Prion DiseasePhase 1/2NCT07832370
A Trial of ALN-6457 in Adult Participants With Symptomatic Prion Disease (PrD)
A Phase 1/2 study testing ALN-6457 in people with Prion Disease, run by Regeneron Pharmaceuticals.
Trial summary
This study will test a Regeneron drug called ALN-6457 ("study drug") to see if it can help treat Prion Disease (PrD). In PrD, the prion protein folds into an abnormal shape. These abnormal proteins build up in the brain and cause damage to brain cells, leading to problems with thinking, memory, and movement. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Prion Disease
- What is being tested?
- ALN-6457
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 23 Oct 2026to 27 Feb 2031
- Phase
- Phase 1/2
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant must meet all of the criteria under either:
- sporadic CJD as described in the protocol or
- genetic PrD, as described in the protocol
- Has a Body Mass Index (BMI) <35 kg/m2 (inclusive) at the screening visit
- Able to understand and complete trial-related questionnaires at screening
Who cannot join
- Clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric or neurological disease (excluding prion disease) that, as assessed by the investigator, may confound the results of the trial or pose an additional risk to the participant during trial participation
- Medical history of brain or spinal disease/injury that would interfere with the Lumbar Puncture (LP) procedure or CSF circulation, as described in the protocol
- Any contraindications to undergo a brain Magnetic Resonance Imaging (MRI)
- An established allergy or intolerance to local anesthetics
- Current history of bleeding diatheses that would increase risk of bleeding upon LP
- Any malignancy that is progressing or requires active treatment, as described in the protocol
- Attempted suicide, suicidal ideation with a plan that required hospital admission and/or change in level of care within 12 months prior to screening
- NOTE: Other Protocol-Defined Inclusion/Exclusion Criteria Apply.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Phase 1/2 Open-Label Trial With Extended Follow-Up to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Multiple Doses of ALN-6457 in Participants With Symptomatic Prion Disease
This study will test a Regeneron drug called ALN-6457 ("study drug") to see if it can help treat Prion Disease (PrD).
In PrD, the prion protein folds into an abnormal shape. These abnormal proteins build up in the brain and cause damage to brain cells, leading to problems with thinking, memory, and movement.
Read more
ALN-6457 is designed to reduce the amount of prion protein made in the brain. ALN-6457 works by targeting the genetic "instructions" that cells use to produce this protein, with the goal of slowing or stopping disease progression.
This study is looking at:
- What side effects ALN-6457 might cause
- How well ALN-6457 works
- What is the best dose of ALN-6457 for treating prion disease
- How much ALN-6457 is in the blood and Cerebrospinal Fluid (CSF, fluid that surrounds the brain and spinal cord) at different times
- Conditions
- Prion Disease
- Being tested
- ALN-6457
- Keywords
- PrD, Symptomatic Prion Disease, Sporadic Prion Disease, Genetic Prion Disease, Inherited Prion Disease, Familial Prion Disease, Gerstmann-Straussler-Scheinker syndrome (GSS), Fatal familial insomnia (FFI), Rapidly-Progressive Dementia, Creutzfeldt-Jakob Disease (CJD), Fatal Familial Insomnia, Prion-Associated Disorder, Prion-Induced Disorder, Dementia, Neurodegenerative Disease, Neurological Decline, Central Nervous System Disease, Central Nervous System Infections, Protein Misfolding Disorder, Transmissible Spongiform Encephalopathy
- Medical subject headings
- Prion Diseases, Gerstmann-Straussler-Scheinker Disease, Insomnia, Fatal Familial, Creutzfeldt-Jakob Syndrome, Dementia, Neurodegenerative Diseases, Central Nervous System Diseases, Central Nervous System Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALN-6457Drug
Also called ALN-PRNP
Administered per the protocol
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | Not described Receives: Drug: ALN-6457 |
| Cohort Expansion | Experimental | Not described Receives: Drug: ALN-6457 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of Treatment Emergent Adverse Events (TEAEs)
Measured: Through Week 156
Severity of TEAEs
Measured: Through Week 156
Percentage change in concentration of Neurofilament Light chain (NfL) in plasma from baseline
Measured: Through Week 130
Secondary outcomes (5)
Concentration of Prion Protein (PrP) in CSF
Measured: Through Week 130
Change from baseline in concentration of PrP in CSF
Measured: Through Week 130
Concentration of ALN-6457 and its major metabolites in plasma
Measured: Through Week 130
Concentration of ALN-6457 and its major metabolites in CSF
Measured: Through Week 130
Overall survival rate
Measured: At Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2026
- Study start23 Oct 2026 (estimated)
- Primary completion27 Feb 2031 (estimated)
- Study completion27 Feb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prion DiseaseStudies of the same condition, open and under way.
- More trials run by Regeneron 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dose Escalation Part: Sequential Cohort Expansion Part: Parallel
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07832370
- Sponsor's protocol ID
- ALN-6457-PD-25129
- Other IDs
- 2026-526727-21-00
- Status last verified
- Sep 2026
- First submitted
- 16 Sep 2026
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.