Safety and Pharmacokinetic Study of Anthrax Immune Globulin Derived From Human Serum
Primary Purpose
Symptoms of Inhalational Anthrax
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
NP-015
Sponsored by
About this trial
This is an interventional treatment trial for Symptoms of Inhalational Anthrax focused on measuring Inhalational Anthrax, Human Immune globulin
Eligibility Criteria
Inclusion Criteria:
- Male or female
- Age 18/19 (dependent on local age of majority) - 55 years
- Body mass index of 19 - 29
- For female subjects that are not surgically sterilized, willingness to use an effective method of contraception throughout the trial including:
- Using hormonal contraception (oral, injectable or implant) continuously for 3 months prior to the start of the trial and willing to continue to use hormonal contraception throughout the entire trial.
- IUD inserted at least 3 months prior to dosing.
- For female subjects who are postmenopausal < 2 years an FSH ≥ 40 mIU/mL must be obtained. If the FSH is < 40 mIU/mL the subject must agree to use an acceptable form of contraception (see above).
- For males that have not had a vasectomy, willingness to use a condom with spermicide for the duration of the study. Also, male subjects must not donate sperm for the duration of the study.
- Normal and healthy as determined by medical history, physical exam, ECG, vital signs and laboratory tests of liver, kidney and hematological functions
- Written informed consent
Exclusion Criteria:
- Heavy smokers (>10 cigarettes/day) or individuals using smokeless tobacco or nicotine containing products
- Use of any investigational product within the past 30 days
- Recipient of any blood product within the past 12 months
- Plasma donation within 7 days or significant blood loss or blood donation within 56 days of baseline
- Females with a hemoglobin level < 12 g/dL
- Males with a hemoglobin level < 13 g/dL
- History of hypersensitivity to blood products
- History of allergy to latex or rubber
- History of IgA deficiency
- Pregnancy or lactation
- Positive serology test for HIV or HCV, positive test for HBV as determined by HBsAg.
- History of, or suspected substance abuse problem (including alcohol)
- Failure of drug test at screening or baseline
- Failure of alcohol test at baseline or consumption of alcoholic beverages within 48 hours of baseline
- History of anthrax vaccination with AVA or any other anthrax vaccine
- Individuals with planned medical procedures that will occur during the study
- Use of prescription medications within 7 days prior to baseline, or anticipated use during the study (with the exception of hormonal contraceptives for females)
- Use of over-the-counter, herbal medications or vitamins within 7 days of study admission
- An opinion of the investigator that it would be unwise to allow participation of the subject in the study
Sites / Locations
- MDS Pharma Services
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
Three Cohorts evaluating three dosage levels: 210, 420 or 840 units TNA. And a Fourth Cohort at 840 units TNA with 2 additional product lots.
Saline (equal volume to 210 U, 420 U, or 840 U TNA dose)
Outcomes
Primary Outcome Measures
Anti-PA antibody and TNA for PK analyses.
Secondary Outcome Measures
Viral Markers for safety.
Dose proportionality analyses.
Blood Chemistry
Urinalysis
Hematology (haptoglobin and free hemoglobin at baseline and day 1)
Full Information
NCT ID
NCT00448253
First Posted
March 14, 2007
Last Updated
March 16, 2020
Sponsor
Emergent BioSolutions
Collaborators
Department of Health and Human Services
1. Study Identification
Unique Protocol Identification Number
NCT00448253
Brief Title
Safety and Pharmacokinetic Study of Anthrax Immune Globulin Derived From Human Serum
Official Title
Safety and Pharmacokinetics of Anthrax Immune Globulin Intravenous (Human), NP-015, in Healthy Volunteers.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2011
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
September 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Emergent BioSolutions
Collaborators
Department of Health and Human Services
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to assess the pharmacokinetics of three doses of NP-015 (210, 420 or 840 units TNA) in healthy volunteers. To evaluate the safety of NP-015 based on adverse events and laboratory assessments. To determine the dose proportionality relation of three different doses of NP-015.
