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1042. Safety of Investigational Microbiota-Based Live Biotherapeutic RBX2660 in Individuals with Recurrent Clostridioides difficile Infection: Data from Five Prospective Clinical Studies

1042. Safety of Investigational Microbiota-Based Live Biotherapeutic RBX2660 in Individuals with... Disclosures. S J Ryan Arends, PhD, AbbVie (formerly Allergan) (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Abby L.  Klauer, n/a, Cidara Therapeutics, Inc. (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Nicole Cotroneo, Spero Therapeutics (Employee, Shareholder) Ian A.  Critchley, Ph.D., Spero Therapeutics (Employee, Shareholder) Rodrigo E.  Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) 1042. Safety of Investigational Microbiota-Based Live Biotherapeutic RBX2660 in Individuals with Recurrent Clostridioides difficile Infection: Data from Five Prospective Clinical Studies 1 2 1 1 Tricia Braun, PharmD ; Beth Guthmueller, AS ; Adam J. Harvey, PhD ; Rebiotix, Table: Summary of culture and CFU log reduction among infected prosthetics A Ferring Company, Roseville, Minnesota; Rebiotix Inc, A Ferring Company, exposed and not exposed to PLG0206 Victoria, Minnesota Conclusion. Overall, these findings support the ongoing development of Session: P-59. New Drug Development PLG0206 as a local irrigation solution at 1 mg/mL concentration in the wound cavity for 15 minutes in patients undergoing treatment of a PJI occurring aer t ft otal knee Background. Microbiota-based treatments have shown promise to reduce recur- arthroplasty. rence, morbidity, and mortality for recurrent Clostridioides dic ffi ile infections (rCDI), Disclosures. David Huang, MD, PhD, Peptilogics (Employee) Nicholas but consistent and reliable safety data are needed to support regulatory approvals and Pachuda, DPM, Peptilogics (Employee) Despina Dobbins, BS, Peptilogics broaden patient access. Here we provide cumulative safety data from 5 prospective (Employee) Jonathan Steckbeck, PhD, Peptilogics (Employee) Kenneth Urish, MD, clinical studies evaluating RBX2660—a standardized, microbiota-based investigational PhD, Peptilogics (Grant/Research Support) live biotherapeutic—for reducing rCDI. Methods. This analysis included three Phase 2 (PUNCH CD, PUNCH CD2, PUNCH CD Open Label) and two Phase 3 trials (PUNCH CD3, PUNCH CD3-OLS ad 1041. In vitro activity of tebipenem against a recent collection of fastidious organ- hoc analysis). Participants were ≥18 years old with documented rCDI who completed isms recovered from respiratory tract infections standard-of-care oral antibiotic therapy prior to treatment with RBX2660. PUNCH 1 1 2 S J Ryan Arends, PhD ; Abby L. Klauer, n/a ; Nicole Cotroneo ; CD3-OLS allowed participants with comorbidities of irritable bowel syndrome (IBS) 2 1 1 Ian A. Critchley, Ph.D. ; Rodrigo E. Mendes, PhD ; JMI Laboratories, North Liberty, or inflammatory bowel disease (IBD). Depending on the trial, assigned study treat - Iowa; Spero Therapeutics ment was 1 or 2 doses of RBX2660 (or placebo), administered rectally. Participants whose CDI recurred within 8 weeks were eligible for additional RBX2660 treatment. Session: P-59. New Drug Development Treatment-emergent adverse events (TEAEs) were recorded for at least 6 months fol- Background. Tebipenem is under development as an oral treatment option for lowing last study treatment; CD2 and CD Open Label recorded TEAEs for 24 months. complicated urinary tract infections and acute pyelonephritis. This study further eval - Results. Among 620 participants who received at least one RBX2660 dose uated the in vitro activity of tebipenem against various fastidious organisms recovered (assigned treatment or aer r ft ecurrence), 324 (52.3%) received 1, 270 (43.5%) received from community-acquired respiratory tract infections (CARTIs). 2, 14 (2.3%) received 3, and 12 (1.9%) received 4. 83 participants received blinded pla- Methods. e s Th tudy included a total of 2,476 fastidious organisms: Haemophilus cebo only. A total of 1980 TEAEs were reported from 432 (69.7%) RBX2660-treated influenzae (692 isolates, including fluoroquinolone-resistant, β-lactamase-positive, participants, compared to 174 TEAEs in 50 (60.2%) placebo-only treated partici- and β-lactamase-negative ampicillin-resistant [BLNAR]), Haemophilus parainu fl enzae pants. Most TEAEs were mild or moderate in severity, with diarrhea common in all (30 isolates, including β-lactamase-positive and BLNAR), Moraxella catarrhalis (490 treatment groups. No potentially life-threatening TEAEs were considered related to isolates), and Streptococcus pneumoniae (1,264 isolates, including penicillin-resistant). RBX2660. Study discontinuation due to TEAEs was minimal (< 1%) with none related e i Th solates were collected primarily from CARTIs (90.8%) and pneumonia in hospi - to RBX2660. There were no reported infections for which the causative pathogen was talized patients (PIHPs, 9.2%). Organisms were tested using reference broth microdi- traced to RBX2660. lution methods in a central laboratory.  Conclusion. Across five clinical studies with consistent investigational product, Results. Tebipenem had MIC values of 0.5  mg/L against H.  inu fl enzae and 90 RBX2660 was well-tolerated in rCDI participants. In aggregate, this data provides com- 1 mg/L against H. parainu fl enzae isolates. All 18 BLNAR isolates from these two spe- pelling and consistent safety data for RBX2660. cies were inhibited at ≤1 mg/L of tebipenem. The MIC values observed for ertapenem 90 Disclosures. Tricia Braun, PharmD, Rebiotix, a Ferring Company (Employee) and meropenem was 0.25  mg/L for these organisms. Tebipenem displayed good ac- Beth Guthmueller, AS, Rebiotix Inc, A  Ferring Company (Employee) Adam tivity against M. catarrhalis (MIC , 0.03 mg/L). Tebipenem inhibited 100% of S. pneu- 90 J. Harvey, PhD, Rebiotix, A Ferring Company (Employee) moniae isolates at ≤1 mg/L. Tebipenem activity (MIC , 0.12 mg/L) was 8-fold greater than ertapenem (MIC , 1 mg/L) against S. pneumoniae isolates. Conclusion. Tebipenem displayed potent activity against fastidious organisms 1043. Activity of Mecillinam Against Enterobacterales Isolates Collected From causing respiratory tract infections. Greater than 99.7% of all Haemophilus isolates, Patients With Urinary Tract Infections (UTIs) in the USA During 2019 1 2 3 1 including all BLNAR, were inhibited at ≤1 mg/L. All M. catarrhalis isolates were inhib- Stephen Hawser, PhD ; Ian Morrissey ; Anne Santerre Henriksen, MS ; IHMA, 2 3 ited at ≤0.03 mg/L. Although tebipenem activity correlated with penicillin resistance, Monthey, Valais, Switzerland; IHMA Europe, Monthey, Valais, Switzerland; Maxel all S. pneumoniae isolates were inhibited at ≤1 mg/L. Tebipenem in vitro activity was Consulting ApS, London, England, United Kingdom greater than ertapenem when tested against S. pneumoniae isolates. This data supports Session: P-59. New Drug Development the possible development of tebipenem as an oral option for combating CARTIs caused by these organisms. Background. Mecillinam is a β-lactam antibiotic that exerts its antibacterial ac- tivity by binding to penicillin-binding protein 2. In the USA, intravenous (IV) mecil- linam is in development for the treatment of complicated UTIs in the hospital setting Table and as step-down therapy transitioning from IV mecillinam to oral pivmecillinam so that patients can continue treatment at home. To support the clinical develop- ment of mecillinam in the USA for the treatment of both complicated and uncom- plicated UTI, this observational study investigated the activity of mecillinam against Enterobacterales isolates from patients with UTI in the USA, collected during 2019.  Methods. This study evaluated the activity of mecillinam and other antimicrobial agents against 1075 selected Enterobacterales clinical isolates collected from patients with UTI in the USA during 2019. Antibiotic activity (minimum inhibitory concentra- tion [MIC]) was determined by Clinical & Laboratory Standards Institute (CLSI) agar dilution methodology, and susceptibility was interpreted according to CLSI guidelines.  Results. Among the selected 1075 isolates, producers of extended-spectrum beta-lactamase (ESBL) represented 9.6% of Escherichia coli and 50% of Klebsiella pneu- moniae. Ninety-five percent of the isolates tested were susceptible to mecillinam (Table 1). The MIC and MIC values for mecillinam were 0.25 and 2 µg/mL, respectively. 50 90 Fosfomycin MIC and MIC were 1 and 32  µg/mL, respectively (97.6% of isolates 50 90 Abstracts • OFID 2021:8 (Suppl 1) • S611 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Open Forum Infectious Diseases Oxford University Press

