Coronavirus, Corona Virus Infection, Covid19, COVID-19, SARS-CoV Infection
Conditions
Brief summary
This is a dose optimisation study in healthy adults aged 18-30 who will be experimentally inoculated with SARS-CoV-2. The aim is to cause PCR-confirmed upper respiratory infection in the majority of challenged individuals with minimal or no illness, providing data on the course of COVID-19 and the immune response to SARS-CoV-2 infection. This will establish an optimised dose and study design that will then be used to evaluate the efficacy of treatment and vaccine candidates plus level and duration of immune protection in follow-on trials.
Interventions
BIOLOGICALSARS-CoV-2 Virus 1x10^1 TCID50
SARS-CoV-2, intranasally, (1x10\^1 TCID50)
DRUGRemdesivir
VEKLURY™
BIOLOGICALSARS-CoV-2 Virus 1x10^2 TCID50
SARS-CoV-2, intranasally, (1x10\^2 TCID50)
BIOLOGICALSARS-CoV-2 Virus 1x10^3 TCID50
SARS-CoV-2, intranasally, (1x10\^3 TCID50)
Sponsors
Hvivo
Royal Free Hospital NHS Foundation Trust
Imperial College London
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Dose Escalation
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
1. An informed consent document signed and dated by the participant and the Investigator. 2. Male or female, age between 18 and 30 years inclusive (at the time of consent) 3. Seronegative to the challenge virus SARS-CoV-2, no history of SARS-CoV-2 infection and no previous participation in a SARS-CoV-2 vaccine trial. 4. Female participants with a documented menstrual period within 28 days before the inoculation (unless using a contraceptive method that suppressed menstruation as indicated in the study protocol) and willing and able to use contraception as described in the study protocol from 2 weeks before the scheduled date of viral challenge until 90 days after receipt of the final dose of rescue medication. Negative urine pregnancy tests will be required at screening and on day 0 prior to inoculation. On admission to the quarantine unit a Negative serum beta human chorionic gonadotropin (β-hCG) is required. Contraceptive requirements: Established use of hormonal methods of contraception described below (for 2 weeks prior to the first study visit). When hormonal methods of contraception are used, male partners are required to use a condom with a spermicide: 1. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: i. oral ii. intravaginal iii. transdermal 2. . progestogen-only hormonal contraception associated with inhibition of ovulation: i. oral ii. injectable iii. implantable 3. Intrauterine device (IUD) 4. . Intrauterine hormone-releasing system (IUS) 5. . Bilateral tubal ligation 6. . Male sterilisation (with the appropriate post vasectomy documentation of the absence of sperm in the ejaculate) where the vasectomised male is the sole partner for that woman. 7. . True abstinence - sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. 5 Men who are willing to use one of the contraception methods described in the study protocol, from the time of the date of viral challenge, until 90 days after receipt of the final dose of study medication. Contraceptive requirements: 1. Use a condom with a spermicide to prevent pregnancy in a female partner or to prevent exposure of any partner (male and female) to the study virus or Remdesivir. 2. Male sterilisation with the appropriate post vasectomy documentation of the absence of sperm in the ejaculate (please note that the use of condom with spermicide will still be required to prevent partner exposure). This applies only to males participating in the study. 3. In addition, for female partners of child bearing potential, that partner must use another form of contraception such as one of the highly effective methods mentioned above for female subjects. 4. True abstinence - sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. In addition to the contraceptive requirements above, male subjects must agree not to donate sperm following discharge from quarantine until 90 days after the date of study virus or Remdesivir. (whichever occurs last). 6 In good health with no history of clinically significant medical conditions (as described in
Exclusion criteria
) that would interfere with subject safety, as defined by medical history, physical examination and routine laboratory tests, ECG, and Chest X-Ray and determined by the Investigator at an admission evaluation. 7 Subjects will have a documented medical history either prior to entering the study and/or following medical history review with the study physician at screening 8 Using the QCOVID tool, an absolute risk of COVID-associated death of 1 in 250,000 (0.0004%) or less and COVID-associated hospital admission of 1 in 5000 (0.02%) or less, unless deemed unnecessary by the CI and PI with advice from the DSMB following a formal interim assessment (see below) 9 Willing and able to commit to participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Unsolicited Adverse Events in Healthy Participants Challenged With Wild Type SARS-CoV-2 | Day 0 to 28 (28 days) | 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. |
| Number of Participants With Laboratory Confirmed Infections | From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days | 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. |
