| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| SARS CoV 2 infection in outpatients |
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| E.1.1.1 | Medical condition in easily understood language |
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| 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 | 23.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10084271 |
| E.1.2 | Term | SARS-CoV-2 test positive |
| E.1.2 | System Organ Class | 10022891 - Investigations |
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| 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 |
Primary Objective (Part 1)
To assess the potential therapeutic efficacy of CT-P59 as determined by time to negative conversion in nasopharyngeal swab specimen based on reverse transcription quantitative polymerase chain reaction (RT-qPCR) or cell culture up to Day 14
Primary Objective (Part 2)
To demonstrate the clinically meaningful therapeutic efficacy of CT-P59 as determined by proportion of patients with clinical symptom requiring hospitalization, oxygen therapy, or experiencing mortality due to SARS-CoV-2 infection up to Day 28
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| E.2.2 | Secondary objectives of the trial |
Key Secondary Objectives (Part 1)
- To assess the potential therapeutic efficacy of CT-P59 as determined by proportion of patient with negative conversion in nasopharyngeal swab specimen based on RT-qPCR or cell culture at each visit up to Day 14
- To assess the potential therapeutic efficacy of CT-P59 as determined by time to clinical recovery up to Day 14
- To assess the clinically meaningful therapeutic efficacy of CT-P59 as determined by proportion of patients with clinical symptom requiring hospitalization, oxygen therapy, or experiencing mortality due to SARS-CoV-2 infection up to Day 28
Secondary Objectives (Part 1 and Part 2)
To evaluate the additional efficacy of CT-P59
To evaluate overall safety of CT-P59, including immunogenicity and potential effects on the incidence of ADE |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Each patient must meet all of the following criteria to be randomized in this study.
1. Adult male or female patient, aged
a. >60 years, or
b. ≥18 and ≤60 years, and having any baseline comorbidities which are known as the risk factors for deterioration to severe SARS-CoV-2 infection (cardiovascular disease, chronic respiratory disease, hypertension, or diabetes mellitus)
2.Patient is diagnosed with SARS-CoV-2 infection at Screening by using the RT-PCR.
Note: If the patient had a RT-PCR result (within 72 hours prior to the study drug administration) confirming SARS-CoV-2 infection even if before signing the ICF, the patient can be enrolled without additional confirmation of SARS-CoV-2 infection at Screening.
Note: During the Screening Period, only one re-test for confirmation of SARS-CoV-2 infection will be allowed, if study drug can be administered no more than 7 days from onset of symptom based on the re-test result.
3.Patient with conditions meeting all of the following criteria:
a.Oxygen saturation > 94% on room air.
b.Not requiring supplemental oxygen.
Note: Patient with clinical signs of pneumonia but no signs of severe pneumonia (as defined in the World Health Organization Guidance, 2020) at the investigator’s discretion is eligible for this study.
4.Patient whose onset of symptom is no more than 7 days prior to the study drug administration. Onset time of symptom is defined as the time when the patient experienced the presence of at least one SARS-CoV-2 infection associated symptom.
5.Patient has one or more of the following (but not limited to) SARS-CoV-2 infection associated symptoms within but not more than 7 days prior to the study drug administration:
Feeling feverish
Cough
Shortness of breath or difficulty breathing
Sore throat
Body pain or muscle pain
Fatigue
Headache
Chills
Nasal obstruction or congestion
Loss of taste or smell
Nausea or vomiting
Diarrhea
6.Patient has one or more of the following SARS-CoV-2 infection associated symptoms present within 48 hours prior to the study drug administration:
Feeling feverish
Cough
Shortness of breath or difficulty breathing
Sore throat
Body pain or muscle pain
Fatigue
Headache
7.Patient (or legal guardian, if applicable) who is informed and given ample time and opportunity to read and/or understand the nature and purpose of this study including possible risks and side effects and must sign the ICF prior to participation in the study.
8.For both male and female patients, the patient and his or her partner of childbearing potential who agree to use a highly effective or medically acceptable methods of contraception during the course of the study and for 6 months following discontinuation of study drug as specified below:
Combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation
Intrauterine devices
True abstinence, when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence of the duration of exposure to investigational drug, and withdrawal are not acceptable methods of contraception.
Condom in addition to use spermicide, hormonal contraceptive or barrier method in female; for male patient with his female partner of childbearing potential only. Spermicide condom (condoms coated with spermicide) use alone is not allowed.
