Pediatric Diabetes 2015 doi: 10.1111/pedi.12283 All rights reserved  2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Pediatric Diabetes Original Article Alpha-1 antitrypsin therapy is safe and well tolerated in children and adolescents with recent onset type 1 diabetes mellitus † Rachmiel M, Strauss P, Dror N, Benzaquen H, Horesh O, Tov N, Weintrob N, Landau Z, Ben-Ami M, Haim A, Phillip M, Bistritzer T, Lewis EC, Lebenthal Y. Alpha-1 antitrypsin therapy is safe and well tolerated in children and adolescents with recent onset type 1 diabetes mellitus. Pediatric Diabetes 2015. Background and objectives: Alpha-1 antitrypsin (AAT) has been shown to reduce pro-inflammatory markers and protect pancreatic islets from autoimmune responses in recent studies. Our aim was to evaluate its safety and tolerability in three different doses, in a pediatric population with recent onset type 1 diabetes mellitus (T1DM). Methods: A 37-wk prospective, open-label, phase I/II interventional trial, comprised of 24 recently diagnosed subjects (12 males; age 12.9 ± 2.4 yr), who received 18 infusions of 40, 60, or 80 mg/kg/dose high-purity, liquid, ready to use AAT over 28 wk (Glassia  ; Kamada Ltd., Ness Ziona, Israel). Primary outcomes: safety and tolerability; secondary outcomes: glycemic control, C-peptide reserve, and autoantibody levels. Possible responders were defined as individuals with peak C-peptide that declined less than 7.5% below baseline. Results: No serious adverse events, diabetic ketoacidosis (DKA), or severe hypoglycemic episodes were reported. Adverse events were dose-independent and transient. Glycemic control parameters improved during the study in all groups, independent of dosage. Hemoglobin A1c (HbA1c) decreased from 8.43 to 7.09% (mean, p < 0.001). At the end of the study, 18 subjects (75%) had a peak C-peptide ≥0.2 pmol/mL. Eight subjects (33.3%) were considered possible responders and were characterized by shorter duration of T1DM at screening (54.5 ± 34.3 vs. 95.9 ± 45.7 d, p = 0.036) and greater decrease in their HbA1c during the study period (−2.94 ± 1.55 vs.−0.95 ± 1.83%, p = 0.016). Conclusions: AAT treatment was safe and well tolerated in pediatric subjects with recently diagnosed autoimmune diabetes. Placebo-controlled studies with larger cohorts and dose range are warranted in order to assess efficacy in maintaining pancreatic beta cell reserve and glycemic control. Marianna Rachmiel a,b , Pnina Strauss c , Nitzan Dror d , Hadassa Benzaquen d , Orit Horesh d , Nave Tov c , Naomi Weintrob b,e , Zohar Landau b,f , Michal Ben-Ami g , Alon Haim h,i , Moshe Phillip b,d , Tzvi Bistritzer a,b , Eli C Lewis i and Yael Lebenthal b,d a Pediatric Diabetes Service, Assaf Harofeh Medical Center, Zerifin, Israel; b Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; c Kamada Ltd, Ness-Ziona, Israel; d The Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children’s Medical Center, Petah-Tikva, Israel; e Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; f Pediatric Endocrine and Diabetes Unit, E. Wolfson Medical Center, Holon, Israel; g Pediatric Endocrine and Diabetes Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat-Gan, Israel; h Pediatric Diabetes Unit, Soroka Medical Center, Beer-Sheva, Israel; and i Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel † Parts of this study were presented in abstract form at the 6th International Conference on Advanced Technologies and Treatment for Diabetes (ATTD), Paris, France February, 2013. Key words: alpha-1 antitrypsin – adverse events – beta cell preservation – children – phase I/II trial – recent onset diabetes 1