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

• Sponsor: ADMA Biologics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01814800
• Collaborator: (none)
• Enrollment: 59
• Locations: 9
• Arm: 1
• Duration (Months): 11
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This is a Phase III, multicenter, open-label study of RI-002 administered as an intravenous infusion of RI-002 (IGIV) every 21 or 28 days in approximately 60 subjects with Primary Immunodeficiency Diseases (PIDD).

Condition or Disease	Intervention/Treatment	Phase
Primary Immune Deficiency Disorder	Biological: RI-002	Phase 3

Detailed Description

Primary immunodeficiency diseases (PIDDs) are genetically determined disorders of the immune system resulting in greatly enhanced susceptibility to infectious disease, autoimmunity and malignancy. As most subjects with PIDDs present with infections, the differential diagnosis and initial investigations for an underlying immune defect are typically guided by the clinical presentation. In subjects with PIDDs, individual infections are not necessarily more severe than those that occur in a normal host. Rather, the clinical features suggestive of an immune defect may be the recurring and/or chronic nature of infections with common pathogens that may result in end organ damage, such as bronchiectasis. Several immune globulin products have already been approved by the FDA.

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Multicenter, Study to Evaluate the Pharmacokinetics, Efficacy and Safety of RI-002 (IGIV) in Subjects With Primary Immunodeficiency Diseases (PIDD)
• Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RI-002 Treatment Drug: RI-002 Dose: 300-800 mg/kg infusion Frequency: Once every 3 to 4 Weeks	Biological: RI-002; Immune Globulin Intravenous (IGIV); Other Names: Immune Globulin (Human)

Outcome Measures

Primary Outcome Measures

1. Number of Serious Bacterial Infections (SBIs) Per Subject Per Year (FDA Guidance for Industry (2008)) [One year]

   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.

Secondary Outcome Measures

1. Incidence of All Infections (Serious and Non-serious) [Up to 1 Year]

2. Number of Days Lost From Work/School/Daycare and Usual Activities Due to Infections and Their Treatment - Combined Days Lost [Up to 1 year]

3. Number of Days Lost From Work/School/Daycare and Usual Activities Due to Infections and Their Treatment - Per Subject-Year [Up to 1 year]

4. Number of Unscheduled Visits to Physician/ER Due to Infections - Total Number of Visits [Up to 1 year]

5. Number of Unscheduled Visits to Physician/ER Due to Infections - Per Subject-Year [Up to 1 year]

6. Time to Resolution of Infections - Duration Per Infection [Up to 1 year]

7. Time to Resolution of Infections - Infection Days Per Subject [Up to 1 year]

8. Number of Hospitalizations Due to Infections [Up to 1 year]

9. Number of Hospitalizations Due to Infections - Per Subject-Year [Up to 1 year]

10. Days of Hospitalization Due to Infections [Up to 1 year]

11. Days of Hospitalization Due to Infections - Per Subject-Year [Up to 1 year]

12. Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) [Up to 1 year]

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

13. Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) - Per Subject-Year [Up to 1 year]

    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

14. Correlation Between Trough Level of RI-002 and Serious and Non-serious Infections [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)

15. Trough Total IgG and Specific Antibody Levels - IgG [Up to 1 year]

    Summary of trough total IgG concentration prior to specified infusion

16. Trough Total IgG and Specific Antibody Levels - Haemophilus Influenzae Type B [Up to 1 year]

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

17. Trough Total IgG and Specific Antibody Levels - Respiratory Syncytial Virus (RSV) [Up to 1 year]

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

18. Trough Total IgG and Specific Antibody Levels - Tetanus [Up to 1 year]

    Summary of trough antibody concentrations prior to specified infusion for Tetanus

19. Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 1 [Up to 1 year]

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

20. Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 3 [Up to 1 year]

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

21. Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 4 [Up to 1 year]

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

22. Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 5 [Up to 1 year]

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

23. Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 6B [Up to 1 year]

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

24. Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 7F [Up to 1 year]

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

25. Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 9V [Up to 1 year]

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

26. Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 14 [Up to 1 year]

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

27. Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 18C [Up to 1 year]

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

28. Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19A [Up to 1 year]

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

29. Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19F [Up to 1 year]

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

30. Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 23F [Up to 1 year]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

To be eligible to participate in this study, the subjects must meet the following criteria:

1. Signed a written informed consent or a specific assent form for minors.

2. Have a diagnosis of primary immunodeficiency disease.

3. Be ≥ 2 years and ≤ 75 years.

4. Have body weight ≥ 12 kg at screening.

5. Have been receiving IGIV at a dose that has not been changed by >50% of the mean dose on a mg/kg basis for at least 3 months prior to study entry and have maintained a trough serum Immunoglobulin G (IgG) level ≥ 500 mg/dL on the previous 2 assessments prior to receiving RI 002. The trough level must be at least 300 mg/dL above the pre-treatment serum IgG level.

