A safety and pharmacodynamics study of temelimab, an antipathogenic human endogenous retrovirus type W envelope monoclonal antibody, in patients with type 1 diabetes

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Curtin, Francois
Champion, Bernard
Davoren, Peter
Duke, Sally
Ekinci, Elif
Gilfillan, Chris
Morbey, Claire
Nathow, Thomas
O'Moore-Sullivan, Trisha
O'Neal, David
Roberts, Adam
Stranks, Stephen
Stuckey, Bronwyn
Vora, Parind
Malpass, Sam
Lloyd, David
Maestracci-Beard, Nicole
Buffet, Benedicte
Kornmann, Gabrielle
Bernard, Corinne
Porchet, Herve
Simpson, Richard
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2020
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Abstract

Aim: To report the first study of temelimab, a monoclonal antibody neutralizing the pathogenic human endogenous retrovirus type W envelope, in patients with type 1 diabetes (T1D). Materials and Methods: This double-blind, placebo-controlled, randomized clinical trial recruited adult patients with T1D within 4 years postdiagnosis and remaining C-peptide secretion. Sixty-four patients were randomized (2:1) to monthly temelimab 6 mg/kg or placebo during 24 weeks, followed by a 24-week, open-label extension, during which all patients received temelimab. The primary objective was the safety and tolerability of temelimab. The secondary objective was to assess the pharmacodynamics response such as C-peptide levels, insulin use, HbA1c, hypoglycaemia and autoantibodies. Results: Temelimab was well tolerated without any group difference in the frequency or severity of adverse events. Concerning exploratory endpoints, there was no difference in the levels of C-peptide, insulin use or HbA1c between treatment groups at weeks 24 and 48. The frequency of hypoglycaemia events was reduced with temelimab (P = 0.0004) at week 24 and the level of anti-insulin antibodies was lower with temelimab (P < 0.01); the other autoantibodies did not differ between groups. Conclusions: Temelimab appeared safe in patients with T1D. Pharmacodynamics signals (hypoglycaemia and anti-insulin antibodies) under temelimab were observed. Markers of β-cell functions were not modified by treatment. These results need to be further explored in younger patients with T1D with earlier disease onset.

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Diabetes, Obesity and Metabolism

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Curtin, F; Champion, B; Davoren, P; Duke, S; Ekinci, EI; Gilfillan, C; Morbey, C; Nathow, T; O'Moore-Sullivan, T; O'Neal, D; Roberts, A; Stranks, S; Stuckey, B; Vora, P; Malpass, S; Lloyd, D; Maëstracci-Beard, N; Buffet, B; Kornmann, G; Bernard, C; Porchet, H; Simpson, R, A safety and pharmacodynamics study of temelimab, an antipathogenic human endogenous retrovirus type W envelope monoclonal antibody, in patients with type 1 diabetes, Diabetes, Obesity and Metabolism, 2020

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