Trial Outcomes & Findings for Black Widow Spider Antivenin for Patients With Systemic Latrodectism (NCT NCT00657540)

Last Updated: 2018-04-03

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

60 participants

Primary outcome timeframe

From start of Dose 1 infusion to 48 hours post treatment

Results posted on

2018-04-03

Participant Flow

Due to the nature of the treatment emergent condition of interest, no patients were actively recruited. Potential subjects presenting with moderate to severe pain associated with diagnosed latrodectism were evaluated at 16 sites across the United States. The first subject was enrolled on 10/08/09. The last subject completed the study on 10/27/14.

Participant milestones

Participant milestones
Measure	Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses	Normal Saline Normal Saline Saline: 50 mL of saline infused over 10 minutes
Overall Study STARTED	29	31
Overall Study COMPLETED	28	27
Overall Study NOT COMPLETED	1	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses	Normal Saline Normal Saline Saline: 50 mL of saline infused over 10 minutes
Overall Study Lost to Follow-up	1	4

Baseline Characteristics

Black Widow Spider Antivenin for Patients With Systemic Latrodectism

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 n=29 Participants Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses	Normal Saline n=31 Participants Normal Saline Saline: 50 mL of saline infused over 10 minutes	Total n=60 Participants Total of all reporting groups
Age, Continuous	37.3 years STANDARD_DEVIATION 15.18 • n=99 Participants	41.0 years STANDARD_DEVIATION 17.84 • n=107 Participants	39.2 years STANDARD_DEVIATION 16.57 • n=206 Participants
Sex: Female, Male Female	11 Participants n=99 Participants	8 Participants n=107 Participants	19 Participants n=206 Participants
Sex: Female, Male Male	18 Participants n=99 Participants	23 Participants n=107 Participants	41 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=99 Participants	17 Participants n=107 Participants	30 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=99 Participants	14 Participants n=107 Participants	30 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=99 Participants	0 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	2 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) White	14 Participants n=99 Participants	20 Participants n=107 Participants	34 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	10 Participants n=99 Participants	11 Participants n=107 Participants	21 Participants n=206 Participants
Region of Enrollment United States	29 Participants n=99 Participants	31 Participants n=107 Participants	60 Participants n=206 Participants
Baseline VAS Pain Score (mm)	79.7 mm STANDARD_DEVIATION 13.16 • n=99 Participants	73.8 mm STANDARD_DEVIATION 16.14 • n=107 Participants	76.7 mm STANDARD_DEVIATION 14.96 • n=206 Participants

PRIMARY outcome

Timeframe: From start of Dose 1 infusion to 48 hours post treatment

Population: The analysis population consists of all subjects that were randomized and received any study drug (modified intent to treat population).

Outcome measures

Outcome measures
Measure	Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 n=29 Participants Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses	Normal Saline n=31 Participants Normal Saline Saline: 50 mL of saline infused over 10 minutes
Number of Participants With Treatment Failure	15 Participants	24 Participants

SECONDARY outcome

Timeframe: 30 minutes post treatment

The number of patients with a clinically significant decrease in pain intensity at 30 minutes post-treatment (after Dose 1 and Dose 2, as applicable) will be measured by the patient's self-assessment of pain intensity using the visual analog scale (VAS). A clinically significant reduction in pain is defined as a decrease in VAS scores of greater than or equal to 13 mm. The VAS ranged from 0 (no pain) to 100 mm (worst possible pain).

Outcome measures

Outcome measures
Measure	Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 n=29 Participants Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses	Normal Saline n=31 Participants Normal Saline Saline: 50 mL of saline infused over 10 minutes
Number of Participants With at Least 13 mm Reduction in Pain Score at 30 Minutes Post-Treatment	13 Participants	11 Participants

SECONDARY outcome

Timeframe: Start of Dose 1 through 17 days post treatment

To evaluate safety of Analatro, the number of subjects experiencing at least one adverse event (AE) that was determined to be related to study drug was computed for each treatment group. All AEs classified as definitely or possibly related to study drug were considered drug-related.