6. For female subjects, be of non-childbearing potential or have a negative pregnancy test prior to study start and be deemed not at risk of becoming pregnant by adherence to a reliable contraceptive method for the duration of the study.

Exclusion Criteria:

Subjects must be excluded if they meet any of the following criteria:

1. Have a known hypersensitivity to immunoglobulin or any excipient in RI-002.

2. Have a history of a severe anaphylactic or anaphylactoid reaction to blood or any blood-derived product.

3. Have a specific Immunoglobulin A (IgA) deficiency, history of allergic reaction to products containing IgA or has demonstrable antibodies to IgA.

4. Have uncompensated hemodynamically significant congenital or other heart disease.

5. Have a medical condition that is known to cause secondary immune deficiency.

6. Have a significant T-cell deficiency or deficiency of granulocyte number or function.

7. Have significant renal impairment or have a history of acute renal failure.

8. Have abnormal liver function.

9. Be receiving chronic anti-coagulation therapy.

10. Have a history of deep vein thrombosis (DVT), thrombotic or thrombo-embolic event, or are at increased risk for thrombotic events.

11. Current daily use of the following medications:

• corticosteroids (> 7.5 mg (or equivalent dose on a mg/kg basis) of prednisone equivalent per day for > 30 days)

• immunomodulatory drugs

• immunosuppressive drugs (excluding topical pimecrolimus (Elidel) and tacrolimus (Protopic))

1. Administration of a hyperimmune or specialty high titer immunoglobulin product.

2. Have uncontrollable arterial hypertension.

3. Have a history of hemolysis or positive Coombs test while undergoing treatment with IGIV therapy.

4. Be morbidly obese as indicated by a Body Mass Index (BMI) ≥ 40

5. Have received any blood product (other than Immunoglobulin G) within 3 months prior to screening.

6. Have received any Respiratory Syncytial Virus (RSV) specific products, including palivizumab (Synagis®) within 3 months prior to screening.

7. Have abused alcohol, opiates, psychotropic agents, or other chemicals or drugs within the past 12 months.

8. Have any condition or abnormal laboratory assessment judged by the investigator to preclude participation in the study.

9. Are currently pregnant or nursing.

10. Have hepatitis A, B, or C.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	IMMUNOe Health Centers	Cenntennial	Colorado	United States	80112
2	Allergy Associates of the Palm Beaches, P.A.	North Palm Beach	Florida	United States	33408
3	Family Allergy Center, PC	Atlanta	Georgia	United States	30342
4	The South Bend Clinic, LLP	South Bend	Indiana	United States	46617
5	Asthma & Immunology Associates	Omaha	Nebraska	United States	68124
6	Mount Sinai School of Medicine	NY	New York	United States	10029
7	Dallas Immunology Research	Dallas	Texas	United States	75230
8	AARA Research Center	Dallas	Texas	United States	75231
9	Baylor Texas Children's Hospital	Houston	Texas	United States	77030

Sponsors and Collaborators

• ADMA Biologics, Inc.

Investigators

• Study Director: James Mond, M.D., Ph.D., ADMA Biologics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ADMA Biologics, Inc.
• ClinicalTrials.gov Identifier: NCT01814800
• Other Study ID Numbers: ADMA-003
• First Posted: Mar 20, 2013
• Last Update Posted: Oct 5, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by ADMA Biologics, Inc.: PIDD, PID, humoral immunity, antibody deficiency
• Additional relevant MeSH terms: Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Immunoglobulins

Study Results

Participant Flow

Arm/Group Title	RI-002 Treatment
Arm/Group Description	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.
Period Title: Overall Study
STARTED	59
COMPLETED	54
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Overall Participants	59
Age (Count of Participants)
<=18 years	13 22%
Between 18 and 65 years	35 59.3%
>=65 years	11 18.6%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	41.8
Sex: Female, Male (Count of Participants)
Female	31 52.5%
Male	28 47.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 5.1%
Not Hispanic or Latino	56 94.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 1.7%
White	58 98.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	59 100%
PIDD Type (participants) [Number]
Common Variable Immunodeficiency	45 76.3%
X-Linked Agammaglobulinemia	6 10.2%
Antibody Deficiencies	4 6.8%
Other	4 6.8%

Outcome Measures

1. Primary Outcome

Title	Number of Serious Bacterial Infections (SBIs) Per Subject Per Year (FDA Guidance for Industry (2008))
Description	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.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Number [SBIs/subject/year]	0

2. Secondary Outcome

Title	Incidence of All Infections (Serious and Non-serious)
Time Frame	Up to 1 Year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Number of Infections (All) per subject-year	3.436
Number of Serious Infections per subject-year	0.018

3. Secondary Outcome

Title	Number of Days Lost From Work/School/Daycare and Usual Activities Due to Infections and Their Treatment - Combined Days Lost
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Number [Days]	243

4. Secondary Outcome

Title	Number of Days Lost From Work/School/Daycare and Usual Activities Due to Infections and Their Treatment - Per Subject-Year
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Number [Days per subject-year]	4.349

5. Secondary Outcome

Title	Number of Unscheduled Visits to Physician/ER Due to Infections - Total Number of Visits
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Number [Number of Visits]	54

6. Secondary Outcome

Title	Number of Unscheduled Visits to Physician/ER Due to Infections - Per Subject-Year
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Number [Number of Visits per subject-year]	0.966

7. Secondary Outcome

Title	Time to Resolution of Infections - Duration Per Infection
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Mean (Standard Deviation) [Days]	16.7 (27.83)

8. Secondary Outcome

Title	Time to Resolution of Infections - Infection Days Per Subject
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Mean (Standard Deviation) [Days per subject]	62.7 (86.80)

9. Secondary Outcome

Title	Number of Hospitalizations Due to Infections
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Number [Number of hospitalizations]	1

10. Secondary Outcome

Title	Number of Hospitalizations Due to Infections - Per Subject-Year
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Number [Hospitalizations per subject-year]	0.018

11. Secondary Outcome

Title	Days of Hospitalization Due to Infections
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Number [Days]	5

12. Secondary Outcome

Title	Days of Hospitalization Due to Infections - Per Subject-Year
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Number [Days per subject-year]	0.089

13. Secondary Outcome

Title	Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection)
Description	Summary of the days of antibiotic therapy in the study for prophylaxis, as treatment for infections, and combined
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Total days of antibiotic use COMBINED	2969
Total days of antibiotic use for INFECTION	1839
Total days of antibiotic use for PROPHYLAXIS	1130

14. Secondary Outcome

Title	Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) - Per Subject-Year
Description	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
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Days of antibiotic use per subject-year COMBINED	53.135
Days of antibiotic per subject-year for INFECTION	32.912
Days of antibiotic per subject-yr for PROPHYLAXIS	20.223

15. Secondary Outcome

Title	Correlation Between Trough Level of RI-002 and Serious and Non-serious Infections
Description	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)
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Forward analysis	-0.0453
Backward analysis	-0.0045

16. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - IgG
Description	Summary of trough total IgG concentration prior to specified infusion
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

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

17. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Haemophilus Influenzae Type B
Description	Summary of trough antibody concentrations prior to specified infusion for Haemophilus influenzae type B
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Infusion 1 (n=59)	3.25 (0.417)
Infusion 4 (n=56)	3.12 (0.454)
Infusion 8 (n=56)	2.93 (0.364)
Infusion 12 (n=54)	3.11 (0.442)
End of Study (Infusion 13 / 17) (n=53)	3.31 (0.404)

18. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Respiratory Syncytial Virus (RSV)
Description	Summary of trough antibody concentrations prior to specified infusion for Respiratory Syncytial Virus (RSV)
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	56
Infusion 1 (n=56)	1211.9 (187.13)
Infusion 4 (n=54)	2220.1 (286.79)
Infusion 8 (n=54)	1936.2 (363.84)
Infusion 12 (n=52)	1632.4 (224.90)
End of Study (Infusion 13 / 17) (n=51)	1862.3 (207.94)

19. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Tetanus
Description	Summary of trough antibody concentrations prior to specified infusion for Tetanus
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Infusion 1 (n=59)	5.98 (0.573)
Infusion 4 (n=56)	7.57 (0.586)
Infusion 8 (n=56)	7.07 (0.523)
Infusion 12 (n=54)	6.97 (0.470)
End of Study (Infusion 13 / 17) (n=53)	6.50 (0.531)

20. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 1
Description	Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 1
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Infusion 1 (n=59)	3.108 (0.5967)
Infusion 4 (n=55)	2.900 (0.4585)
Infusion 8 (n=56)	2.866 (0.5154)
Infusion 12 (n=54)	2.788 (0.6185)
End of Study (Infusion 13 / 17) (n=53)	2.736 (0.5030)

21. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 3
Description	Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 3
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Infusion 1 (n=59)	1.447 (0.1077)
Infusion 4 (n=56)	1.873 (0.1263)
Infusion 8 (n=56)	1.787 (0.1105)
Infusion 12 (n=54)	1.686 (0.1360)
End of Study (Infusion 13 / 17) (n=53)	1.672 (0.1249)

22. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 4
Description	Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 4
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Infusion 1 (n=58)	0.530 (0.0713)
Infusion 4 (n=56)	0.824 (0.1589)
Infusion 8 (n=55)	0.610 (0.0624)
Infusion 12 (n=53)	0.644 (0.0703)
End of Study (Infusion 13 / 17) (n=53)	0.802 (0.1681)

23. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 5
Description	Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 5
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Infusion 1 (n=58)	10.843 (0.7116)
Infusion 4 (n=54)	12.264 (0.8885)
Infusion 8 (n=55)	11.235 (0.8974)
Infusion 12 (n=54)	11.707 (0.8858)
End of Study (Infusion 13 / 17) (n=52)	10.503 (0.8420)

24. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 6B
Description	Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 6B
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Infusion 1 (n=59)	2.121 (0.2529)
Infusion 4 (n=56)	2.496 (0.2503)
Infusion 8 (n=56)	2.166 (0.1849)
Infusion 12 (n=54)	2.026 (0.2199)
End of Study (Infusion 13 / 17) (n=53)	1.862 (0.2054)

25. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 7F
Description	Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 7F
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Infusion 1 (n=57)	3.413 (0.4009)
Infusion 4 (n=55)	3.457 (0.3930)
Infusion 8 (n=55)	2.633 (0.1971)
Infusion 12 (n=54)	2.492 (0.2703)
End of Study (Infusion 13 / 17) (n=53)	3.191 (0.4040)

26. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 9V
Description	Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 9V
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Infusion 1 (n=59)	1.473 (0.1063)
Infusion 4 (n=56)	1.938 (0.1566)
Infusion 8 (n=56)	2.010 (0.2842)
Infusion 12 (n=53)	1.902 (0.1579)
End of Study (Infusion 13 / 17) (n=53)	2.223 (0.3123)

27. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 14
Description	Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 14
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Infusion 1 (n=59)	4.853 (0.4724)
Infusion 4 (n=56)	6.744 (0.3984)
Infusion 8 (n=56)	6.356 (0.3547)
Infusion 12 (n=54)	6.341 (0.4275)
End of Study (Infusion 13 / 17) (n=53)	6.218 (0.4268)

28. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 18C
Description	Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 18C
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Infusion 1 (n=59)	7.259 (0.7462)
Infusion 4 (n=56)	7.461 (0.6143)
Infusion 8 (n=55)	6.588 (0.5627)
Infusion 12 (n=54)	7.146 (0.7852)
End of Study (Infusion 13 / 17) (n=53)	6.566 (0.5452)

29. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19A
Description	Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 19A
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Infusion 1 (n=53)	19.090 (1.6428)
Infusion 4 (n=52)	17.717 (1.3715)
Infusion 8 (n=54)	15.450 (1.2636)
Infusion 12 (n=51)	11.621 (1.0681)
End of Study (Infusion 13 / 17) (n=52)	12.167 (1.4398)

30. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19F
Description	Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 19F
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Infusion 1 (n=59)	6.630 (1.0784)
Infusion 4 (n=55)	7.876 (0.8826)
Infusion 8 (n=56)	7.361 (0.8704)
Infusion 12 (n=53)	7.042 (0.7610)
End of Study (Infusion 13 / 17) (n=53)	7.681 (0.9497)

31. Secondary Outcome

Title	Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 23F
Description	Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 23F
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Infusion 1 (n=59)	1.490 (0.1453)
Infusion 4 (n=55)	1.829 (0.1548)
Infusion 8 (n=56)	1.580 (0.1128)
Infusion 12 (n=54)	1.554 (0.1179)
End of Study (Infusion 13 / 17) (n=53)	1.681 (0.1282)

32. Post-Hoc Outcome

Title	Number of Days Lost From Work/School/Daycare Due to Infections and Their Treatment
Description	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
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Number [Days]	93

33. Post-Hoc Outcome

Title	Number of Days Lost From Work/School/Daycare Due to Infections and Their Treatment - Per Subject-Year
Description	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
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Number [Days per subject-year]	1.66

34. Post-Hoc Outcome

Title	Number of Participants With No Days Lost From Work/School/Daycare Due to Infections and Their Treatment
Description	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
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
Measure Participants	59
Number [participants]	36 61%

Adverse Events

Time Frame	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
Arm/Group Title	RI-002 Treatment
Arm/Group Description	Drug: RI-002 Dose: 300-800 mg/kg infusion RI-002
All Cause Mortality
	RI-002 Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	RI-002 Treatment
	Affected / at Risk (%)	# Events
Total	2/59 (3.4%)
Infections and infestations
Postoperative wound infection	1/59 (1.7%)	1
Nervous system disorders
Migraine	1/59 (1.7%)	1
Other (Not Including Serious) Adverse Events
	RI-002 Treatment
	Affected / at Risk (%)	# Events
Total	58/59 (98.3%)
Gastrointestinal disorders
Abdominal pain	3/59 (5.1%)	5
Abdominal pain upper	7/59 (11.9%)	8
Gastrooesophageal reflux disease	4/59 (6.8%)	4
Nausea	12/59 (20.3%)	17
Vomiting	5/59 (8.5%)	6
General disorders
Adverse drug reaction	5/59 (8.5%)	8
Fatigue	8/59 (13.6%)	19
Pain	3/59 (5.1%)	4
Pyrexia	6/59 (10.2%)	10
Infections and infestations
Acute sinusitis	11/59 (18.6%)	15
Bronchitis	12/59 (20.3%)	14
Ear infection	3/59 (5.1%)	4
Gastroenteritis	4/59 (6.8%)	7
Gastroenteritis viral	13/59 (22%)	16
Influenza	4/59 (6.8%)	4
Nasopharyngitis	13/59 (22%)	23
Sinusitis	16/59 (27.1%)	31
Upper respiratory tract infection	13/59 (22%)	15
Urinary tract infection	6/59 (10.2%)	9
Viral upper respiratory tract infection	8/59 (13.6%)	14
Vulvovaginal mycotic infection	3/59 (5.1%)	4
Injury, poisoning and procedural complications
Contusion	4/59 (6.8%)	4
Excoriation	3/59 (5.1%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	8/59 (13.6%)	10
Back pain	4/59 (6.8%)	5
Muscle spasms	4/59 (6.8%)	5
Myalgia	7/59 (11.9%)	11
Pain in extremity	4/59 (6.8%)	6
Nervous system disorders
Migraine	8/59 (13.6%)	13
Psychiatric disorders
Anxiety	3/59 (5.1%)	3
Reproductive system and breast disorders
Cough	9/59 (15.3%)	11
Respiratory, thoracic and mediastinal disorders
Asthma	4/59 (6.8%)	6
Epistaxis	5/59 (8.5%)	12
Nasal congestion	5/59 (8.5%)	5
Oropharyngeal pain	7/59 (11.9%)	10
Rhinitis allergic	3/59 (5.1%)	4
Rhinorrhoea	3/59 (5.1%)	4
Sinus congestion	3/59 (5.1%)	3
Skin and subcutaneous tissue disorders
Pruritus	3/59 (5.1%)	3
Rash	6/59 (10.2%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.