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

Primary Immunodeficiency Disorders Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01814800
• Other study ID #: ADMA-003
• Status: Completed
• Phase: Phase 3
• First received: March 6, 2013
• Last updated: February 20, 2015
• Start date: February 2014
• Est. completion date: January 2015

Study information

• Verified date: February 2015
• Source: ADMA Biologics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: January 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 75 Years

Eligibility

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 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 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))

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

13. Have uncontrollable arterial hypertension.

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

15. Be morbidly obese as indicated by a Body Mass Index (BMI) = 40

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

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

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

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

20. Are currently pregnant or nursing.

21. Have hepatitis A, B, or C.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Immunologic Deficiency Syndromes
• Primary Immunodeficiency Disorders

Intervention

Biological:
• RI-002

Locations

Country	Name	City	State
United States	Family Allergy Center, PC	Atlanta	Georgia
United States	IMMUNOe Health Centers	Cenntennial	Colorado
United States	AARA Research Center	Dallas	Texas
United States	Dallas Immunology Research	Dallas	Texas
United States	Baylor Texas Children's Hospital	Houston	Texas
United States	Allergy Associates of the Palm Beaches, P.A.	North Palm Beach	Florida
United States	Mount Sinai School of Medicine	NY	New York
United States	Asthma & Immunology Associates	Omaha	Nebraska
United States	The South Bend Clinic, LLP	South Bend	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
ADMA Biologics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Demonstrate that RI-002 prevents the frequency of serious bacterial infections(FDA Guidance for Industry (2008))		Up to 1 year	No
Secondary	Incidence of all infections (serious and non-serious)		Up to 1 Year	No
Secondary	Number of days lost from work/school/usual activities due to infections and their treatment		Up to 1 year	No
Secondary	Number of unscheduled visits to physician/ER due to infections		Up to 1 year	No
Secondary	Time to resolution of infections		Up to 1 year	No
Secondary	Number of hospitalizations and days of hospitalizations due to infections		Up to 1 year	No
Secondary	Number of days of antibiotic therapy		Up to 1 year	No
Secondary	Relationship among dose of RI-002 and serious and non-serious infections		Up to 1 year	No
Secondary	Evaluate trough total IgG and specific antibody levels(streptococcus pneumoniae, H. influenza type B, CMV, measles, tetanus, and RSV)		Up to 1 year	No
Secondary	Relationship among trough level of RI-002 and serious and non-serious infections		Up to 1 year	No