Clinical trial NCT04700163: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Covid19
Keywords: Monoclonal antibody
SARS-CoV-2
Lead sponsor: Rockefeller University
Sponsor class: OTHER
First posted: 2021-01-07
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Grade 2 and Higher Adverse Events 4 Weeks After Administration.
timeFrame: 4 weeks
measure: Grade 3 and Higher Adverse Events 4 Weeks After Administration.
timeFrame: 4 weeks
measure: Related Serious Adverse Events (SAEs) Throughout the Study Period
timeFrame: 48 weeks
measure: Elimination Half-life (t1/2) of C135-LS and C144-LS
timeFrame: 48 weeks
measure: Clearance Rate of C135-LS and C144-LS
timeFrame: 48 weeks
measure: Area Under the Curve of C135-LS and C144-LS
timeFrame: 48 weeks
Secondary outcomes:
measure: Investigational Product (IP)-Related Adverse Events During Study Follow up.
timeFrame: 48 weeks
measure: Anti-C144-LS and Anti-C135-LS Antibodies in All Study Groups.
timeFrame: 48 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: The Rockefeller University
state: New York
Study officials:
affiliation: The Rockefeller University
name: Christian Gaebler, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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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.
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.