Subcutaneous Administration of Therapeutic Monoclonal Antibody Drug Products Using a Syringe in Blinded Clinical Trials: Advances and Key Aspects Related to Blinding/Matching/Masking Strategies for Placebo Formulation.

Abstract

Therapeutic monoclonal antibody (mAb) drug products are increasingly used to treat both chronic and acute diseases. These mAb drug products are often developed for subcutaneous (SC) injection to simplify dosing compared with intravenous (IV) infusion. For SC injection, the mAb liquid drug product is typically filled in a vial for use with a syringe or in a prefilled syringe, which can then be assembled into a safety syringe device or an autoinjector for direct administration. A placebo is an inert formulation (one without an active ingredient) that lacks pharmacological activity or a therapeutic effect. It serves as a control in blinded clinical trials to evaluate the efficacy of a new treatment. A suitable blinding/matching/masking strategy is crucial to ensure that study participants cannot distinguish between the active mAb formulation and the placebo. The success of these strategies is pivotal in ensuring the accuracy and reliability of clinical trial results. This Review summarizes recent advances and key considerations related to placebo strategies. It covers the benefits and challenges of SC injection of therapeutic mAbs compared to IV infusion, the placebo effect, the significance of blinding/matching/masking, and various strategies. Strategies discussed include the use of traditional placebos (e.g., normal saline, 5% w/v dextrose solution, and formulation buffer of the active mAb), syringe blinding, the use of different gauge syringe needles, novel (custom) placebos, dilution, independent administration, and multiple injections. Additional topics covered include the incidence of antidrug antibodies (ADAs), the benefits and challenges associated with different strategies, and regulatory expectations regarding custom placebos. By addressing these critical aspects, the Review aims to contribute to the growing body of knowledge and ongoing efforts to enhance the effectiveness of formulation blinding, matching, and masking in clinical trials.