A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Alpha-1 Antitrypsin (AAT) (Glassia ® ) in the Treatment of Recent-Onset Type 1 Diabetes

• Published in: International journal of molecular sciences 2019-11, Vol.20 (23), p.6032
• Main Authors: Lebenthal, Yael, Brener, Avivit, Hershkovitz, Eli, Shehadeh, Naim, Shalitin, Shlomit, Lewis, Eli C, Elias, Dana, Haim, Alon, Barash, Galia, Loewenthal, Neta, Zuckerman-Levin, Nehama, Stein, Michal, Tov, Naveh, Rachmiel, Marianna
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; alpha 1-Antitrypsin - adverse effects; alpha 1-Antitrypsin - therapeutic use; Beta cells; Child; Clinical outcomes; Cytokines; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - pathology; Double-Blind Method; Double-blind studies; Drug dosages; Female; Hemoglobin; Humans; Immunologic Factors - adverse effects; Immunologic Factors - therapeutic use; Insulin; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - pathology; Male; Multivariate analysis; Patients; Pediatrics; Peptides; Placebo Effect; Placebos; Preservation; Safety; Subgroups; Treatment Outcome; Young Adult
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20236032

Our aim was to assess the efficacy, safety, and tolerability of alpha-1 antitrypsin (AAT) as a therapeutic modality for β-cell preservation in patients with recent-onset type 1 diabetes. Seventy type 1 diabetes patients (37 males; mean age 13.1 ± 4.1years) were randomized to treatment with 22 infusions of AAT (Glassia ) (60 or 120 mg/kg) or placebo. The primary outcome was the area under the curve (AUC) of C-peptide from a 2-h mixed-meal tolerance test after 52 weeks. At week 52, C-peptide was 0.9, 0.45, and 0.48 pmol/mL in the AAT-120, AAT-60, and placebo groups ( = 0.170 and = 0.866 vs. placebo, respectively). The declines in C-peptide glycated hemoglobin (HbA1c) and the total insulin dose (U/kg) were similar across groups. Within the predefined 12-18-years subgroup, the C-peptide AUC decreased significantly in the placebo and AAT-60 groups (-0.34 and -0.54 pmol/mL, respectively, < 0.01), with a borderline decrease in the AAT-120 group (-0.29 pmol/mL, = 0.047). The mean HbA1c level was significantly lower in the AAT-120 group compared to the placebo (6.7% ± 0.9% vs. 8.2 ± 1.4%, = 0.05), and a higher percentage of patients attained HbA1c ≤ 7% (75% vs. 25%, = 0.05). AAT was tolerated well, with a similar safety profile between groups. The AAT intervention showed promise in the subgroup of adolescents with recent-onset type 1 diabetes. Further studies are warranted to determine the impact and proposed mechanism of action of AAT in β-cell preservation.