| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| The prevention of symptomatic coronavirus (CoV) disease 2019 (COVID 19) in adults and adolescents |
|
| E.1.1.1 | Medical condition in easily understood language |
| Coronavirus (CoV) disease 2019 (COVID 19) with symptoms in adults and adolescents with no known history of severe acute respiratory syndrome (SARS) CoV 2 (SARS CoV 2) infection |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 23.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10084529 |
| E.1.2 | Term | 2019 novel coronavirus infection |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
For (Cohort A [PEP])
- To evaluate the efficacy of ADG20 compared with placebo in the
prevention of RT-PCR-confirmed symptomatic COVID-19 through Day 28
in all randomized participants.
-To evaluate the safety and tolerability of ADG20 compared with placebo
following intramuscular administration.
For (Cohort B [PrEP])
-To evaluate the efficacy of ADG20 compared with placebo in the
prevention of RT-PCR-confirmed symptomatic COVID-19 through 6
months in participants with negative SARS-CoV-2 testing (RT-PCR and
serology) at baseline.
-To evaluate the safety and tolerability of ADG20 compared with placebo
following intramuscular administration.
|
|
| E.2.2 | Secondary objectives of the trial |
To evaluate:
Cohort A:
- efficacy of ADG20 compared with placebo in prevention of RT-PCR
confirmed symptomatic COVID-19 through 6 months and 12 months in
all randomized participants;
- efficacy of ADG20 compared with placebo in prevention of SARS-CoV-2
infection (based on RT-PCR or serology) regardless of symptoms in
participants with negative SARS-CoV-2 testing (RT-PCR and serology) at
baseline;
- effect of ADG20 on clinical and virologic parameters in participants
with laboratory-confirmed symptomatic COVID-19 through CLI Day 28
Cohort B:
- efficacy of ADG20 compared with placebo in prevention of RT-PCRconfirmed symptomatic COVID-19 through 12 months, in participants
with negative SARS-CoV-2 testing (RT-PCR and serology) at baseline;
- efficacy of ADG20 compared with placebo in prevention of SARS-CoV-2
infection (based on RT-PCR or serology) regardless of symptoms through
6 & 12 months, in participants with negative SARS-CoV-2 testing (RTPCR and serology) at baseline |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Adult aged ≥18 years or adolescent aged 12 to <18 years and
weighing at least 40 kg at the time of Screening.
Note: Adolescent enrollment will open only upon sponsor communication
to sites after review of Phase 2 data.
2. Tests negative for current or previous SARS-CoV-2 infection by RTPCR and serology at the time of screening.
Note: Cohort A participants may be randomized without RT-PCR and
serology results if these results are not available by Day 5 of Screening.
3. Is at high risk of SARS-CoV-2 infection as assessed by the
Investigator:
a) Cohort A (PEP): recent exposure to an individual with a diagnosis of
SARS-CoV-2 infection (index case).*
Note: Randomization must occur within 5 days (120 hours) from both
exposure to and sample collection from the index case. Participants with
recent exposure to a laboratory-confirmed index case must be
asymptomatic at randomization.
* Exposure is generally defined as repeated contact lasting 15 minutes
or more within a 24-hour period, where the individuals were within 2
meters (approximately 6.5 feet) of each other, and neither party was
wearing a facemask or respirator.
b) Cohort B (PrEP): Occupational, housing, recreational and/or social
conditions that are likely to increase risk of exposure to SARS-CoV-2
4. Agrees to defer receipt of COVID-19 vaccination for minimum of 180
days (6 months) after dosing.
5. Is able and willing to provide informed consent. A legally authorized
representative may be used in cases where inclusion criterion 9 is able
to be fulfilled. In the case of adolescents, informed consent/assent must
also be obtained as required by local guidelines.
6. Participants assigned female sex at birth who are not of reproductive
potential are eligible without requiring the use of contraception and do
not require a pregnancy test. This includes female participants who have
not undergone menarche or who are documented to be surgically sterile
(e.g., hysterectomy, removal of both ovaries, or tubal ligation) or postmenopausal (i.e., amenorrhea >1 year and follicle-stimulating hormone
>40 mIU/mL). Follicle-stimulating hormone is not required in postmenopausal females with amenorrhea for >2
years.
7. Participants assigned female sex at birth and who are of childbearing
potential may be enrolled in the study if the participant has practiced
adequate contraception or has abstained from all sexual activities that
could result in pregnancy for at least 28 days before the day of dosing
(Day 1) and has agreed to continue adequate contraception for sexual
activity that could lead to pregnancy through 6 months following dosing.
