Part IB Of RETAIN Type 1 Diabetes Study Opens For Enrollment

October 3, 2013

Part IB of the ITN’s multi-stage RETAIN study in type 1 diabetes is now open for enrollment. Part I of the RETAIN study (“A Research Trial of Aralast in New Onset Diabetes”) is evaluating the safety and pharmacokinetics of alpha-1 antitrypsin (“AAT”; Aralast NP, Baxter) prior to initiating a fully powered proof-of-concept study (Part II) in new-onset type 1 diabetics.

In Part IA an initial cohort of 16 adult and pediatric new-onset type 1 diabetes patients received two doses of AAT. AAT is a serine protease inhibitor with broad anti-inflammatory and anti-apoptotic effects, as well as a good safety profile, making it a potential candidate for tolerance induction. AAT has not been tested in type 1 diabetes before, and to ensure an appropriate biologic effect the ITN developed a unique ex-vivo whole blood pharmacodynamic assay to measure production of inflammatory cytokines and modulation of relevant genes. This assay revealed that AAT did in fact have a biologic effect, but the drug levels required to produce robust pharmacodynamics changes appeared to be higher than those tested in Part IA. Therefore, Part IB will assess two higher doses of AAT that may potentially strengthen immune responses before initiating Part II. This two-staged approach will ensure the optimal dose of AAT is being tested in the full study.

Clinically, the results from Part IA showed AAT was well tolerated and demonstrated preservation of C-peptide secretion at 18 weeks (see results presented in an abstract in 2012); however these data should be interpreted with caution given the small sample size and lack of control group.  Part II will better confirm the therapeutic effect of AAT in a larger cohort of patients.

For more about the RETAIN study, visit the website.

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