Randomized, Double-Blind, Placebo-Controlled Study: CroFab® vs Placebo for Copperhead Snake Envenomation

This study will evaluate the recovery from copperhead snake bite in patients with mild or
moderate venom effect. Potential subjects will receive CroFab antivenom or placebo. The trial
is conducted by emergency room doctors, toxicologists, or surgeons at hospitals in regions
where copperhead bites are common. After blinded treatment and discharge, the subject returns
to the clinic for follow-up assessments at day 3, 7, 14, and 28 after snake bite. The subject
will also be called by telephone for follow-up assessments on day 10, 17, and 24 after snake
bite. The purpose of this study is to compare recovery in copperhead snake bite patients
treated with antivenom vs placebo (no active drug) as measured by the Patient Specific
Functional Scale (PSFS) at Day 14 follow-up.The primary efficacy endpoint of this study was
achieved. Treatment with CroFab® demonstrated measurable and significant improvement (less
disability) over placebo: in the mITT population, the LS mean total score on the PSFS at Day
14 follow-up and treatment showed less disability in patients randomized to receive CroFab®
than those receiving placebo.

Inclusion Criteria-

- Envenomation by a copperhead snake

a. Snake identified by one of the following means: i.Snake or photograph of snake
brought to Emergency Department ii.Patient chooses copperhead from an array of snake
photographs iii.Patient envenomated in an area where only copperheads are endemic
iv.Patient envenomated by a captive copperhead snake

- Completion of informed consent and eligibility confirmation within 24 hours of
envenomation

- Envenomation on only one extremity, distal to the elbow or knee

- Clinical evidence of mild or moderate venom effect (limb swelling and/or tenderness)
is present (Venom effects need not be progressing.)

- Patient willing and able to complete follow-up schedule of assessments

- Patient is able to read, comprehend and sign the IRB approved consent document(s)

- Patient is able to read and comprehend the written assessment tools (e.g., DASH, LEFS,
PROMIS Physical Function Short Form 10a (PROMIS PF-10), PGIC, etc.)

- Patient is ≥12 years of age

- Patient is sober, competent, and able to complete verbal and written informed consent

Exclusion Criteria-

- Patient has clinical evidence of severe venom effect as defined by meeting any one of
the following parameters:

i. Swelling to an entire extremity (all major joints affected)

1. Lower extremity: swelling crossing hip joint

2. Upper extremity: swelling crossing shoulder joint ii. INR > 2.0 iii. Platelets
<50,000 cells / µL iv. Fibrinogen <50 mg/dL

v. Compartment syndrome vi. Systolic Blood Pressure <90 mmHg vii. More than minimal
bleeding viii. Investigator's clinical discretion

- Patient has already received antivenom for the management of the current envenomation

- Patient is pregnant or breastfeeding

- Patient is a prisoner

- Patient has a distracting injury or condition with acute pain or functional
impairment, and/or is unable to make a reliable self-report of functionality status
based solely on the condition of interest

- Patient had a previous snake envenomation to any body area in the 30 days prior to
screening/enrollment, regardless of whether antivenom was administered for the
previous envenomation

- Patient had an acute traumatic event, surgery, an acute medical event, or exacerbation
of a pre-existing medical or surgical condition affecting the envenomated extremity
within the 30 days prior to screening/enrollment

- Patient has participated in a clinical study involving an investigational
pharmaceutical product or device within the 3 months prior to screening that may have
impact on clinical outcomes of snakebite

- Patient has previously participated in this clinical study

- Patient has a known history of hypersensitivity to any components of CroFab®, or to
papaya or papain

- Patient is otherwise unsuitable for inclusion in this study, based on the opinion of
the Investigator