Detailed Description
The test product is Anthrax Immune Globulin Intravenous (Human), NP-015.
The product is supplied as a sterile liquid suitable for IV administration.
Product potency is expressed in units of anthrax toxin neutralization assays(TNA) per vial.
This study is a phase 1, placebo controlled, dose-ranging study in healthy volunteers. Subjects will receive one of three NP-015 doses (210, 420 or 840 units TNA) or equal volumes of saline placebo.
Enrolment will be sequential, starting at the lowest NP-015 dose with accrual into the next higher dose after all patients at the lower dose have been treated.
The first 3 Cohorts: The Subjects will be recruited in cohorts of 24, with placebo controls included in each dosing group. In each cohort, subjects will be randomized to receive either NP-015 (N = 18/dosing group) or placebo (N = 6/dosing group). For Cohort 4: 20 Subjects will be recruited and dosed at the highest dose with 2 additional product lots (10 subjects per lot).
Plasma samples will be drawn over 84 days. Plasma will be tested for anti-anthrax antibodies by a protective antigen (anti-PA) ELISA and toxin neutralization assay (TNA).
Serological testing for HIV, HBV and HCV will be conducted at screening to determine eligibility. Nucleic acid amplification testing (NAT) and serological testing for HIV, HBV and HCV will be conducted at baseline (day -1) and at the final visit (day 84 or early withdrawal). NAT for parvovirus B19 will be conducted at baseline (day -1), day 14, and the final visit (day 84 or early withdrawal).
Safety data will be collected throughout the 84-day study.
Screening (within 28 days prior to Baseline):
Informed consent
Review of admission criteria
Medical history, general physical examination, vital signs, electrocardiogram and concomitant medications will be recorded
Hematology, blood chemistry, urinalysis, viral serology (anti-HIV-1/2, Anti-HCV, HBsAg, anti-HBc)
Serum pregnancy test for all female subjects
Drug screen (urine)
Blood collection for anti-PA antibody and toxin neutralization assay (TNA) assessment
Baseline (Day -1, within 24 hours prior to Day 0)
Review of admission criteria
Assessment of brief physical exam, vital signs, weight, hematology, blood chemistry, urinalysis, and concomitant medications
Assessment of haptoglobin and free hemoglobin levels
Update of medical history
NAT testing for HIV, HBV, HCV and parvovirus B19, and serological testing for HIV, HBV and HCV
Serum pregnancy test for all female subjects
Alcohol (urine) and drug screen (urine)
Blood collection for baseline anti-PA antibody and TNA assessment
Subjects will be required to stay overnight following their baseline assessment
NP-015 Administration (day 0)
Following baseline assessment, NP-015 will be administered intravenously
Urinalysis will be performed at the end of the infusion period (appearance and color, specific gravity, protein, glucose, pH, occult blood, ketones, microscopic examination)
Assessments following the completion of NP-015 administration (1, 3 and 8 hrs; days 1, 3, 5, 7, 9, 11, 14, 21, 28, 42, 56 and 84 or early withdrawal)
Following NP-015 administration, blood will be collected for anti-PA antibody ELISA analysis and TNA assessment at each of the respective times.
Assessment of vital signs, adverse events and concomitant medications.
Additional Assessments:
Days 1, 3, 7, 14, 28 and 84 or early withdrawal: Assessment of hematology, blood chemistry and urinalysis.
Day 1: Assessment of haptoglobin and free hemoglobin levels.
Day 14: NAT for parvovirus B19.
Day 28: serum pregnancy test for female subjects.
Final (day 84 or early withdrawal) visit: a general physical exam, serum pregnancy test for female subjects, and viral marker testing (NAT for HBV, HCV, HIV and parvovirus B19, and serology for HIV, HBV and HCV) will be performed.
For Cohort 4 there will be no anti anthrax antibody testing and the subjects will be assessed for safety only, up to day 28.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Symptoms of Inhalational Anthrax
Keywords
Inhalational Anthrax, Human Immune globulin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
92 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Three Cohorts evaluating three dosage levels: 210, 420 or 840 units TNA. And a Fourth Cohort at 840 units TNA with 2 additional product lots.
