RI-001 in Immunosuppressed Respiratory Syncytial Virus (RSV) Infected Patients at Risk of Lower Tract RSV Illness

• Sponsor: ADMA Biologics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00632463
• Collaborator: (none)
• Enrollment: 21
• Locations: 19
• Arms: 3
• Duration (Months): 26.9
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Upper Respiratory Tract Infection; Lower Respiratory Tract Infection	Biological: RI-001; Biological: RI-001; Biological: RI-001	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: RI-001 in Immunosuppressed Respiratory Syncytial Virus (RSV) Infected Patients at Risk of Lower Tract RSV Illness
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Dose regimen 1	Biological: RI-001; Dose 1
Experimental: 2 Dose regimen 2	Biological: RI-001; Dose 2
Placebo Comparator: 3 Placebo	Biological: RI-001; Placebo

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Incidence of RSV Progression From Symptomatic Upper Respiratory Tract Infection to Lower Respiratory Tract Infection. [Study day 33]

2. The Number of Patients Achieving at Least a 4-fold Increase in Serum RSV Neutralizing Antibody Titers [18 Days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Francisco	San Francisco	California	United States	94143
2	University of Colorado Health Sciences Center	Aurora	Colorado	United States	80045
3	Children's National Medical Center	Washington	District of Columbia	United States	20010
4	All Children's Hospital	St. Petersburg	Florida	United States	33701
5	Rush University Medical Center	Chicago	Illinois	United States	60612
6	Johns Hopkins Medical Center	Baltimore	Maryland	United States	21205
7	New England Medical Center	Boston	Massachusetts	United States	02111
8	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
9	Schneider Children's Hospital	New Hyde Park	New York	United States	11040
10	University of Rochester Medical Center	Rochester	New York	United States	14642
11	Oregon Health and Science University	Portland	Oregon	United States	97239
12	Children's Medical Center of Dallas	Dallas	Texas	United States	75235
13	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
14	Seattle Children's Hospital and Regional Medical Center	Seattle	Washington	United States	98105
15	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
16	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B6A8
17	Hospital for Sick Children	Toronto	Ontario	Canada	M5G1X8
18	Hopital Maisonneuve Rosemont	Montreal	Quebec	Canada	H1T2M4
19	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T1C5

Sponsors and Collaborators

• ADMA Biologics, Inc.

Investigators

• Principal Investigator: Upton Allen, MBBS, Division of Infectious Diseases, Hospital for Sick Children, Toronto, Ontario, Canada

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ADMA Biologics, Inc.
• ClinicalTrials.gov Identifier: NCT00632463
• Other Study ID Numbers: ADMA-001
• First Posted: Mar 10, 2008
• Last Update Posted: Apr 24, 2013
• Last Verified: Mar 1, 2013

• Keywords provided by ADMA Biologics, Inc.: Transplant; Immunosuppression
• Additional relevant MeSH terms: Infections; Communicable Diseases; Respiratory Tract Infections

Study Results

Participant Flow

Recruitment Details	Patient recruitment period took place between 06Jun2008 and 05Mar2010. Patient recruitment took place in hospitals.

Arm/Group Title	1 (High Dose)	2 (Low Dose)	3 (Placebo)
Arm/Group Description	Dose regimen 1 (High Dose): RI-001 1,500 mg/kg dose on day 1, and 750 mg/kg dose on day 3.	Dose regimen 2 (Low Dose): RI-001 750 mg/kg dose on day 1, and 750 mg/kg dose on day 3.	Placebo (Normal saline): 7.5 mL/kg or 15 mL/kg dose on day 1, and 7.5 mL/kg dose on day 2.
Period Title: Overall Study
STARTED	7	7	7
COMPLETED	7	6	7
NOT COMPLETED	0	1	0

