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| ID | Type | Description | Link |
|---|---|---|---|
| CGA-1015 | Other Identifier | Rockefeller University IRB |
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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| S1 - low dose | Experimental | 100 mg of C144-LS and 100 mg of C135-LS, subcutaneously |
|
| S2 - mid dose | Experimental | 200 mg of C144-LS and 200 mg of C135-LS, subcutaneously |
|
| V1 - low dose | Experimental | 1.5 mg/kg of C144-LS and 1.5 mg/kg of C135-LS, intravenously |
|
| V2 - mid dose | Experimental | 5 mg/kg of C144-LS and 5 mg/kg of C135-LS, intravenously |
|
| V3 - high dose | Experimental | 15 mg/kg of C144-LS and 15 mg/kg of C135-LS, intravenously |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| C144-LS and C-135-LS | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| Related Serious Adverse Events (SAEs) Throughout the Study Period | The number of participants with treatment-related solicited serious adverse events. | 48 weeks |
| 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 |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Investigational Product (IP)-Related Adverse Events During Study Follow up. | The number of participants with treatment-related adverse events | 48 weeks |
| Anti-C144-LS and Anti-C135-LS Antibodies in All Study Groups. |
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Inclusion Criteria:
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:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Christian Gaebler, MD | The Rockefeller University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Rockefeller University | New York | New York | 10065 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33211088 | Background | 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. | |
| 33112236 |
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Participants were screened for participation and screened out if did not meet eligibility criteria.
Participants enrolled sequentially in the study, following a dose escalation scheme as per protocol.
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| ID | Title | Description |
|---|---|---|
| FG000 | S1 - Low Dose | 100 mg of C144-LS and 100 mg of C135-LS, subcutaneously 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 |
| FG001 | S2 - Mid Dose | 200 mg of C144-LS and 200 mg of C135-LS, subcutaneously 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 |
| FG002 | V1 - Low Dose | 1.5 mg/kg of C144-LS and 1.5 mg/kg of C135-LS, intravenously 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 |
| FG003 | V2 - Mid Dose | 5 mg/kg of C144-LS and 5 mg/kg of C135-LS, intravenously 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 |
| FG004 | V3 - High Dose | 15 mg/kg of C144-LS and 15 mg/kg of C135-LS, intravenously 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 |
| FG005 | S3 - Open Label | 200 mg of C144-LS and 200 mg of C135-LS or placebo, subcutaneously. 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | S1 - Low Dose | 100 mg of C144-LS and 100 mg of C135-LS, subcutaneously 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 |
| BG001 | S2 - Mid Dose |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | Posted | Count of Participants | Participants | 4 weeks |
|
48 weeks
Definitions are the definitions from clinicaltrials.gov
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | S1 - Low Dose | 100 mg of C144-LS and 100 mg of C135-LS, subcutaneously 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tenderness | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marina Caskey | The Rockefeller University | 2123277396 | mcaskey@rockefeller.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 6, 2021 | Apr 4, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C000712627 | ogalvibart, crexavibart drug combination |
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Proportion of individuals with treatment-induced anti-drug antibodies against each mAb and magnitude of the response
| 48 weeks |
| Background |
| 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. |
| 33045718 | Background | 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. |
| 32555388 | Result | 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. |
| 34473343 | Derived | 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. |
200 mg of C144-LS and 200 mg of C135-LS, subcutaneously 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 |
| BG002 | V1 - Low Dose | 1.5 mg/kg of C144-LS and 1.5 mg/kg of C135-LS, intravenously 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 |
| BG003 | V2 - Mid Dose | 5 mg/kg of C144-LS and 5 mg/kg of C135-LS, intravenously 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 |
| BG004 | V3 - High Dose | 15 mg/kg of C144-LS and 15 mg/kg of C135-LS, intravenously 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 |
| BG005 | S3 - Open Label | 200 mg of C144-LS and 200 mg of C135-LS or placebo, subcutaneously 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 |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | V1 - Low Dose | 1.5 mg/kg of C144-LS and 1.5 mg/kg of C135-LS, intravenously 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 |
| OG003 | V2 - Mid Dose | 5 mg/kg of C144-LS and 5 mg/kg of C135-LS, intravenously 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 |
| OG004 | V3 - High Dose | 15 mg/kg of C144-LS and 15 mg/kg of C135-LS, intravenously 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 |
| OG005 | S3 - Open Label | 200 mg of C144-LS and 200 mg of C135-LS or placebo, subcutaneously. 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 |
|
|
| 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). | Posted | Count of Participants | Participants | 4 weeks |
|
|
|
| Primary | Related Serious Adverse Events (SAEs) Throughout the Study Period | The number of participants with treatment-related solicited serious adverse events. | Posted | Count of Participants | Participants | 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 | Posted | Mean | Standard Deviation | days | 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 | Posted | Geometric Mean | Geometric Coefficient of Variation | ml/day | 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 | Posted | Geometric Mean | Geometric Coefficient of Variation | (micrograms x day)/ml | 48 weeks |
|
|
|
| Secondary | Investigational Product (IP)-Related Adverse Events During Study Follow up. | The number of participants with treatment-related adverse events | Posted | Count of Participants | Participants | 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 | Posted | Count of Participants | Participants | 48 weeks |
|
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 1 |
| 3 |
| EG001 | S2 - Mid Dose | 200 mg of C144-LS and 200 mg of C135-LS, subcutaneously 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 | 0 | 3 | 0 | 3 | 2 | 3 |
| EG002 | V1 - Low Dose | 1.5 mg/kg of C144-LS and 1.5 mg/kg of C135-LS, intravenously 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 | 0 | 3 | 0 | 3 | 1 | 3 |
| EG003 | V2 - Mid Dose | 5 mg/kg of C144-LS and 5 mg/kg of C135-LS, intravenously 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 | 0 | 3 | 0 | 3 | 1 | 3 |
| EG004 | V3 - High Dose | 15 mg/kg of C144-LS and 15 mg/kg of C135-LS, intravenously 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 | 0 | 3 | 0 | 3 | 2 | 3 |
| EG005 | S3 - Open Label | 200 mg of C144-LS and 200 mg of C135-LS or placebo, subcutaneously. 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 | 0 | 8 | 0 | 8 | 2 | 8 |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Injection Site Pain | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Peripheral edema | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| Increased blood glucose | Endocrine disorders | MedDRA 10.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| SARS-CoV-2 Antibody Positive | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
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| Abnormal uterine bleeding | Reproductive system and breast disorders | MedDRA 10.0 | Systematic Assessment |
|
| Tachypnea | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
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| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| C144-LS Half-life |
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| C144-LS Clearance |
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| C144-LS AUC |
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| C144-LS ADA |
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