First‐in‐human, randomized, double‐blind, placebo‐controlled, dose escalation trial of the anti‐herpes simplex virus monoclonal antibody HDIT101 in healthy volunteers

Abstract

HDIT101 is a first‐in‐class humanized monoclonal antibody recognizing a conserved epitope in glycoprotein B, a target present on the surface of herpes simplex virus 1 (HSV‐1) and HSV‐2 particles as well as on virus‐infected cells. This was a first‐in‐human, single‐center, double‐blind, placebo‐controlled trial in 24 healthy volunteers, randomized 3:1 (placebo:active) in each of the six dose levels with escalating doses up to 12,150 mg HDIT101. HDIT101 was administered intravenously, to study safety, pharmacokinetics (PKs), and immunogenicity. HDIT101 was well‐tolerated in all recipients and no serious or severe adverse events, no infusion‐related reactions, and no events suggestive of dose limiting off‐target toxicity occurred. The mean serum exposure (area under the curve from zero to infinity [AUC0‐∞]) of HDIT101 showed a linear increase from 4340 h*μg/ml at a dose of 50 mg to 1,122,247 h*μg/ml at a dose of 12,150 mg. No immunogenic effects following HDIT101 exposure were observed at any of the applied doses. HDIT101 demonstrated the expected PK properties of a monoclonal antibody was well‐tolerated, and could be safely administered even at excessively high doses that may be required for treatment of patients with septical HSV spread.

Innovations in monoclonal antibody-based multipurpose prevention technology (MPT) for the prevention of sexually transmitted infections and unintended pregnancy

“…2C is a humanized mAb that recognizes a conserved region of glycoprotein-B on the surface of HSV-1 and 2. It was determined to be safe after intravenous administration of escalating doses (maximum dose: 12,150 mg) to healthy volunteers ( 30 ). This antibody is currently being tested in phase 2 clinical trials for the treatment of orolabial HSV-1 lesions (NCT04539483), and anogenital HSV-2 lesions (NCT04165122).…”

Development of a highly effective combination monoclonal antibody therapy against Herpes simplex virus

“…This mechanism allows HDIT101 to neutralize virus particles and effectively inhibit cell-to-cell spread of both HSV-1 and HSV-2. As a result, the antibody has been shown to prevent death in immunodeficient mice challenged with lethal doses of both wild type and multi-resistant HSV strains [ 16 , 17 ].…”

“…After demonstrating excellent tolerability in an intravenous clinical Phase 1 dose escalation trial in healthy volunteers [ 16 ], HDIT101 has advanced to a recently completed randomized Phase 2 clinical trial involving 122 patients suffering from chronic recurrent genital herpes. Aim of the trial was to compare the safety and efficacy of a single infusion of HDIT101 with episodic standard-of-care Valaciclovir (VAL) treatment in highly affected patients who have reported at least 4 anogenital HSV-2 recurrences within the last 12 months prior to study enrolment.…”