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

• ClinicalTrials.gov Identifier: NCT04700163
• Recruitment Status: Completed
• First Posted: January 7, 2021
• Last Update Posted: August 4, 2022
• Sponsor: Rockefeller University
• Information provided by (Responsible Party): Rockefeller University

Tracking Information

• First Submitted Date: January 5, 2021
• First Posted Date: January 7, 2021
• Last Update Posted Date: August 4, 2022
• Actual Study Start Date: January 11, 2021
• Actual Primary Completion Date: February 2, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 5, 2021)

• Grade 2 and higher adverse events 4 weeks after administration. [ Time Frame: 4 weeks ]
  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. [ Time Frame: 4 weeks ]
  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 [ Time Frame: 48 weeks ]
  The number of participants with treatment-related solicited serious adverse events.
• Elimination half-life (t1/2) of C135-LS and C144-LS [ Time Frame: 48 weeks ]
  Half-life of C135-LS and C144-LS when administered intravenously or subcutaneously in healthy volunteers
• Clearance rate of C135-LS and C144-LS [ Time Frame: 48 weeks ]
  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 [ Time Frame: 48 weeks ]
  Area under the curve of C135-LS and C144-LS when administered intravenously or subcutaneously in healthy volunteers

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 5, 2021)

• Investigational product (IP)-related adverse events during study follow up. [ Time Frame: 48 weeks ]
  The number of participants with treatment-related adverse events
• Anti-C144-LS and anti-C135-LS antibodies in all study groups. [ Time Frame: 48 weeks ]
  Proportion of individuals with treatment-induced anti-drug antibodies against each mAb and magnitude of the response
• Serum neutralizing activity against SARS-CoV-2 [ Time Frame: 48 weeks ]
  Serum neutralizing activity against SARS-CoV-2 following C144-LS and C135-LS administration

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: RU Anti-SARS-CoV-2 (COVID-19) mAbs in Healthy Volunteers
• 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
• 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).
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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

Study Arms

• Experimental: S1 - low dose
  100 mg of C144-LS and 100 mg of C135-LS, subcutaneously
  Intervention: Biological: C144-LS and C-135-LS
• Experimental: S2 - mid dose
  200 mg of C144-LS and 200 mg of C135-LS, subcutaneously
  Intervention: Biological: C144-LS and C-135-LS
• Experimental: V1 - low dose
  1.5 mg/kg of C144-LS and 1.5 mg/kg of C135-LS, intravenously
  Intervention: Biological: C144-LS and C-135-LS
• Experimental: V2 - mid dose
  5 mg/kg of C144-LS and 5 mg/kg of C135-LS, intravenously
  Intervention: Biological: C144-LS and C-135-LS
• Experimental: V3 - high dose
  15 mg/kg of C144-LS and 15 mg/kg of C135-LS, intravenously
  Intervention: Biological: C144-LS and C-135-LS

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 23, 2021): 23
• Original Estimated Enrollment (submitted: January 5, 2021): 15
• Actual Study Completion Date: February 2, 2022
• Actual Primary Completion Date: February 2, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04700163
• Other Study ID Numbers: RUCOV1; CGA-1015 ( Other Identifier: Rockefeller University IRB )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Rockefeller University
• Original Responsible Party: Same as current
• Current Study Sponsor: Rockefeller University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Christian Gaebler, MD; The Rockefeller University

• PRS Account: Rockefeller University
• Verification Date: August 2022