Primary Immune Deficiency DisorderPhase 3NCT01814800
Pharmacokinetics, Efficacy, and Safety Study of RI-002 (IGIV) in Subjects With Primary Immunodeficiency Diseases (PIDD)
A Phase 3 study testing RI-002 in people with Primary Immune Deficiency Disorder, run by ADMA Biologics, Inc. at 9 sites in United States.
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). Read more about this study
- Who is it for?
- Ages 2 to 75 years
- Conditions the study is for
- Primary Immune Deficiency Disorder
- What is being tested?
- RI-002
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 9 sitesUnited States
- Study dates
- Feb 2014to Jan 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- To be eligible to participate in this study, the subjects must meet the following criteria:
- Signed a written informed consent or a specific assent form for minors.
- Have a diagnosis of primary immunodeficiency disease.
- Be ≥ 2 years and ≤ 75 years.
- Have body weight ≥ 12 kg at screening.
- 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.
- 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.
Who cannot join
- Subjects must be excluded if they meet any of the following criteria:
- Have a known hypersensitivity to immunoglobulin or any excipient in RI-002.
- Have a history of a severe anaphylactic or anaphylactoid reaction to blood or any blood-derived product.
- Have a specific Immunoglobulin A (IgA) deficiency, history of allergic reaction to products containing IgA or has demonstrable antibodies to IgA.
- Have uncompensated hemodynamically significant congenital or other heart disease.
- Have a medical condition that is known to cause secondary immune deficiency.
Show all 25Show fewer
- Have a significant T-cell deficiency or deficiency of granulocyte number or function.
- Have significant renal impairment or have a history of acute renal failure.
- Have abnormal liver function.
- Be receiving chronic anti-coagulation therapy.
- Have a history of deep vein thrombosis (DVT), thrombotic or thrombo-embolic event, or are at increased risk for thrombotic events.
- 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))
- Administration of a hyperimmune or specialty high titer immunoglobulin product.
- Have uncontrollable arterial hypertension.
- Have a history of hemolysis or positive Coombs test while undergoing treatment with IGIV therapy.
- Be morbidly obese as indicated by a Body Mass Index (BMI) ≥ 40
- Have received any blood product (other than Immunoglobulin G) within 3 months prior to screening.
- Have received any Respiratory Syncytial Virus (RSV) specific products, including palivizumab (Synagis®) within 3 months prior to screening.
- Have abused alcohol, opiates, psychotropic agents, or other chemicals or drugs within the past 12 months.
- Have any condition or abnormal laboratory assessment judged by the investigator to preclude participation in the study.
- Are currently pregnant or nursing.
- Have hepatitis A, B, or C.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Family Allergy Center, PC
Atlanta, Georgia, 30342
IMMUNOe Health Centers
Cenntennial, Colorado, 80112
Dallas Immunology Research
Dallas, Texas, 75230
AARA Research Center
Dallas, Texas, 75231
Baylor Texas Children's Hospital
Houston, Texas, 77030
Mount Sinai School of Medicine
New York, New York, 10029
Allergy Associates of the Palm Beaches, P.A.
North Palm Beach, Florida, 33408
Asthma & Immunology Associates
Omaha, Nebraska, 68124
The South Bend Clinic, LLP
South Bend, Indiana, 46617
About this study
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)
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).
Read the 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.
- Conditions
- Primary Immune Deficiency Disorder
- Being tested
- RI-002
- Keywords
- PIDD, PID, humoral immunity, antibody deficiency
- Medical subject headings
- Primary Immunodeficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RI-002Biological
Also called Immune Globulin (Human)
Immune Globulin Intravenous (IGIV)
| Study group | Role | What they receive |
|---|---|---|
| RI-002 Treatment | Experimental | Drug: RI-002 Dose: 300-800 mg/kg infusion Frequency: Once every 3 to 4 Weeks Receives: Biological: RI-002 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Serious Bacterial Infections (SBIs) Per Subject Per Year (FDA Guidance for Industry (2008))
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.
