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Precision for Medicine

Case Study: Rapid Startup Phase 1 Cardiomyopathy CRISPR Gene Therapy

Case Study: Rapid Startup Phase 1 Cardiomyopathy CRISPR Gene Therapy

Hereditary transthyretin amyloidosis (ATTRv) is extremely rare…estimated at 1 in 100,0001 in European and U.S. populations. Even in northern Sweden, where the Val50Met founder variant is endemic, prevalence is only 1.5%1 of the population.

For this first-in-human (FIH) Phase 1 study, the sponsor evaluated an in vivo CRISPR/Cas9, non-viral-vector therapeutic designed to reduce circulating mutant transthyretin and halt cardiomyopathy progression.

 Therapeutic Area

  • Cardiovascular

 Indication

  • Cardiomyopathy

 Phase

  • 1 (First-in-human)

 Segment

  • Rare, Hereditary

 Sites

  • 10> Sites, Australia, France, New Zealand, Sweden, UK

 Design

  • Patients with hereditary transthyretin amyloidosis with polyneuropathy and patients with transthyretin amyloidosis-related cardiomyopathy

 

Two open-label parts—single-ascending dose and dose expansion—were executed across four countries (France, Sweden, UK, New Zealand). The operational hurdles were immediate:

  • Heightened regulatory and public scrutiny. Gene-editing trials attract detailed safety reviews and media interest.
  • Site feasibility & selection. ATTRv cardiomyopathy patients are scattered; the right investigators—and nations—determine success.
  • Dynamic data requirements. Frequent protocol amendments, interim safety reviews, and “data-cut” requests demanded an agile data-management engine.

 

Precision's Non-Viral Vector Startup Strategy

4-Months Study Start-to-Site Activation
  • Leveraging harmonised contracts, central ethics templates, and parallel local submissions, site activation took four months—fast for a multi-region gene-editing study.
35-Day Site Activation-to-Screening
  • Precision’s feasibility process revealed neurologists had few ATTR-CM patients; cardiologists at amyloid centres held the real pipeline. Pivoting investigators early enabled a 35-day site activation-to-screening window once greenlighted.
37-Day Screening-to-Enrollment
  • Clear cardiology-focused eligibility checklists and concierge scheduling kept screen failure low, delivering first-patient-in 37 days after screening opened.

 

Dynamic Data Management in a First-in-Human  Rare Disease Study

Protocol Amendments & Nimble eCRF Updates
  • As dose-escalation cohorts progressed, the protocol evolved. A flexible EDC build allowed same-week changes—no downtime, no data loss.
High-Volume Safety Data-Cuts
  • Regulators and investor boards requested rolling 28-day safety summaries. Precision’s data-management team generated validated extracts within 48 hours, supporting on-time DSMB reviews and corporate disclosures.
Real-Time PK/PD Review
  • Live dashboards fed anonymized PK/PD points to clinical pharmacologists, enabling rapid dose-escalation decisions without extra query cycles.

Impact on Transthyretin Amyloidosis Cardiomyopathy Timelines

Metric

Result

 Sites activated

  • >10 (Australia, France, Sweden, UK, NZ)

 Patients enrolled

  • >70 adults aged 18–80

 Start → Activation

  • 126 days

 Activation → Screen

  • 35 days

 Screen → Enroll

  • 37 days

 Early safety profile

  • Few adverse events observed in first 28 days

 

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Lessons from This Gene-Editing Trial

  • Plan for added scrutiny. Build regulator FAQs and public facing talking points early; allocate buffer for additional document rounds.
  • Let feasibility drive investigator mix. Cardiologists—not neurologists—held ATTR-CM patient access; early pivot shaved weeks off recruitment.
  • Treat data-management as a living system. Gene-therapy protocols evolve; choose a CRO that can re-engineer eCRFs and run data cuts on 48-hour notice.
  • Cohort-management discipline is non-negotiable. Tight CRO–Sponsor–Site loops kept dose-escalation triggers on schedule.

Precision's Gene-Therapy Clinical Trial Capabilities

Whether you’re advancing CRISPR, base-editing, or RNA-modifying platforms, our gene-therapy trial services unite nimble data-management, seasoned regulatory navigation, and rare disease site networks to keep first-in-human studies on track.

 

Frequently Asked Questions

What made startup so fast in this first-in-human CRISPR trial for cardiomyopathy?

The trial achieved site activation in just 126 days by leveraging harmonized contracts, central ethics templates, and parallel local submissions. This efficient, multi-region strategy helped bypass common delays typical of gene-editing trials under heavy regulatory scrutiny.

How did the team overcome rare-patient recruitment challenges?

Traditional neurology sites had limited access to patients with ATTR-CM. The team quickly pivoted to cardiologists at amyloid centers, where patient volume was higher. This shift reduced screen-to-enroll time to just 37 days, streamlining recruitment.

What data-management strategies supported the study's agility?

The trial relied on a dynamic EDC build, enabling same-week protocol amendments without downtime or data loss. Real-time dashboards fed PK/PD data directly to pharmacologists, and validated safety data-cuts were delivered within 48 hours to meet DSMB and investor needs.

What are the key lessons for sponsors planning gene-editing trials?

Sponsors should:

  • Prepare early for public and regulatory scrutiny
  • Let site feasibility dictate investigator selection
  • Treat data management as adaptive infrastructure
  • Enforce disciplined, tight-loop cohort management

 

References

  1. Sekijima Y, Nakamura K. Hereditary Transthyretin Amyloidosis. 2001 Nov 5 [Updated 2024 May 30]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1194/ 
  2. Precision for Medicine Data on File.