Table 1.

Human antigen-specific tolerance-based clinical trials for autoimmune disease.

Citation	Disease	Antigen Specific Treatment	Results and Safety Observations
16	CD	Nexvax2 mixture of DQ2.5-glia-α1, -α2 DQ2.5-glia-ω1, and ω2 DQ2.5-hor3 immunodominant epitopes Ascending dose study testing 3 intradermal injections of 60 μg, 90 μg, or 150 μg given over 15 days (total exposure max exposure 450 μg)	No efficacy was determined. Biopsy showed no worsening of intestinal pathology in patients receiving Nexvax2. Most common side effects included vomiting, nausea, and headache and were the only treatment-emergent adverse events that occurred in at least 5% of participants. Study showed that administration of immunodominant epitopes to celiac patients shown to be reactive to these epitopes was associated with self-limited acute gastrointestinal symptoms.
16	CD	Nexvax 2 mixture of DQ2.5-glia-α1, -α2 DQ2.5-glia-ω1, and ω2 DQ2.5-hor3 immunodominant epitopes 16 intradermal injections given over 53 days of either 150 μg, or 300 μg (total 4800 μg)	No efficacy was determined. Biopsy showed no worsening of intestinal pathology in patients receiving Nexvax2. Most common side effects included vomiting, nausea, and headache and were the only treatment-emergent adverse events that occurred in at least 5% of participants in either study. Study showed that administration of immunodominant epitopes to celiac patients shown to be reactive to these epitopes was associated with self-limited acute gastrointestinal symptoms.
44	MS	Myelin basic peptide altered peptide ligand 50 mg weekly subcutaneous injections up to 9 months (total exposure 1800 mg).	2 out of 8 patients showed increased brain lesions; 1 showed hypersensitivity; 3 others had non-specific side effects; 1 patient dose lowered to 5 mg and still developed increased MS lesions; Study suspended.
44	MS	Myelin basic peptide altered peptide ligand Randomized, double-blind clinical trial in 142 patients; 5 mg, 20 mg, or 50 mg weekly subcutaneous injections for 4 months and then decreased to 5 mg	No significant difference in relapse rate of treated and placebo groups but volume of new brain lesions was reduced in some of the patients that received 5 mg throughout; 9% developed hypersensitivity to the therapy and the trial was suspended.
45	MS	Glatiramer acetate injection (Trade name Copaxone) Randomized, double-blind trl; dose-comparison of 20 mg and 40 mg subcutaneous injection in relapsing-remitting MS	Higher dose was well tolerated and a decrease in relapse rate observed. Drug is approved for treating MS.
17	MS	Myelin Basic Peptide Intravenous Infusion Randomized, double-blind trail; Phase 2 dose-infusing 500 mg of MBP peptide	Drug was well tolerated but had questionable efficacy. Showed intravenous infusion of 500 mg of immunodominant T cell epitope was safe in MS patients
20	MS	Peptide coupled leukocytes (PBL) Intravenous administration of ECDI-fixed, autologous PBLs coupled with 7 immunodominant myelin peptides; a total estimated dose of 0.5 mg to 3.5 mg of total peptide This is further discussed in Section 3.1.2	Phase 1 clinical trial data show a good safety profile; patients were dosed with 1 × 103 up to 3 × 109 peptide-coupled PBLs. Patients receiving over 1 × 109 peptide-coupled PBLs showed a decrease in the level of peptide-specific CD4+ T cell responses in vitro. Showed that the delivery of immunodominant epitopes attached to the surface of ECDI-fxed cells could be safely administered via intravenous infusion.

CD = Celiac Disease; MS = Multiple Sclerosis.