Phase 1 study of safety, pharmacokinetics, and antiviral activity of SARS‐CoV‐2 neutralizing monoclonal antibody ABBV‐47D11 in patients with COVID‐19. Issue 1 (20th December 2022)

• Record Type: Journal Article
• Authors: Shebley, Mohamad; Wang, Stanley; Ali, Izna; Krishnan, Preethi; Tripathi, Rakesh; Reardon, Joseph M.; Cafardi, John; Rahav, Galia; Caraco, Yoseph; Slim, Jihad; Al Akhrass, Fadi; Yu, Mengjia; Hu, Yiran; Ferreira, Rosa De Abreu; Alami, Negar N.
• Is Part Of: Pharmacology research & perspectives. Volume 11:Issue 1(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-20
• Subjects: ABBV‐47D11 -- COVID‐19 -- first‐in‐human study -- monoclonal antibodies -- SARS‐CoV‐2; Pharmacology -- Periodicals; Drug development -- Periodicals; 615.105
• DOI: 10.1002/prp2.1036
• Languages: English
• ISSNs: 2052-1707

Abstract

Abstract: ABBV‐47D11 is a neutralizing monoclonal antibody that targets a mutationally conserved hydrophobic pocket distal to the ACE2 binding site of SARS‐CoV‐2. This first‐in‐human safety, pharmacokinetics, and antiviral pharmacodynamic assessment in patients with COVID‐19 provide an initial evaluation of this antibody that may allow further development. This multicenter, randomized, double‐blind, and placebo‐controlled single ascending dose study of ABBV‐47D11 (180, 600, or 2400 mg) as an intravenous infusion, was in hospitalized and non‐hospitalized (confined) adults with mild to moderate COVID‐19. Primary outcomes were grade 3 or higher study drug‐related adverse events and infusion‐related reactions. Secondary outcomes were pharmacokinetic parameters and concentration‐time profiles to Day 29, immunogenicity (anti‐drug antibodies), and antiviral activity (change in RT‐PCR viral load) from baseline to Days 15 and 29. ABBV‐47D11 single doses up to 2400 mg were safe and tolerated and no safety signals were identified. The pharmacokinetics of ABBV‐47D11 were linear and showed dose‐proportional increases in serum concentrations with ascending doses. The exploratory anti‐SARS‐CoV‐2 activity revealed a reduction of viral load at and above the 600 mg dose of ABBV‐47D11 regardless of patient demographics and baseline characteristics, however; because of the high inter‐individual variability and small sample size a statistical significance was not reached. There is potential for anti‐SARS‐CoV‐2 activity with ABBV‐47D11 doses of 600 mg or higher, which could be evaluated in future clinical trials designed and powered to assess viral load reductions and clinical benefit. Abstract : Left: CONSORT flow chart. Right: ABBV‐47D11 Dose–Response for SARS‐CoV‐2 Viral Load AUC of Change from Baseline to Day 15. AUC: area under the curve; Box plots represent 25th/75th percentiles, median (solid line), mean (dashed line), whiskers represent min‐max values, and dots represent individual patient data.