Lower Respiratory Tract Infection, Upper Respiratory Tract Infection
Conditions
Keywords
Transplant, Immunosuppression
Brief summary
RSV infections can develop into serious, life threatening conditions among immunocompromised patients. The objective of this study (ADMA 001) is to evaluate the safety and efficacy of RI-001 for the prevention of lower respiratory tract infections in immunocompromised patients identified as being infected with RSV in the upper respiratory tract.
Interventions
BIOLOGICALRI-001
Dose 1
Sponsors
ADMA Biologics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. An IEC/IRB approved written informed consent signed and dated by the patient or by parent(s) or a legally acceptable representative. The consent form or a specific assent form, where required, will be signed and dated by minors. 2. Documented Bone Marrow Transplant (BMT)/Hematopoietic Stem Cell Transplant (HSCT), Pulmonary/Cardiac Transplant, Pulmonary Transplant or Liver Transplant within the 2 years prior to randomization to the study drug. 3. Male/Female patients age: (Pediatric) ≥2 years and \<16 years at the time of informed consent. 4. Male/Female patients age: (Adult) ≥ 16 years and ≤ 65 years at the time of informed consent. 5. Patient must have an URTI as defined by Respiratory Assessment Score (RAS)=1. 6. Patients must be actively taking at least one immunosuppressive agent. 7. Patients must have a positive RSV RT-PCR at the time of the randomization procedures. 8. Female patients must 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. Females of non-childbearing potential are defined as women who have had a hysterectomy, bilateral oophorectomy, tubal ligation or who have been post-menopausal for at least two years, or are considered to be sterile due to recent chemotherapy. 9. Female patients who are not breast-feeding. 10. Patient/legally acceptable representative considered as reliable and capable of adhering to the protocol (e.g. able to understand and complete diaries and questionnaires), visit schedules or treatment regimen according to the judgment of the Investigator.
Exclusion criteria
1. Documented RSV lower respiratory tract infection (respiratory assessment score is greater than 1) as determined by the site investigators or research staff. 2. Requirement for mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure or other mechanical respiratory or cardiac support 3. Unstable respiratory status so severe that survival is not expected for longer than 6 months. 4. End organ dysfunction resulting in anticipated survival of less than 6 months. 5. Known to be HIV positive. 6. Administration of any RSV specific products, including palivizumab (Synagis®) in the 3 months prior to randomization procedures. 7. Previous, current, or planned administration of an investigational RSV vaccine. 8. Known hypersensitivity to immunoglobulin. 9. Known Immunoglobulin (IgA) deficiency 10. Known renal impairment requiring any form of dialysis (HD, PD, CRRT). 11. Known hemodynamically significant congenital heart disease. 12. Previous poor compliance with visit schedules. 13. Severe medical, neurological or psychiatric disorders or laboratory values which may have an impact on the safety of the patient. 14. Concurrent participation in other investigational drug product studies; any exception must be approved by the ADMA Biologics Medical Director.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Circulating RI-001 Titer | Study day 18 | The primary endpoint of this study was the mean fold titer increase from baseline to Day 18 in circulating serum anti-RSV neutralizing antibody following treatment with RI-001. |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of RSV Progression From Symptomatic Upper Respiratory Tract Infection to Lower Respiratory Tract Infection. | Study day 33 |
| The Number of Patients Achieving at Least a 4-fold Increase in Serum RSV Neutralizing Antibody Titers | 18 Days |
Countries
Canada, United States
Participant flow
Recruitment details
Patient recruitment period took place between 06Jun2008 and 05Mar2010. Patient recruitment took place in hospitals.
Participants by arm
| Arm | Count |
|---|---|
| 1 (High Dose) Dose regimen 1 (High Dose): RI-001 1,500 mg/kg dose on day 1, and 750 mg/kg dose on day 3. | 7 |
| 2 (Low Dose) Dose regimen 2 (Low Dose): RI-001 750 mg/kg dose on day 1, and 750 mg/kg dose on day 3. | 7 |
| 3 (Placebo) Placebo (Normal saline): 7.5 mL/kg or 15 mL/kg dose on day 1, and 7.5 mL/kg dose on day 2. | 7 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 1 (High Dose) | 2 (Low Dose) | 3 (Placebo) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 5 Participants | 4 Participants | 12 Participants |
| Age Continuous | 37 years STANDARD_DEVIATION 29.06 | 33 years STANDARD_DEVIATION 23.25 | 44.14 years STANDARD_DEVIATION 25.06 | 38.04 years STANDARD_DEVIATION 25.03 |
| Region of Enrollment Australia | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Canada | 0 participants | 2 participants | 0 participants | 2 participants |
| Region of Enrollment New Zealand | 0 participants | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United States | 7 participants | 4 participants | 6 participants | 17 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 7 | 6 / 7 | 4 / 7 |
| serious Total, serious adverse events | 2 / 7 | 4 / 7 | 1 / 7 |
Outcome results
Primary
Circulating RI-001 Titer
The primary endpoint of this study was the mean fold titer increase from baseline to Day 18 in circulating serum anti-RSV neutralizing antibody following treatment with RI-001.
Time frame: Study day 18
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 1 (High Dose) | Circulating RI-001 Titer | 9.24 Fold Change |
| 2 (Low Dose) | Circulating RI-001 Titer | 4.85 Fold Change |
| 3 (Placebo) | Circulating RI-001 Titer | 1.42 Fold Change |
Secondary
Incidence of RSV Progression From Symptomatic Upper Respiratory Tract Infection to Lower Respiratory Tract Infection.
Time frame: Study day 33
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 (High Dose) | Incidence of RSV Progression From Symptomatic Upper Respiratory Tract Infection to Lower Respiratory Tract Infection. | 1 Participants |
| 2 (Low Dose) | Incidence of RSV Progression From Symptomatic Upper Respiratory Tract Infection to Lower Respiratory Tract Infection. | 2 Participants |
| 3 (Placebo) | Incidence of RSV Progression From Symptomatic Upper Respiratory Tract Infection to Lower Respiratory Tract Infection. | 1 Participants |
Secondary
The Number of Patients Achieving at Least a 4-fold Increase in Serum RSV Neutralizing Antibody Titers
Time frame: 18 Days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 (High Dose) | The Number of Patients Achieving at Least a 4-fold Increase in Serum RSV Neutralizing Antibody Titers | 6 Participants |
| 2 (Low Dose) | The Number of Patients Achieving at Least a 4-fold Increase in Serum RSV Neutralizing Antibody Titers | 3 Participants |
| 3 (Placebo) | The Number of Patients Achieving at Least a 4-fold Increase in Serum RSV Neutralizing Antibody Titers | 0 Participants |