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First-in-Human Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetics of Single Doses of NTM-1633, a Novel Mixture of Monoclonal Antibodies against Botulinum Toxin E.

Publication ,  Journal Article
Raja, SM; Guptill, JT; Juel, VC; Walter, EB; Cohen-Wolkowiez, M; Hill, H; Sendra, E; Hauser, B; Jackson, P; Tomic, M; Espinoza, Y; Swamy, GK
Published in: Antimicrob Agents Chemother
April 19, 2022

Botulism is a rare, life-threatening paralytic disease caused by botulinum neurotoxin (BoNT). Available treatments including an equine antitoxin and human immune globulin are given postexposure and challenging to produce and administer. NTM-1633 is an equimolar mixture of 3 human IgG monoclonal antibodies, E1, E2, and E3, targeting BoNT serotype E (BoNT/E). This first-in-human study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of NTM-1633. This double-blind, single-center, placebo-controlled dose escalation study randomized 3 cohorts of healthy volunteers to receive a single intravenous dose of NTM-1633 (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-1633; 6 placebo), and no deaths were reported. An unrelated serious adverse event was reported in a placebo subject. Adverse events in the NTM-1633 groups were generally mild and similar in frequency and severity to the placebo group, and no safety signal was identified. NTM-1633 has a favorable PK profile with a half-life >10 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-1633 also demonstrated low immunogenicity. NTM-1633 is well tolerated at the administered doses. The favorable safety, PK, and immunogenicity profile supports further development as a treatment for BoNT/E intoxication and postexposure prophylaxis.

Duke Scholars

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

April 19, 2022

Volume

66

Issue

4

Start / End Page

e0173221

Location

United States

Related Subject Headings

  • Microbiology
  • Immunoglobulin G
  • Humans
  • Horses
  • Double-Blind Method
  • Botulism
  • Botulinum Toxins
  • Antibodies, Monoclonal
  • Animals
  • 3214 Pharmacology and pharmaceutical sciences
 

Citation

APA
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MLA
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Raja, S. M., Guptill, J. T., Juel, V. C., Walter, E. B., Cohen-Wolkowiez, M., Hill, H., … Swamy, G. K. (2022). First-in-Human Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetics of Single Doses of NTM-1633, a Novel Mixture of Monoclonal Antibodies against Botulinum Toxin E. Antimicrob Agents Chemother, 66(4), e0173221. https://doi.org/10.1128/aac.01732-21
Raja, S. M., J. T. Guptill, V. C. Juel, E. B. Walter, M. Cohen-Wolkowiez, H. Hill, E. Sendra, et al. “First-in-Human Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetics of Single Doses of NTM-1633, a Novel Mixture of Monoclonal Antibodies against Botulinum Toxin E.Antimicrob Agents Chemother 66, no. 4 (April 19, 2022): e0173221. https://doi.org/10.1128/aac.01732-21.
Raja SM, Guptill JT, Juel VC, Walter EB, Cohen-Wolkowiez M, Hill H, et al. First-in-Human Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetics of Single Doses of NTM-1633, a Novel Mixture of Monoclonal Antibodies against Botulinum Toxin E. Antimicrob Agents Chemother. 2022 Apr 19;66(4):e0173221.
Raja, S. M., et al. “First-in-Human Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetics of Single Doses of NTM-1633, a Novel Mixture of Monoclonal Antibodies against Botulinum Toxin E.Antimicrob Agents Chemother, vol. 66, no. 4, Apr. 2022, p. e0173221. Pubmed, doi:10.1128/aac.01732-21.
Raja SM, Guptill JT, Juel VC, Walter EB, Cohen-Wolkowiez M, Hill H, Sendra E, Hauser B, Jackson P, Tomic M, Espinoza Y, Swamy GK. First-in-Human Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetics of Single Doses of NTM-1633, a Novel Mixture of Monoclonal Antibodies against Botulinum Toxin E. Antimicrob Agents Chemother. 2022 Apr 19;66(4):e0173221.

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

April 19, 2022

Volume

66

Issue

4

Start / End Page

e0173221

Location

United States

Related Subject Headings

  • Microbiology
  • Immunoglobulin G
  • Humans
  • Horses
  • Double-Blind Method
  • Botulism
  • Botulinum Toxins
  • Antibodies, Monoclonal
  • Animals
  • 3214 Pharmacology and pharmaceutical sciences