Trial Outcomes & Findings for SARS-CoV-2 Human Challenge Characterisation Study (NCT NCT04865237)

NCT ID: NCT04865237

Last Updated: 2025-05-16

Results Overview

To evaluate the safety of wild type SARS-CoV-2 challenge in healthy participants by assessing occurrence of unsolicited AEs within 30 days post-viral challenge (Day 0) up to Day 28 follow up.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 36 participants
• Primary outcome timeframe: Day 0 to 28 (28 days)
• Results posted on: 2025-05-16

Participant Flow

This study met the primary outcome of a 50% infection rate in the first, lowest dose group. Therefore, there was no further enrolment into the higher dose level groups (Dose Level 2 or 3).

Participant milestones

Measure	Healthy Volunteers Dose Level 1 Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 dose +/- Remdesivir: VEKLURY™	Healthy Volunteers Dose Level 2 Healthy volunteers given SARS-CoV-2 virus at 10\^2 TCID50 dose +/- Remdesivir: VEKLURY™	Healthy Volunteers Dose Level 3 Healthy volunteers given SARS-CoV-2 virus at 10\^3 TCID50 dose +/- Remdesivir: VEKLURY™
Overall Study STARTED	36	0	0
Overall Study COMPLETED	36	0	0
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

SARS-CoV-2 Human Challenge Characterisation Study

Baseline characteristics by cohort

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 dose +/- Remdesivir: VEKLURY™
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	36 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	21.8 years STANDARD_DEVIATION 2.89 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	33 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Region of Enrollment United Kingdom	36 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0 to 28 (28 days)

Population: All subjects

To evaluate the safety of wild type SARS-CoV-2 challenge in healthy participants by assessing occurrence of unsolicited AEs within 30 days post-viral challenge (Day 0) up to Day 28 follow up.

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
Number of Unsolicited Adverse Events in Healthy Participants Challenged With Wild Type SARS-CoV-2	45 Unsolicited Adverse Events

PRIMARY outcome

Timeframe: Day 0 to 28 (28 days)

Population: Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™

To evaluate the safety of wild type SARS-CoV-2 challenge in healthy participants by assessing occurrence of SAEs related to the viral challenge from the viral challenge (Day 0) up to Day 28 follow up.

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
Number of SAEs Related to Viral Challenge	0 SAE events

PRIMARY outcome

Timeframe: From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days

Population: 36 individuals were challenge but two were excluded from the analysis due to sero-conversion prior to the viral challenge.

To identify a SARS-Cov-2 inoculum dose that safely induces laboratory confirmed infection in ≥50% of participants (ideally between 50% and 70%). Laboratory confirmed infection is defined as two quantifiable greater than lower limit of quantification (≥LLOQ) RT-PCR measurements from mid turbinate and/or throat samples, reported on 2 or more consecutive timepoints, starting from 24 hours post-inoculation and up to discharge from quarantine.

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=34 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
Number of Participants With Laboratory Confirmed Infections	18 infected participants

SECONDARY outcome

Timeframe: From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days

To further assess SARS-CoV-2 viral infection rates in upper respiratory samples in healthy volunteers, by inoculum dose.

To assess the incidence of laboratory confirmed infection rates using a) mid turbinate samples, b) throat swabs, and c) both mid turbinate and throat swabs, as defined by:

• Variant 2: Occurrence of at least two quantifiable (≥LLOQ) RT-PCR measurements, reported on 2 or more consecutive timepoints, starting from 24 hours post-inoculation and up to discharge from quarantine.
• Variant 3: Occurrence of at least two detectable (≥LLOD) RT-PCR measurements, reported on 2 or more consecutive timepoints, starting from 24 hours post-inoculation and up to discharge from quarantine.
• Variant 4: Occurrence of at least one quantifiable (≥LLOQ) SARS-CoV-2 viral cell culture measurement, starting from 24 hours post-inoculation and up to discharge from quarantine.

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=34 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
Number of Patients With Laboratory Confirmed Infections by Mid-turbinate and/or Throat Swabs	18 infected participants

SECONDARY outcome

Timeframe: From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days

Population: Of the 34, participants, 18 participants had confirmed SARS-CoV-2 infections.

To assess the incidence of symptomatic SARS-CoV-2 infection, in healthy volunteers, by inoculum dose To assess the incidence of lab-confirmed symptomatic SARS-CoV-2 infection using a) mid turbinate samples, b) throat swabs, and c) both mid turbinate and throat swabs,

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=18 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
Number of Symptomatic SARS-Cov-2 Infected Participants	14 Participants

SECONDARY outcome

Timeframe: From 24 hours post-inoculation to 312 hours post-inoculation

To assess the viral dynamics using a) mid turbinate samples, and b) throat swabs as measured by the area under the viral load-time curve (VL-AUC) of SARS-CoV-2 as determined by qRT-PCR, starting from 24 hours post-inoculation and up to discharge from quarantine.