Measured: One year
Secondary outcomes (30)
Incidence of All Infections (Serious and Non-serious)
Measured: Up to 1 Year
Number of Days Lost From Work/School/Daycare and Usual Activities Due to Infections and Their Treatment - Combined Days Lost
Measured: Up to 1 year
Number of Days Lost From Work/School/Daycare and Usual Activities Due to Infections and Their Treatment - Per Subject-Year
Measured: Up to 1 year
Number of Unscheduled Visits to Physician/ER Due to Infections - Total Number of Visits
Measured: Up to 1 year
Number of Unscheduled Visits to Physician/ER Due to Infections - Per Subject-Year
Measured: Up to 1 year
Time to Resolution of Infections - Duration Per Infection
Measured: Up to 1 year
Time to Resolution of Infections - Infection Days Per Subject
Measured: Up to 1 year
Number of Hospitalizations Due to Infections
Measured: Up to 1 year
Number of Hospitalizations Due to Infections - Per Subject-Year
Measured: Up to 1 year
Days of Hospitalization Due to Infections
Measured: Up to 1 year
Days of Hospitalization Due to Infections - Per Subject-Year
Measured: Up to 1 year
Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection)
Summary of the days of antibiotic therapy in the study for prophylaxis, as treatment for infections, and combined
Measured: Up to 1 year
Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) - Per Subject-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
Measured: Up to 1 year
Correlation Between Trough Level of RI-002 and Serious and Non-serious Infections
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)
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - IgG
Summary of trough total IgG concentration prior to specified infusion
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Haemophilus Influenzae Type B
Summary of trough antibody concentrations prior to specified infusion for Haemophilus influenzae type B
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Respiratory Syncytial Virus (RSV)
Summary of trough antibody concentrations prior to specified infusion for Respiratory Syncytial Virus (RSV)
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Tetanus
Summary of trough antibody concentrations prior to specified infusion for Tetanus
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 1
Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 1
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 3
Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 3
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 4
Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 4
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 5
Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 5
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 6B
Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 6B
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 7F
Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 7F
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 9V
Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 9V
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 14
Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 14
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 18C
Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 18C
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19A
Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 19A
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19F
Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 19F
Measured: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 23F
Summary of trough antibody concentrations prior to specified infusion for Streptococcus Pneumoniae, Serotype 23F
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2013 (estimated)
- Study startFeb 2014
- Primary completionDec 2014
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary Immune Deficiency DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- ADMA Biologics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James Mond, M.D., Ph.D., Study director, ADMA Biologics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01814800
- Sponsor's protocol ID
- ADMA-003
- Status last verified
- Aug 2016
- First submitted
- 6 Mar 2013
- Last updated
- 5 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01814800
- Acronym / sponsor ID
- ADMA-003
- Conditions
- Primary Immune Deficiency Disorder
- Keywords
- PIDD, PID, humoral immunity, antibody deficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- ADMA Biologics, Inc.Industry (pharma, biotech, devices)
- Study start
- Feb 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 20 Mar 2013 (estimated)
- Results
- Posted 5 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RI-002 Treatment | Experimental | Biological: RI-002Drug: RI-002 Dose: 300-800 mg/kg infusion Frequency: Once every 3 to 4 Weeks |
Who may qualify
- Ages
- 2 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- To be eligible to participate in this study, the subjects must meet the following criteria:
- Signed a written informed consent or a specific assent form for minors.
- Have a diagnosis of primary immunodeficiency disease.
- Be ≥ 2 years and ≤ 75 years.
- Have body weight ≥ 12 kg at screening.
Key exclusion criteria (25 listed)
- Have a known hypersensitivity to immunoglobulin or any excipient in RI-002.
- Have a history of a severe anaphylactic or anaphylactoid reaction to blood or any blood-derived product.
- Have a specific Immunoglobulin A (IgA) deficiency, history of allergic reaction to products containing IgA or has demonstrable antibodies to IgA.
- Have uncompensated hemodynamically significant congenital or other heart disease.
- Have a medical condition that is known to cause secondary immune deficiency.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RI-002Also: Immune Globulin (Human)Immune Globulin Intravenous (IGIV) | Biological | RI-002 Treatment |
Primary outcome
Number of Serious Bacterial Infections (SBIs) Per Subject Per Year (FDA Guidance for Industry (2008))
Time frame: 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.
30 secondary outcomes
Incidence of All Infections (Serious and Non-serious)
Time frame: Up to 1 Year
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
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
Number of Unscheduled Visits to Physician/ER Due to Infections - Total Number of Visits
Time frame: Up to 1 year
Number of Unscheduled Visits to Physician/ER Due to Infections - Per Subject-Year
Time frame: Up to 1 year
Time to Resolution of Infections - Duration Per Infection
Time frame: Up to 1 year
Time to Resolution of Infections - Infection Days Per Subject
Time frame: Up to 1 year
Number of Hospitalizations Due to Infections
Time frame: Up to 1 year
Number of Hospitalizations Due to Infections - Per Subject-Year
Time frame: Up to 1 year
Days of Hospitalization Due to Infections
Time frame: Up to 1 year
Days of Hospitalization Due to Infections - Per Subject-Year
Time frame: Up to 1 year
Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection)
Time frame: Up to 1 year
Number of Days of Antibiotic Therapy (Prophylaxis and Treatment of Infection) - Per Subject-Year
Time frame: Up to 1 year
Correlation Between Trough Level of RI-002 and Serious and Non-serious Infections
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - IgG
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Haemophilus Influenzae Type B
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Respiratory Syncytial Virus (RSV)
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Tetanus
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 1
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 3
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 4
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 5
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 6B
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 7F
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 9V
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 14
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 18C
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19A
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 19F
Time frame: Up to 1 year
Trough Total IgG and Specific Antibody Levels - Streptococcus Pneumoniae, Serotype 23F
Time frame: Up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Mond, M.D., Ph.D. study director
ADMA Biologics, Inc.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing RI-002 in people with Primary Immune Deficiency Disorder, run by ADMA Biologics, Inc. at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Serious Bacterial Infections (SBIs) Per Subject Per Year (FDA Guidance for Industry (2008)) (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2016.