Clinical trial NCT04592549: Study of Monoclonal Antibody Cocktail Being Tested for the Prevention of COVID-19
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Immunogenicity of ADM03820 in Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: SARS-CoV-2
Lead sponsor: Resilience Government Services, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Enabling Biotechnologies (EB)
First posted: 2020-10-19
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a phase 1, randomized, double-blind, placebo-controlled, dose escalation study to evaluate the safety, pharmacokinetics, and immunogenicity of ADM03820 administered as IM injections in healthy adults for the prevention of COVID-19.

Detailed description: The primary objective of this study is to assess the safety and tolerability of escalating IM doses of ADM03820 in healthy adults. Secondary objectives include assessing the pharmacokinetic characteristics and immunogenicity.

Eligibility criteria: Inclusion Criteria:

1. Informed consent understood and signed
2. Healthy male or healthy, non-pregnant, non-lactating female
3. Willingness to comply and be available for all protocol procedures for the duration of the study
4. Between the ages of 18 and 55, inclusive on the day of dosing
5. Body Mass Index (BMI) of ≥18.5 and ≤35 kg/m2
6. Female subjects of childbearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test on Day 1 prior to dosing.

   * Note: A woman is considered of childbearing potential unless post-menopausal (\> or = 1 year without menses without other known or suspected cause and appropriately elevated FSH) or surgically sterilized via bilateral oophorectomy or hysterectomy
7. Females of childbearing potential and males agree to use acceptable contraception for the duration of the study

   * Note: These include progestin implants, intrauterine devices (IUDs), surgical (hysterectomy or tubal ligation; vasectomy) or abstinence. Use of methods such as progestin injectables, combined oral hormonal contraceptives, condoms, and diaphragms will not be acceptable when used alone, but they could be considered, if used in combination with another method (for example, a female using combined oral contraceptives if her male partner is sterile, or if she and her non-sterile male partner use a double-barrier method), after consultation with the Ology Bioservices MM. All males will be required to use a barrier method (condoms) for the duration of the study
8. Screening laboratory tests are within normal ranges or outside the normal ranges and considered not clinically significant by the Principal Investigator

   1. If urinalysis by dipstick is abnormal, a complete urinalysis with microscopic evaluation will be performed and the results will supersede the results of the dipstick for blood, glucose, and protein.
   2. Menstruating females failing inclusion criteria due to a positive blood on urine test may be retested following cessation of menses.
   3. Other laboratory values that are outside the range of eligibility but are thought to be due to an acute condition or collection or laboratory error may be repeated once.
9. The urine drug screen is negative
10. Breathalyzer test or blood/saliva alcohol test is negative and subject agrees to abstain from alcohol consumption for a period of 2 days prior to dosing and 2 days prior to any study visit.
11. Agree to minimize risk of SARS-CoV-2 infection.

Exclusion Criteria:

1. History of chronic medical condition that would either interfere with the accurate assessment of the objectives of the study or increase the risk profile of the subject.
2. Subjects with cardiovascular disease
3. Subjects with diabetes
4. Subjects with pulmonary diseases such as COPD or asthma
5. History of severe allergic reactions of any type to medications, bee stings, food, or environmental factors or hypersensitivity or reaction to immunoglobins.
6. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 milliseconds)
7. Clinically significant abnormal electrocardiogram at screening.

   * Note: Clinically significant abnormal ECG results include but not limited to:

   complete left or right bundle branch block; other ventricular conduction block; 2nd degree or 3rd degree atrioventricular (AV) block; sustained ventricular arrhythmia; sustained atrial arrhythmia; two Premature Ventricular Contractions in a row; pattern of ST elevation felt consistent with cardiac ischemia; or any condition deemed clinically significant by a study investigator
   * Incomplete right bundle branch block is not exclusionary if there are no abnormal ECG findings and there is no clinical history or evidence on physical examination to indicate cardiac disease.
8. Positive serology results for HIV, HBsAg, or HCV antibodies
9. Febrile illness with temperature ≥38°C within 7 days of dosing
10. Female subject who is pregnant or breastfeeding
11. Donated blood within 56 days of enrollment
12. Known allergic reactions to any of the study product components present in the formulation or in the processing, as listed in the Investigator Brochure
13. Treatment with another investigational drug within 28 days of dosing
14. Treatment with a monoclonal antibody within 3 months of enrollment
15. Positive serology results for SARS-CoV-2 antibodies (Not applicable for Cohort 5).
16. Positive results from a reverse transcriptase polymerase chain reaction (RT PCR) test for SARS CoV 2
17. Receipt of antibody (e.g. TIG, VZIG, IVIG, IM gamma globulin) or blood transfusion within 6 months or within 5 half-lives of the specific product given
18. Active drug or alcohol use disorder or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
19. Use of H1 antihistamines or beta-blockers within 5 days of dosing
20. Use of any prohibited medication within 28 days prior to screening or planned use during the study period

    * Note: Prohibited medications include immunosuppressives (except Nonsteroidal Anti-Inflammatory Drugs \[NSAIDS\]); immune modulators; oral corticosteroids (topical/intranasal steroids are acceptable); anti-neoplastic agents
21. Any specific condition that in the judgment of the investigator precludes participation because it could affect subject safety
22. Plans to enroll or is already enrolled in another clinical trial that could interfere with safety assessment of the investigational product at any time during the study period

    * Note: Includes trials that have a study intervention such as a drug, biologic, or device
23. Is a study site employee or staff

    * Note: Site employees or staff include the PIs and sub-investigators or staff who are supervised by the PI or Sub-Investigators
24. Received an approved COVID-19 vaccine (subjects can receive an approved COVID-19 vaccine after completing their Day 90 visit). For Cohort 5, subjects who received a COVID-19 vaccine within 14 days prior to enrollment are excluded.

