Journal of Clinical Trials
Open Access

Abstract

Phase I Clinical Trial with a Novel Altered Peptide Ligand Derived from Human Heat-Shock Protein 60 for Treatment of Rheumatoid Arthritis: Safety, Pharmacokinetics and Preliminary Therapeutic Effects

Dinorah Prada, Jorge Gómez, Norailys Lorenzo, Oreste Corrales, Ana López, Evelio González, Ania Cabrales, Yusimy Reyes, Yuliet Bermudez, Yisel Avila, Lina Pérez, Claudio Molinero, Osmel Martinez, Leonardo Oramas, Yaysel Miñoso, Yassel Ramos, Hilda Garay, Ever Pérez, Matilde López, Osvaldo Reyes2, Yolan

Background: CIGB 814 is an Altered Peptide Ligand (APL) from a CD4+ T-cell epitope of human heat shock protein 60 (HSP60), an auto-antigen involved in the pathogenesis of rheumatoid arthritis (RA). It induced mechanisms associated with restoration of peripheral tolerance in preclinical studies. This clinical trial was conducted to assess safety and pharmacokinetics (PK) of CIGB-814 in patients with RA.
Method: 20 patients with moderated active RA were included in an open label trial. Sequential dose-escalation of 1, 2.5 and 5 mg of CIGB-814 was studied. Consecutive groups of six, five and nine patients received a subcutaneous dose weekly of the peptide during the first month and one dose monthly during the next five months. Clinical response in patients was evaluated according to the American College of Rheumatology (ACR) and Disease Activity Score in 28 joints (DAS 28) criteria. Function and health-related quality of life, quantification of proinflammatory cytokines and radiographic changes in patients by magnetic resonance imaging (MRI) were also assessed.
Result: The treatment was well tolerated at all doses. Only mild events were observed. PK study showed that CIGB-814 reached the maximum concentration in plasma in 30 min and was cleared mostly after 4 h. CIGB-814 reduced disease activity and MRI score in patients. This effect was less marked with the dose of 5 mg. Five and eleven out of 18 patients achieved ACR 50 and ACR 70 respectively at the end of the treatment. In addition, patients showed decreases of DAS28 scores, during treatment and at the end of the follow-up. This therapy improved function and health-related quality of life of patients. CIGB-814 significantly decreased interleukin (IL)-17 in patients treated with 2.5 mg. Therapy with 1 mg and 2.5 mg of CIGB-814 led to significant reduction of interferon gamma (IFN-γ).
Conclusion: Phase I concluded showing safety of CIGB-814. The PK profile revealed that peptide is cleared from plasma very rapidly. Results indicated preliminary evidences of clinical efficacy and support further clinical investigation of this peptide for treatment of RA.
Trial registration: RPCEC00000238.