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
SARS-CoV-2 Viral Dynamics (VL-AUC) in Upper Respiratory Samples in Healthy Volunteers	171.154 hours*Log10 FFU/mL Standard Deviation 193.2885

SECONDARY outcome

Timeframe: From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days

Sum total symptoms diary card score: sum total clinical symptoms (TSS) as measured by graded symptom scoring system, starting one day post-viral challenge (Day 1) up to discharge from quarantine. Symptoms are graded on a scale from 0 (no symptoms) to 3 (bothersome symptoms impacting involvement in activities). The sum total symptom score was based on the symptom diary cards that were filled out 3 times per day from the first (morning) assessment on Day 1 until the first (morning) assessment on Day 14 (planned day of quarantine discharge). Each assessment consisted of the grades given by the subjects to a list of 19 symptoms on the symptom diary card. Individual total symptom scores were derived for each assessment as the total of all of the grades given on the individual diary card. This could range from 0 (if all symptoms graded as 0) to 59 (if all symptoms graded as 3 and shortness of breath and wheeze were graded as 4).

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
SARS-CoV-2 Induced Symptoms in Healthy Volunteers by the Mean Sum Total Symptom Score	26.8 Sum Total Symptom Score Standard Deviation 42.25

SECONDARY outcome

Timeframe: Day 0 to discharge from Quarantine, up to a maximum of 17 days

The incidence of:

• Upper Respiratory Tract illness (URT)
• Lower Respiratory Tract illness (LRT)
• Systemic illness (SI)
• Febrile illness (FI)
• Proportion of Subjects with Grade 3 symptoms on any occasion at any time from the last assessment on Day 0 to quarantine discharge
• Proportion of Subjects with Grade 2 or higher symptoms on any occasion at any time from the last assessment on Day 0 to quarantine discharge
• Proportion of Subjects with Grade 2 or higher Symptoms on two separate occasions at any time from the last assessment on Day 0 to quarantine discharge
• Proportion of Subjects with any symptom (grade >=1) on any occasion at any time from the last assessment on Day 0 to quarantine discharge
• Proportion of Subjects with any symptom (grade >=1) on two separate occasions at any time from the last assessment on Day 0 to quarantine discharge

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
Number of Participants With Incidence of SARS-CoV-2 Illness in Healthy Volunteers	20 participants

SECONDARY outcome

Timeframe: From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days

To assess the viral dynamics using a) mid turbinate samples, and b) throat swabs as measured by peak viral load of SARS-CoV-2 as defined by the maximum viral load determined by quantifiable (≥LLOQ) qRT-PCR measurements, starting from 24 hours post-inoculation and up to discharge from quarantine.

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
SARS-CoV-2 Viral Dynamics (Peak Viral Load) in Upper Respiratory Samples in Healthy Volunteers	4.5764 log10 copies/mL Standard Deviation 4.50600

SECONDARY outcome

Timeframe: From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days

To assess the viral dynamics using a) mid turbinate samples, and b) throat swabs as measured by duration of SARS-CoV-2 quantifiable (≥LLOQ) qRT-PCR measurements, starting from 24 hours post-inoculation and up to discharge from quarantine. Duration is defined as the time (hours) from the first quantifiable of the two viral quantifiable positives used to assess infection until first confirmed undetectable assessment after their peak measure (after which no further virus is detected).

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
SARS-CoV-2 Viral Dynamics (Duration) in Upper Respiratory Samples in Healthy Volunteers	12.52 Duration in Days (Mid-Turbinate) Interval 11.5 to 14.5

SECONDARY outcome

Timeframe: From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days

To assess the viral dynamics using a) mid turbinate samples, and b) throat swabs as measured incubation period of SARS-CoV-2 qRT-PCR measurements. Incubation period is defined as the time (hours) from inoculation to the first quantifiable of the two viral quantifiable positives used to assess infection, starting from 24 hours post-inoculation and up to discharge from quarantine.

