Randomized, Double-Blind, Phase I Pharmacokinetic Study of Subcutaneous Recombinant Human Superoxide Dismutase (rhSOD) in Healthy Volunteers

Sep 30, 2026

Uploaded by Kyle

Randomized, double-blind, placebo-controlled Phase I evidence evaluates rhSOD (recombinant human Cu/Zn-SOD, SOD1) administered subcutaneously for safety, tolerability, and pharmacokinetics in healthy volunteers. The study targets oxidative-stress biology, where excess superoxide anion production contributes to cancers, inflammatory, neurodegenerative, and metabolic disorders, and where SOD supplementation could mitigate ROS-driven damage. Assessments include standardized injection-site erythema quantification and 72–92-hour PK sampling.

LanguageEnglish

CategoryHealthcare

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Pages10

Reading Time25 min

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Abstract

Background

Methods

Results

Conclusions

Introduction

Clinical Pharmacokinetics (2026) 65:71–80 [https://doi.org/10.1007/s40262-025-01578-1](https://doi.org/10.1007/s40262-025-01578-1) Randomized, Double‑Blind, Phase I Pharmacokinetic Study of Subcutaneous Recombinant Human Superoxide Dismutase (rhSOD) in Healthy Volunteers Valentin al Jalali1 · Martin Bauer1 · Anselm Jorda1 · Felix Bergmann1 · Michael Wölfl‑Duchek1,2 · Richard Partl3 · Brigitta Vcelar4 · Dietmar Katinger4 · Rawad Bashur5 · Harald Schnidar5 · Markus Zeitlinger1 Received: 4 June 2025 / Accepted: 31 August 2025 / Published online: 18 October 2025 © The Author(s) 2025 Abstract Background Excessive production of reactive oxygen species (ROS), particularly superoxide anion ( ), is a key mechanism in diseases such as cancer, inflammatory disorders, neurodegenerative conditions, and metabolic diseases. Evidence also suggests that microgravity-induced oxidative stress, primarily driven by elevated levels, may contribute to the adverse physiological effects observed in astronauts during extended space missions. Superoxide dismutase (SOD) is critical for mitigating oxidative stress, and exogenous SOD supplementation offers a potential therapeutic strategy. Methods This randomized, double-blind, placebo-controlled Phase I study evaluated the safety, tolerability, and pharmacokinetics of recombinant human Cu/Zn-SOD (rhSOD, SOD1) following subcutaneous administration of 40 mg every 12 hours in 16 healthy volunteers. Eight subjects were enrolled each in the single-dose (SD) and multiple-dose (MD) cohorts. Study assessments, including pharmacokinetic sampling, were performed for 72 (SD) or 92 hours (MD) . Injection site erythema was objectively assessed using the innovative Standardized Erythema Value (SEV*) method, derived from photographs taken with Scarletred®Vision software (SCARLETRED Holding GmbH) . Results No serious adverse events occurred, and all treatment-related adverse events were mild. Injection site erythema was objectively assessed using the innovative standardized erythema value (SEV*) method, derived from photographs taken with Scarletred® Vision software (SCARLETRED Holding GmbH) . The Visual Analog Scale scores and SEV* assessments were comparable between the rhSOD and placebo groups. Beyond safety and tolerability, pharmacokinetic analysis revealed that the volume of distribution, clearance, and half-life at presumed steady state were 129 ± 66.3 L, 5.97 ± 1.25 L/h, and 15.0 ± 6.69 h, respectively. Compared with the rapid systemic elimination after intravenous administration of SOD, subcutaneous administration resulted in a favorable plasma concentration-time profile. Conclusions These findings suggest that subcutaneous rhSOD may be a promising therapeutic candidate for conditions characterized by excessive exposure or diminished endogenous SOD activity. Further clinical studies are warranted to assess its anti-inflammatory potential in relevant patient populations. EudraCT Number: 2022-000173-11. * Markus Zeitlinger [markus.zeitlinger@meduniwien.ac.at](markus.zeitlinger@meduniwien.ac.at) 1 Department of Clinical Pharmacology, Vienna University Hospital, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria 2 Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria 3 Department of Therapeutic Radiology and Oncology, Comprehensive Cancer Center, Medical University of Graz, Graz, Austria 4 Polymun Scientific Immunbiologische Forschung GmbH, 3400 Klosterneuburg, Austria 5 SCARLETRED Holding GmbH, 1030 Vienna, Austria 1 Introduction Numerous studies have shown that chronic inflammation plays a central role in many of the most challenging diseases of our time. These include inflammatory diseases (e.g., arthritis, rheumatism, chronic inflammatory bowel diseases, joint inflammations), metabolic disorders (e.g. , diabetes, obesity), neurological conditions (e.g., Alzheimer's disease), heart diseases, atheros

FAQs

What was the main objective of the Phase I study?

To evaluate safety, tolerability, and pharmacokinetics of recombinant human Cu/Zn-SOD (rhSOD) after subcutaneous administration in healthy volunteers.

How was injection-site erythema assessed?

Using the Standardized Erythema Value (SEV*) method derived from photographs taken with Scarletred®Vision software.

What did pharmacokinetic analysis show after subcutaneous dosing?

Key parameters at presumed steady state included volume of distribution, clearance, and half-life, and the plasma concentration-time profile was favorable compared with the rapid elimination seen after intravenous administration.

Sep 30, 2026

Uploaded by Kyle