Clinical Trial: Phase I, Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of NTM-1632

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase I, Double-Blind, Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of NTM-1632 vs Placebo Administered Intravenously in Healthy Adults

Brief Summary: This is a Phase I, randomized, double-blind, placebo controlled dose escalation trial to evaluate NTM-1632 in three dose cohorts (A: 0.033 mg/kg, B: 0.165 mg/kg, and C: 0.33 mg/kg). NTM-1632 is a mixture of three monoclonal antibodies designed to treat botulinum neurotoxin BoNT/B poisoning in adults. Dose cohorts A, B, and C will be randomized 2:6, placebo:therapeutic, with a total study population of 24. The study duration is projected to be approximately 8 months, with subject participation in cohort A being approximately 13 weeks, and subject participation in cohort B and C being approximately 17 weeks. The primary objectives of this study are to assess the safety and tolerability of escalating doses of NTM-1632 administered intravenously in healthy adults.

Detailed Summary: This is a Phase I, randomized, double-blind, placebo controlled dose escalation trial to evaluate NTM-1632 in three dose cohorts (A: 0.033 mg/kg, B: 0.165 mg/kg, and C: 0.33 mg/kg). NTM-1632 is a mixture of three monoclonal antibodies designed to treat botulinum neurotoxin BoNT/B poisoning in adults. Dose cohorts A, B, and C will be randomized 2:6, placebo:therapeutic, with a total study population of 24. The study duration is projected to be approximately 8 months, with subject participation in cohort A being approximately 13 weeks, and subject participation in cohort B and C being approximately 17weeks. The primary objectives of this study are to assess the safety and tolerability of escalating doses of NTM-1632 administered intravenously in healthy adults. The secondary objectives are to 1) assess the pharmacokinetic characteristics of NTM-1632 following a single intravenous administration and 2) assess the immunogenicity of NTM-1632 following a single intravenous administration.
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • The occurrence of Adverse Events from administration of NTM-1632 [ Time Frame: Day 1 to 57 ]
  • The occurrence of changes from baseline in clinical safety laboratory values following administration of NTM-1632 [ Time Frame: Screening, days -1, 2, 4, 8, 15, 29, 91 ]
  • The occurrence of changes from baseline in ECG parameters post administration of NTM-1632 [ Time Frame: Screening, day 1 ]
  • The occurrence of changes from baseline in physical examination following administration of NTM-1632 [ Time Frame: Screening, days -1, 1, 2 ]
  • The occurrence of changes from baseline in vital signs following administration of NTM-1632 [ Time Frame: Screening, days -1, 1, 2, 3, 4, 8, 15, 29, 43, 57, 91, 121 ]
  • The occurrence of Serious Adverse Events following administration of NTM-1632 [ Time Frame: Day 1 to 121 ]


Original Primary Outcome:

  • The occurrence of Serious Adverse Events following administration of NTM-1632 [ Time Frame: Day 1 to 121 ]
  • The occurrence of Adverse Events from administration of NTM-1632 [ Time Frame: Day 1 to 57 ]
  • The occurrence of changes from baseline in physical examination following administration of NTM-1632 [ Time Frame: Screening, days -1, 1, 2 ]
  • The occurrence of changes from baseline in ECG parameters post administration of NTM-1632 [ Time Frame: Screening, day 1 ]
  • The occurrence of changes from baseline in clinical safety laboratory values following administration of NTM-1632 [ Time Frame: Screening, days -1, 2, 4, 8, 15, 29, 91 ]
  • The occurrence of changes from baseline in vital signs following administration of NTM-1632 [ Time Frame: Screening, days -1, 1, 2, 3, 4, 8, 15, 29, 43, 57, 91, 121 ]


Current Secondary Outcome:

  • The assessment of area-under-the-curve for concentration vs time (AUC(0-t)) for each of the three monoclonal antibodies of NTM-1632 [ Time Frame: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 91, 121 ]
  • The assessment of maximum plasma titer/concentration (Cmax) for each of the three monoclonal antibodies of NTM-1632 [ Time Frame: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 91, 121 ]
  • The assessment of time to maximum concentration (Tmax) for each of the three monoclonal antibodies of NTM-1632 [ Time Frame: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 91, 121 ]
  • The presence of human anti-human antibodies in 0.165 mg/kg and 0.33 mg/kg dosing cohorts [ Time Frame: Day 121 ]
  • The presence of human anti-human antibodies in all dosing cohorts [ Time Frame: Days -1, 1, 29, 57, 91 ]


Original Secondary Outcome:

  • The assessment of maximum plasma titer/concentration (Cmax) for each of the three monoclonal antibodies of NTM-1632 [ Time Frame: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 91, 121 ]
  • The assessment of area-under-the-curve for concentration vs time (AUC(0-t)) for each of the three monoclonal antibodies of NTM-1632 [ Time Frame: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 91, 121 ]
  • The presence of human anti-human antibodies in all dosing cohorts [ Time Frame: Days -1, 1, 29, 57, 91 ]
  • The presence of human anti-human antibodies in 0.165 mg/kg and 0.33 mg/kg dosing cohorts [ Time Frame: Day 121 ]
  • The assessment of time to maximum concentration (Tmax) for each of the three monoclonal antibodies of NTM-1632 [ Time Frame: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 91, 121 ]


Information By: National Institute of Allergy and Infectious Diseases (NIAID)

Dates:
Date Received: May 12, 2016
Date Started: August 1, 2016
Date Completion: May 27, 2017
Last Updated: April 13, 2017
Last Verified: April 5, 2017