FDA Approves Phase 3 Trial to Evaluate Oral Carbapenem for Treatment of cUTI

The US Food and Drug Administration (FDA) has accepted Spero Therapeutics’ Investigational New Drug application for SPR994, a candidate being developed as an oral carbapenem antibiotic for the treatment of complicated urinary tract infections (cUTI).

With the acceptance of the application, the company will initiate enrollment of a phase 3 clinical trial in the United States.

The candidate, SPR994, has an oral formulation of tebipenem, which is a carbapenem-class antibiotic that has been marketed in Japan since 2009 for pediatric infections of pneumonia, otitis media, and sinusitis.

Spero Therapeutics conducted a phase 1, double-blind, placebo-controlled, dosing study in Australia, which enabled dose selection for the phase 3 trial. The company also reports that the candidate has shown potent antibiotic activity against gram-negative bacteria, including E coli-producing extended-spectrum beta-lactamases (ESBLs) and ESBL-producing Klebsiella pneumoniae, similar to IV-administered ertapenem in preclinical studies.

The phase 3 clinical trial, ADAPT-PO, is designed as a double-blind trial that will evaluate the investigational candidate with the current intravenous standard of care, ertapenem. The trial will enroll approximately 2400 patients with either cUTI or acute pyelonephritis in 1 of 2 treatment arms, with participants randomized 1:1 at the point of enrollment.

“With the FDA’s acceptance of our IND application for SPR994, we are excited to continue our Phase 3 initiation efforts, including opening clinical trial sites for enrollment in the US," Ankit Mahadevia, MD, chief executive officer of Spero Therapeutics, said in a statement. "We look forward to enrolling patients in our single pivotal Phase 3 clinical trial with the hope, following approval, of providing patients with the option for an oral carbapenem to address the serious unmet need of multi-drug resistant infections.”

According to the company, the primary endpoint of the trial is combined clinical and microbiological response at the test of cure with a 10% non-inferiority margin versus IV ertapenem.

The trial will feature a lead-in cohort of 70 patients with intensive pharmacokinetics to assess the dose and exposure in cUTI patients. Additionally, the company will conduct parallel ancillary pharmacology studies including a renal insufficiency study.

The interim pharmacokinetic data from the lead-in cohort is expected in the second half of 2019.

Spero Therapeutics also reports that the project has received funding from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority.