Trial Outcomes & Findings for Pharmacokinetics, Efficacy, and Safety Study of RI-002 (IGIV) in Subjects With Primary Immunodeficiency Diseases (PIDD) (NCT NCT01814800)

NCT ID: NCT01814800

Last Updated: 2016-10-05

Results Overview

The primary objective of this study was to demonstrate that RI-002 (IGIV) reduces the frequency of serious bacterial infections (SBIs), as defined by the Diagnostic Criteria for Serious Infection Types guideline, in subjects with primary humoral immunodeficiency.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 59 participants
• Primary outcome timeframe: One year
• Results posted on: 2016-10-05

Participant Flow

Participant milestones

Measure	RI-002 Treatment Drug: RI-002 Dose: 300-800 mg/kg IV infusion Frequency: Every 3 or 4 weeks Initial dose selection based on prior IGIV regimen, doses adjusted during study to maintain trough Immunoglobulin G (IgG) concentration of 500 mg/dL or greater according to investigator decision.
Overall Study STARTED	59
Overall Study COMPLETED	54
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Measure	RI-002 Treatment Drug: RI-002 Dose: 300-800 mg/kg IV infusion Frequency: Every 3 or 4 weeks Initial dose selection based on prior IGIV regimen, doses adjusted during study to maintain trough Immunoglobulin G (IgG) concentration of 500 mg/dL or greater according to investigator decision.
Overall Study Adverse Event	2
Overall Study Pregnancy	1
Overall Study Sponsor decision	1
Overall Study Subject relocation	1

Baseline Characteristics

Pharmacokinetics, Efficacy, and Safety Study of RI-002 (IGIV) in Subjects With Primary Immunodeficiency Diseases (PIDD)

Baseline characteristics by cohort

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Age, Categorical <=18 years	13 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	35 Participants n=5 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants
Age, Continuous	41.8 years n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	56 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	58 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	59 participants n=5 Participants
PIDD Type Common Variable Immunodeficiency	45 participants n=5 Participants
PIDD Type X-Linked Agammaglobulinemia	6 participants n=5 Participants
PIDD Type Antibody Deficiencies	4 participants n=5 Participants
PIDD Type Other	4 participants n=5 Participants

PRIMARY outcome

Timeframe: One year

Population: Analysis included 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

The primary objective of this study was to demonstrate that RI-002 (IGIV) reduces the frequency of serious bacterial infections (SBIs), as defined by the Diagnostic Criteria for Serious Infection Types guideline, in subjects with primary humoral immunodeficiency.

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Number of Serious Bacterial Infections (SBIs) Per Subject Per Year (FDA Guidance for Industry (2008))	0 SBIs/subject/year

SECONDARY outcome

Timeframe: Up to 1 Year

Population: Analysis included 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Incidence of All Infections (Serious and Non-serious) Number of Infections (All) per subject-year	3.436 events per subject-year
Incidence of All Infections (Serious and Non-serious) Number of Serious Infections per subject-year	0.018 events per subject-year

SECONDARY outcome

Timeframe: Up to 1 year

Population: Analysis included 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Number of Days Lost From Work/School/Daycare and Usual Activities Due to Infections and Their Treatment - Combined Days Lost	243 Days

SECONDARY outcome

Timeframe: Up to 1 year

Population: Analysis included 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Number of Days Lost From Work/School/Daycare and Usual Activities Due to Infections and Their Treatment - Per Subject-Year	4.349 Days per subject-year

SECONDARY outcome

Timeframe: Up to 1 year

Population: Analysis included 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Number of Unscheduled Visits to Physician/ER Due to Infections - Total Number of Visits	54 Number of Visits

SECONDARY outcome

Timeframe: Up to 1 year

Population: Analysis included 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Number of Unscheduled Visits to Physician/ER Due to Infections - Per Subject-Year	0.966 Number of Visits per subject-year

SECONDARY outcome

Timeframe: Up to 1 year

Population: Analysis included 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Time to Resolution of Infections - Duration Per Infection	16.7 Days Standard Deviation 27.83

SECONDARY outcome

Timeframe: Up to 1 year

Population: Analysis included 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Time to Resolution of Infections - Infection Days Per Subject	62.7 Days per subject Standard Deviation 86.80

SECONDARY outcome

Timeframe: Up to 1 year

Population: Analysis included 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Number of Hospitalizations Due to Infections	1 Number of hospitalizations

SECONDARY outcome

Timeframe: Up to 1 year

Population: Analysis included 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Number of Hospitalizations Due to Infections - Per Subject-Year	0.018 Hospitalizations per subject-year

SECONDARY outcome

Timeframe: Up to 1 year

Population: Analysis included 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Days of Hospitalization Due to Infections	5 Days

SECONDARY outcome

Timeframe: Up to 1 year

Population: Analysis included 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Days of Hospitalization Due to Infections - Per Subject-Year	0.089 Days per subject-year

SECONDARY outcome

Timeframe: Up to 1 year

Population: Analysis included 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Summary of the days of antibiotic therapy in the study for prophylaxis, as treatment for infections, and combined

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) Total days of antibiotic use COMBINED	2969 Days
Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) Total days of antibiotic use for INFECTION	1839 Days
Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) Total days of antibiotic use for PROPHYLAXIS	1130 Days

SECONDARY outcome

Timeframe: Up to 1 year

Population: Analysis included 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Summary of the days of antibiotic therapy in the study for prophylaxis, as treatment for infections, and combined, per subject-year of treatment with RI-002

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) - Per Subject-Year Days of antibiotic use per subject-year COMBINED	53.135 Days per subject-year
Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) - Per Subject-Year Days of antibiotic per subject-year for INFECTION	32.912 Days per subject-year
Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) - Per Subject-Year Days of antibiotic per subject-yr for PROPHYLAXIS	20.223 Days per subject-year

SECONDARY outcome

Timeframe: Up to 1 year

The relationship between trough IgG concentrations and the number of infections of any kind/seriousness was evaluated using Pearson linear correlation coefficients using forward analysis (outcomes after infusion) and backward analysis (outcomes prior to infusion; outcomes post last infusion were excluded)

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Correlation Between Trough Level of RI-002 and Serious and Non-serious Infections Forward analysis	-0.0453 Linear Correlation Coefficients
Correlation Between Trough Level of RI-002 and Serious and Non-serious Infections Backward analysis	-0.0045 Linear Correlation Coefficients

SECONDARY outcome

Timeframe: Up to 1 year

Summary of trough total IgG concentration prior to specified infusion

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - IgG Infusion 1 (n=59)	1000 mg/dL Standard Error 36.32
Trough Total IgG and Specific Antibody Levels - IgG Infusion 2 (n=57)	1024.3 mg/dL Standard Error 33.38
Trough Total IgG and Specific Antibody Levels - IgG Infusion 3 (n=55)	1007.5 mg/dL Standard Error 33.26
Trough Total IgG and Specific Antibody Levels - IgG Infusion 4 (n=56)	1017.4 mg/dL Standard Error 34.96
Trough Total IgG and Specific Antibody Levels - IgG Infusion 5 (n=55)	1008.1 mg/dL Standard Error 32.49
Trough Total IgG and Specific Antibody Levels - IgG Infusion 6 (n=56)	1016.1 mg/dL Standard Error 34.18
Trough Total IgG and Specific Antibody Levels - IgG Infusion 7 (n=55)	1039.5 mg/dL Standard Error 37.50
Trough Total IgG and Specific Antibody Levels - IgG Infusion 8 (n=56)	957.7 mg/dL Standard Error 35.49
Trough Total IgG and Specific Antibody Levels - IgG Infusion 9 (n=56)	1030.5 mg/dL Standard Error 36.77
Trough Total IgG and Specific Antibody Levels - IgG Infusion 10 (n=54)	1021.7 mg/dL Standard Error 37.27
Trough Total IgG and Specific Antibody Levels - IgG Infusion 11 (n=55)	1018.9 mg/dL Standard Error 34.85
Trough Total IgG and Specific Antibody Levels - IgG Infusion 12 (n=54)	1000.6 mg/dL Standard Error 33.62
Trough Total IgG and Specific Antibody Levels - IgG Infusion 13 (n=53)	992.8 mg/dL Standard Error 35.34
Trough Total IgG and Specific Antibody Levels - IgG Infusion 14 (3-week cycle only) (n=16)	1165.3 mg/dL Standard Error 79.59
Trough Total IgG and Specific Antibody Levels - IgG Infusion 15 (3-week cycle only) (n=16)	1160.9 mg/dL Standard Error 77.96
Trough Total IgG and Specific Antibody Levels - IgG Infusion 16 (3-week cycle only) (n=16)	1147.9 mg/dL Standard Error 74.93
Trough Total IgG and Specific Antibody Levels - IgG Infusion 17 (3-week cycle only) (n=16)	1136.3 mg/dL Standard Error 70.78

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 53-59 subjects

Summary of trough antibody concentrations prior to specified infusion for Haemophilus influenzae type B

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Haemophilus Influenzae Type B Infusion 1 (n=59)	3.25 ug/mL Standard Error 0.417
Trough Total IgG and Specific Antibody Levels - Haemophilus Influenzae Type B Infusion 4 (n=56)	3.12 ug/mL Standard Error 0.454
Trough Total IgG and Specific Antibody Levels - Haemophilus Influenzae Type B Infusion 8 (n=56)	2.93 ug/mL Standard Error 0.364
Trough Total IgG and Specific Antibody Levels - Haemophilus Influenzae Type B Infusion 12 (n=54)	3.11 ug/mL Standard Error 0.442
Trough Total IgG and Specific Antibody Levels - Haemophilus Influenzae Type B End of Study (Infusion 13 / 17) (n=53)	3.31 ug/mL Standard Error 0.404

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 51-56 subjects

Summary of trough antibody concentrations prior to specified infusion for Respiratory Syncytial Virus (RSV)

Outcome measures

Measure	RI-002 Treatment n=56 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Respiratory Syncytial Virus (RSV) Infusion 1 (n=56)	1211.9 titer Standard Error 187.13
Trough Total IgG and Specific Antibody Levels - Respiratory Syncytial Virus (RSV) Infusion 4 (n=54)	2220.1 titer Standard Error 286.79
Trough Total IgG and Specific Antibody Levels - Respiratory Syncytial Virus (RSV) Infusion 8 (n=54)	1936.2 titer Standard Error 363.84
Trough Total IgG and Specific Antibody Levels - Respiratory Syncytial Virus (RSV) Infusion 12 (n=52)	1632.4 titer Standard Error 224.90
Trough Total IgG and Specific Antibody Levels - Respiratory Syncytial Virus (RSV) End of Study (Infusion 13 / 17) (n=51)	1862.3 titer Standard Error 207.94

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 53-59 subjects

Summary of trough antibody concentrations prior to specified infusion for Tetanus

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Tetanus Infusion 1 (n=59)	5.98 IU/mL Standard Error 0.573
Trough Total IgG and Specific Antibody Levels - Tetanus Infusion 4 (n=56)	7.57 IU/mL Standard Error 0.586
Trough Total IgG and Specific Antibody Levels - Tetanus Infusion 8 (n=56)	7.07 IU/mL Standard Error 0.523
Trough Total IgG and Specific Antibody Levels - Tetanus Infusion 12 (n=54)	6.97 IU/mL Standard Error 0.470
Trough Total IgG and Specific Antibody Levels - Tetanus End of Study (Infusion 13 / 17) (n=53)	6.50 IU/mL Standard Error 0.531

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 53-59 subjects

Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 1

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 1 Infusion 1 (n=59)	3.108 ug/mL Standard Error 0.5967
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 1 Infusion 4 (n=55)	2.900 ug/mL Standard Error 0.4585
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 1 Infusion 8 (n=56)	2.866 ug/mL Standard Error 0.5154
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 1 Infusion 12 (n=54)	2.788 ug/mL Standard Error 0.6185
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 1 End of Study (Infusion 13 / 17) (n=53)	2.736 ug/mL Standard Error 0.5030

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 53-59 subjects

Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 3

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 3 Infusion 1 (n=59)	1.447 ug/mL Standard Error 0.1077
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 3 Infusion 4 (n=56)	1.873 ug/mL Standard Error 0.1263
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 3 Infusion 8 (n=56)	1.787 ug/mL Standard Error 0.1105
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 3 Infusion 12 (n=54)	1.686 ug/mL Standard Error 0.1360
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 3 End of Study (Infusion 13 / 17) (n=53)	1.672 ug/mL Standard Error 0.1249

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 53-58 subjects

Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 4

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 4 Infusion 1 (n=58)	0.530 ug/mL Standard Error 0.0713
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 4 Infusion 4 (n=56)	0.824 ug/mL Standard Error 0.1589
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 4 Infusion 8 (n=55)	0.610 ug/mL Standard Error 0.0624
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 4 Infusion 12 (n=53)	0.644 ug/mL Standard Error 0.0703
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 4 End of Study (Infusion 13 / 17) (n=53)	0.802 ug/mL Standard Error 0.1681

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 52-58 subjects

Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 5

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 5 Infusion 1 (n=58)	10.843 ug/mL Standard Error 0.7116
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 5 Infusion 4 (n=54)	12.264 ug/mL Standard Error 0.8885
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 5 Infusion 8 (n=55)	11.235 ug/mL Standard Error 0.8974
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 5 Infusion 12 (n=54)	11.707 ug/mL Standard Error 0.8858
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 5 End of Study (Infusion 13 / 17) (n=52)	10.503 ug/mL Standard Error 0.8420

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 53-59 subjects

Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 6B

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 6B Infusion 12 (n=54)	2.026 ug/mL Standard Error 0.2199
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 6B End of Study (Infusion 13 / 17) (n=53)	1.862 ug/mL Standard Error 0.2054
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 6B Infusion 1 (n=59)	2.121 ug/mL Standard Error 0.2529
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 6B Infusion 4 (n=56)	2.496 ug/mL Standard Error 0.2503
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 6B Infusion 8 (n=56)	2.166 ug/mL Standard Error 0.1849

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 53-57 subjects

Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 7F

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 7F Infusion 1 (n=57)	3.413 ug/mL Standard Error 0.4009
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 7F Infusion 4 (n=55)	3.457 ug/mL Standard Error 0.3930
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 7F Infusion 8 (n=55)	2.633 ug/mL Standard Error 0.1971
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 7F Infusion 12 (n=54)	2.492 ug/mL Standard Error 0.2703
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 7F End of Study (Infusion 13 / 17) (n=53)	3.191 ug/mL Standard Error 0.4040

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 53-59 subjects

Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 9V

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 9V Infusion 1 (n=59)	1.473 ug/mL Standard Error 0.1063
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 9V Infusion 4 (n=56)	1.938 ug/mL Standard Error 0.1566
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 9V Infusion 8 (n=56)	2.010 ug/mL Standard Error 0.2842
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 9V Infusion 12 (n=53)	1.902 ug/mL Standard Error 0.1579
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 9V End of Study (Infusion 13 / 17) (n=53)	2.223 ug/mL Standard Error 0.3123

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 53-59 subjects

Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 14

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 14 Infusion 1 (n=59)	4.853 ug/mL Standard Error 0.4724
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 14 Infusion 4 (n=56)	6.744 ug/mL Standard Error 0.3984
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 14 Infusion 8 (n=56)	6.356 ug/mL Standard Error 0.3547
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 14 Infusion 12 (n=54)	6.341 ug/mL Standard Error 0.4275
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 14 End of Study (Infusion 13 / 17) (n=53)	6.218 ug/mL Standard Error 0.4268

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 53-59 subjects

Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 18C

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 18C Infusion 1 (n=59)	7.259 ug/mL Standard Error 0.7462
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 18C Infusion 4 (n=56)	7.461 ug/mL Standard Error 0.6143
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 18C Infusion 8 (n=55)	6.588 ug/mL Standard Error 0.5627
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 18C Infusion 12 (n=54)	7.146 ug/mL Standard Error 0.7852
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 18C End of Study (Infusion 13 / 17) (n=53)	6.566 ug/mL Standard Error 0.5452

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 51-54 subjects

Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 19A

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19A Infusion 1 (n=53)	19.090 ug/mL Standard Error 1.6428
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19A Infusion 4 (n=52)	17.717 ug/mL Standard Error 1.3715
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19A Infusion 8 (n=54)	15.450 ug/mL Standard Error 1.2636
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19A Infusion 12 (n=51)	11.621 ug/mL Standard Error 1.0681
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19A End of Study (Infusion 13 / 17) (n=52)	12.167 ug/mL Standard Error 1.4398

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 53-59 subjects

Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 19F

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19F Infusion 12 (n=53)	7.042 ug/mL Standard Error 0.7610
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19F End of Study (Infusion 13 / 17) (n=53)	7.681 ug/mL Standard Error 0.9497
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19F Infusion 1 (n=59)	6.630 ug/mL Standard Error 1.0784
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19F Infusion 4 (n=55)	7.876 ug/mL Standard Error 0.8826
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19F Infusion 8 (n=56)	7.361 ug/mL Standard Error 0.8704

SECONDARY outcome

Timeframe: Up to 1 year

Population: Number available for analysis varied by infusion; 53-59 subjects

Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 23F

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 23F Infusion 1 (n=59)	1.490 ug/mL Standard Error 0.1453
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 23F Infusion 4 (n=55)	1.829 ug/mL Standard Error 0.1548
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 23F Infusion 8 (n=56)	1.580 ug/mL Standard Error 0.1128
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 23F Infusion 12 (n=54)	1.554 ug/mL Standard Error 0.1179
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 23F End of Study (Infusion 13 / 17) (n=53)	1.681 ug/mL Standard Error 0.1282

POST_HOC outcome

Timeframe: Up to 1 year

Population: Analysis includes 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Additional analysis performed to separate the number of days lost from work, school and/or daycare from the days missed from normal activities, due to infection

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Number of Days Lost From Work/School/Daycare Due to Infections and Their Treatment	93 Days

POST_HOC outcome

Timeframe: Up to 1 year

Population: Analysis includes 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Additional analysis performed to separate the number of days lost from work, school and/or daycare from the days missed from normal activities, due to infection

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Number of Days Lost From Work/School/Daycare Due to Infections and Their Treatment - Per Subject-Year	1.66 Days per subject-year

POST_HOC outcome

Timeframe: Up to 1 year

Population: Analysis includes 59 treated subjects, with a total of 55.88 subject-years of treatment with RI-002

Additional analysis performed to separate the number of days lost from work, school and/or daycare from the days missed from normal activities, due to infection. Presenting the number of subjects with no (0) days lost from work/school/daycare due to infection

Outcome measures

Measure	RI-002 Treatment n=59 Participants Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Number of Participants With No Days Lost From Work/School/Daycare Due to Infections and Their Treatment	36 participants

Adverse Events

RI-002 Treatment

Serious events: 2 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Measure	RI-002 Treatment n=59 participants at risk Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Infections and infestations Postoperative wound infection	1.7% 1/59 • Number of events 1 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Nervous system disorders Migraine	1.7% 1/59 • Number of events 1 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up

