Healthy VolunteersPhase 1NCT00636519
Botulism Antitoxin Effects on Paralysis Induced by Botulinum Neurotoxins in the EDB Muscle
A Phase 1 study testing Botulism Antitoxin Bivalent (Equine) Types A and B and Botulism Antitoxin Heptavalent (Equine) Types A-G in people with Healthy Volunteers, run by Emergent BioSolutions at 2 sites in United States.
Trial summary
The primary purpose of this study is: 1. To evaluate the model determined by the ability of botulism antitoxin (bivalent, Aventis) to neutralize Botulinum toxin in the Extensor Digitorum Brevis model of muscle paralysis in Stage A. 2. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Botulism Antitoxin Bivalent (Equine) Types A and B and Botulism Antitoxin Heptavalent (Equine) Types A-G
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2008to Oct 2009
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female
- Age 18 - 55 years
- Body-mass index 19-30
- Normal and healthy as determined by medical history, physical examination, ECG, NCS, vital signs and tests of liver, kidney and hematological functions
- Adequate form of contraception for female subjects
- For women with child-bearing potential-using hormonal contraception (oral, injectable or implant) continuously for 3 months prior to the start of the study and willing to continue to use hormonal contraception throughout the entire study. IUD inserted or use of condoms for at least 2 months prior to dosing
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- Other forms of contraception may be considered as adequate at physician's discretion
- Surgically-sterilized female subjects
- For female subjects who are postmenopausal, an FSH ≥ than 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 acceptable forms of contraception)
- Signed written Informed Consent
Who cannot join
- Previously injected with BOTOX®, BOTOX® COSMETIC or MYOBLOC®
- Any known or documented Botulinum infection/intoxication
- Any known or documented allergies to horses (e.g. rash, wheezing, rhinitis etc. after exposure to horses)
- Any known or documented allergies to horse serum (observation of adverse events after treatment with any kind of product containing horse serum)
- Any moderate or severe food allergies, seasonal allergies or hay fever requiring treatment with peroral or parenteral immunosuppressive drug
- Any known or documented hypersensitivity to blood products derived from a human or equine source
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- Any known or documented hypersensitivity to albumin
- Positive result for Botulism Antitoxin skin sensitivity testing
- Any known or documented allergy to rubber, latex or plastic
- Known acute or chronic moderate or severe asthma requiring treatment with peroral and / or parenteral immunosuppressive drugs
- Previously diagnosed or currently suspected Multiple Sclerosis or other neuromuscular degenerative disorder
- Previously diagnosed or currently suspected motor neuron disease
- Previously or currently diagnosed peripheral neuropathy of lower extremities' nerves
- Current infection of the skin / skin problems at the injection site (foot)
- Scar tissue or tattoo of the skin over the extensor digitorum brevis muscles.
- Previously diagnosed or currently suspected diabetes
- Previously diagnosed or currently suspected coagulopathies
- Previously diagnosed or currently suspected vasculitis
- Current treatment or treatment in the past 7 days with aminoglycosides, clindamycin, quinolines or aminopyridine
- Heavy smokers (>10 cigarettes/day)
- History of, or suspected substance abuse (including alcohol) or failure of drug screen at screening or at baseline
- Use of any investigational product within the past 30 days (prior to screening)
- Pregnancy or lactation
- Positive serological test for diagnosis of HIV infection, HBV hepatitis, or HCV hepatitis
- Abnormal (based on principle investigator assessment) nerve conduction study (NCS) results
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Dr. Gordon Peterson
Loma Linda, California, 92354
R. Richard Sloop, M. D.
Yakima, Washington, 98902
About this study
Official title: Botulism Antitoxin Effects on Paralysis Induced by Type A and Type B Botulinum Neurotoxins in the Extensor Digitorum Brevis Muscle
The primary purpose of this study is:
- To evaluate the model determined by the ability of botulism antitoxin (bivalent, Aventis) to neutralize Botulinum toxin in the Extensor Digitorum Brevis model of muscle paralysis in Stage A.
- To assess the ability of botulism antitoxin (heptavalent, Cangene) to neutralize Botulinum toxin in the Extensor Digitorum Brevis model of muscle paralysis in Stage B.
Read the detailed description
Botulism is a rare disease; however Botulinum toxins (neurotoxins) may be used as biological weapon especially in the form of aerosol. Botulism is caused by neurotoxins that are produced by the obligate anaerobic, gram-positive, spore-forming bacterium Clostridium botulinum (1). C. botulinum produces 8 serologically distinct neurotoxins identified as serotypes A, B, C1, C2, D, E, F, and G (2).
