BotulismPhase 1NCT01357213
Phase 1 PK Study of XOMA 3AB
A Phase 1 study testing XOMA 3AB in people with Botulism, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Botulism
- What is being tested?
- XOMA 3AB
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- May 2011to May 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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
- Pregnant or breastfeeding
- Donated blood within 56 days of enrollment
- Known allergic reactions to any of the study product components present in the formulation or in the processing, as listed in the Investigator Brochure.
- Treatment with another investigational drug within 30 days of dosing
- Receipt of a monoclonal antibody at any time in the past
- 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
- Receipt of any live vaccines within the previous 3 months or within 5 half-lives of the specific vaccine given
- Receipt of any killed vaccines within the previous 1 month
- Lack of ability to fully understand the informed consent (e.g. cannot speak or read English)
- Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
- Use of H1 antihistamines or beta-blockers within 5 days of dosing.
- Use of any of the following medications within 30 days prior to study entry or planned use during the study period:
- immunosuppressives (except Nonsteroidal Anti-Inflammatory Drugs (NSAIDS))
- immune modulators
- oral corticosteroids (topical steroids are acceptable)
- anti-neoplastic agents
- any vaccine (licensed or investigational)
- Previous exposure to botulinum toxin, receipt of antibodies against botulinum toxin, or previous treatment with equine antitoxin
- Any previous injection or planned injection within 12 months after enrollment of botulinum toxin for cosmetic reasons, spastic dysphonia, torticollis, or any other reason
- Any specific condition that in the judgment of the investigator precludes participation because it could affect subject safety;
- Co-enrollment in another study
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins Bayview Medical Center - Infectious Diseases
Baltimore, Maryland, 21224-2735
About this study
Official title: A Phase I, Blinded, Placebo-controlled, Dose-escalation Study of the Safety and Pharmacokinetics of XOMA 3AB Administered Intravenously in Healthy Adults
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.
Read the detailed description
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
- Being tested
- XOMA 3AB, Placebo
- Keywords
- Botulism, Clostridium
- Medical subject headings
- Botulism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XOMA 3ABDrug
Single intravenous infusion of XOMA 3AB in three cohorts at different concentrations.
PlaceboOther
Normal saline 100 ml
| Study group | Role | What they receive |
|---|---|---|
| Arm 2 | Placebo comparator | Placebo in all three cohorts Receives: Other: Placebo |
| Arm 1 | Experimental | XOMA 3AB in 3 dose levels/cohorts A, B or C. Receives: Drug: XOMA 3AB |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of XOMA 3AB: occurrence of adverse events and serious adverse events.
Measured: 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.
Measured: 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
Measured: 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))
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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 rate constant (gimel z)
Measured: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort)
Pharmacokinetics of XOMA 3AB: Area under the curve to infinity (AUC(inf))
Measured: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort)
Pharmacokinetics of XOMA 3AB: Time to Cmax (Tmax) measured from end of infusion
Measured: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort)
Pharmacokinetics of XOMA 3AB: Maximum plasma titer/concentration (Cmax)
Measured: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort)
Pharmacokinetics of XOMA 3AB: Mean residence time (MRT)
Measured: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2011 (estimated)
- Study startMay 2011
- Primary completionMay 2012
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for BotulismStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01357213
- Sponsor's protocol ID
- 06-0091
- Other IDs
- N01AI80026C
- Status last verified
- May 2013
- First submitted
- 5 May 2011
- Last updated
- 5 Dec 2014
- Results posted
- No
Publications
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.
PubMed 24913160
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Blinded, Placebo-controlled, Dose-escalation Study of the Safety and Pharmacokinetics of XOMA 3AB Administered Intravenously in Healthy Adults
- ClinicalTrials.gov ID
- NCT01357213
- Acronym / sponsor ID
- 06-0091
- Conditions
- Botulism
- Keywords
- Botulism, Clostridium
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- May 2011
- Primary completion
- May 2012 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 20 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 2 | Placebo comparator | Other: PlaceboPlacebo in all three cohorts |
| Arm 1 | Experimental | Drug: XOMA 3ABXOMA 3AB in 3 dose levels/cohorts A, B or C. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (36 listed)
- 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:
- 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
- Pregnant or breastfeeding
- Donated blood within 56 days of enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XOMA 3ABSingle intravenous infusion of XOMA 3AB in three cohorts at different concentrations. | Drug | Arm 1 |
| PlaceboNormal saline 100 ml | Other | Arm 2 |
Primary outcome
Safety and tolerability of XOMA 3AB: occurrence of adverse events and serious adverse events.
Time frame: 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.
Time frame: Day 0, 1, 2, 3, 7, 14, 28, 42, 56, Day 90 and to 120 days (depending on dose cohort).
10 secondary outcomes
Immunogenicity: measuring Human anti-human antibodies (HAHA) to XOMA 3AB
Time frame: 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))
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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 rate constant (gimel z)
Time frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort)
Pharmacokinetics of XOMA 3AB: Area under the curve to infinity (AUC(inf))
Time frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort)
Pharmacokinetics of XOMA 3AB: Time to Cmax (Tmax) measured from end of infusion
Time frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort)
Pharmacokinetics of XOMA 3AB: Maximum plasma titer/concentration (Cmax)
Time frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort)
Pharmacokinetics of XOMA 3AB: Mean residence time (MRT)
Time frame: Serially on day 0, 1, 2, 3, 7, 14, 28, 42, 56, 90 and 120 days (depending on dose cohort)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2014.
- Background: PubMed 24913160Nayak 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing XOMA 3AB in people with Botulism, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of XOMA 3AB: occurrence of adverse events and serious adverse events. (time frame: Day 0 to Day 90 and to Day 120 (depending on dose cohort).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01357213, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2014.