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

Covid19 Clinical Trial

— RU  

Official title:

A Phase 1, Open Label, Dose-escalation Study of the Safety and Pharmacokinetics of a Combination of Two Anti-SARS-CoV-2 mAbs (C144-LS and C135-LS) in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04700163
• Other study ID #: RUCOV1
• Secondary ID: CGA-1015
• Status: Completed
• Phase: Phase 1
• Start date: January 11, 2021
• Est. completion date: February 2, 2022

Study information

• Verified date: August 2022
• Source: Rockefeller University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: February 2, 2022
• Est. primary completion date: February 2, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

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

Locations

Country	Name	City	State
United States	The Rockefeller University	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Rockefeller University

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

Robbiani DF, Gaebler C, Muecksch F, Lorenzi JCC, Wang Z, Cho A, Agudelo M, Barnes CO, Gazumyan A, Finkin S, Hägglöf 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, — View Citation

Schäfer 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). pii: e20201993. doi: 10.1084/jem.20201993. — View Citation

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. pii: e61312. doi: 10.7554/eLife.61312. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Grade 2 and higher adverse events 4 weeks after administration.	The number of participants with treatment-related solicited and unsolicited grade 2 adverse events (including confirmed laboratory abnormalities).	4 weeks
Primary	Grade 3 and higher adverse events 4 weeks after administration.	The number of participants with treatment-related solicited and unsolicited grade 3 adverse events (including confirmed laboratory abnormalities).	4 weeks
Primary	Related Serious adverse events (SAEs) throughout the study period	The number of participants with treatment-related solicited serious adverse events.	48 weeks
Primary	Elimination half-life (t1/2) of C135-LS and C144-LS	Half-life of C135-LS and C144-LS when administered intravenously or subcutaneously in healthy volunteers	48 weeks
Primary	Clearance rate of C135-LS and C144-LS	Clearance rate of C135-LS and C144-LS when administered intravenously or subcutaneously in healthy volunteers	48 weeks
Primary	Area under the curve of C135-LS and C144-LS	Area under the curve of C135-LS and C144-LS when administered intravenously or subcutaneously in healthy volunteers	48 weeks
Secondary	Investigational product (IP)-related adverse events during study follow up.	The number of participants with treatment-related adverse events	48 weeks
Secondary	Anti-C144-LS and anti-C135-LS antibodies in all study groups.	Proportion of individuals with treatment-induced anti-drug antibodies against each mAb and magnitude of the response	48 weeks
Secondary	Serum neutralizing activity against SARS-CoV-2	Serum neutralizing activity against SARS-CoV-2 following C144-LS and C135-LS administration	48 weeks