Hallmarks of Protective Immunity in Sequential Rhinovirus Infections in Humans

• Sponsor: University of Virginia (Other)
• Overall Status: Completed
• CT.gov ID: NCT02796001
• Collaborator: (none)
• Enrollment: 46
• Location: 1
• Arms: 3
• Actual Duration (Months): 31.2
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the relationship between rhinovirus specific T-cell immunity and the human host response to primary rhinovirus challenge and subsequent secondary challenge with either homologous or heterologous rhinovirus serotypes.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Biological: human rhinovirus; Other: no intervention	Phase 1/Phase 2

Detailed Description

The primary objective of this study is to assess the relationship between RV-specific T-cell immunity and the human host response to primary RV challenge and subsequent secondary challenge with either homologous or heterologous RV serotypes. The overall hypothesis that will be addressed by the mechanistic studies in this proposal is that T helper (Th) and T follicular helper (Tfh) cells directed against conserved RV epitopes expand upon RV exposure and some of these cells persist as stable cross-reactive memory populations capable of displaying lineage-specific protective functions upon re-infection with related or unrelated strains of RV. The human specimens collected in this study will be analyzed with a variety of state-of-the-art techniques to provide an in depth description of T-cell responses to RV infection, and the correlation of these responses with viral infection, antibody responses, and illness. Beyond this objective, by using a systems biology approach, we aim to gain new insight into the role of diverse cell types involved in adaptive immunity to RV. .

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Volunteers who were infected with RV16 by experimental challenge were eligible for participation by re-challenge with either RV16 or RV39 to assess the host response to homologous or heterologous rechallenge.Volunteers who were infected with RV16 by experimental challenge were eligible for participation by re-challenge with either RV16 or RV39 to assess the host response to homologous or heterologous rechallenge.
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Hallmarks of Protective Immunity in Sequential Rhinovirus Infections in Humans
• Actual Study Start Date: Sep 25, 2017
• Actual Primary Completion Date: May 1, 2020
• Actual Study Completion Date: May 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: RV16 infected volunteers re-challenged with RV16 volunteers re-challenged with RV16	Biological: human rhinovirus; human rhinovirus
Active Comparator: RV infected volunteers re-challenged with RV39 volunteers re-challenged with RV39	Biological: human rhinovirus; human rhinovirus
Other: RV infected not rechallenged Volunteers who were infected with RV16 and eligible for re-challenge but who were not re-challenged due to voluntary withdrawal (3) or removal for exclusion criteria	Other: no intervention; 4 volunteers were not re-challenged and did not participate in the second challenge

Outcome Measures

Primary Outcome Measures

1. Virus Infection [Volunteers were cultured daily for detection of virus shedding for 5 days after the virus re-challenge and serum was collected for viral serology 4 weeks after virus re-challenge]

   Number infected after re-challenge with RV16 compared to RV39 as determined by virus isolation in cell culture or viral serology

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Subject must be 18-40 years of age

2. Subject must read and sign a copy of the approved Consent Form

3. Subject must have a serum neutralizing antibody titer of ≤1:2 to rhinovirus type 39 and rhinovirus type 16

4. Female subjects must be using an effective birth control method.

5. Total IgE <150 IU/ml.

Exclusion Criteria:

1. Any clinically significant abnormalities of the upper respiratory tract

2. Any clinically significant acute or chronic respiratory illness

3. Any clinically significant bleeding tendency by history

4. Hypertension that requires treatment with antihypertensive medications

5. History of angina or other clinically significant cardiac disease

6. Any upper respiratory infection or allergic rhinitis in the two weeks prior to the start of the study

7. Any medical condition that in the opinion of the Investigator is cause for exclusion from the study

8. Use of any anti-inflammatory (steroids or NSAIDs) or cough/cold preparation in the 1 month prior to the study

9. Regular use of tobacco in the last 6 months (ie. more than 2 days out of 7) or inability to refrain from smoking during the study

10. Inability to refrain from the use of common cold therapies in the 5 days after each rhinovirus challenge.

11. Participation in any other clinical drug trial in the month prior to the study

12. Female subjects with a positive urine pregnancy screen.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Virginia	Charlottesville	Virginia	United States	22908

Sponsors and Collaborators

• University of Virginia

Investigators

• Principal Investigator: Ronald Turner, MD, Univ of Virginia

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 13, 2017

More Information

Publications

None provided.

• Responsible Party: Ronald B Turner, Professor of Pediatrics, University of Virginia
• ClinicalTrials.gov Identifier: NCT02796001
• Other Study ID Numbers: 16-0055
• First Posted: Jun 10, 2016
• Last Update Posted: Jun 6, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Infections

Study Results

Participant Flow

Recruitment Details

Volunteers who participated in the study were individuals who had previously been challenged and infected with RV16 in the human rhinovirus experimental challenge model and agreed to be re-challenged with either RV16 or RV39

Pre-assignment Detail

Volunteers were initially challenged with RV16 to provide a uniform baseline for the subsequent randomization and re-challenge with either a homologous serotype (RV16) or a heterologous serotype (RV39). 46 subjects met the baseline criteria but 3 declined further participation and 1 was ill on the day of re-challenge and was removed from the study by the investigator. 42 subjects were randomized and re-challenged with rhinovirus.

