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.
The therapeutic hypothesis for the use of losmapimod in COVID-19 disease is that increased
disease severity and consequent increased mortality is caused by p38 mitogen-activated
protein kinase (MAPK)-mediated exaggerated acute inflammatory response resulting from
SARS-CoV-2 infection.
It is anticipated that the early initiation of p38α/β inhibitor therapy in patients with
moderate COVID-19 will prevent further clinical deterioration and reduce the need for both
increased respiratory support as well as mortality. This is the main hypothesis for this
study.
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 with COVID-19 disease.
Losmapimod is currently in Phase 2 clinical trials for the treatment of facioscapulohumeral
dystrophy (FSHD) and has previously been administered to more than 3600 adult healthy
volunteers and subjects including participants in a large Phase 3 trial which looked at
clinical outcomes and safety after major cardiovascular events.
Patients will participate in this study for approximately 34 days. The total treatment
duration will be 14 days. Subjects will be evaluated during a 3 day pre-treatment period
(Screening and Baseline Visits) to establish pre-treatment baseline assessments and
eligibility. Subjects will then be randomized to treatment with losmapimod or placebo for 14
days and assessed frequently for changes from pre-treatment in various clinical outcome
assessments. Patients must have a confirmed diagnosis of COVID-19 by viral PCR prior to
randomization and first dosing. Patients will receive 15 mg of losmapimod, or placebo twice
daily given as two 7.5 mg tablets per dose by mouth: for a total of 4 pills or 30 mg daily
for 14 consecutive days. All study visits during the first week of treatment are anticipated
to be conducted in the inpatient setting while later visits are anticipated to be conducted
as outpatient.
The primary endpoint of the study is to assess the efficacy of losmapimod tablets compared
with placebo for the treatment of COVID-19 when administered concurrently with the local
standard of care. Secondary endpoints include evaluating the effect of losmapimod compared
with placebo on clinical outcomes, clinical status, effect on survival, safety, and
tolerability and to characterize changes in the levels of SARS-CoV-2 infection.
Drug: Losmapimod oral tablet
This study includes a 14-day treatment period. Patients will receive losmapimod 15 mg twice daily given as two 7.5 mg tablets per dose by mouth: for a total of 4 pills or 30 mg daily. The study drug should be taken with food when possible.
Drug: Placebo oral tablet
This study includes a 14-day treatment period. Patients will receive Placebo twice daily given as two tablets per dose by mouth: for a total of 4 tablets daily. The study drug should be taken with food when possible.
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
University of California Irvine - Irvine Medical Center
Irvine, California, United States
University of Miami
Miami, Florida, United States
University of South Florida
Tampa, Florida, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Memorial Hermann Hospital South West
Houston, Texas, United States
University of Texas Health Science Center at Houston
Houston, Texas, United States
United Medical Memorial Hospital
Houston, Texas, United States
Hospital Universitario Cassiano Antonio de Moraes-HUCAM/Hospital das Clinicas
Vitória, ES, Brazil
Santa Casa de Misericordia de Belo Horizonte
Belo Horizonte, MG, Brazil
Irmandade de Santa Casa de Misericordia de Porto Alegre
Porto Alegre, SC, Brazil
Hospital Santa Paula
San Paolo, SP, Brazil
Hospital Civil Fray Antonio Alcalde
Guadalajara, Jalisco, Mexico
Nuevo Hospital Civil de Guadalajara
Guadalajara, JC, Mexico
JM Research Cuernavaca
Cuernavaca, Morelos, Mexico
Centro para el Desarrollo de la Medicina y de Asistencia Médica Especializada, S.C.
Culiacán, Sinaloa, Mexico
Hospital Nacional Carlos Alberto Seguín Escobedo - EsSalud Arequipa
Arequipa, AR, Peru
John Ziegler, MD, FASA, Study Director
Fulcrum Therapeutics