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
SARS-CoV-2 Viral Dynamics (Incubation Period) in Upper Respiratory Samples in Healthy Volunteers	75.527 Incubation Period (Hours) (Mid-Turbinate Standard Deviation 35.8999

SECONDARY outcome

Timeframe: From 24 hours post-inoculation to 312 hours post-inoculation

Area under the curve over time (TSS-AUC) of total clinical symptoms (TSS) as measured by graded symptom scoring system (categorical and visual analogue scales), starting one day post-viral challenge (Day 1) up to discharge from quarantine. Symptoms are graded on a scale from 0 (no symptoms) to 3 (bothersome symptoms impacting involvement in activities). The sum total symptom score was based on the symptom diary cards that were filled out 3 times per day from the first (morning) assessment on Day 1 until the first (morning) assessment on Day 14 (planned day of quarantine discharge). Each assessment consisted of the grades given by the subjects to a list of 19 symptoms on the symptom diary card. Individual total symptom scores were derived for each assessment as the total of all of the grades given on the individual diary card. This could range from 0 (if all symptoms graded as 0) to 59 (if all symptoms graded as 3 and shortness of breath and wheeze were graded as 4).

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
SARS-CoV-2 Induced Symptoms in Healthy Volunteers According to Area Under the Curve Over Time (TSS-AUC) of Total Clinical Symptoms (TSS).	213.444 Total Symptom Score AUC (hours*score) Standard Deviation 337.8488

SECONDARY outcome

Timeframe: From 24 hours post-inoculation until 312 hours post-inoculation

Peak symptoms diary card score: peak total clinical symptoms (TSS) as measured by graded symptom scoring system (categorical and visual analogue scales, starting one day post-viral challenge (Day 1) up to discharge from quarantine. Symptoms are graded on a scale from 0 (no symptoms) to 3 (bothersome symptoms impacting involvement in activities). The sum total symptom score was based on the symptom diary cards that were filled out 3 times per day from the first (morning) assessment on Day 1 until the first (morning) assessment on Day 14 (planned day of quarantine discharge). Each assessment consisted of the grades given by the subjects to a list of 19 symptoms on the symptom diary card. Individual total symptom scores were derived for each assessment as the total of all of the grades given on the individual diary card. This could range from 0 (if all symptoms graded as 0) to 59 (if all symptoms graded as 3 and shortness of breath and wheeze were graded as 4).

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
SARS-CoV-2 Induced Symptoms in Healthy Volunteers According to Peak Symptom Diary Card Scores	2.8 Peak Total Symptom Score Standard Deviation 2.86

SECONDARY outcome

Timeframe: From 24 hours post-inoculation until 312 hours post-inoculation

Peak daily symptom score: Individual maximum daily sum of Symptom score starting one day post-viral challenge (Day 1) up to the end of quarantine. Symptoms are graded on a scale from 0 (no symptoms) to 3 (bothersome symptoms impacting involvement in activities). The sum total symptom score was based on the symptom diary cards that were filled out 3 times per day from the first (morning) assessment on Day 1 until the first (morning) assessment on Day 14 (planned day of quarantine discharge). Each assessment consisted of the grades given by the subjects to a list of 19 symptoms on the symptom diary card.

Individual total symptom scores were derived for each assessment as the total of all of the grades given on the individual diary card. This could range from 0 (if all symptoms graded as 0) to 59 (if all symptoms graded as 3 and shortness of breath and wheeze were graded as 4).

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
SARS-CoV-2 Induced Symptoms in Healthy Volunteers According to Peak Daily Symptom Score.	5.8 Peak Daily Total Symptom Score Standard Deviation 6.98

SECONDARY outcome

Timeframe: From 24 hours post-inoculation until 312 hours post-inoculation

Number (%) of participants with Grade 2 or higher symptoms. Symptoms are graded on a scale from 0 (no symptoms) to 3 (bothersome symptoms impacting involvement in activities). The sum total symptom score was based on the symptom diary cards that were filled out 3 times per day from the first (morning) assessment on Day 1 until the first (morning) assessment on Day 14 (planned day of quarantine discharge). Each assessment consisted of the grades given by the subjects to a list of 19 symptoms on the symptom diary card. Individual total symptom scores were derived for each assessment as the total of all of the grades given on the individual diary card. This could range from 0 (if all symptoms graded as 0) to 59 (if all symptoms graded as 3 and shortness of breath and wheeze were graded as 4).

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
Number (%) of Participants With Grade 2 or Higher SARS-CoV-2 Induced Symptoms	14 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 to 28 (28 days)

To explore safety related measures of wild type SARS-CoV-2 challenge in healthy participants by assessing changes in smell (anosmia/parosmia) measured by the University of Pennsylvania Smell Identification Test (UPSIT). The USPIT test has 40 smells to "scratch and sniff". Each smell has a possible of 4 answers with one being correct, therefore the potential scores can range from 0-40.

