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.

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

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.

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.