Adequate contraception for participants assigned female sex at birth is
defined as consistent and correct use of a contraceptive approved by the
local Health Authority and used in accordance with the product label. For example:
a) Barrier method (such as condoms, diaphragm, or cervical cap) used
in conjunction with spermicide.
b) Intrauterine device.
c) Hormonal contraceptive taken or administered via oral (pill),
transdermal (patch), intravaginal, implantable, or injectable method.
d) Sterilization of a female participant's male partner before entry into
the study.
e) Sexual abstinence.*
Note: periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception.
*Sexual abstinence is considered an effective method only if defined as
refraining from heterosexual intercourse from providing consent until 6
months after dosing. The reliability of sexual abstinence needs to be
evaluated in relation to the duration of the study and the preferred
and usual lifestyle of the participant.
8. Participants assigned male sex at birth with partner(s) of childbearing
potential who agree to use adequate contraception through 6 months
after dosing. If their partner is pregnant, males must agree to use a
condom. Male participants must also refrain from sperm donation
through 6 months after dosing.
9. Able to understand and comply with study requirements/procedures
(if applicable, with assistance by caregiver, surrogate, or legally
authorized representative) based on the assessment of the Investigator
|
|
| E.4 | Principal exclusion criteria |
1. Prior receipt of COVID-19 vaccine, convalescent plasma, or mAb,
including in the setting of a clinical trial.
Note: immune compromised participants (e.g., due to hematological
malignancy, anti-CD20 medication use, etc.) who have completed a
COVID-19 vaccine series and who have a documented negative SARSCoV-2 Spike ("S") protein serum antibody test drawn a minimum of four
weeks after completion of the recommended dosing series may be
screened and subsequently enrolled if other criteria are met, including a
confirmatory negative "S" protein antibody test at the time of screening.
This test must be confirmed negative prior to enrollment in either Cohort
A or Cohort B.
2. Receipt of any investigational product within 30 days or 5 half-lives
before the day of enrollment.
3. Is acutely ill or has any of the following symptoms:
Fever ≥38°C (≥100.4°F).
Shortness of breath/difficulty breathing
Chills (shivering)
Cough
Fatigue (low energy or tiredness)
Muscle or body aches
Headache
Loss of taste
Loss of smell
Sore throat
Congestion (stuffy or runny nose)
Nausea
Vomiting
Diarrhea
Participants meeting this criterion may be rescheduled within the relevant window periods.
4. Has received or plans to receive a non-COVID-19 vaccine within 28
days before or after dosing (except for seasonal influenza vaccine, which
is not permitted within 14 days before or after dosing).
5. Known allergy/sensitivity or hypersensitivity to the study drug,
including excipients.
6. Is pregnant, as confirmed with a positive pregnancy test at Screening
or on the day of dosing (Day 1), or breastfeeding.
7. Clinically significant bleeding disorder (e.g., factor deficiency,
coagulopathy, or platelet disorder), or prior history of significant
bleeding or bruising following IM injections or venipuncture.
8. Severe and/or uncontrolled cardiovascular disease, respiratory
disease, gastrointestinal disease, liver disease, renal disease, endocrine
disorder, autoimmune disease or immune compromise, or neurological
illness, as judged by the Investigator (mild/moderate well-controlled
comorbidities are allowed.
9. Any serious concomitant systemic disease, condition, or disorder that,
in the opinion of the Investigator, might confound the results of the
study or confer an additional risk to the participant by their participation
in the study |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Cohort A [PEP]:
Proportion of participants with RT-PCR confirmed symptomatic COVID-
19 through Day 28.
Assessment of safety based on:
- Incidence of treatment-emergent adverse events.
- Incidence of solicited injection site reactions through Day 4.
- Changes from baseline in clinical laboratory tests (i.e., complete blood
count with differential and serum chemistry).
- Changes from baseline in vital signs (body temperature, heart rate,
respiration rate, and systolic and diastolic blood pressure)
Cohort B [PrEP]:
- Proportion of participants with RT-PCR-confirmed symptomatic COVID-
19 through 6 months.
- Suplementary:
o Time from randomization to RT-PCR-confirmed symptomatic COVID-19
diagnosis.
o Probability for RT-PCR-confirmed symptomatic COVID-19 through 6
months.
Assessment of safety based on:
o Incidence of treatment-emergent adverse events.
o Incidence of solicited injection site reactions through Day 4.
o Changes from baseline in clinical laboratory tests (i.e., complete blood
count with differential and serum chemistry).
o Changes from baseline in vital signs (body temperature, heart rate,
respiration rate, and systolic and diastolic blood pressure). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Proportion of participants with RT-PCR confirmed symptomatic COVID-19 through 6 months and 12 months.
|
|
| E.5.2 | Secondary end point(s) |
Cohort A [PEP]:
Proportion of participants with RT-PCR-confirmed symptomatic COVID-
19 through 6 months and 12 months.
