TTR-mediated AmyloidosisPhase 2NCT01617967
Safety and Tolerability of Patisiran (ALN-TTR02) in Transthyretin (TTR) Amyloidosis
A Phase 2 study testing Patisiran in people with TTR-mediated Amyloidosis, run by Alnylam Pharmaceuticals at 10 sites in 7 countries.
Trial summary
This was a multiple dose, dose escalation study designed to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of patisiran (ALN-TTR02) in participants 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?
- Patisiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 10 sitesin 7 countries
- Study dates
- May 2012to Jan 2014
- Phase
- Phase 2
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
- Body mass index must be between 17 kg/m^2 and ≤ 33 kg/m^2;
- Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must use appropriate contraception;
- Males agree to use appropriate contraception;
- Diagnosis of TTR amyloidosis;
- Adequate blood counts, liver and renal function;
- Willing to give written informed consent and are willing to comply with the study requirements.
Who cannot join
- Known human immunodeficiency virus (HIV) positive status or known or suspected systemic bacterial, viral, parasitic, or fungal infection;
- Received an investigational agent, other than tafamidis or diflunisal, within 30 days prior to first dose study drug administration;
- Prior liver transplant;
- Poor cardiac function;
- Considered unfit for the study by the Principal Investigator;
- Employee or family member of the sponsor or the clinical study site personnel.
Trial locations and contacts
10 sites in 7 countries.
10 sites in 7 countries
France2 sites
Clinical Trial Site
Le Kremlin-Bicêtre
Clinical Trial Site
Marseille
About this study
Official title: A Phase 2, Open-Label, Multi-Dose, Dose Escalation Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous Infusions of ALN-TTR02 in Patients With TTR Amyloidosis
This was a multiple dose, dose escalation study designed to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of patisiran (ALN-TTR02) in participants with transthyretin (TTR) mediated amyloidosis (ATTR).
- Conditions
- TTR-mediated Amyloidosis
- Being tested
- Patisiran
- Keywords
- RNAi therapeutic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PatisiranDrug
Also called ALN-TTR02
Participants received a single dose of patisiran as an intravenous (IV) infusion on Day 0 and Day 28 (Q4W). Optional cohorts received an alternative dosing regimen (once every 3 weeks [Q3W]: Day 0 and Day 21) and an alternative premedication regimen.
| Study group | Role | What they receive |
|---|---|---|
| Patisiran (ALN-TTR02) | Experimental | Two administrations of patisiran will be administered once every 4 weeks [Q4W]) in 4 sequential cohorts with escalating doses followed by optional cohorts with an alternative dosing regimen (once every 3 weeks [Q3W]), and an alternative premedication regimen. Receives: Drug: Patisiran |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation
The number of participants experiencing at least one adverse event (AE), at least one serious adverse event (SAE) and study drug discontinuation (due to any reason).
Measured: Up to 56 days post first dose
Secondary outcomes (7)
Percentage Change From Baseline in Serum Transthyretin (TTR) Protein
Percentage change of TTR relative to pretreatment/baseline levels is reported. For arms with a dosing regimen of Q4W TTR protein samples were measured on Days 28 and 56. For the arms with a dosing regimen of Q3W TTR protein samples were measured on Days 21 and 42.
Measured: Baseline to Day 21/28 and Day 42/56 depending on dosing regimen (Q3W/Q4W)
Pharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)
Pharmacokinetic profiles for patisiran (ALN-TTR02) were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
Measured: Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing regimen (Q3W/Q4W)
Pharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)
Pharmacokinetic profiles for patisiran (ALN-TTR02) were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
Measured: Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing regimen (Q3W/Q4W)
Pharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)
Pharmacokinetic profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
Measured: Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing frequency
Pharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)
Pharmacokinetic profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
Measured: Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing frequency
Pharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)
Pharmacokinetic profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
Measured: Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing frequency
Pharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)
Pharmacokinetic profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
Measured: Predose (within 1 h of planned dosing start) and post-infusion at 0-6 h (pooled) on Day 0 and Day 21/28 depending on dosing frequency
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2012 (estimated)
- Study startMay 2012
- Primary completionOct 2013
- Study completionJan 2014
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
- 29 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
- NCT01617967
- Sponsor's protocol ID
- ALN-TTR02-002
- Other IDs
- 2012-000467-24
- Status last verified
- Oct 2018
- First submitted
- 7 Jun 2012
- Last updated
- 19 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- 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.
- Expanded access
- Available
Publications
Suhr OB, Coelho T, Buades J, Pouget J, Conceicao I, Berk J, Schmidt H, Waddington-Cruz M, Campistol JM, Bettencourt BR, Vaishnaw A, Gollob J, Adams D. Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study. Orphanet J Rare Dis. 2015 Sep 4;10:109. doi: 10.1186/s13023-015-0326-6.
PubMed 26338094