Therapy for botulism includes supportive care and passive immunization with antitoxin. Antitoxin should be administered to patients with neurologic signs of botulism as soon as possible after clinical diagnosis (3). Botulism antitoxin is prepared from plasma obtained from horses that have been immunized with a specific subtype of botulism toxoid and toxin.
The BT-002 is an exploratory pharmacodynamic study that is being performed to evaluate the effect of Botulism Antitoxins in preventing paralysis of extensor digitorum brevis muscle following BOTOX®/ MYOBLOC® administration. This study will compare bivalent and heptavalent products to a placebo. Safety data will be collected.
NP-018 (heptavalent equine-derived botulinum antitoxin) is prepared from plasma obtained from horses that have been immunized with a specific subtype of botulinum toxoid and toxin. Each individual horse is immunized against a single botulinum toxin subtype. Plasma is pooled from horses that have been immunized with the same botulinum toxin subtype. For each antitoxin serotype (A-G), a despeciated product will be produced by pepsin digestion of the IgG monomer in the equine plasma, yielding predominantly F(ab')2 fragment. Following the formulation, the seven antitoxin serotypes will be blended into a heptavalent product and filled into single-use vials. '
This research study will be conducted in two stages - Stage A and Stage B. If enrolled in the Stage A of the study, the subject will have an equal chance of getting either bivalent botulism antitoxin or placebo. If enrolled in Stage B of the study, the subject will have an equal chance of getting heptavalent botulism antitoxin (NP-018) or placebo. The subject will be receiving injections of Botox and Myobloc on the next day after the antitoxin administration in the left and right foot respectively. The subject's participation in this study will be for maximum of 57 days.
- Conditions
- Healthy Volunteers
- Being tested
- Botulism Antitoxin Bivalent (Equine) Types A and B, Botulism Antitoxin Heptavalent (Equine) Types A-G
- Keywords
- Botulism Antitoxin,Heptavalent,Bivalent,EDB Muscle,Paralysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botulism Antitoxin Bivalent (Equine) Types A and BBiological
One vial of Botulism Antitoxin Bivalent(Equine) Types A and B (1:10 in saline) or an Equivalent Volume of Placebo on Day 0 in Stage A
Botulism Antitoxin Heptavalent (Equine) Types A-GBiological
One vial of Heptavalent Botulism Antitoxin (1:10 in saline) or an Equivalent Volume of Placebo on Day 0 in Stage B
| Study group | Role | What they receive |
|---|---|---|
| Stage A | Experimental | Botulism Antitoxin Bivalent (Equine) Types A and B Vs. Placebo Receives: Biological: Botulism Antitoxin Bivalent (Equine) Types A and B |
| Stage B | Experimental | Botulism Antitoxin Heptavalent (Equine) Types A-G Vs. Placebo Receives: Biological: Botulism Antitoxin Heptavalent (Equine) Types A-G |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nerve Conduction Study
Measured: Screening, Baseline (Day 0, -3 hrs), Day 1 (-1 hr), Day 3, Day 4, Day 7, Day 14, Day 21, Day 28 or Early Withdrawal
Secondary outcomes (8)
Hematology
Measured: Screening, Baseline (Day 0, -3 hr), Day 7, Day 14, Day 21, Day 28 or Early Withdrawal
Blood Chemistry
Measured: Screening, Baseline (Day 0, -3 hr), Day 7, Day 14, Day 21, Day 28 or Early Withdrawal
Urinalysis
Measured: Screening, Baseline (Day 0, -3 hr), Day 7, Day 14, Day 21, Day 28 or Early Withdrawal
Serum anti-Botulism Antitoxin Reactivity
Measured: Baseline, Day 28 or Early Withdrawal
Adverse Events
Measured: Day 0, Day 1( -1 hr), Day 1, Day 3, Day 4, Day 7, Day 14, Day 21, and Day 28 or Early Withdrawal
Vital Signs
Measured: Screening, Day 0 (-3 hrs), Day 0, Day 1 (-1 hr), Day 1, Day 3, Day 4, Day 7, Day 14, Day 21, and Day 28 or Early Withdrawal
Physical Examination
Measured: Screening, Baseline (Day 0, -3 hrs), Day 1 (-1 hr), Day 3, Day 4, Day 7, Day 21 and Day 28 or Early Withdrawal
12-lead ECG
Measured: Screening/ Day 28 or Early Withdrawal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2008 (estimated)
- Study startFeb 2008
- Primary completionOct 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- 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
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emergent BioSolutions
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Department of Health and Human Services
- Responsible party
- Sponsor
- Investigators
- Richard Sloop, M. D., Principal investigator, R. Richard Sloop, M. D.Gordon Peterson, Dr., Principal investigator, Faculty Physicains & Surgeons of Loma Linda University School of Medicine, Department of Neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00636519
- Sponsor's protocol ID
- BT002
- Status last verified
- Mar 2024
- First submitted
- 11 Mar 2008
- Last updated
- 18 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
Publications
Benedetto AV. The cosmetic uses of Botulinum toxin type A. Int J Dermatol. 1999 Sep;38(9):641-55. doi: 10.1046/j.1365-4362.1999.00722.x. No abstract available.