Supplementary: Time from randomization to RT-PCR-confirmed
symptomatic COVID-19 diagnosis and probability of RT-PCR confirmed
symptomatic COVID-19 through 6 months and 12 months.
o Proportion of participants with SARS-CoV-2 infection (asymptomatic or
symptomatic) as determined by positive RT-PCR or serology through Day
28.
o Proportion of participants with SARS-CoV-2 infection (asymptomatic or
symptomatic COVID-19) as determined by positive RT-PCR or serology
through 6 and 12 months.
o Proportion of participants with asymptomatic SARS-CoV-2 infection as
determined by RT-qPCR (nasal sample) on Days 8 and 15 after
randomization.
o Proportion of participants with asymptomatic SARS-CoV-2 infection as
determined by serology on Day 28 and 6 and 12 months.
o Peak SARS-CoV-2 titer as measured by RT-qPCR
o SARS-CoV-2 viral load AUC from the first positive SARS-CoV-2 sample
assessed by RT-qPCR at baseline or Day 8 through Day 15.
- Proportion of participants with RT-PCR-confirmed mild, moderate, or
severe/critical COVID-19 through CLI Day 28.
- Time to sustained resolution of COVID-19 symptoms through CLI Day
28.
- Proportion of participants with at least 1 COVID-19-related medically
attended outpatient visit (physician's office, telemedicine, emergency
rooms, or urgent care centers) through CLI Day 28 after the first positive
SARS-CoV-2 sample.
- Proportion of participants with a COVID-19 related hospitalization
through CLI Day 28 after first positive SARS-CoV-2 sample.
- COVID-19 related mortality through CLI Day 28 after first positive
SARS-CoV-2 sample.
- All-cause-mortality through CLI Day 28 after first positive SARS-CoV-2
sample.
- Duration of viral shedding from first positive SARS-CoV-2 saliva sample
through Day 21 as assessed by RT-qPCR.
- Viral load AUC from the first positive SARS-CoV-2 saliva sample
assessed by RT-qPCR to Days 3, 5, 8, 11, 14 and 21.
- Change from baseline in SARS-CoV-2 viral load (log10 copies/mL) to
Days 3, 5, 8, 11, 14 and 21 assessed by RT-qPCR from saliva samples.
- SARS-CoV-2 viral clearance (Days 3, 5, 8, 11, 14, 21) assessed by RTqPCR from saliva samples.
- PK parameters of ADG20 including but not limited to: AUC0-inf, AUC0-
last, Cmax, Tmax, CL, t1/2, and Vss.
- Incidence of ADAs against ADG20
Cohort B [PrEP]:
- Proportion of participants with RT-PCR-confirmed symptomatic COVID-
19 through 12 months.
Supplementary: Probability for RT-PCR-confirmed symptomatic COVID-
19 through 12 months.
- Proportion of participants with SARS-CoV-2 infection (asymptomatic or
symptomatic) as determined by positive RT-PCR or serology through 6
and 12 months.
- Proportion of participants with asymptomatic SARS-CoV-2 infection as
determined by serology on Month 6 and 12.
- Proportion of participants with RT-PCR-confirmed mild, moderate, or
severe/critical COVID-19 through CLI Day 28 after the first positive
SARS-CoV-2 sample.
- Time to sustained resolution of COVID-19 symptoms through CLI Day
28.
Proportion of participants with at least 1 COVID-19-related medically
attended outpatient visit (physician's office, telemedicine, emergency
rooms, or urgent care centers) through CLI Day 28 after the first positive
SARS-CoV-2 sample.
- Proportion of participants with a COVID-19-related hospitalization
through CLI Day 28 after first positive SARS-CoV-2 sample.
- COVID-19 related mortality through CLI Day 28 after first positive
SARS-CoV-2 sample.
- All-cause mortality through CLI Day 28 after first positive SARS-CoV-2
sample.
o Duration of viral shedding from first positive SARS-CoV-2 saliva sample
through Day 21 as assessed by RT-qPCR.
o Viral load AUC from the first positive SARS-CoV-2 RT-qPCR saliva
sample to Days 3, 5, 8, 11, 14 and 21.
o Change from baseline in SARS-CoV-2 viral load (log10 copies/mL) to
Days 3, 5, 8, 11, 14 and 21 assessed by RT-qPCR from saliva samples.
o SARS-CoV-2 viral clearance (Days 3, 5, 8, 11, 14, 21) assessed by RTqPCR from saliva samples.
- PK parameters of ADG20 including but not limited to: AUC0-inf, AUC0-
last, Cmax, Tmax, CL, t1/2, and Vss.
- Incidence of ADAs against ADG20 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Colombia |
| Georgia |
| Moldova, Republic of |
| Peru |
| Serbia |
| Ukraine |
| United States |
| Bulgaria |
| Germany |
| Poland |
| Romania |
| Czechia |
| Argentina |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 22 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 22 |
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