ALLN-177, oral enzyme therapy for hyperoxaluria

PURPOSE: To evaluate the potential of ALLN-177, an orally administered, oxalate-specific enzyme therapy to reduce urine oxalate (UOx) excretion in patients with secondary hyperoxaluria. METHODS: Sixteen male and female subjects with both hyperoxaluria and a kidney stone history were enrolled in an open-label study. Subjects continued their usual diets and therapies. During a 3-day baseline period, two 24-h (24-h) urines were collected, followed by a 4-day treatment period with ALLN-177 (7,500 units/meal, 3 × day) when three 24-h urines were collected. The primary endpoint was the change in mean 24-h UOx from baseline. Safety assessments and 24-h dietary recalls were performed throughout. RESULTS: The study enrolled 5 subjects with enteric hyperoxaluria and 11 with idiopathic hyperoxaluria. ALLN-177 was well tolerated. Overall mean (SD) UOx decreased from 77.7 (55.9) at baseline to 63.7 (40.1) mg/24 h while on ALLN-177 therapy, with the mean reduction of 14 mg/24 h, (95% CI - 23.71, - 4.13). The calcium oxalate-relative urinary supersaturation ratio in the overall population decreased from a mean of 11.3 (5.7) to 8.8 (3.8) (- 2.8; 95% CI - 4.9, - 0.79). This difference was driven by oxalate reduction alone, but not any other urinary parameters. Mean daily dietary oxalate, calcium, and fluid intake recorded by frequent diet recall did not differ by study periods. CONCLUSION: ALLN-177 reduced 24-h UOx excretion, and was well tolerated. The results of this pilot study provided justification for further investigation of ALLN-177 in patients with secondary hyperoxaluria

Antecedents of Social Sustainability Noncompliance in the Indian Apparel Sector

Consumers expect global apparel suppliers to adhere to strict social sustainability standards following several deadly noncompliance incidents. This study provides a unique contribution to social sustainability governance by utilizing a causal-effect analysis to classify noncompliance antecedents into causal and effect groups and analyze the interactions. Combining a structured Delphi technique, involving thirty senior manufacturing professionals in the Indian apparel sector, with a fuzzy Decision-Making Trial and Evaluation Laboratory method (DEMATEL) revealed specific antecedents related to the adherence to social sustainability standards. The most influential antecedents identified were manufacturing cluster behavior, stringent regulations, multiple standards, business continuity, and buyer preference. Notably, the study theorizes that a supplier’s compliance deliberations intertwine with operational considerations around business volumes, costs, inappropriate governance, and regional cultural norms. Stakeholder theory and the theory of reasoned action help explain the institutional logics underlying the interactions between antecedents and highlight the crucial need for local production hubs to adopt universal social compliance codes. To our knowledge, this research is the first to identify manufacturing cluster behavior as a leading cause of noncompliance, highlighting the need to recognize clusters as essential stakeholders. The study has notable implications for brands, suppliers, governments, manufacturing councils, and non-governmental organizations (NGOs) that call for coordinated action and new forms of governance to minimize the incidences of noncompliance by apparel suppliers