Skip to main content
OpenTrials
Not yet recruiting

NCT Number: NCT07832370

A Trial of ALN-6457 in Adult Participants With Symptomatic Prion Disease (PrD)

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.

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

Not yet recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Prion Disease Brain Diseases Central Nervous System Diseases Central Nervous System Infections Congenital, Hereditary, and Neonatal Diseases and Abnormalities Creutzfeldt-Jakob Syndrome Dementia Dyssomnias Genetic Diseases, Inborn Gerstmann-Straussler-Scheinker Disease Heredodegenerative Disorders, Nervous System Infections Insomnia, Fatal Familial Mental Disorders Metabolic Diseases Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Nutritional and Metabolic Diseases Prion Diseases Proteostasis Deficiencies Sleep Disorders, Intrinsic Sleep Initiation and Maintenance Disorders Sleep Wake Disorders

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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

Key Exclusion Criteria:

  • 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.

Treatment and study plan

ALN-6457

Drug

Administered per the protocol

Other names: ALN-PRNP

Primary outcomes

  1. Occurrence of Treatment Emergent Adverse Events (TEAEs)

    Time frame: Through Week 156

  2. Severity of TEAEs

    Time frame: Through Week 156

  3. Percentage change in concentration of Neurofilament Light chain (NfL) in plasma from baseline

    Time frame: Through Week 130

Secondary outcomes

  1. Concentration of Prion Protein (PrP) in CSF

    Time frame: Through Week 130

  2. Change from baseline in concentration of PrP in CSF

    Time frame: Through Week 130

  3. Concentration of ALN-6457 and its major metabolites in plasma

    Time frame: Through Week 130

  4. Concentration of ALN-6457 and its major metabolites in CSF

    Time frame: Through Week 130

  5. Overall survival rate

    Time frame: At Week 52

Interested in participating?

Not yet recruiting

Trial opening soon.

Get Notified

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2026
Primary completion
2031
Study completion
2031
First posted
Sep 22, 2026
Registry last updated
Sep 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.