Phase 3 Multicenter Comparative Study to Confirm Safety and Effectiveness of the F(ab)2 Antivenom Anavip.

Instituto Bioclon

Status and phase: Completed; Phase 3

Conditions: Snake Bite

Treatments: Biological: Crotalinae (pit viper) equine immune F(ab)2; Biological: Crotalidae Polyvalent Immune Fab, ovine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00636116

YA-07/02

Details and patient eligibility

About

The purpose of this study is to establish if F(ab)2 antivenom (Anavip) is safe for crotalinae envenomation. Confirm its effectiveness in preventing the occurrence of delayed coagulopathies and compare the safety and efficacy with Fab antivenom (CroFab) in patients with Crotalinae envenomation.

Full description

Fewer than 200,000 crotaline envenomations occur annually in the US.Crotaline venoms contain a broad variety of toxins, venom variability and injection quantity among individual snakes and across species result in broadly variable patient presentations. Clinical consequences of crotaline envenomation include local and systemic effects, both of which may progress for hours to days.The best studied systemic consequence is coagulopathy, which may in its complexity mimic disseminated intravascular coagulation. Platelet and clotting disorders respond rapidly to administration of polyvalent antivenom.

Crotaline viper envenomation in the United States is treated with one of two licensed products: Wyeth Antivenin (Crotalidae) Polyvalent (Polyvalent), or CroFab® (antivenin Crotalidae polyvalent immune Fab, ovine). In recent years, both of these products have been in critically short supply. Use of Wyeth Polyvalent has been associated with a greater than 75% incidence of adverse reactions, including acute type 1 and delayed type 2 immune reactions.These phenomena are an inherent risk in the use of whole immunoglobulin. CroFab´s low molecular weight creates a pharmacokinetic mismatch with crotaline venom which leds to a recurrent venom effects.

Anavip is pharmacologically and pharmacokinetically different.Because of the elimination of the Fc portion of the immunoglobulin molecule, Anavip is expected to produce far fewer adverse reactions than seen with whole immunoglobulin antivenoms and unlike Fab molecules, F(ab)2 molecules exceed the size threshold for renal clearance and thus are expected to remain in circulation for a significantly longer time and substantially reduce the incidence of recurrent coagulopathy.

Enrollment: 121 patients

Sex: All

Ages: 2 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Men and women 2 to 80 years of age
• Presenting for emergency treatment of pit viper bite
• Informed consent document read and signed by patient (or parent/legal guardian)

Exclusion criteria

• Current use of any antivenom, or use within the last month
• Current participation in a clinical drug study, or participation within the last month
• Positive urine or blood pregnancy test at screening
• Breast-feeding
• Allergy to horse serum, sheep serum, or papaya
• Underlying medical conditions that significantly alter platelet count or fibrinogen; thrombocytopenia, hemophilia, familial dysfibrinogenemia, leukemia
• Use of any medication expected to affect platelet count, coagulation factors or fibrinogen: chemotherapeutic agents, warfarin, heparin
• No clinical indications of snake bite requiring antivenom for treatment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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121 participants in 3 patient groups

Group 1

Experimental group

Description:

Anavip with Anavip Maintenance Therapy

Treatment:

Biological: Crotalinae (pit viper) equine immune F(ab)2

Biological: Crotalinae (pit viper) equine immune F(ab)2

Group 2

Experimental group

Description:

Anavip with Placebo Maintenance Therapy

Treatment:

Biological: Crotalinae (pit viper) equine immune F(ab)2

Biological: Crotalinae (pit viper) equine immune F(ab)2

Group 3

Active Comparator group

Description:

CroFab with CroFab Maintenance Therapy

Treatment:

Biological: Crotalidae Polyvalent Immune Fab, ovine