Other adverse events

Measure	RI-002 Treatment n=59 participants at risk Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Gastrointestinal disorders Abdominal pain	5.1% 3/59 • Number of events 5 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Gastrointestinal disorders Abdominal pain upper	11.9% 7/59 • Number of events 8 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Gastrointestinal disorders Gastrooesophageal reflux disease	6.8% 4/59 • Number of events 4 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Gastrointestinal disorders Nausea	20.3% 12/59 • Number of events 17 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Gastrointestinal disorders Vomiting	8.5% 5/59 • Number of events 6 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
General disorders Adverse drug reaction	8.5% 5/59 • Number of events 8 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
General disorders Fatigue	13.6% 8/59 • Number of events 19 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
General disorders Pain	5.1% 3/59 • Number of events 4 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
General disorders Pyrexia	10.2% 6/59 • Number of events 10 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Infections and infestations Acute sinusitis	18.6% 11/59 • Number of events 15 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Infections and infestations Bronchitis	20.3% 12/59 • Number of events 14 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Infections and infestations Ear infection	5.1% 3/59 • Number of events 4 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Infections and infestations Gastroenteritis	6.8% 4/59 • Number of events 7 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Infections and infestations Gastroenteritis viral	22.0% 13/59 • Number of events 16 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Infections and infestations Influenza	6.8% 4/59 • Number of events 4 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Infections and infestations Nasopharyngitis	22.0% 13/59 • Number of events 23 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Infections and infestations Sinusitis	27.1% 16/59 • Number of events 31 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Infections and infestations Upper respiratory tract infection	22.0% 13/59 • Number of events 15 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Infections and infestations Urinary tract infection	10.2% 6/59 • Number of events 9 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Infections and infestations Viral upper respiratory tract infection	13.6% 8/59 • Number of events 14 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Infections and infestations Vulvovaginal mycotic infection	5.1% 3/59 • Number of events 4 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Injury, poisoning and procedural complications Contusion	6.8% 4/59 • Number of events 4 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Injury, poisoning and procedural complications Excoriation	5.1% 3/59 • Number of events 3 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Musculoskeletal and connective tissue disorders Arthralgia	13.6% 8/59 • Number of events 10 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Musculoskeletal and connective tissue disorders Back pain	6.8% 4/59 • Number of events 5 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Musculoskeletal and connective tissue disorders Muscle spasms	6.8% 4/59 • Number of events 5 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Musculoskeletal and connective tissue disorders Myalgia	11.9% 7/59 • Number of events 11 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Musculoskeletal and connective tissue disorders Pain in extremity	6.8% 4/59 • Number of events 6 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Nervous system disorders Migraine	13.6% 8/59 • Number of events 13 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Psychiatric disorders Anxiety	5.1% 3/59 • Number of events 3 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Respiratory, thoracic and mediastinal disorders Asthma	6.8% 4/59 • Number of events 6 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Reproductive system and breast disorders Cough	15.3% 9/59 • Number of events 11 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Respiratory, thoracic and mediastinal disorders Epistaxis	8.5% 5/59 • Number of events 12 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.5% 5/59 • Number of events 5 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	11.9% 7/59 • Number of events 10 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	5.1% 3/59 • Number of events 4 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.1% 3/59 • Number of events 4 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Respiratory, thoracic and mediastinal disorders Sinus congestion	5.1% 3/59 • Number of events 3 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Skin and subcutaneous tissue disorders Pruritus	5.1% 3/59 • Number of events 3 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up
Skin and subcutaneous tissue disorders Rash	10.2% 6/59 • Number of events 6 • Subjects were treated with RI-002 every 3 or 4-weeks for up to 12 months, with Adverse Events reported from time of consent through the last study follow-up

Additional Information

Jimmy Mond, M.D., Ph.D

ADMA Biologics

Phone: 201-478-5552

Email: jmond@admabio.com

Results disclosure agreements

• Principal investigator is a sponsor employee Following the first publication (sponsor coordinated), the Institution/PI may publish data or results from the study, if the material is reviewed by the sponsor at least 60 days prior to the proposed deadline; sponsor may remove any information considered confidential other than study data and results. If a multi-center publication is not submitted within 24 months after conclusion of the study at all sites, the Institution/PI may publish the study results following review by the Sponsor.
• Publication restrictions are in place

Restriction type: OTHER