Score of less than 19 = anosmia. Score of 19 to 25 = severe microsmia. Score of 26 to 30 in females or 26 to 29 in males = microsmia Score of 31 to 24 in females or 30 to 33 in males = mild microsmia Score of 35 or more in females or 34 or more in males = normosmia

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
Average Change in Smell Measured by the University of Pennsylvania Smell Identification Test (UPSIT)	-0.5 score on a scale Interval -0.5 to -0.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 to 28 (28 days)

To explore the safety of wild type SARS-CoV-2 human challenge model in healthy adults by assessing pulmonary changes due to experimental infection, as measured by Spirometry FEV1 and FVC. FEV1 and FVC will both be used for FEV1/FVC ratio.

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
Average Pulmonary Changes Measured by Spirometry (FEV1, FVC)	-0.4 ratio Standard Deviation 4.06

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 to 28 (28 days)

To explore the safety of wild type SARS-CoV-2 human challenge model in healthy adults by assessing the occurrence of haematological and biochemical laboratory abnormalities during the quarantine period. Haematological and biochemical laboratory abnormalities will be identified from blood sampling analysis.

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
Number of Haematological and Biochemical Laboratory Abnormalities During the Quarantine Period	13 Laboratory Test Results reported as AEs

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 0 to 28 (28 days)

To explore the safety of wild type SARS-CoV-2 human challenge model in healthy adults by assessing the use of concomitant medications within 30 days post-viral challenge (Day 0 up to Day 28 follow up).

Outcome measures

Measure	Healthy Volunteers Dose Level 1 n=36 Participants Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
Number of Participants Using Concomitant Medication Within 30 Days Post-viral Challenge	26 Participants

Adverse Events

Healthy Volunteers Dose Level 1

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Measure	Healthy Volunteers Dose Level 1 n=36 participants at risk Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
Renal and urinary disorders Left Side Renal Pain	2.8% 1/36 • Number of events 1 • Day 0 to Day 360

Other adverse events

Measure	Healthy Volunteers Dose Level 1 n=36 participants at risk Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
Investigations Fibrin D dimer increased	16.7% 6/36 • Day 0 to Day 360
Investigations Neutrophil count decreased	8.3% 3/36 • Day 0 to Day 360
Investigations Alanine aminotransferase increased	5.6% 2/36 • Day 0 to Day 360
Investigations Lymphocyte count decreased	2.8% 1/36 • Day 0 to Day 360
Investigations Platelet count decreased	2.8% 1/36 • Day 0 to Day 360
Investigations Troponin increased	2.8% 1/36 • Day 0 to Day 360
Investigations White blood cell count decreased	2.8% 1/36 • Day 0 to Day 360
General disorders Medical device site rash	13.9% 5/36 • Day 0 to Day 360
General disorders Vessel puncture site bruise	2.8% 1/36 • Day 0 to Day 360
General disorders Catheter site rash	2.8% 1/36 • Day 0 to Day 360
Skin and subcutaneous tissue disorders Dry skin	11.1% 4/36 • Day 0 to Day 360
Skin and subcutaneous tissue disorders Rash	2.8% 1/36 • Day 0 to Day 360
Skin and subcutaneous tissue disorders Dermatitis	2.8% 1/36 • Day 0 to Day 360
Skin and subcutaneous tissue disorders Pruritus	2.8% 1/36 • Day 0 to Day 360
Nervous system disorders Anosmia	11.1% 4/36 • Day 0 to Day 360
Nervous system disorders Hypoaesthesia	2.8% 1/36 • Day 0 to Day 360
Nervous system disorders Paraesthesia	2.8% 1/36 • Day 0 to Day 360
Nervous system disorders Syncope	2.8% 1/36 • Day 0 to Day 360
Infections and infestations COVID-19	5.6% 2/36 • Day 0 to Day 360
Infections and infestations Tooth infection	2.8% 1/36 • Day 0 to Day 360
Infections and infestations Upper respiratory tract infection	2.8% 1/36 • Day 0 to Day 360
Gastrointestinal disorders Toothache	2.8% 1/36 • Day 0 to Day 360
Gastrointestinal disorders Mouth ulceration	2.8% 1/36 • Day 0 to Day 360
Reproductive system and breast disorders Epididymal tenderness	2.8% 1/36 • Day 0 to Day 360
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.8% 1/36 • Day 0 to Day 360
Blood and lymphatic system disorders Neutropenia	2.8% 1/36 • Day 0 to Day 360

Additional Information

Professor Christopher Chiu

Imperial College London

Phone: 02083832301

Email: c.chiu@imperial.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place