Pneumococcal Conjugate Vaccine in Aging Renal Transplant

NCT03802994 | Terminated Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: INFB-019-17FCX001568
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of the research proposed in the current application is to first define how much antibody aging renal transplant and dialysis recipients make after they are vaccinated with the pneumonia vaccine and how this compares to similar aged persons with good renal function and healthy young adults. The investigators will study differences in the kind of B cells and markers on the B cells that are known to be important in the response to the pneumonia vaccine in aging renal transplant and aging dialysis recipients compared to similarly aged and young healthy controls. Finally, the investigators will study how safe the pneumonia vaccine is in aging renal transplants. The answers to these questions will help in designing a better vaccine for older people with a renal transplant or on dialysis.

Conditions

Renal Transplantation; Aging

Keywords

Prevnar; pneumococcal conjugate vaccine; aging; renal transplant recipient

Outcome Measures

Primary Outcomes (3)

• Anti-pneumococcal IgG Antibody (ug/ml) Change

  Measure the opsonic antibody response against streptococcus pneumonia serotypes 14, 19A and 23F at days 0 and 30. Comparing elderly RT recipients versus healthy elderly and elderly with DM/HTN.

  Baseline, 30 days

• Opsonophagocytic Antibody Titer Serum Dilution Difference Between Healthy Elderly, Elderly With DM/HTN and Elderly With RT.

  Measure the serum opsonophagocytic activity against streptococcus pneumonia serotypes 14, 19A and 23F on days 0 and 30 by opsonophagocytic assay.

  Baseline and 30 days

• Percentage of Polysaccharide Specific B Cells (% Cells/mL)

  percentage of polysaccharide specific B cells, and percentage of IgM memory B cells/mL in % cells/mL induced by vaccination with PCV13

  day 7

Secondary Outcomes (1)

• Inflammatory Markers Serum Levels Pre-immunization

  Day 0 pre-immunization

Study Arms (5)

1.Aging RT

EXPERIMENTAL

Renal transplant recipients between 65-75 years of age, on stable immunosuppression. who previously (\>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23). Cause or renal failure was either DMII or HTN.

Other: Peripheral blood sample

2.Young RT

ACTIVE COMPARATOR

Renal transplant recipients between 35-45 years of age, on stable immunosuppression. who previously (\>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23). Cause or renal failure was either DMII or HTN.

Other: Peripheral blood sample

3.Healthy elderly

ACTIVE COMPARATOR

Healthy persons between the ages 65-75 who previously (\>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23)

Other: Peripheral blood sample

4.Elderly DMII or HTN and normal renal function

ACTIVE COMPARATOR

Persons between the ages 65-75 with DMII or hypertension but normal renal function who previously (\>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23)

Other: Peripheral blood sample

5.Healthy young

EXPERIMENTAL

Healthy persons between the ages 35-45 who previously (\>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23) or are willing to receive PPV23 and 1 year later Prevnar 13.

Drug: 23 valent pneumococcal polysaccharide vaccine; Biological: 13 valent conjugated pneumococcal vaccine; Other: Peripheral blood sample

Interventions

23 valent pneumococcal polysaccharide vaccine DRUG

FDA approved pneumococcal polysaccharide vaccine containing capsular polysaccharide of 23 different pneumococcal serotypes. Only group 5 will potentially receive this as an intervention.

Also known as: Pneumovax 23 or PPV23

5.Healthy young

13 valent conjugated pneumococcal vaccine BIOLOGICAL

FDA approved pneumococcal polysaccharide vaccine containing capsular polysaccharide of 13 different pneumococcal serotypes conjugated to CRM197. Only group 5 will receive this as an intervention. In all other groups Prevnar 13 will be given as standard of care.

Also known as: Prevnar 23 or PCV13

5.Healthy young

Peripheral blood sample OTHER

Peripheral blood samples (30-60 mL) will be collected at day 0 (pre-immune), day 7, and day 30 (4 weeks post-PPV23) for groups 1-4 and at days 366, 373 and 396 for group 5. In addition, day 5, and 10 blood samples will be obtained from a limited (n=10) number of elderly RT participants to determine the optimal time point for circulation of PPS-specific B cells. Yearly blood samples will be obtained thereafter for serum antibody and OPA analyses to test longevity of antibody and OPA responses. Samples obtained from days 0, 30 and yearly samples will be used for antibody titers and opsonophagocytic assays. Samples from day 0 (day of vaccination with PCV13) and day 7 will be used for flow cytometric analysis.

Also known as: blood draw

1.Aging RT; 2.Young RT; 3.Healthy elderly; 4.Elderly DMII or HTN and normal renal function; 5.Healthy young

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Groups 1 (65-75 yrs) and 2 (35-45 yrs) Renal Transplant populations
• End stage renal disease cause either DM2 and/or hypertension (HTN)
• Renal transplant \>12 months ago
• Group 3: Diabetic/hypertensive 65-75 year old controls
• With DM2 and/or HTN
• Previous immunization with PPV23 \>1 year prior
• Willingness to be tested for HIV, HBV and HCV
• "normal kidney function" defined as glomerular filtration rate (GFR) of 60% or above
• Group 4: Healthy Control 65-75 yr old
• Without DM2
• May have high blood pressure (systolic\>140 and/or diastolic\>90) as long as it is well controlled (systolic\<140 and/or diastolic \<90) and has not affected kidney function.
• Previous receipt of PPV23 \> 1 year prior
• Willingness to be tested for HIV, HBV and HCV
• Group 5: Healthy Control 35-45 yr old
• Without DM2.

You may not qualify if:

• Previous immunization with PCV13.
• Pregnancy, no contraceptive practice in women of childbearing age, or breastfeeding
• Known anaphylaxis, hypersensitivity or "bad allergic reaction" to the pneumonia vaccine. This does not include egg allergy or previous Guillan Barre syndrome.
• Those who received blood products or gamma globulin within 3 months.
• Inability to comprehend or sign the informed consent form
• Previous/present illness that may affect immune response to the vaccine
• previous pneumococcal disease
• disease
• removal of the spleen
• auto-immune disease such as lupus or rheumatoid arthritis
• end-stage liver disease
• cancer
• Significant abnormalities (3xULN and all those considered to be critical values) in CBC, chemistries including glucose.
• HIV, HBsAg or HCV positivity
• Receipt of PPV23 within 1 year

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (2)

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, 29401-5799, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Interventions

23-valent pneumococcal capsular polysaccharide vaccine; Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

Early termination leading to small numbers of enrolled subjects due to the COVID pandemic

Results Point of Contact

• Title: ACOS/R, R. Amanda C. LaRue
• Organization: Ralph H. Johnson VA Medical Center

Rutha.LaRue@va.gov

843-789-6707

Study Officials

• Maria J Westerink, MD

  Ralph H. Johnson VA Medical Center, Charleston, SC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Immune response to immunization with Prevnar in elderly aging renal transplant compared to comparison groups: healthy young, healthy elderly, healthy elderly hypertension (HTN) and young renal transplants.

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: January 14, 2019
• Study Start: November 1, 2018
• Primary Completion: February 28, 2020
• Study Completion: February 28, 2020
• Last Updated: April 30, 2021
• Results First Posted: April 30, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)