1042. Safety of Investigational Microbiota-Based Live Biotherapeutic RBX2660 in Individuals with Recurrent Clostridioides difficile Infection: Data from Five Prospective Clinical Studies

Open Forum Infectious Diseases , Volume 8 (Supplement_1): 1 – Dec 4, 2021

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Oxford University Press
Copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
eISSN
2328-8957
DOI
10.1093/ofid/ofab466.1236
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Abstract

Disclosures. S J Ryan Arends, PhD, AbbVie (formerly Allergan) (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Abby L.  Klauer, n/a, Cidara Therapeutics, Inc. (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Nicole Cotroneo, Spero Therapeutics (Employee, Shareholder) Ian A.  Critchley, Ph.D., Spero Therapeutics (Employee, Shareholder) Rodrigo E.  Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) 1042. Safety of Investigational Microbiota-Based Live Biotherapeutic RBX2660 in Individuals with Recurrent Clostridioides difficile Infection: Data from Five Prospective Clinical Studies 1 2 1 1 Tricia Braun, PharmD ; Beth Guthmueller, AS ; Adam J. Harvey, PhD ; Rebiotix, Table: Summary of culture and CFU log reduction among infected prosthetics A Ferring Company, Roseville, Minnesota; Rebiotix Inc, A Ferring Company, exposed and not exposed to PLG0206 Victoria, Minnesota Conclusion. Overall, these findings support the ongoing development of Session: P-59. New Drug Development PLG0206 as a local irrigation solution at 1 mg/mL concentration in the wound cavity for 15 minutes in patients undergoing treatment of a PJI occurring aer t ft otal knee Background. Microbiota-based treatments have shown promise to reduce recur- arthroplasty. rence, morbidity, and mortality for recurrent Clostridioides dic ffi ile infections (rCDI), Disclosures. David Huang, MD, PhD, Peptilogics (Employee) Nicholas but consistent and reliable safety data are needed to support regulatory approvals and Pachuda, DPM, Peptilogics (Employee) Despina Dobbins, BS, Peptilogics broaden patient access. Here we provide cumulative safety data from 5 prospective (Employee) Jonathan Steckbeck, PhD, Peptilogics (Employee) Kenneth Urish, MD, clinical studies evaluating RBX2660—a standardized, microbiota-based investigational PhD, Peptilogics (Grant/Research Support) live biotherapeutic—for reducing rCDI. Methods. This analysis included three Phase 2 (PUNCH CD, PUNCH CD2, PUNCH CD Open Label) and two Phase 3 trials (PUNCH CD3, PUNCH CD3-OLS ad 1041. In vitro activity of tebipenem against a recent collection of fastidious organ- hoc analysis). Participants were ≥18 years old with documented rCDI who completed isms recovered from respiratory tract infections standard-of-care oral antibiotic therapy prior to treatment with RBX2660. PUNCH 1 1 2 S J Ryan Arends, PhD ; Abby L. Klauer, n/a ; Nicole Cotroneo ; CD3-OLS allowed participants with comorbidities of irritable bowel syndrome (IBS) 2 1 1 Ian A. Critchley, Ph.D. ; Rodrigo E. Mendes, PhD ; JMI Laboratories, North Liberty, or inflammatory bowel disease (IBD). Depending on the trial, assigned study treat - Iowa; Spero Therapeutics ment was 1 or 2 doses of RBX2660 (or placebo), administered rectally. Participants whose CDI recurred within 8 weeks were eligible for additional RBX2660 treatment. Session: P-59. New Drug Development Treatment-emergent adverse events (TEAEs) were recorded for at least 6 months fol- Background. Tebipenem is under development as an oral treatment option for lowing last study treatment; CD2 and CD Open Label recorded TEAEs for 24 months. complicated urinary tract infections and acute pyelonephritis. This study further eval - Results. Among 620 participants who received at least one RBX2660 dose uated the in vitro activity of tebipenem against various fastidious organisms recovered (assigned treatment or aer r ft ecurrence), 324 (52.3%) received 1, 270 (43.5%) received from community-acquired respiratory tract infections (CARTIs). 2, 14 (2.3%) received 3, and 12 (1.9%) received 4. 