Outcome measures

Outcome measures
Measure	Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 n=29 Participants Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses	Normal Saline n=31 Participants Normal Saline Saline: 50 mL of saline infused over 10 minutes
Drug-related Adverse Events	16 Participants	18 Participants

SECONDARY outcome

Timeframe: Start of Dose 1 to any post-infusion time point

The number of patients with a clinically significant decrease in pain intensity relative to baseline at any time point during the treatment phase was measured by the patient's self-assessment of pain intensity using the visual analog scale (VAS). A clinically significant reduction in pain was defined as a decrease in VAS scores of greater than or equal to 13 mm. The VAS ranged from 0 (no pain) to 100 mm (worst possible pain).

Outcome measures

Outcome measures
Measure	Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 n=29 Participants Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses	Normal Saline n=31 Participants Normal Saline Saline: 50 mL of saline infused over 10 minutes
Number of Participants With at Least 13 mm Reduction in Pain Score at Any Time Point	19 Participants	18 Participants

SECONDARY outcome

Timeframe: Start of Dose 1 through 17 days post treatment

The number of subjects with drug-related serious adverse events.

Outcome measures

Outcome measures
Measure	Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 n=29 Participants Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses	Normal Saline n=31 Participants Normal Saline Saline: 50 mL of saline infused over 10 minutes
Drug-related Serious Adverse Events	0 Participants	0 Participants

Adverse Events

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

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

Normal Saline

Serious events: 2 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 n=29 participants at risk Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses	Normal Saline n=31 participants at risk Normal Saline Saline: 50 mL of saline infused over 10 minutes
Skin and subcutaneous tissue disorders Cellulitis	0.00% 0/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	3.2% 1/31 • Number of events 1 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Injury, poisoning and procedural complications Inadequate Pain Control	0.00% 0/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	3.2% 1/31 • Number of events 1 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.

Other adverse events

Additional Information

Victoria Anderson - Research Projects Manager

Rocky Mountain Poison and Drug Center

Phone: 303-389-1236

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 n=29 participants at risk Antivenin Latrodectus (Black Widow) Equine Immune F(ab)2 Analatro: 30 mL of lyophilized antivenom, reconstituted in 50 mL saline infused over 10 minutes, up to 2 doses	Normal Saline n=31 participants at risk Normal Saline Saline: 50 mL of saline infused over 10 minutes
Gastrointestinal disorders Constipation	0.00% 0/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	19.4% 6/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Gastrointestinal disorders Nausea	10.3% 3/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	3.2% 1/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Gastrointestinal disorders Vomiting	3.4% 1/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	6.5% 2/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
General disorders Chills	10.3% 3/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	22.6% 7/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
General disorders Fatigue	3.4% 1/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	6.5% 2/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
General disorders Inflammation	6.9% 2/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	0.00% 0/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
General disorders Pyrexia	6.9% 2/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	12.9% 4/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Metabolism and nutrition disorders Decreased appetite	3.4% 1/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	6.5% 2/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Musculoskeletal and connective tissue disorders Arthralgia	24.1% 7/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	19.4% 6/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Musculoskeletal and connective tissue disorders Myalgia	10.3% 3/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	12.9% 4/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Musculoskeletal and connective tissue disorders Pain in extremity	13.8% 4/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	9.7% 3/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Nervous system disorders Headache	17.2% 5/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	12.9% 4/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Nervous system disorders Paraesthesia	10.3% 3/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	0.00% 0/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Psychiatric disorders Anxiety	0.00% 0/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	6.5% 2/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Psychiatric disorders Insomnia	3.4% 1/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	9.7% 3/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.4% 1/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	6.5% 2/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Skin and subcutaneous tissue disorders Pruritus	62.1% 18/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	54.8% 17/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Skin and subcutaneous tissue disorders Rash	13.8% 4/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	25.8% 8/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.
Skin and subcutaneous tissue disorders Urticaria	6.9% 2/29 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.	0.00% 0/31 • Subjects were monitored for adverse events from the time of consent through 17 days post start of Dose 1.