Table 1.
Preclinical and Clinical Trials using Spherical Nucleic Acids in Skin.
| Clinical Phase; Status | Skin Disease | Target (Treatment, Dose) | Administration (Sample Size) | Primary Outcome Measure | Secondary Outcome Measures | Results/Outcomes |
|---|---|---|---|---|---|---|
| Pre-clinical (human 3D, mouse); Completed | Psoriasis | TNFα (L-SNA; 50 mM) | Topical, every other day for 1 week (n = 12 per group) | Psoriasis severity | Psoriatic marker expression, proliferation | Decreased psoriatic severity, epidermal thickness, immune infiltration, normalization of psoriatic mRNA markers |
| Pre-clinical (human 3D, mouse); Completed | Psoriasis | IL-17RA (L-SNA; 50 mM) | Topical, daily for 1 week (n ≥ 6 per group) | Psoriasis severity | Psoriatic marker expression, proliferation | Decreased psoriatic severity, epidermal thickness and immune infiltration, normalization of psoriatic mRNA markers |
| Pre-clinical; Completed | Impaired wound healing | GM3S (Au-NP-SNA; 50 nM) | Topical, every other day (n = 8 per group) | Wound closure | Granulation tissue, metabolic signaling | Increased wound healing, granulation tissue and IGF1R/EGFR signaling |
| Phase 1; Completed | Psoriasis | TNFα (AST-005) L-SNA; each subject received vehicle, 0.1%, 0.3%, and 1% | Topical, daily for 28 days (n = 15) | Adverse events | TNFA knockdown, safety, tolerability, dosing | Well tolerated, no adverse events, significant TNFA knockdown |
| Phase 1; Completed | Psoriasis | IL-17RA (XCUR17) L-SNA; dosage information not available | Topical, daily for 25 days (n = 21) | Adverse events | IL17RA knockdown, safety, tolerability, dosing, skin inflammation, psoriatic gene expression | Well tolerated, no adverse events, no IL17RA knockdown, decreased expression of K16 and inflammatory genes |
| Phase 1; Completed | Healthy subjects | Toll-like receptor 9 (TLR9) agonist (AST-008) L-SNA: 2–32 mg | Subcutaneous injection, weekly for 9 weeks, then every 3 weeks (n = 16) | Adverse events | Recommended dosage, immune response, cytokine/chemokine levels | No serious adverse events: minor injection site reactions and flu-like symptoms reported; increased cytokine/chemokine and immune responses |
| Phase 1b; Completed | Primarily advanced melanoma, Merkel cell carcinoma (MCC), cutaneous squamous cell carcinoma (cSCC) | TLR9 agonist (AST-008) L-SNA; 2–32 mg with anti-PD-1 antibody (pembrolizumab) | Subcutaneous injection, weekly for 9 weeks then once every 3 weeks (n = 20) | Dose escalation study (2–32 mg): adverse events in combination with pembrolizumab | Recommended dosage, immune response | No serious adverse events; dose-related injection site reactions and flu-like symptoms, esp. at 32 mg; dose-related systemic immune activation; more diverse tumoral cellular infiltrate vs. non-injected tumor; increased tumoral cell infiltrate with addition of one dose pembrolizumab |
| Phase 2; Recruiting | MCC, cSCC | TLR9 agonist (AST-008) L-SNA; 32 mg alone or with anti-PD-1 (MCC; pembrolizumab) or anti-PD-L1 (cSCC; cemiplimab) antibody | Subcutaneous injection, weekly for 9 weeks then once every 3 weeks | Adverse events in combination with pembrolizumab or cemiplimab | Immune and cytokine/chemokine response, tumor size, disease-free survival | Not available; trial ongoing |
AST-008: TLR9 agonist L-SNA, now called cavrotolimod; cSCC: Cutaneous squamous cell carcinoma; EGFR: Epidermal growth factor receptor; IGF1R: Insulin-like growth factor-1 receptor; IL-17RA: Interleukin 17 receptor A; L-SNA: Liposomal spherical nucleic acid; MCC: Merkel cell carcinoma; PD-1: Programmed cell death protein-1; TLR9: Toll-like receptor 9, TNFα: Tumor necrosis factor-alpha. An Au-NP SNA targeting Bcl2L12 is currently in a phase 1 clinical trial for glioblastoma (NCT03020017).