcutaneous (sc) injection | Drug | All Patients |
Primary outcome
Percentage Change From Baseline in Serum TTR at Month 6
Time frame: Month 6
A negative percentage change from baseline at Month 6 indicates a reduction in serum TTR level.
4 secondary outcomes
Percentage Change From Baseline in Serum TTR Over 18 Months
Time frame: Weeks 3, 7, 12, 18, 24, 26 (Month 6), 39 (Month 9), 52 (Month 12), 57, 78 (Month 18)
Change From Baseline in Modified Neurological Impairment Score (mNIS +7) Composite Score Over 18 Months
Time frame: Baseline, Months 6, 12, 18
Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) Questionnaire Score
Time frame: Baseline, Months 6, 12, 18
Number of Participants in Each Polyneuropathy Disability (PND) Stage Based on Worst Post-Baseline Score
Time frame: Baseline, Months 6, 12, 18
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
John Vest, MD study director
Alnylam Pharmaceuticals
6 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Revusiran in people with Transthyretin (TTR)-Mediated Amyloidosis and Familial Amyloidotic Polyneuropathy (FAP), run by Alnylam Pharmaceuticals at 6 sites in 6 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 2 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 28 Mar 2019. 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 France, Germany, Portugal, Spain, Sweden and 1 more country. 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 28 Mar 2019). 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 Change From Baseline in Serum TTR at Month 6 (time frame: Month 6). 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 28 Mar 2019.