PubMed 10517680Carruthers A, Carruthers J. Cosmetic uses of botulinum A exotoxin. Adv Dermatol. 1997;12:325-47; discussion 348. No abstract available.
PubMed 8973746Tacket CO, Shandera WX, Mann JM, Hargrett NT, Blake PA. Equine antitoxin use and other factors that predict outcome in type A foodborne botulism. Am J Med. 1984 May;76(5):794-8. doi: 10.1016/0002-9343(84)90988-4.
PubMed 6720725
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Botulism Antitoxin Effects on Paralysis Induced by Type A and Type B Botulinum Neurotoxins in the Extensor Digitorum Brevis Muscle
- ClinicalTrials.gov ID
- NCT00636519
- Acronym / sponsor ID
- BT002
- Conditions
- Healthy Volunteers
- Keywords
- Botulism Antitoxin,Heptavalent,Bivalent,EDB Muscle,Paralysis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Emergent BioSolutionsIndustry (pharma, biotech, devices)
- Collaborators
- Department of Health and Human Services
- Study start
- Feb 2008
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 14 Mar 2008 (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.
The primary purpose of this study is:
- To evaluate the model determined by the ability of botulism antitoxin (bivalent, Aventis) to neutralize Botulinum toxin in the Extensor Digitorum Brevis model of muscle paralysis in Stage A.
- To assess the ability of botulism antitoxin (heptavalent, Cangene) to neutralize Botulinum toxin in the Extensor Digitorum Brevis model of muscle paralysis in Stage B.
Detailed description
Botulism is a rare disease; however Botulinum toxins (neurotoxins) may be used as biological weapon especially in the form of aerosol. Botulism is caused by neurotoxins that are produced by the obligate anaerobic, gram-positive, spore-forming bacterium Clostridium botulinum (1). C. botulinum produces 8 serologically distinct neurotoxins identified as serotypes A, B, C1, C2, D, E, F, and G (2).
Therapy for botulism includes supportive care and passive immunization with antitoxin. Antitoxin should be administered to patients with neurologic signs of botulism as soon as possible after clinical diagnosis (3). Botulism antitoxin is prepared from plasma obtained from horses that have been immunized with a specific subtype of botulism toxoid and toxin.
The BT-002 is an exploratory pharmacodynamic study that is being performed to evaluate the effect of Botulism Antitoxins in preventing paralysis of extensor digitorum brevis muscle following BOTOX®/ MYOBLOC® administration. This study will compare bivalent and heptavalent products to a placebo. Safety data will be collected.
