Clinical trial NCT04644120: Study to Assess Adverse Events and How Intravenous (IV) ABBV-47D11 and IV ABBV-2B04 Given Alone and in Combination Moves Through the Body of Adult Participants With Coronavirus Disease 2019 (COVID-19)
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of ABBV-47D11 and ABBV-2B04 as Monotherapy or Combination Therapy in Adults With COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: CoronaVirus Disease-2019 (COVID-19)
Keywords: CoronaVirus Disease-2019
COVID-19
Severe Acute Respiratory Syndrome Coronavirus-2
SARS-CoV-2
ABBV-47D11
ABBV-2B04
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2020-11-25
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lung failure is the main cause of death related to COVID-19 infection. The main objective of this study is to evaluate the safety and tolerability of ABBV-47D11 and ABBV-2B04 given alone and in combination to participants with COVID-19 infection. In addition, this study will evaluate the pharmacokinetics (how the body handles the study drug) and anti-viral activity of the study drug.

ABBV-47D11 and ABBV-2B04 are investigational anti-SARS-CoV-2 monoclonal antibodies being developed for the treatment of COVID-19. Study will be conducted in two parts. In part A, participants will receive ABBV-47D11 or placebo. There is a 1 in 4 chance that participants will be assigned to placebo. In part B, participants will receive ABBV-2B04 alone or in combination with ABBV-47D11 or placebo. There is a 1 in 5 chance that participants will be assigned to placebo. Around 54 adult participants with COVID-19 will be enrolled in approximately 10 to 30 sites globally.

In part A participants will receive single intravenous (into the veins) infusion of ABBV-47D11 or placebo on Day 1. In part B participants will receive single intravenous (into the veins) infusion of ABBV-2B04 alone or in combination with ABBV-47D11 or placebo on Day 1. Participants will be followed up for 106 days.

There may be higher treatment burden for participants in this trial compared to their standard of care. The effect of the treatment will be checked by medical assessments, blood tests, nasal swabs and presence of side effects.

Detailed description: Part B of this study was not conducted.

Eligibility criteria: Inclusion Criteria:

* Confirmed SARS-CoV-2 infection based on initial nucleic acid or antigen testing from respiratory swab, saliva, or other bodily fluid within 7 days prior to randomization.
* Must have \>= 1 symptom associated with COVID-19 with an onset of \<= 8 days prior to randomization.
* Hospitalized or plans for hospital admission due to COVID-19 at the time of randomization or not currently hospitalized and does not have plans for hospital admission at the time of randomization, but is willing to be confined for ≥ 48 hours post-dose for the purposes of participating in this research study

Exclusion Criteria:

* Have an oxygen saturation (SpO2) \< 88% on room air at rest for 5 minutes OR ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) \<= 200 mmHg at randomization.
* Requiring high-flow nasal cannula oxygen therapy/non-invasive or invasive mechanical ventilation/extracorporeal membrane oxygenation (ECMO) or anticipated impending need for high-flow nasal cannula oxygen therapy/non-invasive or invasive mechanical ventilation/ECMO.
* Prior treatment with a SARS-CoV-2 specific monoclonal antibody or convalescent COVID-19 plasma.

Primary outcomes:
measure: Number of Participants With Study-Drug Related Grade 3 or Higher Adverse Events (AEs)
timeFrame: Up to Day 106
measure: Number of Participants With Study-Drug Related Grade 3 or Higher Infusion-Related Reactions
timeFrame: Up to Day 106
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of ABBV-47D11
timeFrame: Up to Day 85
measure: Time to Cmax (Tmax) of ABBV-47D11
timeFrame: Up to Day 85
measure: Area Under the Serum Concentration-Time Curve (AUC) From Day 1 (0 hour) to Day 29 (672 hour) (AUC0-672h) of ABBV-47D11
timeFrame: Up to Day 29
measure: Terminal Phase Elimination Half-Life (t1/2) of ABBV-47D11
timeFrame: Up to Day 85
measure: AUC From Time 0 to Infinity (AUCinf) of ABBV-47D11
timeFrame: Up to Day 85
measure: Detection of Anti-Drug Antibodies (ADA) for ABBV-47D11
timeFrame: Up to Day 85
measure: Detection of Neutralizing Anti-Drug Antibodies (nADA) for ABBV-47D11
timeFrame: Up to Day 85
measure: AUC for Change From Baseline (Day 1) in SARS-CoV-2 Ribose Nucleic Acid (RNA) Reverse Transcription-Polymerase Chain Reaction (RT-PCR)
timeFrame: Baseline (Day 1) through Day 29
measure: Time to Negative SARS-CoV-2 by RT-PCR
timeFrame: Up to Day 29
measure: Negative SARS-CoV-2 RNA by RT-PCR
timeFrame: Up to Day 15
measure: Maximum Observed Serum Concentration (Cmax) of ABBV-2B04
timeFrame: Up to Day 85
measure: Time to Cmax (Tmax) of ABBV-2B04
timeFrame: Up to Day 85
measure: Area Under the Serum Concentration-Time Curve (AUC) From Day 1 (0 hour) to Day 29 (672 hour) (AUC0-672h) of ABBV-2B04
timeFrame: Up to Day 29
measure: Terminal Phase Elimination Half-Life (t1/2) of ABBV-2B04
timeFrame: Up to Day 85
measure: AUC From Time 0 to Infinity (AUCinf) of ABBV-2B04
timeFrame: Up to Day 85
measure: Detection of Anti-Drug Antibodies (ADA) for ABBV-2B04
timeFrame: Up to Day 85
measure: Detection of Neutralizing Anti-Drug Antibodies (nADA) for ABBV-2B04
timeFrame: Up to Day 85
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Glendale Adventist Medical Center /ID# 225188
state: California
city: Cutler Bay
country: United States
facility: Beautiful Minds Clinical Research Center /ID# 228708
state: Florida
city: Miami
country: United States
facility: University of Miami /ID# 225038
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute /ID# 228612
state: Florida
city: Chicago
country: United States
facility: University of Illinois Hospital and Health Sciences System /ID# 224323
state: Illinois
city: Pikeville
country: United States
facility: Pikeville Medical Center /ID# 224539
state: Kentucky
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital /ID# 225183
state: New Jersey
city: Newark
country: United States
facility: Saint Michael's Medical Center /ID# 225258
state: New Jersey
city: Cincinnati
country: United States
facility: The Christ Hospital /ID# 224541
state: Ohio
city: Greenville
country: United States
facility: Prisma Health Children's Hospital Upstate /ID# 224556
state: South Carolina
city: Beaumont
country: United States
facility: Gadolin Research, LLC /ID# 229394
state: Texas
city: Budapest
country: Hungary
facility: Betegapolo Irgalmasrend Budai Irgalmasrendi Korhaz /ID# 226015
city: Budapest
country: Hungary
facility: Semmelweis Egyetem /ID# 226016
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Hebrew University /ID# 225827
city: Tel Hashomer, Ramat Gan
country: Israel
facility: Sheba Medical Center /ID# 225857
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht /ID# 225919
city: Caguas
country: Puerto Rico
facility: San Juan Bautista School of Medicine /ID# 225963
city: Manati
country: Puerto Rico
facility: Manati Medical Center /ID# 225936
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
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.