Losmapimod Safety and Efficacy in COVID-19 (LOSVID)
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|ClinicalTrials.gov Identifier: NCT04511819|
Recruitment Status : Terminated (Study terminated due to the rapidly evolving environment for the treatment of Covid-19 and ongoing challenges to identify and enroll qualified patients to participate.)
First Posted : August 13, 2020
Last Update Posted : August 9, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|COVID-19||Drug: Losmapimod oral tablet Drug: Placebo oral tablet||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||52 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||This study is a randomized, double-blind, placebo-controlled study.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||This study will be performed in a double-blind fashion. The investigator, study staff, subjects, Sponsor, and monitor will remain blinded to the treatment until study closure.|
|Official Title:||A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Losmapimod in Adult Subjects With COVID-19 (LOSVID STUDY)|
|Actual Study Start Date :||August 28, 2020|
|Actual Primary Completion Date :||March 31, 2021|
|Actual Study Completion Date :||March 31, 2021|
COVID-19 patients with PCR confirmation 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 for 14 days.
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.
Placebo Comparator: Placebo
COVID-19 patients with PCR confirmation will receive Placebo twice daily given as two tablets per dose by mouth; for a total of 4 tablets daily for 14 days.
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.
- Day 28 Mortality [ Time Frame: Day 28 ]The efficacy of Losmapimod will be assessed by the development of progression to critical disease as evidence of mortality or development of respiratory failure by Day 28.
- Clinical Status Assessment [ Time Frame: Day 7 and Day 14 ]The change from baseline in clinical disease status will be evaluated using the 9-point World Health Organization (WHO) ordinal scale: 0 indicating, no clinical evidence of SARS-CoV-2 infection and 8 indicating death.
- Respiratory Failure Assessment [ Time Frame: Day 28 ]The response to treatment with Losmapimod in COVID-19 patients will be assessed by the total number of study days not requiring oxygen supplementation.
- Treatment Survival [ Time Frame: Day 28 ]To assess the effect on survival following treatment with Losmapimod, mortality will be evaluated by the number of days alive by Day 28.
- Treatment-Emergent Adverse Events [ Time Frame: Screening, Date of enrollment and Days 2-14 and 7 and 14 days after the last dose of study drug ]To evaluate the safety and tolerability of Losmapimod, the incidence of treatment-emergent adverse events will be assessed by clinically significant changes in laboratory test results and vital signs.
- Treatment-Emergent Adverse Events [ Time Frame: Day 7 ]To characterize changes in SARS-CoV-2 infection following treatment with losmapimod versus placebo.
- Changes in C-Reactive Protein [ Time Frame: Days 1, 4, 7 and 14 ]The change from baseline in levels of C-reactive protein (CRP), a biomarker of systemic inflammatory response to infection with the SARS-CoV-2 virus will be evaluated in serum by immunoturbidimetric assay.
- Changes in Levels of Cytokines [ Time Frame: Days 1, 4, 7 and 14 ]The change from baseline in the levels of cytokines (IFNγ, IL-2, IL-10 in normalized protein expression (NPX)) in response to the SARS-CoV-2 virus in serum will be evaluated using the Olink immunoassay panel.
- Changes in Levels of Chemokines [ Time Frame: Days 1, 4, 7 and 14 ]The change from baseline in the levels of chemokines (CXCL10, CXCL9 in normalized protein expression (NPX)) in response to the SARS-CoV-2 virus in serum will be evaluated using the Olink immunoassay panel.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04511819
|United States, California|
|University of California Irvine - Irvine Medical Center|
|Irvine, California, United States, 92697|
|United States, Florida|
|University of Miami|
|Miami, Florida, United States, 33136|
|University of South Florida|
|Tampa, Florida, United States, 33606|
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|United States, Texas|
|Memorial Hermann Hospital South West|
|Houston, Texas, United States, 77030|
|University of Texas Health Science Center at Houston|
|Houston, Texas, United States, 77030|
|United Medical Memorial Hospital|
|Houston, Texas, United States, 77091|
|Hospital Universitario Cassiano Antonio de Moraes-HUCAM/Hospital das Clinicas|
|Vitória, ES, Brazil, 29043260|
|Santa Casa de Misericordia de Belo Horizonte|
|Belo Horizonte, MG, Brazil, 30150221|
|Irmandade de Santa Casa de Misericordia de Porto Alegre|
|Porto Alegre, SC, Brazil, 90035-075|
|Hospital Santa Paula|
|San Paolo, SP, Brazil, 04550-000|
|Hospital Civil Fray Antonio Alcalde|
|Guadalajara, Jalisco, Mexico, 44280|
|Nuevo Hospital Civil de Guadalajara|
|Guadalajara, JC, Mexico, 44340|
|JM Research Cuernavaca|
|Cuernavaca, Morelos, Mexico, 662284|
|Centro para el Desarrollo de la Medicina y de Asistencia Médica Especializada, S.C.|
|Culiacán, Sinaloa, Mexico, 80230|
|Hospital Nacional Carlos Alberto Seguín Escobedo - EsSalud Arequipa|
|Arequipa, AR, Peru, 04001|
|Study Director:||John Ziegler, MD, FASA||Fulcrum Therapeutics|