Adjunctive Pascolizumab in Rifampicin-Susceptible Pulmonary Tuberculosis: Proof-of-Concept, Partially-Randomized,...

Area of Science:

• Immunology
• Infectious Diseases
• Pharmacology

Background:

• Interleukin 4 (IL-4) levels are elevated in tuberculosis (TB) infection and may hinder bacterial clearance.
• Preclinical studies indicate that blocking IL-4 can be beneficial in TB animal models.
• Pascolizumab, a humanized monoclonal antibody targeting IL-4, was investigated as an adjunctive therapy for TB.

Purpose of the Study:

• To evaluate the safety and efficacy of pascolizumab when used as an add-on treatment to standard tuberculosis therapy.
• To assess the safety profile of pascolizumab in patients with rifampicin-susceptible pulmonary tuberculosis.
• To explore the preliminary efficacy of pascolizumab by measuring sputum culture time-to-positivity (TTP).

Main Methods:

• A single intravenous infusion of pascolizumab or placebo was administered to participants receiving standard 6-month tuberculosis treatment.
• Dosing escalated across nonrandomized and randomized cohorts, with doses of 0.05 mg/kg, 0.5 mg/kg, 2.5 mg/kg, and 10 mg/kg pascolizumab.
• Coprimary safety outcomes included study-drug-related grade 4 or serious adverse events (G4/SAE); coprimary efficacy outcomes were week 8 sputum culture TTP in randomized cohorts.

Main Results:

• Pascolizumab achieved levels that neutralized IL-4 for at least 8 weeks in 78%-100% of participants in higher dose cohorts.
• No study-drug-related G4/SAEs were reported, indicating a favorable safety profile.
• While median week-8 TTP was similar between groups (42 days), a greater rate of TTP increase was observed with pascolizumab compared to placebo.

Conclusions:

• Blocking IL-4 with pascolizumab was found to be safe in this study population.
• Preliminary efficacy findings align with results from animal models, suggesting a potential benefit.
• Further investigation in larger Phase 2 trials is supported to confirm the efficacy of anti-IL-4 interventions as adjunctive TB therapy.