Baseline Characteristics

Arm/Group Title	1 (High Dose)	2 (Low Dose)	3 (Placebo)	Total
Arm/Group Description	Dose regimen 1 (High Dose): RI-001 1,500 mg/kg dose on day 1, and 750 mg/kg dose on day 3.	Dose regimen 2 (Low Dose): RI-001 750 mg/kg dose on day 1, and 750 mg/kg dose on day 3.	Placebo (Normal saline): 7.5 mL/kg or 15 mL/kg dose on day 1, and 7.5 mL/kg dose on day 2.	Total of all reporting groups
Overall Participants	7	7	7	21
Age (Count of Participants)
<=18 years	3 42.9%	2 28.6%	2 28.6%	7 33.3%
Between 18 and 65 years	3 42.9%	5 71.4%	4 57.1%	12 57.1%
>=65 years	1 14.3%	0 0%	1 14.3%	2 9.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37 (29.06)	33 (23.25)	44.14 (25.06)	38.04 (25.03)
Sex: Female, Male (Count of Participants)
Female	5 71.4%	5 71.4%	3 42.9%	13 61.9%
Male	2 28.6%	2 28.6%	4 57.1%	8 38.1%
Region of Enrollment (participants) [Number]
United States	7 100%	4 57.1%	6 85.7%	17 81%
Canada	0 0%	2 28.6%	0 0%	2 9.5%
Australia	0 0%	1 14.3%	0 0%	1 4.8%
New Zealand	0 0%	0 0%	1 14.3%	1 4.8%

Outcome Measures

1. Primary Outcome

Title	Circulating RI-001 Titer
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 (High Dose)	2 (Low Dose)	3 (Placebo)
Arm/Group Description	Dose regimen 1 (High Dose): RI-001 1,500 mg/kg dose on day 1, and 750 mg/kg dose on day 3.	Dose regimen 2 (Low Dose): RI-001 750 mg/kg dose on day 1, and 750 mg/kg dose on day 3.	Placebo (Normal saline): 7.5 mL/kg or 15 mL/kg dose on day 1, and 7.5 mL/kg dose on day 2.
Measure Participants	7	7	7
Mean (95% Confidence Interval) [Fold Change]	9.24	4.85	1.42

2. Secondary Outcome

Title	Incidence of RSV Progression From Symptomatic Upper Respiratory Tract Infection to Lower Respiratory Tract Infection.
Time Frame	Study day 33

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 (High Dose)	2 (Low Dose)	3 (Placebo)
Arm/Group Description	Dose regimen 1 (High Dose): RI-001 1,500 mg/kg dose on day 1, and 750 mg/kg dose on day 3.	Dose regimen 2 (Low Dose): RI-001 750 mg/kg dose on day 1, and 750 mg/kg dose on day 3.	Placebo (Normal saline): 7.5 mL/kg or 15 mL/kg dose on day 1, and 7.5 mL/kg dose on day 2.
Measure Participants	7	7	7
Number [Participants]	1 14.3%	2 28.6%	1 14.3%

3. Secondary Outcome

Title	The Number of Patients Achieving at Least a 4-fold Increase in Serum RSV Neutralizing Antibody Titers
Time Frame	18 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1 (High Dose)	2 (Low Dose)	3 (Placebo)
Arm/Group Description	Dose regimen 1 (High Dose): RI-001 1,500 mg/kg dose on day 1, and 750 mg/kg dose on day 3.	Dose regimen 2 (Low Dose): RI-001 750 mg/kg dose on day 1, and 750 mg/kg dose on day 3.	Placebo (Normal saline): 7.5 mL/kg or 15 mL/kg dose on day 1, and 7.5 mL/kg dose on day 2.
Measure Participants	7	7	7
Number [Participants]	6 85.7%	3 42.9%	0 0%

