An Artificial Intelligence-powered Approach to Precision Immunotherapy of Human Arthritis

To estimate effect size needed to ascertain the power i.e. the number of patients to be tested in the future study to prove superiority of the combination dnaJP1 and HCQ versus placebo and HCQ - To determine this ACR20 will be employed

An American College of Rheumatology (ACR) 20% response (ACR20) response was defined as at least 20% improvement in both the tender joint count and the swollen joint count and at least 20% improvement in 3 of the 5 other core set measures listed below. The core set required the inclusion of 7 clinical end points for all RA trials: swollen joint count, tender joint count, physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, and patient's assessment of physical function, and levels of an acute-phase reactant (either the C-reactive protein \[CRP\] level or the erythrocyte sedimentation rate \[ESR\]).

A primary endpoint of the study will be to determine safety and tolerability of the experimental treatment in terms of AEs, SAEs, TEAEs

Reporting of Adverse Events

A mechanistic predictor of clinical efficacy at enrolment before first dosing related to immune changes in the cell activation

A combination of high dimensionality technologies will be employed, which will include single cell proteomics, a single cell RNA SEQ flow cytometry and mechanistic studies in vitro

A mechanistic biomarker of treatment response based on 20% change from baseline in increase in Tregs and decrease in inflammatory T cells

Immunological analysis performed on patients samples

To estimate the effect size needed to ascertain the power i.e. the number of patients to be tested in the future study to prove superiority of the combination dnaJP1 and HCQ versus placebo and HCQ - ACR50

The American College of Rheumatology (ACR) 50% response (ACR50) response is the same instruments with improvement levels defined as 50% versus 20% for ACR20

To estimate the effect size needed to ascertain the power i.e. the number of patients to be tested in the future study to prove superiority of the combination dnaJP1 and HCQ versus placebo and HCQ - ACR70

The American College of Rheumatology (ACR) 70% response (ACR70) response is the same instruments with improvement levels defined as 70% versus 20% for ACR20

To estimate the effect size needed to ascertain the power i.e. the number of patients to be tested in the future study to prove superiority of the combination dnaJP1 and HCQ versus placebo and HCQ - DAS28-ESR

Disease Activity Score-28 for Rheumatoid Arthritis with erythrocyte sedimentation rate (DAS28- ESR) describes severity of rheumatoid arthritis using clinical and laboratory data, specifically ESR. The number "28" describes the number of different joints examined in the assessment. The DAS-ESR values range from 2.0 to 10.0 while higher values indicate higher disease activity. A DAS28-ESR score of ≤ 2.6 indicates remission or ≤ 3.2 indicates low disease activity.

To estimate the effect size needed to ascertain the power i.e. the number of patients to be tested in the future study to prove superiority of the combination dnaJP1 and HCQ versus placebo and HCQ - DAS28-hsCRP

Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) is a modification of the DAS28-ESR, DAS28-CRP uses the C-Reactive Protein (CRP) value instead of erythrocyte sedimentation rate (ESR). The DAS28-CRP values range from 2.0 to 10.0 while higher values indicate higher disease activity.