| Number of SAEs Related to Viral Challenge | Day 0 to 28 (28 days) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SARS-CoV-2 Viral Dynamics (VL-AUC) in Upper Respiratory Samples in Healthy Volunteers | 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. |
| SARS-CoV-2 Induced Symptoms in Healthy Volunteers by the Mean Sum Total Symptom Score | 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). |
| Number of Participants With Incidence of SARS-CoV-2 Illness in Healthy Volunteers | 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 |
| SARS-CoV-2 Viral Dynamics (Peak Viral Load) in Upper Respiratory Samples in Healthy Volunteers | 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. |
| Number of Patients With Laboratory Confirmed Infections by Mid-turbinate and/or Throat Swabs | 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. |
| Number of Symptomatic SARS-Cov-2 Infected Participants | From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days | 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, |
| SARS-CoV-2 Induced Symptoms in Healthy Volunteers According to Area Under the Curve Over Time (TSS-AUC) of Total Clinical Symptoms (TSS). | 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). |
| SARS-CoV-2 Induced Symptoms in Healthy Volunteers According to Peak Symptom Diary Card Scores | 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). |
| SARS-CoV-2 Induced Symptoms in Healthy Volunteers According to Peak Daily Symptom Score. | 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). |
| Number (%) of Participants With Grade 2 or Higher SARS-CoV-2 Induced Symptoms | 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). |
| SARS-CoV-2 Viral Dynamics (Duration) in Upper Respiratory Samples in Healthy Volunteers | 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). |
| SARS-CoV-2 Viral Dynamics (Incubation Period) in Upper Respiratory Samples in Healthy Volunteers | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Average Change in Smell Measured by the University of Pennsylvania Smell Identification Test (UPSIT) | 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 |
| Number of Participants Using Concomitant Medication Within 30 Days Post-viral Challenge | 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). |
| Number of Haematological and Biochemical Laboratory Abnormalities During the Quarantine Period | 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. |
| Average Pulmonary Changes Measured by Spirometry (FEV1, FVC) | 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. |
Countries
United Kingdom
Participant flow
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| Healthy Volunteers Dose Level 1 Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 dose +/- Remdesivir: VEKLURY™ | 36 |
| Total | 36 |
Baseline characteristics
| Characteristic | Healthy Volunteers Dose Level 1 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants |
| Age, Continuous | 21.8 years STANDARD_DEVIATION 2.89 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Region of Enrollment United Kingdom | 36 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 36 |
| other Total, other adverse events | 24 / 36 |
| serious Total, serious adverse events | 1 / 36 |
Outcome results
Primary
Number of Participants With Laboratory Confirmed Infections
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healthy Volunteers Dose Level 1 | Number of Participants With Laboratory Confirmed Infections | 18 infected participants |
Primary
Number of SAEs Related to Viral Challenge
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.
Time frame: Day 0 to 28 (28 days)
Population: Healthy volunteers given SARS-CoV-2 virus at 10\^1 TCID50 +/- Remdesivir: VEKLURY™
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healthy Volunteers Dose Level 1 | Number of SAEs Related to Viral Challenge | 0 SAE events |
Primary
Number of Unsolicited Adverse Events in Healthy Participants Challenged With Wild Type SARS-CoV-2
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.
Time frame: Day 0 to 28 (28 days)
Population: All subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healthy Volunteers Dose Level 1 | Number of Unsolicited Adverse Events in Healthy Participants Challenged With Wild Type SARS-CoV-2 | 45 Unsolicited Adverse Events |
Secondary
Number (%) of Participants With Grade 2 or Higher SARS-CoV-2 Induced Symptoms
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).
Time frame: From 24 hours post-inoculation until 312 hours post-inoculation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Healthy Volunteers Dose Level 1 | Number (%) of Participants With Grade 2 or Higher SARS-CoV-2 Induced Symptoms | 14 Participants |
Secondary
Number of Participants With Incidence of SARS-CoV-2 Illness in Healthy Volunteers
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
Time frame: Day 0 to discharge from Quarantine, up to a maximum of 17 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healthy Volunteers Dose Level 1 | Number of Participants With Incidence of SARS-CoV-2 Illness in Healthy Volunteers | 20 participants |
Secondary
Number of Patients With Laboratory Confirmed Infections by Mid-turbinate and/or Throat Swabs
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.
