RU Anti-SARS-CoV-2 (COVID-19) mAbs in Healthy Volunteers (RU)
Primary Purpose
Covid19
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
C144-LS and C-135-LS
Sponsored by
About this trial
This is an interventional treatment trial for Covid19 focused on measuring Monoclonal antibody, SARS-CoV-2
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.
Sites / Locations
- The Rockefeller University
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
S1 - low dose
S2 - mid dose
V1 - low dose
V2 - mid dose
V3 - high dose
Arm Description
100 mg of C144-LS and 100 mg of C135-LS, subcutaneously
200 mg of C144-LS and 200 mg of C135-LS, subcutaneously
1.5 mg/kg of C144-LS and 1.5 mg/kg of C135-LS, intravenously
5 mg/kg of C144-LS and 5 mg/kg of C135-LS, intravenously
15 mg/kg of C144-LS and 15 mg/kg of C135-LS, intravenously
Outcomes
Primary Outcome Measures
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).
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).
Related Serious adverse events (SAEs) throughout the study period
The number of participants with treatment-related solicited serious adverse events.
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
Clearance rate of C135-LS and C144-LS
Clearance rate of C135-LS and C144-LS when administered intravenously or subcutaneously in healthy volunteers
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
Secondary Outcome Measures
Investigational product (IP)-related adverse events during study follow up.
The number of participants with treatment-related adverse events
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
Serum neutralizing activity against SARS-CoV-2
Serum neutralizing activity against SARS-CoV-2 following C144-LS and C135-LS administration
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04700163
Brief Title
RU Anti-SARS-CoV-2 (COVID-19) mAbs in Healthy Volunteers
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
January 11, 2021 (Actual)
Primary Completion Date
February 2, 2022 (Actual)
Study Completion Date
February 2, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rockefeller University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
Keywords
Monoclonal antibody, SARS-CoV-2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
S1 - low dose
Arm Type
Experimental
Arm Description
100 mg of C144-LS and 100 mg of C135-LS, subcutaneously
Arm Title
S2 - mid dose
Arm Type
Experimental
Arm Description
200 mg of C144-LS and 200 mg of C135-LS, subcutaneously
Arm Title
V1 - low dose
Arm Type
Experimental
Arm Description
1.5 mg/kg of C144-LS and 1.5 mg/kg of C135-LS, intravenously
Arm Title
V2 - mid dose
Arm Type
Experimental
Arm Description
5 mg/kg of C144-LS and 5 mg/kg of C135-LS, intravenously
Arm Title
V3 - high dose
Arm Type
Experimental
Arm Description
15 mg/kg of C144-LS and 15 mg/kg of C135-LS, intravenously
Intervention Type
Biological
Intervention Name(s)
C144-LS and C-135-LS
Intervention Description
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
Primary Outcome Measure Information:
Title
Grade 2 and higher adverse events 4 weeks after administration.
Description
The number of participants with treatment-related solicited and unsolicited grade 2 adverse events (including confirmed laboratory abnormalities).
Time Frame
4 weeks
Title
Grade 3 and higher adverse events 4 weeks after administration.
Description
The number of participants with treatment-related solicited and unsolicited grade 3 adverse events (including confirmed laboratory abnormalities).
Time Frame
4 weeks
Title
Related Serious adverse events (SAEs) throughout the study period
Description
The number of participants with treatment-related solicited serious adverse events.
Time Frame
48 weeks
Title
Elimination half-life (t1/2) of C135-LS and C144-LS
Description
Half-life of C135-LS and C144-LS when administered intravenously or subcutaneously in healthy volunteers
Time Frame
48 weeks
Title
Clearance rate of C135-LS and C144-LS
Description
Clearance rate of C135-LS and C144-LS when administered intravenously or subcutaneously in healthy volunteers
Time Frame
48 weeks
Title
Area under the curve of C135-LS and C144-LS
Description
Area under the curve of C135-LS and C144-LS when administered intravenously or subcutaneously in healthy volunteers
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Investigational product (IP)-related adverse events during study follow up.
Description
The number of participants with treatment-related adverse events
Time Frame
48 weeks
Title
Anti-C144-LS and anti-C135-LS antibodies in all study groups.
Description
Proportion of individuals with treatment-induced anti-drug antibodies against each mAb and magnitude of the response
Time Frame
48 weeks
Title
Serum neutralizing activity against SARS-CoV-2
Description
Serum neutralizing activity against SARS-CoV-2 following C144-LS and C135-LS administration
Time Frame
48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christian Gaebler, MD
Organizational Affiliation
The Rockefeller University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Rockefeller University
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33211088
Citation
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.
Results Reference
background
PubMed Identifier
33112236
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:e61312. doi: 10.7554/eLife.61312.
Results Reference
background
PubMed Identifier
33045718
Citation
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.
Results Reference
background
PubMed Identifier
32555388
Citation
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.
Results Reference
result
PubMed Identifier
34473343
Citation
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.
Results Reference
derived
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RU Anti-SARS-CoV-2 (COVID-19) mAbs in Healthy Volunteers
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