Losmapimod Safety and Efficacy in COVID-19

• Status: Terminated
• Trial end date: 2021-03-31
• Target enrollment: 0
• Participant gender: All

Summary

The therapeutic hypothesis for the use of losmapimod in COVID-19 disease is that increased mortality and severe disease is caused by p38 mitogen-activated protein kinase (MAPK)-mediated exaggerated acute inflammatory response resulting from SARS-CoV-2 infection.

The study Sponsor hypothesize's that the early initiation of p38α/β inhibitor therapy in patients hospitalized with moderate COVID-19 who are at increased risk of a poor prognosis based on older age and elevated systemic inflammation will reduce clinical deterioration including progression to respiratory failure and death.

To address this hypothesis, Fulcrum Therapeutics is conducting a Phase 3, multicenter, randomized, double-blind, placebo-controlled study that will evaluate the safety and efficacy of losmapimod versus placebo in subjects 50 and older who are hospitalized with moderate COVID-19 disease.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fulcrum Therapeutics

Criteria

Inclusion Criteria:

• Able and willing to provide written informed consent

• Willing and able to comply with all study procedures

• Age ≥50 years at time of screening

• Confirmed infection with SARS-CoV-2 virus at or before the baseline visit by polymerase chain reaction (PCR) testing

• ≤7 days to the time of randomization from the time of collection of the specimen that tested positive for the SARS-CoV-2 virus

• Hospitalization at the time of the baseline visit

• ≥90% oxygen saturation on room air and/or ≥94% oxygen saturation on oxygen administration at 2 L/min by nasal cannula at the baseline visit

• Radiographic (X-ray or computed tomography scan, per local standard of care) and/or clinical evidence of pulmonary involvement consistent with COVID-19 at screening or baseline, per the judgment of the investigator

• Clinical syndrome consistent with COVID-19 at screening, per the judgment of the investigator (CDC 2020)

• CRP at screening >15 mg/L (i.e., >1.5 mg/dL) on local laboratory testing

• Agrees to practice an approved method of birth control

Exclusion Criteria:

• Inability to take oral medication at screening or baseline visit

• Evidence at screening or baseline of critical COVID-19 disease (e.g., cardiac failure, septic shock) or severe pulmonary involvement)

• Positive pregnancy test at screening for women of childbearing potential

• Lactating female at baseline for women of childbearing potential Note: A female will be considered eligible who is lactating at screening if she agrees to discontinue breastfeeding for the duration of the trial plus 14 days post last dose

• ≥5 × upper limit of normal (ULN) for alanine or aspartate aminotransferases or total bilirubin >1.5 × ULN at screening or known history of Child-Pugh Class C, hepatitis B or C, or HIV infection

• Glomerular filtration rate <30 mL/min/1.73 m2 at screening

• QTcF >450 msec for male or >470 msec for females or evidence of cardiac dysrhythmia at screening

• Significant history or evidence of clinically significant disorder, condition, current illness, illicit drug or other addiction, or disease that, in the opinion of the Investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion

• Has been treated with immunomodulators or immunosuppressants including, but not limited to, interleukin (IL)-6 inhibitors, tumor necrosis factor (TNF) inhibitors, anti-IL-1 agents, and Janus kinase inhibitors, within 5 half-lives or 30 days, whichever is longer, prior to randomization, or plan to receive these agents any time during the study period

• Treatment with hydroxychloroquine/ chloroquine in the past 30 days or plan to receive these agents as part of investigational clinical trials or SOC any time during the study period

• Recent (within 30 days) or current participation in other COVID-19 therapeutic trials or expanded access programs

• Prior or current participation in COVID-19 vaccine trials