This is a first-in-human, open label, single dose, dose-escalation phase 1 study to evaluate the safety and pharmacokinetics of a combination of two highly neutralizing anti-SARS-CoV-2 mAbs targeting two distinct epitopes on the receptor protein binding domain (RBD) of the SARS-CoV-2 spike protein in healthy volunteers.
The study has a standard 3+3 phase 1 dose escalation design. Study participants will receive
subcutaneous injections of C144-LS and C135-LS at 4ml (approximately 100mg of each antibody
administered separately) or 8ml (approximately 200mg of each antibody administered
separately), or sequential intravenous infusions of C144-LS and C135-LS, at one of three
increasing dose levels (1.5 mg/kg, 5 mg/kg and 15 mg/kg of each antibody).
Biological: C144-LS and C-135-LS
A combination of two highly neutralizing anti-SARS-CoV-2 mAbs targeting two distinct epitopes on the receptor protein binding domain (RBD) of the SARS-CoV-2 spike protein
Inclusion Criteria:
- Aged 18 or older.
- If sexually active male or female, and participating in sexual activity that could
lead to pregnancy, agrees to use one effective method of contraception from 10 days
prior to the antibody administration until 6 months after investigational product (IP)
administration.
Exclusion Criteria:
- Weight > 110 kg for groups S1 and S2 only
- History of prior positive SARS-CoV-2 RT-PCR or SARS-CoV-2 serology.
- Active respiratory or non-respiratory symptoms consistent with COVID-19.
- Medically attended acute illness or hospitalization (ie, >24 hours) for any reason
within 30 days prior to screening.
- Acute exacerbation of a chronic pulmonary condition (eg, chronic obstructive pulmonary
disease [COPD], asthma exacerbations, or uncontrolled hypertension, as defined by a
systolic blood pressure > 180 and/or diastolic blood pressure > 120, in the presence
or absence of anti-hypertensive medications) in the past 6 months prior to screening.
- Use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications
considered significant by the trial physician within the last 6 months.
- Other clinically significant acute or chronic medical condition that in the opinion of
the investigator would preclude participation.
- Laboratory abnormalities in the parameters listed:
- Absolute neutrophil count less than 1,500 K/mcL;
- Hemoglobin less than 10.5 gm/dL if female; less than 11 gm/dL if male;
- Platelet count less than 125,000 K/mcL;
- ALT less than 1.25 x ULN; AST less than 1.25 x ULN;
- Total bilirubin less than 1.25 x ULN;
- Creatinine less than 1.1 x ULN;
- Pregnancy or lactation.
- Any vaccination within 14 days prior to SARS-CoV-2 mAbs administration (except
influenza vaccine).
- History of prior receipt of any SARS-CoV-2 vaccine or antibodies, including
convalescent plasma.
- Known allergy/sensitivity or any hypersensitivity to components of the investigational
agents.
- History of severe reaction to a vaccine or monoclonal antibody administration or
history of severe allergic reactions.
- Participation in another clinical study of an investigational product currently or
within past 12 weeks, or expected participation during this study.
The Rockefeller University
New York, New York, United States
Christian Gaebler, MD, Principal Investigator
The Rockefeller University