Phase 2, Randomized, Double-blind, Placebo-controlled Study of Fiztasovimab (NPC-21) for Kidney Transplant Recipients at High Risk of Cytomegalovirus Infection (LionHeart21).
Ichimaru, N., et alTransplantation 2024 [record in progress].
Aims
They aim to evaluate whether monthly intravenous fiztasovimab (NPC-21) prevents cytomegalovirus (CMV) infection through week 16 in kidney-transplant (KT) recipients with the highest risk profile (donor-seropositive/recipient-seronegative, D+/R-).
Interventions
Arm 1: NPC-21 at 6 mg kg⁻¹ (n = 38) Arm 2: NPC-21 at 12 mg kg⁻¹ (n = 11) Arm 3: Placebo (Volume-matched IV saline) (n = 38) Infusions for all arms were given IV on day 1 and weeks 4, 8, 12.
Participants
87 adult (18–75) first single-organ kidney recipients from a CMV-D+ donor, CMV-R–, body-weight ≤ 120 kg from 31 transplant centres across US and Japan. Excluded were those with prior transplants, IVIG within 28 days and planned plasmapheresis.
Outcomes
The primary outcome was CMV infection. Secondary outcomes included: CMV disease, Asymptomatic DNAemia, Median days to first DNAemia, Peak viral load (IU mL⁻¹) and adverse events.
Follow-up
28 weeks
CET Conclusions
The authors present a well-designed, double-blind phase-2 trial shows fiztasovimab was safe but failed to reduce overall CMV infection compared with placebo in D+/R- kidney transplant recipients managed without antiviral prophylaxis. A numerical reduction in CMV disease (0–5 % vs 13 %) and lower initial/peak viraemia, especially at 12 mg/kg, is possibly suggestive of potential mitigation of severity rather than infection risk. Power was limited due to incomplete recruitment, which was a COVID-19-related shortfall with only 11 patients at 12 mg/kg. No infusion reactions or haematological toxicity were observed, underlining a good safety profile. The current first-line prophylaxis remains (val)ganciclovir or letermovir. There has been no evidence that NPC-21 monotherapy can replace them, but it may have an adjunct role in preventing severe or late-onset CMV or in patients intolerant/resistant to antivirals. Larger, adequately powered trials which explore higher doses, combination with antivirals, and extended pharmacokinetic targets are warranted.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT04225923; jRCT - jRCT2041200019