NP-018 (heptavalent equine-derived botulinum antitoxin) is prepared from plasma obtained from horses that have been immunized with a specific subtype of botulinum toxoid and toxin. Each individual horse is immunized against a single botulinum toxin subtype. Plasma is pooled from horses that have been immunized with the same botulinum toxin subtype. For each antitoxin serotype (A-G), a despeciated product will be produced by pepsin digestion of the IgG monomer in the equine plasma, yielding predominantly F(ab')2 fragment. Following the formulation, the seven antitoxin serotypes will be blended into a heptavalent product and filled into single-use vials. '
This research study will be conducted in two stages - Stage A and Stage B. If enrolled in the Stage A of the study, the subject will have an equal chance of getting either bivalent botulism antitoxin or placebo. If enrolled in Stage B of the study, the subject will have an equal chance of getting heptavalent botulism antitoxin (NP-018) or placebo. The subject will be receiving injections of Botox and Myobloc on the next day after the antitoxin administration in the left and right foot respectively. The subject's participation in this study will be for maximum of 57 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stage A | Experimental | Biological: Botulism Antitoxin Bivalent (Equine) Types A and BBotulism Antitoxin Bivalent (Equine) Types A and B Vs. Placebo |
| Stage B | Experimental | Biological: Botulism Antitoxin Heptavalent (Equine) Types A-GBotulism Antitoxin Heptavalent (Equine) Types A-G Vs. Placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Male or female
- Age 18 - 55 years
- Body-mass index 19-30
- Normal and healthy as determined by medical history, physical examination, ECG, NCS, vital signs and tests of liver, kidney and hematological functions
- Adequate form of contraception for female subjects
Key exclusion criteria (25 listed)
- Previously injected with BOTOX®, BOTOX® COSMETIC or MYOBLOC®
- Any known or documented Botulinum infection/intoxication
- Any known or documented allergies to horses (e.g. rash, wheezing, rhinitis etc. after exposure to horses)
- Any known or documented allergies to horse serum (observation of adverse events after treatment with any kind of product containing horse serum)
- Any moderate or severe food allergies, seasonal allergies or hay fever requiring treatment with peroral or parenteral immunosuppressive drug
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 |
|---|---|---|
| Botulism Antitoxin Bivalent (Equine) Types A and BOne vial of Botulism Antitoxin Bivalent(Equine) Types A and B (1:10 in saline) or an Equivalent Volume of Placebo on Day 0 in Stage A | Biological | Stage A |
| Botulism Antitoxin Heptavalent (Equine) Types A-GOne vial of Heptavalent Botulism Antitoxin (1:10 in saline) or an Equivalent Volume of Placebo on Day 0 in Stage B | Biological | Stage B |
Primary outcome
Nerve Conduction Study
Time frame: Screening, Baseline (Day 0, -3 hrs), Day 1 (-1 hr), Day 3, Day 4, Day 7, Day 14, Day 21, Day 28 or Early Withdrawal
8 secondary outcomes
Hematology
Time frame: Screening, Baseline (Day 0, -3 hr), Day 7, Day 14, Day 21, Day 28 or Early Withdrawal
Blood Chemistry
Time frame: Screening, Baseline (Day 0, -3 hr), Day 7, Day 14, Day 21, Day 28 or Early Withdrawal
Urinalysis
Time frame: Screening, Baseline (Day 0, -3 hr), Day 7, Day 14, Day 21, Day 28 or Early Withdrawal
Serum anti-Botulism Antitoxin Reactivity
Time frame: Baseline, Day 28 or Early Withdrawal
Adverse Events
Time frame: Day 0, Day 1( -1 hr), Day 1, Day 3, Day 4, Day 7, Day 14, Day 21, and Day 28 or Early Withdrawal
Vital Signs
Time frame: Screening, Day 0 (-3 hrs), Day 0, Day 1 (-1 hr), Day 1, Day 3, Day 4, Day 7, Day 14, Day 21, and Day 28 or Early Withdrawal
Physical Examination
Time frame: Screening, Baseline (Day 0, -3 hrs), Day 1 (-1 hr), Day 3, Day 4, Day 7, Day 21 and Day 28 or Early Withdrawal
12-lead ECG
Time frame: Screening/ Day 28 or Early Withdrawal
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 18 Mar 2024.
- Background: PubMed 10517680Benedetto AV. The cosmetic uses of Botulinum toxin type A. Int J Dermatol. 1999 Sep;38(9):641-55. doi: 10.1046/j.1365-4362.1999.00722.x. No abstract available.
- Background: PubMed 8973746Carruthers A, Carruthers J. Cosmetic uses of botulinum A exotoxin. Adv Dermatol. 1997;12:325-47; discussion 348. No abstract available.
- Background: PubMed 6720725Tacket CO, Shandera WX, Mann JM, Hargrett NT, Blake PA. Equine antitoxin use and other factors that predict outcome in type A foodborne botulism. Am J Med. 1984 May;76(5):794-8. doi: 10.1016/0002-9343(84)90988-4.
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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.
Richard Sloop, M. D. principal investigator
R. Richard Sloop, M. D.
Gordon Peterson, Dr. principal investigator
Faculty Physicains & Surgeons of Loma Linda University School of Medicine, Department of Neurology
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Botulism Antitoxin Bivalent (Equine) Types A and B and Botulism Antitoxin Heptavalent (Equine) Types A-G in people with Healthy Volunteers, run by Emergent BioSolutions at 2 sites 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 10 inclusion and 25 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 18 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. 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?
Nerve Conduction Study (time frame: Screening, Baseline (Day 0, -3 hrs), Day 1 (-1 hr), Day 3, Day 4, Day 7, Day 14, Day 21, Day 28 or Early Withdrawal). 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 NCT00636519, which also lists 3 linked publications.
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 18 Mar 2024.