D3.446 - PROTECT Phase I/IIa Clinical Trial Demonstrated Strong Correlation Between Humoral Immune Response and Dose of VLP Peanut in Healthy Participants

VLP Peanut (CuMV_TT/CuMV_TT-Ara h2) is being developed as an innovative nanoparticle-based hypoallergenic therapeutic candidate for peanut allergy. Safety and clinical proof of concept for VLP Peanut have been evaluated in the Phase I/IIa clinical trial (PROTECT) in healthy and peanut-allergic (PA) adults, which has entered its final stage of the highest dose assessment. To achieve maximum clinical efficacy, a combination of optimal dosing regimen and systemic distribution of VLP Peanut is required. Induction of humoral immune responses (CuMV_TT sIgG) at systemic level (serum) and correlation to the dose administered was evaluated in the open-label part (Phase I, healthy participants) of the PROTECT study. 

Healthy participants (n=16 [4 cohorts]) received four escalating subcutaneous doses (lowest, low, medium and high) of VLP Peanut at 3 dosing days every 4 weeks. Serum CuMV_TT sIgG end-point titers were measured one week after each dose administration via ELISA and correlation analysis was conducted to evaluate level of CuMV_TT sIgG vs dose administered.

Evaluation of the systemic immunogenic potential of VLP Peanut in healthy participants demonstrated dose-dependent induction of CuMV_TT sIgG across all 4 cohorts. Maximum level of CuMV_TT sIgG was measured after the dosing day 3 with the highest titers demonstrated for Cohort 3 (mean (titer) ± SEM: 17600±4800) and Cohort 4 (mean (titer) ± SEM: 27200±9191) participants, who received the highest doses of VLP Peanut. No induction of CuMV_TT sIgG was seen after the first dose administration in each of the treatment cohorts. Statistically significant strong positive correlation between sIgG CuMV_TT end-point titer and administered dose of VLP Peanut was demonstrated across all four cohorts (Pearson correlation: r=0.787, p=0.002, 95% CI [0.389:0.937]).

Serum sIgG induced by the carrier component of VLP Peanut (CuMV_TT/CuMV_TT-Ara h2) demonstrated dose-dependent induction and strong statistically significant correlation with the dose administered. Therefore, this immunological parameter can be positioned as a potential pharmacokinetic (PK) indicator of systemic exposure to VLP Peanut following subcutaneous administration and utilized in subsequent clinical development of VLP Peanut for planning optimal dose regimen.