83 participants received blinded pla- Methods. e s Th tudy included a total of 2,476 fastidious organisms: Haemophilus cebo only. A total of 1980 TEAEs were reported from 432 (69.7%) RBX2660-treated influenzae (692 isolates, including fluoroquinolone-resistant, β-lactamase-positive, participants, compared to 174 TEAEs in 50 (60.2%) placebo-only treated partici- and β-lactamase-negative ampicillin-resistant [BLNAR]), Haemophilus parainu fl enzae pants. Most TEAEs were mild or moderate in severity, with diarrhea common in all (30 isolates, including β-lactamase-positive and BLNAR), Moraxella catarrhalis (490 treatment groups. No potentially life-threatening TEAEs were considered related to isolates), and Streptococcus pneumoniae (1,264 isolates, including penicillin-resistant). RBX2660. Study discontinuation due to TEAEs was minimal (< 1%) with none related e i Th solates were collected primarily from CARTIs (90.8%) and pneumonia in hospi - to RBX2660. There were no reported infections for which the causative pathogen was talized patients (PIHPs, 9.2%). Organisms were tested using reference broth microdi- traced to RBX2660. lution methods in a central laboratory.  Conclusion. Across five clinical studies with consistent investigational product, Results. Tebipenem had MIC values of 0.5  mg/L against H.  inu fl enzae and 90 RBX2660 was well-tolerated in rCDI participants. In aggregate, this data provides com- 1 mg/L against H. parainu fl enzae isolates. All 18 BLNAR isolates from these two spe- pelling and consistent safety data for RBX2660. cies were inhibited at ≤1 mg/L of tebipenem. The MIC values observed for ertapenem 90 Disclosures. Tricia Braun, PharmD, Rebiotix, a Ferring Company (Employee) and meropenem was 0.25  mg/L for these organisms. Tebipenem displayed good ac- Beth Guthmueller, AS, Rebiotix Inc, A  Ferring Company (Employee) Adam tivity against M. catarrhalis (MIC , 0.03 mg/L). Tebipenem inhibited 100% of S. pneu- 90 J. Harvey, PhD, Rebiotix, A Ferring Company (Employee) moniae isolates at ≤1 mg/L. Tebipenem activity (MIC , 0.12 mg/L) was 8-fold greater than ertapenem (MIC , 1 mg/L) against S. pneumoniae isolates. Conclusion. Tebipenem displayed potent activity against fastidious organisms 1043. Activity of Mecillinam Against Enterobacterales Isolates Collected From causing respiratory tract infections. Greater than 99.7% of all Haemophilus isolates, Patients With Urinary Tract Infections (UTIs) in the USA During 2019 1 2 3 1 including all BLNAR, were inhibited at ≤1 mg/L. All M. catarrhalis isolates were inhib- Stephen Hawser, PhD ; Ian Morrissey ; Anne Santerre Henriksen, MS ; IHMA, 2 3 ited at ≤0.03 mg/L. Although tebipenem activity correlated with penicillin resistance, Monthey, Valais, Switzerland; IHMA Europe, Monthey, Valais, Switzerland; Maxel all S. pneumoniae isolates were inhibited at ≤1 mg/L. Tebipenem in vitro activity was Consulting ApS, London, England, United Kingdom greater than ertapenem when tested against S. pneumoniae isolates. This data supports Session: P-59. New Drug Development the possible development of tebipenem as an oral option for combating CARTIs caused by these organisms. Background. Mecillinam is a β-lactam antibiotic that exerts its antibacterial ac- tivity by binding to penicillin-binding protein 2. In the USA, intravenous (IV) mecil- linam is in development for the treatment of complicated UTIs in the hospital setting Table and as step-down therapy transitioning from IV mecillinam to oral pivmecillinam so that patients can continue treatment at home. To support the clinical develop- ment of mecillinam in the USA for the treatment of both complicated and uncom- plicated UTI, this observational study investigated the activity of mecillinam against Enterobacterales isolates from patients with UTI in the USA, collected during 2019.  Methods. This study evaluated the activity of mecillinam and other antimicrobial agents against 1075 selected Enterobacterales clinical isolates collected from patients with UTI in the USA during 2019. Antibiotic activity (minimum inhibitory concentra- tion [MIC]) was determined by Clinical & Laboratory Standards Institute (CLSI) agar dilution methodology, and susceptibility was interpreted according to CLSI guidelines.  Results. Among the selected 1075 isolates, producers of extended-spectrum beta-lactamase (ESBL) represented 9.6% of Escherichia coli and 50% of Klebsiella pneu- moniae. Ninety-five percent of the isolates tested were susceptible to mecillinam (Table 1). The MIC and MIC values for mecillinam were 0.25 and 2 µg/mL, respectively. 50 90 Fosfomycin MIC and MIC were 1 and 32  µg/mL, respectively (97.6% of isolates 50 90 Abstracts • OFID 2021:8 (Suppl 1) • S611

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Open Forum Infectious DiseasesOxford University Press

Published: Dec 4, 2021

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