Phase 1 PK Study of XOMA 3AB

NCT01357213 | Completed Phase 1

• 2 other identifiers: 06-0091N01AI80026C
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, single-center, placebo-controlled, double-blinded, dose escalation study of anti-botulinum toxin monoclonal antibodies in healthy adult volunteers. Volunteers will be hospitalized in the Johns Hopkins Phase 1 unit during the infusion and until after the 24-hour blood draw. Three escalating dose cohorts of a combination of three anti-botulinum monoclonal antibodies will be evaluated. Each cohort will consist of eight volunteers in which they will receive a single intravenous infusion of active drug or placebo. Placebo will be normal saline. Volunteers will be followed for safety for up to 120 days after infusion depending on dose cohort.

Conditions

Botulism

Keywords

Botulism, Clostridium

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of XOMA 3AB: occurrence of adverse events and serious adverse events.

  Day 0 to Day 90 and to Day 120 (depending on dose cohort).

• Safety and tolerability of XOMA 3AB: Changes from baseline in vital signs, physical examinations, chemistry and complete blood count with differential laboratory studies, dipstick urinalysis, and electrocardiograms.

  Day 0, 1, 2, 3, 7, 14, 28, 42, 56, Day 90 and to 120 days (depending on dose cohort).

Secondary Outcomes (10)

• Immunogenicity: measuring Human anti-human antibodies (HAHA) to XOMA 3AB

  Day 0, 28, 56, 90 and 120 days (depending on dose cohort).

• Pharmacokinetics of XOMA 3AB:Area under the curve to the last time with a measurable value (AUC(0-t))

  Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort)

• Pharmacokinetics of XOMA 3AB: Volume of distribution (Vz)

  Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort)

• Pharmacokinetics of XOMA 3AB: Total clearance (CL)

  Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort)

• Pharmacokinetics of XOMA 3AB: Elimination half-life (t½)

  Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort)

Study Arms (2)

Arm 2

PLACEBO COMPARATOR

Placebo in all three cohorts

Other: Placebo

Arm 1

EXPERIMENTAL

XOMA 3AB in 3 dose levels/cohorts A, B or C.

Drug: XOMA 3AB

Interventions

XOMA 3AB DRUG

Single intravenous infusion of XOMA 3AB in three cohorts at different concentrations.

Arm 1

Placebo OTHER

Normal saline 100 ml

Arm 2

Eligibility Criteria

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

You may qualify if:

• Informed consent understood and signed
• Healthy male or healthy, non-pregnant, non-lactating female
• Willingness to comply and be available for all protocol procedures
• Age between 18 and 45 years, inclusive on the day of infusion
• Body Mass Index of \< 35
• Blood pressure within acceptable limits (systolic blood pressure \</=140mmHg and diastolic blood pressure \</=90mmHg). If subject is receiving anti-hypertensive medications, blood pressure must be well controlled with no changes in anti-hypertensive medications for at least 3 months.
• If the subject is female and of childbearing potential, negative serum pregnancy test at screening and negative urine or serum pregnancy test within 24 hours prior to infusion.
• If the subject is female and of childbearing potential, she agrees to practice abstinence from sexual intercourse with men or use acceptable contraception, for the duration of the study:
• A woman is considered of childbearing potential unless post-menopausal (\>/= 1 year without menses) or surgically sterilized (tubal ligation, bilateral oophorectomy, or hysterectomy)
• Acceptable contraception methods are restricted to effective devices (Intrauterine Contraceptive Devices (IUDs), NuvaRing®) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination, condoms with spermicidal agents, monogamous relationship with a vasectomized partner, or successful Essure placement with documented confirmation test at least 3 months after the procedure.
• All requested screening laboratory values are within the range specified in the table, "Acceptable Ranges of Screening Labs and Vital Sign Measurements" (Appendix B).
• Has adequate venous access for the infusion.
• The drug screen is negative
• Breathalyzer test is negative.

You may not qualify if:

• History of a chronic medical conditions including, but not limited to, disorders of the liver, kidney, lung, heart or nervous system, or other metabolic and autoimmune/inflammatory conditions that would either interfere with the accurate assessment of the objectives of the study or increase the risk profile of the subject such as:
• Diabetes
• Asthma requiring use of medication in the year before screening
• Autoimmune disorder, such as lupus, Wegener's, rheumatoid arthritis
• Coronary artery disease
• History of malignancy except low-grade (squamous and basal cell) skin cancer thought to be cured
• Chronic renal hepatic or pulmonary disease (except previous asthma which has required no treatment for the past year)
• History of severe allergic reaction of any type to medications, bee stings, food, or environmental factors or hypersensitivity or reaction to immunoglobulins. Severe allergic reaction is defined as any of the following:
• Anaphylaxis
• Urticaria
• Angioedema
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 milliseconds)
• Clinically significant abnormal electrocardiogram at screening in the judgment of the investigator
• Positive serology results for Human Immunodeficiency Virus (HIV), Hepatitis B Surface Antigen (HBsAg), or Hepatitis C Virus (HCV) antibodies
• Febrile illness with temperature \>37.6°C within 7 days of dosing

Sponsors & Collaborators

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

Study Sites (1)

Johns Hopkins Bayview Medical Center - Infectious Diseases

Baltimore, Maryland, 21224-2735, United States

Location

Related Publications (1)

• Nayak SU, Griffiss JM, McKenzie R, Fuchs EJ, Jurao RA, An AT, Ahene A, Tomic M, Hendrix CW, Zenilman JM. Safety and pharmacokinetics of XOMA 3AB, a novel mixture of three monoclonal antibodies against botulinum toxin A. Antimicrob Agents Chemother. 2014 Sep;58(9):5047-53. doi: 10.1128/AAC.02830-14. Epub 2014 Jun 9.

  PMID: 24913160 BACKGROUND

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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2011
• First Posted: May 20, 2011
• Study Start: May 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2013
• Last Updated: December 5, 2014

Record last verified: 2013-05

Locations

US (1)