Botulism Antitoxin Effects on Paralysis Induced by Botulinum Neurotoxins in the EDB Muscle - Full Text View

Sponsors and Collaborators:	Cangene Corporation Department of Health and Human Services
Information provided by:	Cangene Corporation
ClinicalTrials.gov Identifier:	NCT00636519

Purpose

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.

Condition	Intervention	Phase
Healthy Volunteers	Biological: Botulism Antitoxin Bivalent (Equine) Types A and B Biological: Botulism Antitoxin Heptavalent (Equine) Types A-G	Phase I

MedlinePlus related topics: Botulism Paralysis

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Single Group Assignment, Pharmacodynamics Study
Official Title:	Botulism Antitoxin Effects on Paralysis Induced by Type A and Type B Botulinum Neurotoxins in the Extensor Digitorum Brevis Muscle

Further study details as provided by Cangene Corporation:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Hematology [ Time Frame: Screening, Baseline (Day 0, -3 hr), Day 7, Day 14, Day 21, Day 28 or Early Withdrawal ] [ Designated as safety issue: Yes ]
Blood Chemistry [ Time Frame: Screening, Baseline (Day 0, -3 hr), Day 7, Day 14, Day 21, Day 28 or Early Withdrawal ] [ Designated as safety issue: Yes ]
Urinalysis [ Time Frame: Screening, Baseline (Day 0, -3 hr), Day 7, Day 14, Day 21, Day 28 or Early Withdrawal ] [ Designated as safety issue: Yes ]
Serum anti-Botulism Antitoxin Reactivity [ Time Frame: Baseline, Day 28 or Early Withdrawal ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
12-lead ECG [ Time Frame: Screening/ Day 28 or Early Withdrawal ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	36
Study Start Date:	February 2008
Estimated Study Completion Date:	January 2010
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Stage A: Experimental Botulism Antitoxin Bivalent (Equine) Types A and B Vs. Placebo	Biological: Botulism Antitoxin Bivalent (Equine) Types A and B 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
Stage B: Experimental Botulism Antitoxin Heptavalent (Equine) Types A-G Vs. Placebo	Biological: Botulism Antitoxin Heptavalent (Equine) Types A-G One vial of Heptavalent Botulism Antitoxin (1:10 in saline) or an Equivalent Volume of Placebo on Day 0 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.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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
- 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

Exclusion Criteria:

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
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00636519

Locations

United States, California
Dr. Gordon Peterson	Recruiting
Loma Linda, California, United States, 92354
Contact: Gordon Peterson, MD 909-558-7019 GPeterson@LLU.edu
Contact: Dharmaseeli (Dee) Moses (909) 558 2037 ext pager 5470 DMoses@ahs.llumc.edu
Principal Investigator: Gordon Peterson, MD
United States, Washington
R. Richard Sloop, M. D.	Completed
Yakima, Washington, United States, 98902

Sponsors and Collaborators

Cangene Corporation

Department of Health and Human Services

Investigators

Principal Investigator:	Richard Sloop, M. D.	R. Richard Sloop, M. D.
Principal Investigator:	Gordon Peterson, Dr.	Faculty Physicains & Surgeons of Loma Linda University School of Medicine, Department of Neurology

More Information

Publications:

Benedetto AV. The cosmetic uses of Botulinum toxin type A. Int J Dermatol. 1999 Sep;38(9):641-55. Review. No abstract available.

Carruthers A, Carruthers J. Cosmetic uses of botulinum A exotoxin. Adv Dermatol. 1997;12:325-47; discussion 348. Review. No abstract available.

Tacket 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.

Responsible Party:	Cangene Corporation ( Christine Hall, Ph.D./ Manager, Clinical Science & Acting Manager, Clinical Operations )
Study ID Numbers:	BT-002
Study First Received:	March 11, 2008
Last Updated:	January 30, 2009
ClinicalTrials.gov Identifier:	NCT00636519 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by Cangene Corporation:

Botulism Antitoxin,Heptavalent,Bivalent,EDB Muscle,Paralysis

Study placed in the following topic categories:

Bacterial Infections
Antitoxins
Immunologic Factors
Neurotoxicity Syndromes
Botulism
Botulinum Antitoxin
Poisoning
Disorders of Environmental Origin

Healthy
Paralysis
Signs and Symptoms
Gram-Positive Bacterial Infections
Neuromuscular Diseases
Neurologic Manifestations
Clostridium Infections

Additional relevant MeSH terms:

Antitoxins
Bacterial Infections
Immunologic Factors
Neurotoxicity Syndromes
Botulism
Physiological Effects of Drugs
Nervous System Diseases
Food Poisoning
Botulinum Antitoxin
Poisoning

Disorders of Environmental Origin
Pharmacologic Actions
Paralysis
Signs and Symptoms
Gram-Positive Bacterial Infections
Neuromuscular Diseases
Neuromuscular Junction Diseases
Neurologic Manifestations
Clostridium Infections

ClinicalTrials.gov processed this record on May 07, 2009