Primary outcomes:
measure: The Number of Participants With Serious Adverse Events Following Administration of ADM03820 to the Final Visit
timeFrame: 540 days for Cohorts 1-4, 365 days for Cohort 5, and up to 540 days for placebo
measure: The Number of Participants With AEs Following Administration of ADM03820 to the Final Visit
timeFrame: 540 days for Cohorts 1-4, 365 days for Cohort 5, and up to 540 days for placebo
measure: The Number of Participants With Changes From Baseline in Physical Examination, Vital Signs, and Clinical Safety Laboratory Values Following Administration of ADM03820 to the Final Visit
timeFrame: 540 days
Secondary outcomes:
measure: The Assessment of Peak Plasma Concentration (Cmax) for Total Antibodies of ADM03820 as Measured by Enzyme-linked Immunosorbent Assay (ELISA) Methods Designed for Total Monoclonal Antibody in the Drug Product (Cohorts 1-2).
timeFrame: pre-dose, 2, 4, 8, and 24 hours post-dose, and on Days 3, 4, 8, 15, 30, 45, 60, 90, 120, 150, 180, and 365
measure: The Assessment of Tmax for Total Antibodies of ADM03820 as Measured by Enzyme-linked Immunosorbent Assay (ELISA) Methods Designed for Total Monoclonal Antibody in the Drug Product (Cohorts 1-2).
timeFrame: pre-dose, 2, 4, 8, and 24 hours post-dose, and on Days 3, 4, 8, 15, 30, 45, 60, 90, 120, 150, 180, and 365
measure: The Assessment of the Area Under the Plasma Concentration (AUC(0-t)) for the Total Antibodies of ADM03820 as Measured by Enzyme-linked Immunosorbent Assay (ELISA) Methods Designed for Total Monoclonal Antibody in the Drug Product (Cohorts 1-2).
timeFrame: pre-dose, 2, 4, 8, and 24 hours post-dose, and on Days 3, 4, 8, 15, 30, 45, 60, 90, 120, 150, 180, and 365
measure: The Assessment of Peak Plasma Concentration (Cmax) for Each of the Monoclonal Antibodies of ADM03820 as Measured by Enzyme-linked Immunosorbent Assay (ELISA) Methods Designed for Total Monoclonal Antibody in the Drug Product (Cohorts 3-5).
timeFrame: pre-dose, 2, 4, 8, and 24 hours post-dose, and on Days 3, 4, 8, 15, 30, 45, 60, 90, 120, 150, 180, and 365
measure: The Assessment of Tmax for Each of the Monoclonal Antibodies of ADM03820 as Measured by Enzyme-linked Immunosorbent Assay (ELISA) Methods Designed for Total Monoclonal Antibody in the Drug Product (Cohorts 3-5).
timeFrame: pre-dose, 2, 4, 8, and 24 hours post-dose, and on Days 3, 4, 8, 15, 30, 45, 60, 90, 120, 150, 180, and 365
measure: The Assessment of Area Under the Plasma Concentration (AUC(0-t)) for Each of the Monoclonal Antibodies of ADM03820 as Measured by Enzyme-linked Immunosorbent Assay (ELISA) Methods Designed for Total Monoclonal Antibody in the Drug Product (Cohorts 3-5).
timeFrame: pre-dose, 2, 4, 8, and 24 hours post-dose, and on Days 3, 4, 8, 15, 30, 45, 60, 90, 120, 150, 180, and 365
measure: Presence of Anti-drug Antibody (ADA) Levels
timeFrame: pre-dose, and Day 15, 30, 45, 60, 90, 120, 150, and 180
measure: The Number of Participants With SARS-CoV-2 RT-PCR Positive Symptomatic Illness Occurring After Dosing
timeFrame: 365 days
measure: The Number of Participants With SARS-CoV-2 RT-PCR Positive Severe or Critical Symptomatic Illness Occurring After Dosing
timeFrame: 365 days
measure: The Number of Participants With COVID-19 Related Emergency Department Visits Occurring After Dosing
timeFrame: 365 days
measure: The Presence of Neutralizing Antibody Concentrations of ADM03820 as Measured by Microneutralization (MN) Methods
timeFrame: 180 days
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem, LLC
state: North Carolina
city: San Antonio
country: United States
facility: ICON Early Phase Services, LLC
state: Texas
Study officials:
References:
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.