Instituto Bioclon S.A. de C.V. has developed Analatro®, an antibody fragment (Fab2) containing widow spider (Latrodectus) antivenom, and proposes to conduct a clinical trial in hospital emergency departments to assess the efficacy and safety of this product in patients with moderate to severe pain associated with Latrodectus envenomation (latrodectism). The primary objectives of this Phase III, multi-center, double-blind, controlled study are as follows:
To determine the efficacy of Analatro compared to control for the treatment of latrodectism as measured by the proportion of patients in whom pain control is not achieved (e.g., treatment failure)
To further characterize the safety profile of Analatro, including comparison of the rate of drug-related adverse events to control for the treatment of latrodectism
The flow of study procedures are illustrated in the chart on the following page. All patients who consent to participate will be given a visual analog scale (VAS, 0=no pain to 100mm=worst possible pain) for assessing pain intensity. Patients that meet all study enrollment requirements, including a minimum age of 10 years, a clinical diagnosis of latrodectism and a VAS pain score of ≥40 mm (moderate to severe pain) will be randomly assigned to be treated with Analatro or control. A screening phase will be completed, during which time preliminary procedures will be performed by the investigator (medical history, physical exam, and pregnancy test as applicable) and two doses of Analatro or two doses of saline control will be prepared. Fentanyl may be administered intravenously as needed for pain relief during the screening phase at a dosage not to exceed 1.5 µg/kg/hr. At the end of the screening phase, baseline measurements (vital signs, VAS pain score) will be performed. Patients must have a baseline VAS score ≥40 mm to receive study medication.
Eligible patients will begin a 2.5 hour treatment phase. Dose 1 of study medication (50 mL) will be infused intravenously over 10 minutes. Thirty minutes after the start of Dose 1, pain intensity will be assessed (VAS2), vital signs will be recorded (VS2), and a blood sample collected (B2). Clinical improvement in this study will be defined as a VAS score that is at least 13mm less than the baseline VAS score (VAS1). Patients that fail to show clinical improvement at 30 minutes will receive Dose 2 of study medication (Dose 2 will be identical to Dose 1). Patients showing clinical improvement will not receive Dose 2.
Thirty minutes after VAS2 (or after the start of Dose 2, if applicable), VAS3 will be administered, vital signs (VS3) will be recorded, and a blood sample (B3) will be collected. If the patient has not clinically improved relative to baseline, the patient will be deemed a treatment failure; the treatment phase will be discontinued, and the patient will be treated in accordance with standard of care by the investigator and/or treating physician. Patients that have clinically improved will remain in the treatment arm.
The remaining 1.5 hours of the treatment arm will consist of serial assessments of pain intensity (VAS4, 5 and 6), vital signs (VS4, 5 and 6), and collection of one blood sample (B4, 5 and 6) every 30 minutes. After each VAS, the patient must continue to show clinical improvement relative to baseline to remain in the treatment arm. Otherwise, the patient will exit the treatment phase and be treated in accordance with standard of care. No analgesics will be allowed during the treatment phase to eliminate the potential confounding effect of pain medication on assessing the effectiveness of the study medication on clinical improvement. Routine decision points for treatment failure (every thirty minutes) will promote accurate identification of treatment failures without compromising timely provision of pain medication in absence of clinical improvement.
All patients will be closely monitored for adverse events during Dose 1 of treatment until the time of discharge from the emergency department. Follow-up for possible adverse events and recurring/residual symptoms will be conducted by telephone on Days 2, 10, and 17 after discharge from the emergency department.
Treatment failure will be defined as (1) early exit from the treatment phase due to absence of clinical improvement relative to baseline and/or (2) patient requires prescription pain medication or Antivenin Latrodectus Mactans (Merck) for pain associated with the study condition being treated at any time after the treatment phase up to 48 hours after the time of discharge from the emergency department. To improve accurate identification of treatment failure after discharge, no preventative pain medication will be administered or prescribed to patients that successfully complete the treatment phase. Patients will be encouraged to call the investigator or return to the emergency department, if necessary, for proper evaluation and treatment.
