Black Widow Spider Antivenin for Patients With Systemic Latrodectism

NCT00657540 | Completed Phase 3 Results DMC

• 1 other identifier: XF-07/03
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 16

Brief Summary

The purpose of this study is to test the efficacy and safety of a new antivenom called Analatro® for treating black widow spider bites in patients who present to a hospital emergency room within 24 hours of symptom onset. This study will be a phase III, multi-center, double-blind, randomized controlled study that takes place in emergency departments. The primary aim of this study is to determine the proportion of patients in which pain control was not achieved by 48 hours post treatment. Secondary aims are as follows: 1) a reduction in pain intensity at the end of the treatment phase compared to baseline; 2) the proportion of patients with a clinically significant decrease in pain intensity at 30 minutes post-treatment; 3) the proportion of patients in which drug-related adverse events occurred; and 4) to determine if serious, drug-related adverse events in Analatro-treated patients occurred at a rate greater than one in 10 (10%).

Conditions

Latrodectism

Keywords

black widow spider; antivenom; latrodectism

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Failure

  The primary efficacy endpoint for this study was the number of subjects in which pain control was not achieved 48 hours post-study drug infusion as identified by treatment failure. A treatment failure was defined as a subject who did not achieve pain control during the treatment phase, up to 48 hours after Dose 1 infusion start time. Subjects were deemed treatment failures if they met one or more of the following criteria: * Subject did not complete the treatment phase due to absence of clinically significant improvement in pain intensity relative to baseline at 60, 90, 120, or 150 minutes post start of Dose 1. * Subject required treatment with commercially available antivenin or prescription pain medication for signs and symptoms associated with latrodectism at any time during the treatment phase up to 48 hours after Dose 1 infusion start time.

  From start of Dose 1 infusion to 48 hours post treatment

Secondary Outcomes (4)

• Number of Participants With at Least 13 mm Reduction in Pain Score at 30 Minutes Post-Treatment

  30 minutes post treatment

• Drug-related Adverse Events

  Start of Dose 1 through 17 days post treatment

• Number of Participants With at Least 13 mm Reduction in Pain Score at Any Time Point

  Start of Dose 1 to any post-infusion time point

• Drug-related Serious Adverse Events

  Start of Dose 1 through 17 days post treatment

Study Arms (2)

Analatro

EXPERIMENTAL

Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2

Drug: Analatro

Normal Saline Placebo

PLACEBO COMPARATOR

Normal Saline

Drug: Saline

Interventions

Analatro DRUG

30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses

Analatro

Saline DRUG

50 mL of saline infused over 10 minutes

Also known as: Placebo

Normal Saline Placebo

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Moderate to severe pain intensity measured using the visual analog scale (VAS score ≥ 40mm) at the start of screening phase (VAS 0)
• Diagnosis of latrodectism by the Investigator, with concurrence of diagnosis by a physician not directly involved with the study
• Moderate to severe pain intensity measured using the visual analog scale (VAS score ≥ 40mm) at Baseline (VAS 1)

You may not qualify if:

• Less than 10 years of age
• Presents to the emergency department of any healthcare facility greater than 24 hours after onset of symptoms
• Has a known (self-reported) hypersensitivity to fentanyl, morphine, diazepam, or equine serum
• History of significant cardiac, respiratory, hepatic or renal disease, psychiatric disorder or chronic pain syndrome that in the investigator's assessment would confound efficacy or safety endpoint assessment (e.g., a bite to the leg of a patient with reflex sympathetic dystrophy)
• History or suspected history or substance abuse
• Pregnant or breast-feeding
• Has a distracting injury with acute pain, or is unable to make a reliable self-report of pain intensity to pain relief based solely on the condition of interest
• Was already treated with Merck Antivenin Latrodectus Mactans for signs/symptoms related to the current widow spider bite
• Unable to provide a telephone number to be contacted for follow-up interviews on Days 2, 10, and 17 after discharge from the emergency department

Sponsors & Collaborators

• Instituto Bioclon S.A. de C.V.: lead
• Rare Disease Therapeutics Inc.: collaborator

Study Sites (16)

Banner Good Samaritan Medical Center

Phoenix, Arizona, 85006, United States

Location

Maricopa Medical Center

Phoenix, Arizona, 85008, United States

Location

University of California Davis

Davis, California, 95616, United States

Location

University California San Francisco - Fresno

Fresno, California, 93701, United States

Location

University of California Irvine

Irvine, California, 92697, United States

Location

Loma Linda University

Loma Linda, California, 92354, United States

Location

University of California San Diego

San Diego, California, 92103, United States

Location

San Diego Children's Hospital

San Diego, California, 92123, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80010, United States

Location

Denver Health and Hospital Authority

Denver, Colorado, 80204, United States

Location

Cape Coral Hospital

Cape Coral, Florida, 33990, United States

Location

University of Florida, Department of Emergency Medicine

Gainesville, Florida, 32610, United States

Location

LSU Health Sciences

Shreveport, Louisiana, 71106, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

Texas Tech - West Texas Regional Poison Center

El Paso, Texas, 79905, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• Dart RC, Bush SP, Heard K, Arnold TC, Sutter M, Campagne D, Holstege CP, Seifert SA, Lo JCY, Quan D, Borron S, Meurer DA, Burnham RI, McNally J, Garcia-Ubbelohde W, Anderson VE. The Efficacy of Antivenin Latrodectus (Black Widow) Equine Immune F(ab')2 Versus Placebo in the Treatment of Latrodectism: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial. Ann Emerg Med. 2019 Sep;74(3):439-449. doi: 10.1016/j.annemergmed.2019.02.007. Epub 2019 Mar 27.

  PMID: 30926190 DERIVED

MeSH Terms

Conditions

Spider Bites

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Bites and Stings; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

The study is limited by the small sample size; however this trial was powered appropriately for an orphan indication. The study is also limited by the difficulty in confirming latrodectism without a spider or clear history of seeing a spider.

Results Point of Contact

• Title: Victoria Anderson - Research Projects Manager
• Organization: Rocky Mountain Poison and Drug Center

victoria.anderson@rmpdc.org

303-389-1236

Study Officials

• Richard C Dart, MD, PhD

  Rocky Mountain Poison & Drug Center - Denver Health

  PRINCIPAL INVESTIGATOR

• Walter Garcia, MD

  Instituto Bioclon S.A. de C.V.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2008
• First Posted: April 14, 2008
• Study Start: October 1, 2009
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: April 3, 2018
• Results First Posted: September 18, 2017

Record last verified: 2018-03

Locations

US (16)