Trial Outcomes & Findings for OK432 (Picibanil) in the Treatment of Lymphatic Malformations (NCT NCT03427619)

Last Updated: 2021-11-23

Results Overview

Clinical success was defined as having either a complete (90% 100%) or substantial (60% 89%) reduction in lymphatic malformation (LM) volume after treatment. Response was determined using post treatment imaging studies at approximately 1 to 6 months after completion of treatment

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

275 participants

Primary outcome timeframe

1 to 6 Months Post-Therapy

Results posted on

2021-11-23

Participant Flow

The study was conducted in 14 centers across the United States between September 2005 and November 2017.

After informed consent, subjects who met all eligibility criteria were enrolled into the study. Study completion data was analyzed retrospectively for subjects with observed, non-missing data. Results presented in this report were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses.

Participant milestones

Participant milestones
Measure	OK-432 OK 432 is a lyophilized biological preparation for injection containing nonviable cells of Streptococcus pyogenes (A group, type 3) Su strain treated with benzylpenicillin. OK-432 was administered intracystically at a concentration of 0.01 to 0.05 mg/mL. A 4-dose injection series of OK-432 was planned for all subjects. All injections were spaced approximately 6 to 12 weeks apart
Overall Study STARTED	275
Overall Study Safety Population	275
Overall Study Modified Intention to Treat Population	143
Overall Study COMPLETED	209
Overall Study NOT COMPLETED	66

Reasons for withdrawal

Reasons for withdrawal
Measure	OK-432 OK 432 is a lyophilized biological preparation for injection containing nonviable cells of Streptococcus pyogenes (A group, type 3) Su strain treated with benzylpenicillin. OK-432 was administered intracystically at a concentration of 0.01 to 0.05 mg/mL. A 4-dose injection series of OK-432 was planned for all subjects. All injections were spaced approximately 6 to 12 weeks apart
Overall Study Physician Decision	3
Overall Study Withdrawal by Subject	4
Overall Study Lost to Follow-up	5
Overall Study Administrative	4
Overall Study Other	2
Overall Study Unknown or Missing Completion Status	48

Baseline Characteristics

Demographic information for age was available for 273 subjects. Missing for 2 subjects.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OK-432 n=275 Participants OK 432 is a lyophilized biological preparation for injection containing nonviable cells of Streptococcus pyogenes (A group, type 3) Su strain treated with benzylpenicillin. OK-432 was administered intracystically at a concentration of 0.01 to 0.05 mg/mL. A 4-dose injection series of OK-432 was planned for all subjects. All injections were spaced approximately 6 to 12 weeks apart
Age, Continuous	5.481 years STANDARD_DEVIATION 6.6382 • n=273 Participants • Demographic information for age was available for 273 subjects. Missing for 2 subjects.
Sex: Female, Male Female	151 Participants n=274 Participants • Demographic information for gender was available for 274 subjects. Missing for 1 subject.
Sex: Female, Male Male	123 Participants n=274 Participants • Demographic information for gender was available for 274 subjects. Missing for 1 subject.
Race/Ethnicity, Customized Hispanic or Latino	36 Participants n=266 Participants • Demographic data on race/ethnicity was available for 266 subjects. Data was missing for 9 subjects. Please note that participants could report more than one Race/Ethnicity.
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=266 Participants • Demographic data on race/ethnicity was available for 266 subjects. Data was missing for 9 subjects. Please note that participants could report more than one Race/Ethnicity.
Race/Ethnicity, Customized White	191 Participants n=266 Participants • Demographic data on race/ethnicity was available for 266 subjects. Data was missing for 9 subjects. Please note that participants could report more than one Race/Ethnicity.
Race/Ethnicity, Customized Black or African American	29 Participants n=266 Participants • Demographic data on race/ethnicity was available for 266 subjects. Data was missing for 9 subjects. Please note that participants could report more than one Race/Ethnicity.
Race/Ethnicity, Customized Asian	10 Participants n=266 Participants • Demographic data on race/ethnicity was available for 266 subjects. Data was missing for 9 subjects. Please note that participants could report more than one Race/Ethnicity.
Race/Ethnicity, Customized Other	7 Participants n=266 Participants • Demographic data on race/ethnicity was available for 266 subjects. Data was missing for 9 subjects. Please note that participants could report more than one Race/Ethnicity.
Region of Enrollment United States	275 participants n=275 Participants