Male and female patients and their partners who have been surgically sterilized for less than 6 months prior to the date of informed consent must agree to use any highly effective or medically acceptable methods of contraception. Menopausal females must have experienced their last period more than 12 months prior to the date of informed consent to be classified as not of childbearing potential.
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| E.4 | Principal exclusion criteria |
Patients meeting any of the following criteria will be excluded from the study:
1.Patient with current serious condition meeting one of the following criteria:
a.Previously or currently hospitalized or requires hospitalization for treatment of serious SARS-CoV-2 related conditions (severe disease as defined in the World Health Organization. Guidance, 2020).
b.Respiratory distress with respiratory rate ≥ 30 breaths/min.
c.Requires supplemental oxygen.
d.Experience shock.
e.Complicated with other organs failure, and intensive care unit monitoring treatment is needed by investigator’s discretion.
2.Patient who has received or has a plan to receive any of following prohibited medications or treatments:
a.Drugs with actual or possible antiviral drugs and/or possible anti-SARS-CoV-2 activity including but not limited to remdesivir, chloroquine, hydroxychloroquine, dexamethasone (or alternative corticosteroids to dexamethasone), interferon beta-1b, ribavirin, and other immunomodulatory agents and human immunodeficiency virus (HIV) protease inhibitors (lopinavir-ritonavir, etc.) for therapeutic purpose of SARS-CoV-2 infection prior to study drug administration.
b.Any SARS-CoV-2 human intravenous immunoglobulin, convalescent plasma for the treatment of SARS-CoV-2 infection prior to study drug administration.
c.Any other investigational device or medical product including but not limited to any monoclonal antibody (tocilizumab, sarilumab, etc.), fusion proteins or biologics for the treatment of SARS-CoV-2 infection prior to the study drug administration.
d.Use of medications that are contraindicated with SoC.
e.SARS-CoV-2 vaccine prior to the study drug administration.
3.Patient has known allergy or hypersensitivity reaction to any monoclonal antibody or to any components of study drug.
4.Patient who has a current or history of any of the following infections:
a.Any active infection other than SARS-CoV-2 requiring systemic treatment.
b. Documented current infection with HIV, hepatitis B or hepatitis C.
c.Severe infection, in the investigator’s opinion, within 30 days prior to the administration of study drug that required parenteral antibiotic use or hospitalization.
5.Patient who has a medical condition including one or more of the following at Screening:
a.Any uncontrolled clinically significant respiratory disease in the investigator’s opinion (e.g., chronic obstructive pulmonary disease, cystic fibrosis, bronchiectasis, asthma).
b.Abnormal liver function values including but not limited to the aspartate transaminase, alanine transaminase or alkaline phosphatase ≥5 × upper limit normal
c.Renal impairment (estimated glomerular filtration rate <30 mL/min/1.73m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis.
d.History or presence of congestive heart failure with symptoms consistent with New York Heart Association Class III or IV functional status within 6 months prior to the study drug administration.
e.Presence of clinically significant abnormality on a 12-lead ECG at Screening that, at the investigator's clinical judgment, may compromise the safety of the patient or affect the outcome of the study.
f.Uncontrolled diabetes mellitus or hypertension, at the discretion of investigator.
g.Any active malignancy.
h.Currently immunocompromised, whether due to underlying medical condition (e.g., malignancy, transplantation) or medical therapy (e.g., medications, chemotherapy, radiation).
i.Any co-morbidity requiring surgery within <7 days prior to the study drug administration, or that is considered life threatening within 30 days prior to study drug administration.
j.Any conditions significantly affecting the nervous system (i.e., neuropathic conditions or nervous system damage)
k.Patient shows evidence of a condition (psychological, emotional problems, any disorders or resultant therapy) that is likely to invalidate health information, consent, or limit the ability of the patient to comply with the protocol requirements in the opinion of the investigator.
l.Any medical condition that, in the opinion of the site investigator, would place the patient at an unreasonably increased risk through participation in this study, including any past or concurrent conditions that would preclude randomization to one or more of the assigned treatment arms.
Patient who currently abuses alcohol or drugs or has a history of alcohol or drug abuse within 12 months prior to the study drug administration.
Patient who has received any other investigational device or medical product within 4 weeks prior to the study drug administration or 5 half-lives, whichever is longer.