Adverse Events

Arm/Group Title	1 (High Dose)		2 (Low Dose)		3 (Placebo)
Arm/Group Description	Dose regimen 1 (High Dose): RI-001 1,500 mg/kg dose on day 1, and 750 mg/kg dose on day 3.		Dose regimen 2 (Low Dose): RI-001 750 mg/kg dose on day 1, and 750 mg/kg dose on day 3.		Placebo (Normal saline): 7.5 mL/kg or 15 mL/kg dose on day 1, and 7.5 mL/kg dose on day 2.
All Cause Mortality
	1 (High Dose)		2 (Low Dose)		3 (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	1 (High Dose)		2 (Low Dose)		3 (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/7 (28.6%)		4/7 (57.1%)		1/7 (14.3%)
Blood and lymphatic system disorders
Lymphadenopathy	1/7 (14.3%)	1	0/7 (0%)	0	0/7 (0%)	0
Neutropenia	1/7 (14.3%)	1	0/7 (0%)	0	0/7 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/7 (0%)	0	2/7 (28.6%)	2	0/7 (0%)	0
General disorders
Pyrexia	1/7 (14.3%)	1	0/7 (0%)	0	0/7 (0%)	0
Infections and infestations
Pneumonia	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Lower respiratory tract infection	1/7 (14.3%)	1	0/7 (0%)	0	0/7 (0%)	0
Pneumonia respiratory syncytial viral	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1
Pneumonia streptococcal	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Post transplant lymphoproliferative disorder	1/7 (14.3%)	1	0/7 (0%)	0	0/7 (0%)	0
Nervous system disorders
Altered state of consciousness	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Syncope	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonitis	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Other (Not Including Serious) Adverse Events
	1 (High Dose)		2 (Low Dose)		3 (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/7 (57.1%)		6/7 (85.7%)		4/7 (57.1%)
Blood and lymphatic system disorders
Anaemia	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Cardiac disorders
Tachycardia	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Eye disorders
Eyelid ptosis	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Gastrointestinal disorders
Nausea	1/7 (14.3%)	1	1/7 (14.3%)	1	1/7 (14.3%)	1
Diarrhoea	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Constipation	1/7 (14.3%)	1	0/7 (0%)	0	0/7 (0%)	0
Gastroesophageal reflux disease	1/7 (14.3%)	1	0/7 (0%)	0	0/7 (0%)	0
Vomiting	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Dry mouth	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1
General disorders
Pyrexia	0/7 (0%)	0	1/7 (14.3%)	1	1/7 (14.3%)	1
Chills	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1
Chest Pain	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1
Crepitations	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1
Immune system disorders
Graft versus host disease	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Hypersensitivity	1/7 (14.3%)	1	0/7 (0%)	0	0/7 (0%)	0
Infections and infestations
Sinusitis	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1
Investigations
Platelet count decreased	0/7 (0%)	0	2/7 (28.6%)	2	0/7 (0%)	0
Blood albumin decreased	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Blood lactate dehydrogenase increased	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Blood magnesium decreased	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Blood phosphorus decreased	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Blood potassium decreased	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Haemoglobin decreased	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Heart rate increased	1/7 (14.3%)	1	0/7 (0%)	0	0/7 (0%)	0
Breath sounds abnormal	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/7 (14.3%)	1	1/7 (14.3%)	1	0/7 (0%)	0
musculoskeletal stiffness	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Nervous system disorders
Dysguesia	1/7 (14.3%)	1	0/7 (0%)	0	0/7 (0%)	0
Somnolence	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Headache	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1
Paraesthesia	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1
Psychiatric disorders
Delirium	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Panic Attack	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Renal and urinary disorders
Polyuria	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Renal failure	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/7 (14.3%)	1	1/7 (14.3%)	1	2/7 (28.6%)	4
Sinus Congestion	1/7 (14.3%)	1	0/7 (0%)	0	1/7 (14.3%)	1
Dyspnoea	1/7 (14.3%)	1	0/7 (0%)	0	0/7 (0%)	0
Nasal Congestion	1/7 (14.3%)	1	0/7 (0%)	0	0/7 (0%)	0
Tachypnoea	1/7 (14.3%)	2	0/7 (0%)	0	0/7 (0%)	0
Throat irritation	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1
Productive cough	0/7 (0%)	0	1/7 (14.3%)	1	1/7 (14.3%)	1
Epistaxis	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1
Pharyngolaryngeal pain	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1
Skin and subcutaneous tissue disorders
Erythema	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Vascular disorders
Hypertension	1/7 (14.3%)	2	0/7 (0%)	0	0/7 (0%)	0
Labile blood pressure	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Orthostatic hypotension	0/7 (0%)	0	1/7 (14.3%)	1	0/7 (0%)	0
Flushing	0/7 (0%)	0	0/7 (0%)	0	1/7 (14.3%)	1

Limitations/Caveats

Unfortunately enrollment in this study was suspended early due to slow accrual rates.

More Information

Certain Agreements

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