Evaluate the Safety Pharmacokinetics of a Human Monoclonal Antibody S315 Against Diphtheria Toxin in Healthy Subjects (S315)

A Phase 1 Study in Healthy Subjects to Evaluate the Safety and Pharmacokinetics of a Human Monoclonal Antibody (mAb) S315 Against Diphtheria Toxin

This study will examine the use of a single infusion of S315 at different doses in healthy volunteers to help understand its safety and tolerability. S315 is a monoclonal antibody that is being developed for treatment of diphtheria. The study will assess for any side effects when S315 and will also look at the levels of S315 in the blood over time.

Study Overview

• Status: Completed
• Conditions: Diphtheria
• Intervention / Treatment: Drug: S315; Drug: 0.9% Sodium Chloride (NaCl)

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • PAREXEL Early Phase Clinical Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Capable of giving written informed consent and able to effectively communicate with the Investigator and study personnel. A signed informed consent document (ICD) must be on file prior to initiating the screening procedures.

   Willing and able to complete all study requirements, restrictions, visits and procedures.

2. Age 18 to 55 years, inclusive.
3. Weight 50 kg to 90 kg, inclusive.
4. Systolic blood pressure less than 140 mmHg and diastolic less than 90 mmHg on two separate readings at least one minute apart.

5. Women of child bearing potential, defined as all women physiologically capable of becoming pregnant must agree not to become pregnant and must use a method of birth control during the entire study.

   Women of non-child bearing potential may be included. Women are considered post-menopausal and not of childbearing potential if, they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile or have had surgical total hysterectomy or tubal ligation at least six weeks ago.

6. Males of reproductive potential must use a barrier method of contraception during the course of the study.

7. Screening laboratory values must meet the following criteria:

   • White blood cell (WBC) 3.5 - Upper Limit of Normal (ULN)
   • Platelets > 100,000/mm3
   • Hemoglobin ≥ Lower Limit of Normal (LLN)
   • Creatinine ≤ ULN
   • Aspartate Aminotransferase (AST) ≤ ULN
   • Alanine Aminotransferase (ALT) ≤ ULN
   • Alkaline Phosphatase ≤ ULN
   • Bilirubin ≤ ULN
   • HgbA1c

Exclusion Criteria:

• 1. Previous receipt of humanized or human monoclonal antibody whether licensed or investigational.

  2. History of or any current medical condition that could compromise the safety of the participant in the study, as determined by the Investigator.

  3. History of suicidal behavior within 12 months prior to screening.

  4. Donated blood or plasma within 60 days prior to dosing.

  5. Clinically significant gastrointestinal, cardiovascular, neurologic, psychiatric, substance abuse, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease, as determined by the Investigator.

  6. Drug or alcohol abuse within previous 12 months or a positive test at screening and at Day -1 within 24 hours of study product administration.

  7. History of a previous severe allergic reaction with generalized urticaria, angioedema or anaphylaxis.

  8. Physical finding on examination considered clinically significant such as murmur (other than functional), hepatosplenomegaly, lymphadenopathy or focal neurological deficit.

  9. Urinalysis positive for > trace protein, > 5 Red Blood Cell (RBC)/hpf or > 5 WBC/hpf.

  10. Positive serology for HIV antibody, Hepatitis C Virus (HCV) antibody or Hepatitis B surface antigen at screening.

  11. Positive serum pregnancy test during screening or within 24 hours of study product administration, or an unwillingness to undergo pregnancy testing.

  12. Pregnant within 6 months or breast-feeding within 3 months prior to screening.

  13. Receipt of licensed vaccine containing diphtheria toxoid (Td, Tdap, pneumococcal conjugate vaccines, meningococcal conjugate vaccines) within the last year.

  14. Treatment with another investigational drug or other intervention within 30 days from screening.

  15. Any other condition that in the opinion of the investigator would jeopardize the safety or rights of the subject participating in the study.

  16. Safety laboratory abnormalities at Screening or Day -1, which are clinically significant as determined by the Investigator.

  17. Tobacco, e-cigarettes, and/or nicotine use within 30 days prior to screening confirmed by urine cotinine test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S315 human monoclonal antibody; 5 cohorts of 8 subjects each randomized 6:2 (S315:Placebo (0.9% Sodium Chloride)) with escalation of a fixed dose of S315	Drug: S315; Human monoclonal antibody against Diphtheria Toxin
Placebo Comparator: 0.9% sodium chloride (NaCl); 5 cohorts of 8 subjects each randomized 6:2 (S315:Placebo(0.9% Sodium Chloride)) with escalation of a fixed dose of S315	Drug: 0.9% Sodium Chloride (NaCl); Placebo 0.9% Sodium Chloride (NaCl)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of Participants with adverse events as assessed by the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table (Draft revised November 2007) adapted by the Division of Microbiology and Infectious Diseases, NIAID, NIH.	Adverse events assessed for safety	Day -1 through Day 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serial measurements of S315 concentration in the serum.	Pharmacokinetics	Day 1 pre-dose and Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, day 29, Day 43 and Day 60 post-dose

Collaborators and Investigators

• Sponsor: MassBiologics
• Investigators: Principal Investigator: Ronald Goldwater, MD, Parexel; Study Director: John Z Sullivan-Bólyai, MD, MPH, MassBiologics of the University of Massachusetts

Publications and helpful links

General Publications

• Smith HL, Cheslock P, Leney M, Barton B, Molrine DC. Potency of a human monoclonal antibody to diphtheria toxin relative to equine diphtheria anti-toxin in a guinea pig intoxication model. Virulence. 2016 Aug 17;7(6):660-8. doi: 10.1080/21505594.2016.1171436. Epub 2016 Apr 12.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2019
• Primary Completion (Actual): October 7, 2019
• Study Completion (Actual): October 7, 2019

Study Registration Dates

• First Submitted: August 15, 2019
• First Submitted That Met QC Criteria: August 29, 2019
• First Posted (Actual): August 30, 2019

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 4, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Corynebacterium Infections; Diphtheria
• Other Study ID Numbers: MBL-DIPH-19-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No