Female patient is currently pregnant or breastfeeding or planning to be pregnant or to breastfeed, or male patient is planning to father a child or donate sperms throughout the study (up to 6 months after the study drug administration). |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
For Part 1, the primary endpoint is defined as:
Time to negative conversion in nasopharyngeal swab specimen based on RTqPCR or cell culture up to Day 14
For Part 2, the primary endpoint is defined as:
Proportion of patients with clinical symptom requiring hospitalization, oxygen therapy, or experiencing mortality due to SARS-CoV-2 infection up to Day 28.
Key Secondary Endpoints
The following key secondary endpoints will be analyzed for Part 1.
•Proportion of patient with negative conversion in nasopharyngeal swab specimen based on RT-qPCR or cell culture at each visit up to Day 14
•Time to clinical recovery up to Day 14
•Proportion of patients with clinical symptom requiring hospitalization, or oxygen therapy, or experiencing mortality due to SARS-CoV-2 infection up to Day 28
Clinical recovery is defined as all symptoms on the SARS-CoV-2 Infection Symptom Checklist 1 being recorded as ‘absent’ or ‘mild’ in intensity for at least 48 hours. To meet the clinical recovery, symptoms ‘moderate’ or ‘severe’ in intensity at baseline should be changed to ‘mild’ or ‘absent’, or symptoms ‘mild’ in intensity at baseline should be changed to ‘absent’, after the study drug administration. If a symptom ‘absent’ in intensity at baseline becomes ‘severe’, ‘moderate’, or ‘mild’ during the study, this should be changed back to ‘absent’ for at least 48 hours. Symptoms of SARS-CoV-2 Infection Symptom Checklist 1 are defined as feeling feverish, cough, shortness of breath or difficulty breathing, sore throat, body pain or muscle pain, fatigue, and headache
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
Secondary endpoints
The following secondary endpoints will be analyzed for both Part 1 and Part 2 throughout the study.
Efficacy
The following secondary efficacy endpoints will be assessed up to Day 14 and up to Day 28.
•Proportion of patients requiring supplemental oxygen due to SARS-CoV-2 infection
•Proportion of patients with intensive care unit transfer due to SARS-CoV-2 infection
•Proportion of patients with all-cause mortality
•Time to clinical recovery
•Duration of fever defined as the last day in the patient diary on which the temperature > 38°C (100.4°F) is recorded, or a potentially antipyretic drug (acetaminophen or ibuprofen) is taken
•Proportion of patients with hospital admission due to SARS-CoV-2 infection
- Proportion of mechanical ventilation due to SARS-CoV-2 infection
- Proportion of patients requiring rescue therapy due to SARS-CoV-2 infection
- Proportion of patients with negative conversion in nasopharyngeal swab specimen based on RT-qPCR or cell culture at each visit
- Time to negative conversion in nasopharyngeal swab specimen based on RT-qPCR or cell culture
- Time to NEWS2 of 0
- Scores of other known SARS-CoV-2 infection symptoms such as vomiting, diarrhea, loss of taste or smell
Rescue therapy is defined as the prohibited medication administered due to SARS-CoV-2 infection after the study drug administration on Day 1.
Safety
Safety assessments will occur throughout the study.
The following safety parameters are determined as secondary safety endpoints:
•Adverse events (including SAEs)
•Adverse events of special interest (Infusion related reactions [hypersensitivity/ anaphylactic reactions])
•Potential effects on the incidence of ADE
•Immunogenicity
•Vital sign measurements (blood pressure, heart rate, respiratory rate, SpO2 and body temperature), weight and BMI
•Hypersensitivity monitoring
•12-lead electrocardiogram
•Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection related signs and symptoms
•Radiography (chest x-ray or chest CT)
•Physical examination findings
•Clinical laboratory analyses (clinical chemistry, hematology and urinalysis)
•Pregnancy testing (serum)
•Prior and concomitant medications
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 14
Day 28
Throughout the study |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| 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 | Yes |
| 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 | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| 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 |
| Brazil |
| India |
| Korea, Republic of |
| Mexico |
| Peru |
| Russian Federation |
| South Africa |
| Ukraine |
| United States |
| Ireland |
| Poland |
| Romania |
| Spain |
| Sweden |
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| 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
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| 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 | 5 |
| E.8.9.1 | In the Member State concerned days | |
| 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 |
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