Eli Lilly's Ixekizumab (Taltz®) Launches Phase I/II Clinical Trial for COVID-19 Treatment Targeting IL-17A Pathway

On the 10th, according to the Chinese Clinical Trial Registry, a randomized, blinded, controlled, multicenter clinical trial was registered for “Ixekizumab” to evaluate its efficacy and safety in coronavirus disease 2019 (COVID-19) (Registration No. ChiCTR2000030703).

The objective of this clinical trial is to preliminarily evaluate the efficacy and safety of ixekizumab in combination with conventional antiviral therapy for coronavirus disease 2019 (COVID-19).

This trial will be conducted in two phases.

01Phase I

Open-label trial enrolling three patients with COVID-19 to evaluate the safety and efficacy of ixekizumab plus antiviral therapy (aerosolized alpha-interferon, lopinavir/ritonavir, chloroquine, ribavirin, or arbidol; no more than three agents) over a 7-day observation period.

02Phase II

A prospective, randomized, assessor-blinded, controlled design will be adopted, with 40 COVID-19 patients enrolled and randomly assigned in a 1:1 ratio to two intervention groups for a 14-day observation period.

1) Experimental group (20 cases): Ixekizumab plus antiviral therapy (nebulized inhalation of α-interferon, lopinavir/ritonavir, chloroquine, ribavirin, arbidol, with no more than three agents used);

2) Control group (20 cases): Antiviral therapy (nebulized inhalation of α-interferon, lopinavir/ritonavir, chloroquine, ribavirin, and arbidol, with no more than 3 agents used).

The Phase II study will be conducted after the Phase I results are submitted to the Ethics Committee for review and approval. If the efficacy in the experimental group significantly exceeds that in the control group, the sample sizes of the two groups will be adjusted, or the trial will be terminated early.

It is worth noting that elevated IL-6 levels were included in the patient inclusion criteria.

Inclusion Criteria

Aged 18–75 years, gender unrestricted.

Confirmed as novel coronavirus pneumonia by RT-PCR or gene sequencing according to the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 6 and Updated Versions)," with clinical classification as moderate type (including high-risk factors for severe illness) or severe type.

Elevated IL-6 (Roche chemiluminescence assay recommended).

The patient voluntarily signed the informed consent form.

Ixekizumab is an IL-17A inhibitor that was approved by the U.S. FDA on March 22, 2016. To date, three indications have been approved.

Free Data Source: Yao Fenxiang Plus

In August 2018, it was included in the list of 48 urgently needed new drugs already marketed overseas by the National Medical Products Administration (NMPA). On August 29, 2019, Eli Lilly’s ixekizumab received marketing approval from the NMPA for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Regarding the use of ixekizumab in the treatment of patients with COVID-19 pneumonia, the editor estimates that its potential efficacy may be related not only to cytokine storm but also to the pathological autopsy findings of patients who died from COVID-19.

On February 17, The Lancet published a case report by the team of Academician Wang Fusheng from the Fifth Medical Center of the Chinese PLA General Hospital.

The research group performed flow cytometric analysis on patients' peripheral blood and found a significant reduction in the numbers of CD4+ and CD8+ T cells; however, these cells exhibited a hyperactivated state, characterized by a high frequency of HLA-DR and CD38 double-positive cells. The proportion of highly stimulatory CCR4+CCR6+ Th17 cells within the CD4+ T cell population was increased.

The study results indicate that the hyperactivation of T cells, characterized by an increase in Th17 cells and high cytotoxicity of CD8+ T cells, partially explains why this patient developed severe immune damage.

IL-17 family cytokines are primarily produced by T helper 17 (Th17) cells. Based on this finding, for precision treatment regimens targeting patients with severe COVID-19 pneumonia, IL-17 inhibitors such as ixekizumab and secukinumab, which target Th17 cell activation, can be utilized.

The clinical trial registered herein includes not only patients with mild to moderate COVID-19 but also those with severe disease. Among the numerous clinical trials for COVID-19 currently registered, only a small proportion target patients with severe disease, and therapeutic options for these patients are very limited. We also look forward to demonstrating the efficacy of ixekizumab in patients with severe COVID-19.

Original Title: Pathology-Anatomy-Based Targeting of Th17! Eli Lilly’s “Ixekizumab” Initiates COVID-19 Clinical Trials