Transthyretin-Mediated AmyloidosisPhase 1NCT05661916
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALN-TTRSC04 in Healthy Subjects
A Phase 1 study testing ALN-TTRSC04 in people with Transthyretin-Mediated Amyloidosis, run by Alnylam Pharmaceuticals at 1 site in United Kingdom.
Trial summary
The purpose of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of single ascending doses of ALN-TTRSC04. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Transthyretin-Mediated Amyloidosis
- What is being tested?
- ALN-TTRSC04
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 16 Jan 2023to 30 Sep 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Body mass index (BMI) ≥18.0 kg/m^2 and ≤30 kg/m^2 assessed at Screening.
Who cannot join
- Has an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73m^2 at screening.
- Has alanine aminotransferase (ALT), aspartate aminotransferase (AST) or direct bilirubin above the upper limit of normal (ULN).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Randomized, Double-Blind, Placebo Controlled, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Subcutaneously Administered ALN-TTRSC04 in Healthy Subjects
The purpose of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of single ascending doses of ALN-TTRSC04.
- Conditions
- Transthyretin-Mediated Amyloidosis
- Being tested
- ALN-TTRSC04, Placebo
- Keywords
- ATTR amyloidosis, siRNA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALN-TTRSC04Drug
ALN-TTRSC04 will be administered by subcutaneous (SC) injection.
PlaceboDrug
Placebo will be administered by SC injection.
| Study group | Role | What they receive |
|---|---|---|
| ALN-TTRSC04 | Experimental | Participants will be administered a single dose of ALN-TTRSC04. Receives: Drug: ALN-TTRSC04 |
| Placebo | Placebo comparator | Participants will be administered a single dose of placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Adverse Events
Measured: Up to 20 months
Secondary outcomes (5)
Change from Baseline in Serum Transthyretin (TTR) Levels Over Time
Measured: Up to 18 months
Maximum Observed Plasma Concentration (Cmax) of ALN-TTRSC04
Measured: Day 1 up to Day 4
Time to Maximum Observed Plasma Concentration (Tmax) of ALN-TTRSC04
Measured: Day 1 up to Day 4
Area Under the Concentration-time Curve (AUC) of ALN-TTRSC04
Measured: Day 1 up to Day 4
Fraction of ALN-TTRSC04 Excreted in the Urine (fe)
Measured: Up to Day 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2022
- Study start16 Jan 2023
- Primary completion30 Sep 2025
- Study completion30 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Transthyretin-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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 96 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
- NCT05661916
- Sponsor's protocol ID
- ALN-TTRSC04-001
- Status last verified
- Feb 2026
- First submitted
- 15 Dec 2022
- Last updated
- 17 Feb 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Badri P, Kolachana K, Duong A, Lasko M, Nandi T, Mehrotra N, Robbie GJ. Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules. Clin Pharmacokinet. 2026 Feb;65(2):293-311. doi: 10.1007/s40262-025-01606-0. Epub 2025 Dec 12.
PubMed 41388232
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Double-Blind, Placebo Controlled, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Subcutaneously Administered ALN-TTRSC04 in Healthy Subjects
- ClinicalTrials.gov ID
- NCT05661916
- Acronym / sponsor ID
- ALN-TTRSC04-001
- Conditions
- Transthyretin-Mediated Amyloidosis
- Keywords
- ATTR amyloidosis, siRNA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 16 Jan 2023 (actual)
- Primary completion
- 30 Sep 2025 (actual)
- Study completion
- 30 Sep 2025 (actual)
- First posted
- 22 Dec 2022 (actual)
- Results
- Not posted in the source record
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, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of single ascending doses of ALN-TTRSC04.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ALN-TTRSC04 | Experimental | Drug: ALN-TTRSC04Participants will be administered a single dose of ALN-TTRSC04. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will be administered a single dose of placebo. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Body mass index (BMI) ≥18.0 kg/m^2 and ≤30 kg/m^2 assessed at Screening.
Key exclusion criteria (2 listed)
- Has an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73m^2 at screening.
- Has alanine aminotransferase (ALT), aspartate aminotransferase (AST) or direct bilirubin above the upper limit of normal (ULN).
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-TTRSC04ALN-TTRSC04 will be administered by subcutaneous (SC) injection. | Drug | ALN-TTRSC04 |
| PlaceboPlacebo will be administered by SC injection. | Drug | Placebo |
Primary outcome
Frequency of Adverse Events
Time frame: Up to 20 months
5 secondary outcomes
Change from Baseline in Serum Transthyretin (TTR) Levels Over Time
Time frame: Up to 18 months
Maximum Observed Plasma Concentration (Cmax) of ALN-TTRSC04
Time frame: Day 1 up to Day 4
Time to Maximum Observed Plasma Concentration (Tmax) of ALN-TTRSC04
Time frame: Day 1 up to Day 4
Area Under the Concentration-time Curve (AUC) of ALN-TTRSC04
Time frame: Day 1 up to Day 4
Fraction of ALN-TTRSC04 Excreted in the Urine (fe)
Time frame: Up to Day 2
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
- Derived from this study: PubMed 41388232Badri P, Kolachana K, Duong A, Lasko M, Nandi T, Mehrotra N, Robbie GJ. Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules. Clin Pharmacokinet. 2026 Feb;65(2):293-311. doi: 10.1007/s40262-025-01606-0. Epub 2025 Dec 12.
- Individual participant dataSharing planned: No
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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.
Medical Director study director
Alnylam Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ALN-TTRSC04 in people with Transthyretin-Mediated Amyloidosis, run by Alnylam Pharmaceuticals at 1 site in United Kingdom.
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 1 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 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Frequency of Adverse Events (time frame: Up to 20 months). 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 NCT05661916, 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 17 Feb 2026.