Skip to main content

Safety, Tolerability, and Pharmacokinetics of NTM-1632, a Novel Mixture of Three Monoclonal Antibodies against Botulinum Toxin B.

Publication ,  Journal Article
Guptill, JT; Raja, SM; Juel, VC; Walter, EB; Cohen-Wolkowiez, M; Hill, H; Sendra, E; Hauser, B; Jackson, P; Swamy, GK
Published in: Antimicrob Agents Chemother
June 17, 2021

Botulism is a rare, life-threatening paralytic disease caused by Clostridium botulinum neurotoxin (BoNT). Available treatments, including an equine antitoxin and human immune globulin, are given postexposure and challenging to produce and administer. NTM-1632 is an equimolar mixture of 3 human IgG monoclonal antibodies, B1, B2, and B3, targeting BoNT serotype B (BoNT/B). This first-in-human study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of NTM-1632. This double-blind, single-center, placebo-controlled dose escalation study randomized 3 cohorts of healthy volunteers to receive a single intravenous dose of NTM-1632 (0.033, 0.165, or 0.330 mg/kg) or saline placebo. Safety monitoring included physical examinations, clinical laboratory studies, and vital signs. Blood sampling was performed at prespecified time points for PK and immunogenicity analyses. Twenty-four subjects received study product (18 NTM-1632; 6 placebo), and no deaths or serious adverse events were reported. Adverse events in the NTM-1632 groups were generally mild and similar in frequency and severity to the placebo group, and no safety signal was identified. NTM-1632 has a favorable PK profile with a half-life of >20 days for the 0.330-mg/kg dose and an approximately linear relationship with respect to maximum concentration and area under the concentration-time curve (AUC0→t). NTM-1632 demonstrated low immunogenicity with only a few treatment-emergent antidrug antibody responses in the low and middle dosing groups and none at the highest dose. NTM-1632 is well tolerated at the administered doses. The favorable safety, PK, and immunogenicity profile of NTM-1632 supports further clinical development as a treatment for BoNT/B intoxication and postexposure prophylaxis. (This study has been registered at ClinicalTrials.gov under identifier NCT02779140.).

Duke Scholars

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

June 17, 2021

Volume

65

Issue

7

Start / End Page

e0232920

Location

United States

Related Subject Headings

  • Microbiology
  • Immunoglobulin G
  • Humans
  • Healthy Volunteers
  • Double-Blind Method
  • Botulism
  • Antibodies, Monoclonal
  • 3214 Pharmacology and pharmaceutical sciences
  • 3207 Medical microbiology
  • 3107 Microbiology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Guptill, J. T., Raja, S. M., Juel, V. C., Walter, E. B., Cohen-Wolkowiez, M., Hill, H., … Swamy, G. K. (2021). Safety, Tolerability, and Pharmacokinetics of NTM-1632, a Novel Mixture of Three Monoclonal Antibodies against Botulinum Toxin B. Antimicrob Agents Chemother, 65(7), e0232920. https://doi.org/10.1128/AAC.02329-20
Guptill, J. T., S. M. Raja, V. C. Juel, E. B. Walter, M. Cohen-Wolkowiez, H. Hill, E. Sendra, B. Hauser, P. Jackson, and G. K. Swamy. “Safety, Tolerability, and Pharmacokinetics of NTM-1632, a Novel Mixture of Three Monoclonal Antibodies against Botulinum Toxin B.Antimicrob Agents Chemother 65, no. 7 (June 17, 2021): e0232920. https://doi.org/10.1128/AAC.02329-20.
Guptill JT, Raja SM, Juel VC, Walter EB, Cohen-Wolkowiez M, Hill H, et al. Safety, Tolerability, and Pharmacokinetics of NTM-1632, a Novel Mixture of Three Monoclonal Antibodies against Botulinum Toxin B. Antimicrob Agents Chemother. 2021 Jun 17;65(7):e0232920.
Guptill, J. T., et al. “Safety, Tolerability, and Pharmacokinetics of NTM-1632, a Novel Mixture of Three Monoclonal Antibodies against Botulinum Toxin B.Antimicrob Agents Chemother, vol. 65, no. 7, June 2021, p. e0232920. Pubmed, doi:10.1128/AAC.02329-20.
Guptill JT, Raja SM, Juel VC, Walter EB, Cohen-Wolkowiez M, Hill H, Sendra E, Hauser B, Jackson P, Swamy GK. Safety, Tolerability, and Pharmacokinetics of NTM-1632, a Novel Mixture of Three Monoclonal Antibodies against Botulinum Toxin B. Antimicrob Agents Chemother. 2021 Jun 17;65(7):e0232920.

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

June 17, 2021

Volume

65

Issue

7

Start / End Page

e0232920

Location

United States

Related Subject Headings

  • Microbiology
  • Immunoglobulin G
  • Humans
  • Healthy Volunteers
  • Double-Blind Method
  • Botulism
  • Antibodies, Monoclonal
  • 3214 Pharmacology and pharmaceutical sciences
  • 3207 Medical microbiology
  • 3107 Microbiology