Botulism Antitoxin Effects on Paralysis Induced by Botulinum Neurotoxins in the EDB Muscle
Condition: Healthy Volunteers
MeSH terms: Botulism; Paralysis
Study type: Interventional
Phase: Phase 1

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. 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.
    

Intervention name(s): Botulism Antitoxin Bivalent (Equine) Types A and B; Botulism Antitoxin Heptavalent (Equine) Types A-G
Intervention type(s): Biological; Biological
Intervention description(s): 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; One vial of Heptavalent Botulism Antitoxin (1:10 in saline) or an Equivalent Volume of Placebo on Day 0 in Stage B
Intervention MeSH terms: Antitoxins; Botulinum Antitoxin
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Botulism Antitoxin,Heptavalent,Bivalent,EDB Muscle,Paralysis