PRIMARY outcome

Timeframe: 1 to 6 Months Post-Therapy

Population: The modified Intent to Treat (mITT) Population includes all enrolled subjects treated with at least one injection of OK 432 who either have post-therapy imaging assessment data or at least one investigator assessment of overall response throughout the study (N = 148). The efficacy data were presented as observed for subjects with non-missing data in the mITT Population (N = 78).

Outcome measures

Outcome measures
Measure	OK-432 n=78 Participants OK 432 is a lyophilized biological preparation for injection containing nonviable cells of Streptococcus pyogenes (A group, type 3) Su strain treated with benzylpenicillin. OK-432 was administered intracystically at a concentration of 0.01 to 0.05 mg/mL. A 4-dose injection series of OK-432 was planned for all subjects. All injections were spaced approximately 6 to 12 weeks apart
Number of Participants With Clinical Success at 1 to 6 Months Post-Therapy as Assessed by Imaging	57 Participants

SECONDARY outcome

Timeframe: 1 to 6 Months Post-Therapy

Population: The mITT includes all enrolled subjects treated with at least one injection of OK 432 who either have post-therapy imaging assessment data or at least one investigator assessment of overall response throughout the study (N = 148). The efficacy data were presented as observed for subjects with non-missing data in the mITT Population (N = 78).

Number of participants who demonstrated a complete (90%-100% reduction in LM volume), substantial (60%-89% reduction in LM volume), intermediate (20%-59% reduction in LM volume), or no (\< 20% reduction in LM volume) response 1 to 6 months post-therapy as assessed by imaging

Outcome measures

Outcome measures
Measure	OK-432 n=78 Participants OK 432 is a lyophilized biological preparation for injection containing nonviable cells of Streptococcus pyogenes (A group, type 3) Su strain treated with benzylpenicillin. OK-432 was administered intracystically at a concentration of 0.01 to 0.05 mg/mL. A 4-dose injection series of OK-432 was planned for all subjects. All injections were spaced approximately 6 to 12 weeks apart
Number of Participants With Clinical Response 1 to 6 Months Post-Therapy as Assessed by Imaging Number of subjects who achieved a complete response	43 Participants
Number of Participants With Clinical Response 1 to 6 Months Post-Therapy as Assessed by Imaging Number of subjects who achieved a substantial response	14 Participants
Number of Participants With Clinical Response 1 to 6 Months Post-Therapy as Assessed by Imaging Number of subjects who achieved an intermediate response	5 Participants
Number of Participants With Clinical Response 1 to 6 Months Post-Therapy as Assessed by Imaging Number of subjects who achieved no response	16 Participants

SECONDARY outcome

Timeframe: 1 to 6 Months Post-Therapy

Population: The mITT Population includes all enrolled subjects treated with at least one injection of OK 432 who either have post-therapy imaging assessment data or at least one investigator assessment of overall response throughout the study (N = 148). The investigator assessed response data were presented as observed for subjects with non-missing data in the mITT Population (N = 98).

Investigator evaluated post-therapy clinical response based on physical exam and/or ultrasound was categorized as "Clinical Improvement" or "No Change" in the size of the cyst.

Outcome measures

Outcome measures
Measure	OK-432 n=98 Participants OK 432 is a lyophilized biological preparation for injection containing nonviable cells of Streptococcus pyogenes (A group, type 3) Su strain treated with benzylpenicillin. OK-432 was administered intracystically at a concentration of 0.01 to 0.05 mg/mL. A 4-dose injection series of OK-432 was planned for all subjects. All injections were spaced approximately 6 to 12 weeks apart
Number of Participants With Investigator-Evaluated Overall Response	80 Participants

SECONDARY outcome

Timeframe: Baseline and 1 to 6 Months Post-Therapy

Percent change from baseline in lesion volume - pre-therapy to post therapy assessed by imaging.