Arm/Group Title	RV16 Infected Volunteers Re-challenged With RV16	RV16 Infected Volunteers Re-challenged With RV39	no Intervention
Arm/Group Description	volunteers re-challenged with RV16 human rhinovirus: human rhinovirus	volunteers re-challenged with RV39 human rhinovirus: human rhinovirus	4 volunteers were infected with RV16 and were eligible to be randomized to re-challenge. Three of these volunteers declined re-challenge and one was removed from the study prior to re-challenge
Period Title: Overall Study
STARTED	20	22	4
COMPLETED	20	22	4
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	RV16 Infected Volunteers Re-challenged With RV16	RV16 Infected Volunteers Re-challenged With RV39	no Intervention	Total
Arm/Group Description	volunteers re-challenged with RV16 human rhinovirus: human rhinovirus	volunteers re-challenged with RV39 human rhinovirus: human rhinovirus	4 volunteers were infected with RV16 and were eligible for re-challenge. Three volunteers declined re-challenge and one was removed from the study prior to re-challenge	Total of all reporting groups
Overall Participants	20	22	4	46
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	20.7 (2.43)	19.8 (1.87)	19.25 (0.5)	20.1 (1.91)
Sex: Female, Male (Count of Participants)
Female	12 60%	10 45.5%	2 50%	24 52.2%
Male	8 40%	12 54.5%	2 50%	22 47.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	3 15%	2 9.1%	0 0%	5 10.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 4.5%	0 0%	1 2.2%
White	15 75%	19 86.4%	3 75%	37 80.4%
More than one race	2 10%	0 0%	1 25%	3 6.5%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	20 100%	22 100%	4 100%	46 100%
previously infected with RV16 (Count of Participants)
Count of Participants [Participants]	20 100%	22 100%	4 100%	46 100%

Outcome Measures

1. Primary Outcome

Title	Virus Infection
Description	Number infected after re-challenge with RV16 compared to RV39 as determined by virus isolation in cell culture or viral serology
Time Frame	Volunteers were cultured daily for detection of virus shedding for 5 days after the virus re-challenge and serum was collected for viral serology 4 weeks after virus re-challenge

Outcome Measure Data

Analysis Population Description

all volunteers re-challenged

Arm/Group Title	RV16 Infected Volunteers Re-challenged With RV16	RV16 Infected Volunteers Re-challenged With RV39
Arm/Group Description	volunteers re-challenged with RV16 human rhinovirus: human rhinovirus	volunteers re-challenged with RV39 human rhinovirus: human rhinovirus
Measure Participants	20	22
Count of Participants [Participants]	8 40%	18 81.8%

Adverse Events

Time Frame	Adverse events were collected at each study visit from the virus challenge/re-challenge to 15 weeks.
Adverse Event Reporting Description	Adverse events were collected by interactive interview with study staff at each study visit between challenge/re-challenge and week 15. 46 subjects were initially challenged with RV16. 42 subjects were re-challenged with either RV16 or RV39. Three subjects voluntarily withdrew from the study before re-challenge and one subject had common cold symptoms on the scheduled day of the re-challenge and was removed from the study by the investigator.
Arm/Group Title	Volunteers Initially Challenged With RV16		RV16 Infected Volunteers Re-challenged With RV16		RV16 Infected Volunteers Re-challenged With RV39
Arm/Group Description	Volunteers challenged with RV16 to produce RV16 infected volunteers for subsequent arms Human rhinovirus		volunteers re-challenged with RV16 human rhinovirus: human rhinovirus		volunteers re-challenged with RV39 human rhinovirus: human rhinovirus
All Cause Mortality
	Volunteers Initially Challenged With RV16		RV16 Infected Volunteers Re-challenged With RV16		RV16 Infected Volunteers Re-challenged With RV39
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/46 (0%)		0/20 (0%)		0/22 (0%)
Serious Adverse Events
	Volunteers Initially Challenged With RV16		RV16 Infected Volunteers Re-challenged With RV16		RV16 Infected Volunteers Re-challenged With RV39
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/46 (0%)		0/20 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Volunteers Initially Challenged With RV16		RV16 Infected Volunteers Re-challenged With RV16		RV16 Infected Volunteers Re-challenged With RV39
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/46 (4.3%)		1/20 (5%)		1/22 (4.5%)
Musculoskeletal and connective tissue disorders
Headache	1/46 (2.2%)	1	0/20 (0%)	0	0/22 (0%)	0
Respiratory, thoracic and mediastinal disorders
bloody nose	0/46 (0%)	0	1/20 (5%)	1	0/22 (0%)	0
cough	1/46 (2.2%)	1	0/20 (0%)	0	1/22 (4.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.