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

NCT02779140 | Completed Phase 1 FDA Drug

• 2 other identifiers: 14-0024HHSN272201300017I
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Botulism

Keywords

BoNT; botulinum; Botulism; Clostridium; Neurotoxin; NTM-1632

Outcome Measures

Primary Outcomes (6)

• The occurrence of Adverse Events from administration of NTM-1632

  Day 1 to 57

• The occurrence of changes from baseline in clinical safety laboratory values following administration of NTM-1632

  Screening, days -1, 2, 4, 8, 15, 29, 91

• The occurrence of changes from baseline in ECG parameters post administration of NTM-1632

  Screening, day 1

• The occurrence of changes from baseline in physical examination following administration of NTM-1632

  Screening, days -1, 1, 2

• The occurrence of changes from baseline in vital signs following administration of NTM-1632

  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

  Day 1 to 121

Secondary Outcomes (5)

• The assessment of area-under-the-curve for concentration vs time (AUC(0-t)) for each of the three monoclonal antibodies of NTM-1632

  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

  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

  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

  Day 121

• The presence of human anti-human antibodies in all dosing cohorts

  Days -1, 1, 29, 57, 91

Study Arms (3)

0.033 mg/kg NTM-1632

EXPERIMENTAL

N=6 administered 0.033 mg/kg NTM-1632 IV, N=2 administered placebo IV

Biological: NTM-1632; Other: Placebo

0.165 mg/kg NTM-1632

EXPERIMENTAL

N=6 administered 0.165 mg/kg NTM-1632 IV, N=2 administered placebo IV

Biological: NTM-1632; Other: Placebo

0.33 mg/kg NTM-1632

EXPERIMENTAL

N=6 administered 0.33 mg/kg NTM-1632 IV, N=2 administered placebo IV

Biological: NTM-1632; Other: Placebo

Interventions

NTM-1632 BIOLOGICAL

Monoclonal antibody mixture of XB10, XB18, and XB23

0.033 mg/kg NTM-1632; 0.165 mg/kg NTM-1632; 0.33 mg/kg NTM-1632

Placebo OTHER

Placebo

0.033 mg/kg NTM-1632; 0.165 mg/kg NTM-1632; 0.33 mg/kg NTM-1632

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• \. History of a chronic medical condition that would either interfere with the accurate assessment of the objectives of the study or increase the risk profile of the subject. Note: Chronic medical conditions include diabetes; Asthma requiring use of medication in the year before screening; Autoimmune disorder such as lupus, Wegener's, rheumatoid arthritis, thyroid disease; Coronary artery disease; Chronic hypertension; History of malignancy except low-grade (squamous and basal cell) skin cancer thought to be cured; chronic renal, hepatic, pulmonary, or endocrine disease (except previous asthma which has required no treatment for the past year); 2. History of severe allergic reaction of any type to medications, bee stings, food, or environmental factors or hypersensitivity or reaction to immunoglobulins. Note: Severe allergic reaction is defined as any of the following: anaphylaxis, urticaria, or angioedema 3. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 milliseconds) 4. Clinically significant abnormal electrocardiogram at screening. Note: Clinically significant abnormal ECG results include: complete left or right bundle branch block; other ventricular conduction block; 2nd degree or 3rd degree atrioventricular (AV) block; sustained ventricular arrhythmia; sustained atrial arrhythmia; two Premature Ventricular Contractions in a row; pattern of ST elevation felt consistent with cardiac ischemia; or any condition deemed clinically significant by a study investigator 5. Positive serology results for HIV, HBsAg, or HCV antibodies 6. Febrile illness with temperature \>37.6°C within 7 days of dosing 7. Pregnant or breastfeeding 8. Donated blood within 56 days of enrollment 9. Known allergic reactions to any of the study product components present in the formulation or in the processing, as listed in the Investigator Brochure 10. Treatment with another investigational drug within 28 days of dosing 11. Treatment with a monoclonal antibody at any time in the past 12. Receipt of antibody (e.g. TIG, VZIG, IVIG, IM gamma globulin) or blood transfusion within 6 months or within 5 half-lives of the specific product given 13. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements 14. Use of H1 antihistamines or beta-blockers within 5 days of dosing 15. Use of any prohibited medication within 28 days prior to study entry or planned use during the study period Note: Prohibited medications include immunosuppressives (except Nonsteroidal Anti-Inflammatory Drugs \[NSAIDS\]); immune modulators; oral corticosteroids (topical/intranasal steroids are acceptable); anti-neoplastic agents; any vaccine (licensed or investigational) 16. Previous exposure to botulinum toxin, receipt of antibodies against botulinum toxin, or previous treatment with equine antitoxin 17. Any previous injection or planned injection within 4 months after enrollment of botulinum toxin for cosmetic reasons, spastic dysphonia, torticollis, or any other reason 18. Any specific condition that in the judgment of the investigator precludes participation because it could affect subject safety 19. Plans to enroll or is already enrolled in another clinical trial\* that could interfere with safety assessment of the investigational product at any time during the study period. Note: Includes trials that have a study intervention such as a drug, biologic, or device 20. Is a study site employee or staff who are paid entirely or partially by the OCRR contract for the DMID-funded trial. Note: Site employees or staff include the PIs and sub-investigators or staff who are supervised by the PI or Sub-Investigators 21. Systolic blood pressure \>140 mm Hg or diastolic blood pressure \>90 mm Hg 22. Resting heart rate \<50 or \>100 beats per minute 23. Oral temperature = 38°C (100.4°F)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Duke Human Vaccine Institute - Duke Clinical Vaccine Unit

Durham, North Carolina, 27704, United States

Location

Related Publications (1)

• 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. doi: 10.1128/AAC.02329-20. Epub 2021 Jun 17.

  PMID: 33875433 DERIVED

MeSH Terms

Conditions

Botulism

Condition Hierarchy (Ancestors)

Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Neuromuscular Junction Diseases; Neuromuscular Diseases; Nervous System Diseases; Neurotoxicity Syndromes; Foodborne Diseases; Poisoning; Chemically-Induced Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2016
• First Posted: May 20, 2016
• Study Start: August 1, 2016
• Primary Completion: May 31, 2017
• Study Completion: May 31, 2017
• Last Updated: October 29, 2018

Record last verified: 2017-04

Locations

US (1)