Outcome measures

Outcome measures
Measure	OK-432 n=76 Participants OK 432 is a lyophilized biological preparation for injection containing nonviable cells of Streptococcus pyogenes (A group, type 3) Su strain treated with benzylpenicillin. OK-432 was administered intracystically at a concentration of 0.01 to 0.05 mg/mL. A 4-dose injection series of OK-432 was planned for all subjects. All injections were spaced approximately 6 to 12 weeks apart
Change From Baseline in Lesion Volume	-44.92 percent change Standard Deviation 110.561

Adverse Events

OK-432

Serious events: 11 serious events

Other events: 112 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OK-432 n=114 participants at risk；n=275 participants at risk OK 432 is a lyophilized biological preparation for injection containing nonviable cells of Streptococcus pyogenes (A group, type 3) Su strain treated with benzylpenicillin. OK-432 was administered intracystically at a concentration of 0.01 to 0.05 mg/mL. A 4-dose injection series of OK-432 was planned for all subjects. All injections were spaced approximately 6 to 12 weeks apart
General disorders Pyrexia	1.8% 5/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
General disorders Injection site swelling	0.73% 2/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
General disorders Swelling	0.73% 2/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Metabolism and nutrition disorders Dehydration	0.73% 2/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Metabolism and nutrition disorders Decreased appetite	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Metabolism and nutrition disorders Hypophagia	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Gastrointestinal disorders Vomiting	1.1% 3/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Gastrointestinal disorders Odynophagia	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Infections and infestations Furuncle	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Infections and infestations Infected cyst	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Infections and infestations Viral infection	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Respiratory, thoracic and mediastinal disorders Cough	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Respiratory, thoracic and mediastinal disorders Snoring	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Cardiac disorders Bradycardia	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Immune system disorders Milk allergy	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Injury, poisoning and procedural complications Airway complication of anaesthesia	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Nervous system disorders Febrile convulsion	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Psychiatric disorders Insomnia	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
Surgical and medical procedures Hospitalisation	0.36% 1/275 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)

Other adverse events

Other adverse events
Measure	OK-432 n=114 participants at risk；n=275 participants at risk OK 432 is a lyophilized biological preparation for injection containing nonviable cells of Streptococcus pyogenes (A group, type 3) Su strain treated with benzylpenicillin. OK-432 was administered intracystically at a concentration of 0.01 to 0.05 mg/mL. A 4-dose injection series of OK-432 was planned for all subjects. All injections were spaced approximately 6 to 12 weeks apart
General disorders Swelling	98.2% 112/114 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
General disorders Pain	98.2% 112/114 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
General disorders Redness	96.5% 110/114 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
General disorders Fever	63.2% 72/114 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
General disorders Fatigue	57.9% 66/114 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
General disorders Decreased appetite	55.3% 63/114 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
General disorders Nausea/vomiting	30.7% 35/114 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
General disorders Headache	28.1% 32/114 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
General disorders Chills	18.4% 21/114 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
General disorders Joint pain	15.8% 18/114 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)
General disorders Rash	6.1% 7/114 • Nonserious AEs (Subject Diary): Up to 14 days after each injection Treatment Emergent SAEs: Day 1 to 35 days after last injection All Cause Mortality: Day 1 to study completion ie, 2 years after treatment completion (All-Cause Mortality) Note: Results presented were based on a retrospective analysis of source-verified data and therefore only non-missing data is presented. Therefore there are differences in the number of subjects for different analyses. In this study, "serious adverse event" (SAE) was defined as any deviation from expected response to OK-432 immunotherapy. Treatment emergent SAE (TESAE) was defined as any SAE occurring or worsening on or after the first dose of study drug and within 35 days after the last dose of study drug. Other AEs were collected via Subject Diaries were presented as observed for subjects who provided diary data. Therefore the participants at risk for Other AEs (N = 114) is less than for SAEs (N = 275)

Additional Information

Dr. Richard Smith

University of Iowa

Phone: 319-356-2177

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place