Time frame: From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healthy Volunteers Dose Level 1 | Number of Patients With Laboratory Confirmed Infections by Mid-turbinate and/or Throat Swabs | 18 infected participants |
Secondary
Number of Symptomatic SARS-Cov-2 Infected Participants
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,
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Healthy Volunteers Dose Level 1 | Number of Symptomatic SARS-Cov-2 Infected Participants | 14 Participants |
Secondary
SARS-CoV-2 Induced Symptoms in Healthy Volunteers According to Area Under the Curve Over Time (TSS-AUC) of Total Clinical Symptoms (TSS).
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).
Time frame: From 24 hours post-inoculation to 312 hours post-inoculation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers Dose Level 1 | 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
SARS-CoV-2 Induced Symptoms in Healthy Volunteers According to Peak Daily Symptom Score.
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).
Time frame: From 24 hours post-inoculation until 312 hours post-inoculation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers Dose Level 1 | 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
SARS-CoV-2 Induced Symptoms in Healthy Volunteers According to Peak Symptom Diary Card Scores
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).
Time frame: From 24 hours post-inoculation until 312 hours post-inoculation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers Dose Level 1 | 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
SARS-CoV-2 Induced Symptoms in Healthy Volunteers by the Mean Sum Total Symptom Score
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).
Time frame: From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers Dose Level 1 | 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
SARS-CoV-2 Viral Dynamics (Duration) in Upper Respiratory Samples in Healthy Volunteers
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).
Time frame: From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Healthy Volunteers Dose Level 1 | SARS-CoV-2 Viral Dynamics (Duration) in Upper Respiratory Samples in Healthy Volunteers | 12.52 Duration in Days (Mid-Turbinate) |
Secondary
SARS-CoV-2 Viral Dynamics (Incubation Period) in Upper Respiratory Samples in Healthy Volunteers
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.
Time frame: From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers Dose Level 1 | 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
SARS-CoV-2 Viral Dynamics (Peak Viral Load) in Upper Respiratory Samples in Healthy Volunteers
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.
Time frame: From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers Dose Level 1 | SARS-CoV-2 Viral Dynamics (Peak Viral Load) in Upper Respiratory Samples in Healthy Volunteers | 4.5764 log10 copies/mL | Standard Deviation 4.506 |
Secondary
SARS-CoV-2 Viral Dynamics (VL-AUC) in Upper Respiratory Samples in Healthy Volunteers
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.
Time frame: From 24 hours post-inoculation to 312 hours post-inoculation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers Dose Level 1 | SARS-CoV-2 Viral Dynamics (VL-AUC) in Upper Respiratory Samples in Healthy Volunteers | 171.154 hours*Log10 FFU/mL | Standard Deviation 193.2885 |
Other Pre-specified
Average Change in Smell Measured by the University of Pennsylvania Smell Identification Test (UPSIT)
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
Time frame: Day 0 to 28 (28 days)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Healthy Volunteers Dose Level 1 | Average Change in Smell Measured by the University of Pennsylvania Smell Identification Test (UPSIT) | -0.5 score on a scale |
Other Pre-specified
Average Pulmonary Changes Measured by Spirometry (FEV1, FVC)
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.
Time frame: Day 0 to 28 (28 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers Dose Level 1 | Average Pulmonary Changes Measured by Spirometry (FEV1, FVC) | -0.4 ratio | Standard Deviation 4.06 |
Other Pre-specified
Number of Haematological and Biochemical Laboratory Abnormalities During the Quarantine Period
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.
Time frame: Day 0 to 28 (28 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healthy Volunteers Dose Level 1 | Number of Haematological and Biochemical Laboratory Abnormalities During the Quarantine Period | 13 Laboratory Test Results reported as AEs |
Other Pre-specified
Number of Participants Using Concomitant Medication Within 30 Days Post-viral Challenge
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).
Time frame: Day 0 to 28 (28 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Healthy Volunteers Dose Level 1 | Number of Participants Using Concomitant Medication Within 30 Days Post-viral Challenge | 26 Participants |