Mivelsiran: cAPPricorn-1 Study

Mivelsiran: cAPPricorn-1 Study

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 Summary

Index

Study Design – Abbreviations – References

 Study Design

The cAPPricorn-1 study is an ongoing, global, randomized, double-blind, placebo-controlled, phase 2 study designed to evaluate the efficacy, safety, tolerability, and PD of mivelsiran in patients with sporadic or Dutch-type CAA. Enrolled patients will be randomized to receive intrathecal injections of mivelsiran or placebo during the 24-month double-blind treatment period, followed by an optional 18‑month OLE period. The estimated duration of study participation, inclusive of the 60‑day screening period, the double-blind treatment period, the optional OLE, and the 6‑month additional safety follow‑up, is up to 50 months (Figure 1).1,2

Figure 1. cAPPricorn-1 Study Design.1

The primary endpoint is the annualized rate of new lobar CMBs on brain MRI in patients with sporadic CAA.1

Secondary endpoints include1,2:

      Global rank based on severity, count, symptom burden, and timing of new clinical hemorrhagic events and hemorrhagic lesions on brain MRI

      Change from baseline in the total CAA small vessel disease score on brain MRI

      Incidence of new cerebral hemorrhagic lesions

      Assessment of vascular physiology through the change from baseline in cerebrovascular vasoreactivity on BOLD-fMRI

      Assessment of non-hemorrhagic disease progression through the incidence of white matter hyperintensities assessed on brain MRI

      Pharmacodynamic evaluation of the change from baseline in CSF sAPPα and sAPPβ concentrations

Safety will be assessed by the frequency of AEs for up to 48 months.1

Select study inclusion criteria include1:

      Able to complete MRI and tolerate lumbar puncture

      BMI ≥18 and ≤34 kg/m2

      Supportive psychosocial circumstances

      Sporadic CAA patients: ≥50 years with a probable CAA diagnosis per the Boston criteria version 2.0 with adaptations

      Dutch-type CAA patients: ≥30 years with a known E693Q APP gene variant

Select study exclusion criteria include1:

      Moderate or severe AD (CDR global score 2.0 or 3.0) or severe CI (MMSE <22)

      History of previous ICH with onset <90 days prior to randomization

      Any treatment with amyloid-targeting antibody

 Abbreviations

Aβ = amyloid beta; AD = Alzheimer’s disease; AE = adverse event; APP = Aβ precursor protein; BMI = body mass index; BOLD = blood oxygenation level dependent; CAA = cerebral amyloid angiopathy; CDR = clinical dementia rating; CI = cognitive impairment; CMB = cerebral microbleed; CNS = central nervous system; CSF = cerebral spinal fluid; EOAD = early onset Alzheimer's disease; eGFR = estimated glomerular filtration rate; ICH = clinical intracerebral hemorrhage; IT = intrathecal; MMSE = Mini Mental State Examination; MRI = magnetic resonance imaging; mRNA = messenger ribonucleic acid; OLE =  open‑label extension; PD = pharmacodynamics; R = randomization; RNAi = ribonucleic acid interference; sAPPα = soluble amyloid precursor protein alpha; sAPPβ = amyloid precursor protein beta; ULN = upper limit of normal.

Updated 26 March 2026

References

1.  Lee J, van Etten ES, van Osch MJP, et al. Design and rationale of cAPPricorn-1, a phase 2 study of mivelsiran in patients with cerebral amyloid angiopathy. Presented at: Clinical Trials on Alzheimer’s Disease (CTAD) Conference; October 29–November 1, 2024; Madrid, Spain.

2.  Alnylam Pharmaceuticals: A phase 2 trial of ALN-APP in patients with cerebral amyloid angiopathy (cAPPricorn-1). Available from: https://clinicaltrials.gov/study/NCT06393712. Accessed March 26, 2026.