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Saline (equal volume to 210 U, 420 U, or 840 U TNA dose)
Intervention Type
Biological
Intervention Name(s)
NP-015
Other Intervention Name(s)
Anthrax Immune Globulin (AIG)
Intervention Description
Three Cohorts evaluating three dosage levels: 210, 420 or 840 units TNA, or placebo.
And a Fourth Cohort at 840 units TNA with 2 additional product lots.
Primary Outcome Measure Information:
Title
Anti-PA antibody and TNA for PK analyses.
Time Frame
screen, baseline, and D0 hours 1,3,8 and day(s) 1,3,5,7,9,11,14,21,28,42,56 and 84
Secondary Outcome Measure Information:
Title
Viral Markers for safety.
Time Frame
screen, baseline, and Day(s)14 and 84
Title
Dose proportionality analyses.
Time Frame
screen, baseline, and D0 hours 1,3,8 and day(s) 1,3,5,7,9,11,14,21,28,42,56 and 84
Title
Blood Chemistry
Time Frame
screen, baseline, and D0 hours 0,1,2 and day(s) 1,3,7,14,28, and 84
Title
Urinalysis
Time Frame
screen, baseline, and D0 hours 0 and day(s) 1,3,7,14,28, and 84
Title
Hematology (haptoglobin and free hemoglobin at baseline and day 1)
Time Frame
screen, baseline, Day(s) 1,3,7,14,28, and 84
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male or female
Age 18/19 (dependent on local age of majority) - 55 years
Body mass index of 19 - 29
For female subjects that are not surgically sterilized, willingness to use an effective method of contraception throughout the trial including:
Using hormonal contraception (oral, injectable or implant) continuously for 3 months prior to the start of the trial and willing to continue to use hormonal contraception throughout the entire trial.
IUD inserted at least 3 months prior to dosing.
For female subjects who are postmenopausal < 2 years an FSH ≥ 40 mIU/mL must be obtained. If the FSH is < 40 mIU/mL the subject must agree to use an acceptable form of contraception (see above).
For males that have not had a vasectomy, willingness to use a condom with spermicide for the duration of the study. Also, male subjects must not donate sperm for the duration of the study.
Normal and healthy as determined by medical history, physical exam, ECG, vital signs and laboratory tests of liver, kidney and hematological functions
Written informed consent
Exclusion Criteria:
Heavy smokers (>10 cigarettes/day) or individuals using smokeless tobacco or nicotine containing products
Use of any investigational product within the past 30 days
Recipient of any blood product within the past 12 months
Plasma donation within 7 days or significant blood loss or blood donation within 56 days of baseline
Females with a hemoglobin level < 12 g/dL
Males with a hemoglobin level < 13 g/dL
History of hypersensitivity to blood products
History of allergy to latex or rubber
History of IgA deficiency
Pregnancy or lactation
Positive serology test for HIV or HCV, positive test for HBV as determined by HBsAg.
History of, or suspected substance abuse problem (including alcohol)
Failure of drug test at screening or baseline
Failure of alcohol test at baseline or consumption of alcoholic beverages within 48 hours of baseline
History of anthrax vaccination with AVA or any other anthrax vaccine
Individuals with planned medical procedures that will occur during the study
Use of prescription medications within 7 days prior to baseline, or anticipated use during the study (with the exception of hormonal contraceptives for females)
Use of over-the-counter, herbal medications or vitamins within 7 days of study admission
An opinion of the investigator that it would be unwise to allow participation of the subject in the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan S Marion, MD, PhD
Organizational Affiliation
MDS Pharma Services
Official's Role
Principal Investigator
Facility Information:
Facility Name
MDS Pharma Services
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68502
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety and Pharmacokinetic Study of Anthrax Immune Globulin Derived From Human Serum
We'll reach out to this number within 24 hrs