RU Anti-SARS-CoV-2 (COVID-19) mAbs in Healthy Volunteers

NCT ID: NCT04700163

Last Updated: 2025-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-11
• Study Completion Date: 2022-02-02

Brief Summary

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.

Detailed Description

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).

Conditions

Covid19

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

S1 - low dose

100 mg of C144-LS and 100 mg of C135-LS, subcutaneously

Group Type: EXPERIMENTAL

C144-LS and C-135-LS

Intervention Type: BIOLOGICAL

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

S2 - mid dose

200 mg of C144-LS and 200 mg of C135-LS, subcutaneously

Group Type: EXPERIMENTAL

C144-LS and C-135-LS

Intervention Type: BIOLOGICAL

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

V1 - low dose

1.5 mg/kg of C144-LS and 1.5 mg/kg of C135-LS, intravenously

Group Type: EXPERIMENTAL

C144-LS and C-135-LS

Intervention Type: BIOLOGICAL

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

V2 - mid dose

5 mg/kg of C144-LS and 5 mg/kg of C135-LS, intravenously

Group Type: EXPERIMENTAL

C144-LS and C-135-LS

Intervention Type: BIOLOGICAL

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

V3 - high dose

15 mg/kg of C144-LS and 15 mg/kg of C135-LS, intravenously

Group Type: EXPERIMENTAL

C144-LS and C-135-LS

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Rockefeller University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian Gaebler, MD

Role: PRINCIPAL_INVESTIGATOR

The Rockefeller University

Locations

The Rockefeller University

New York, New York, United States

Countries

United States

References

Schafer A, Muecksch F, Lorenzi JCC, Leist SR, Cipolla M, Bournazos S, Schmidt F, Maison RM, Gazumyan A, Martinez DR, Baric RS, Robbiani DF, Hatziioannou T, Ravetch JV, Bieniasz PD, Bowen RA, Nussenzweig MC, Sheahan TP. Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo. J Exp Med. 2021 Mar 1;218(3):e20201993. doi: 10.1084/jem.20201993.

Reference Type: BACKGROUND

PMID: 33211088 (View on PubMed)

Weisblum Y, Schmidt F, Zhang F, DaSilva J, Poston D, Lorenzi JC, Muecksch F, Rutkowska M, Hoffmann HH, Michailidis E, Gaebler C, Agudelo M, Cho A, Wang Z, Gazumyan A, Cipolla M, Luchsinger L, Hillyer CD, Caskey M, Robbiani DF, Rice CM, Nussenzweig MC, Hatziioannou T, Bieniasz PD. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife. 2020 Oct 28;9:e61312. doi: 10.7554/eLife.61312.

Reference Type: BACKGROUND

PMID: 33112236 (View on PubMed)

Barnes CO, Jette CA, Abernathy ME, Dam KA, Esswein SR, Gristick HB, Malyutin AG, Sharaf NG, Huey-Tubman KE, Lee YE, Robbiani DF, Nussenzweig MC, West AP Jr, Bjorkman PJ. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature. 2020 Dec;588(7839):682-687. doi: 10.1038/s41586-020-2852-1. Epub 2020 Oct 12.

Reference Type: BACKGROUND

PMID: 33045718 (View on PubMed)

Robbiani DF, Gaebler C, Muecksch F, Lorenzi JCC, Wang Z, Cho A, Agudelo M, Barnes CO, Gazumyan A, Finkin S, Hagglof T, Oliveira TY, Viant C, Hurley A, Hoffmann HH, Millard KG, Kost RG, Cipolla M, Gordon K, Bianchini F, Chen ST, Ramos V, Patel R, Dizon J, Shimeliovich I, Mendoza P, Hartweger H, Nogueira L, Pack M, Horowitz J, Schmidt F, Weisblum Y, Michailidis E, Ashbrook AW, Waltari E, Pak JE, Huey-Tubman KE, Koranda N, Hoffman PR, West AP Jr, Rice CM, Hatziioannou T, Bjorkman PJ, Bieniasz PD, Caskey M, Nussenzweig MC. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature. 2020 Aug;584(7821):437-442. doi: 10.1038/s41586-020-2456-9. Epub 2020 Jun 18.

Reference Type: RESULT

PMID: 32555388 (View on PubMed)

Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Reference Type: DERIVED

PMID: 34473343 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CGA-1015

Identifier Type: OTHER

Identifier Source: secondary_id

RUCOV1

Identifier Type: -

Identifier Source: org_study_id