MP1032 Treatment in Patients With Moderate to Severe COVID-19
- Registration Number
- NCT04932941
- Lead Sponsor
- MetrioPharm AG
- Brief Summary
The purpose of this study is to evaluate the efficacy and safety of MP1032 with standard of care (SoC) verses placebo with SoC in hospitalized adults participants with moderate to severe coronavirus disease 2019 (COVID-19).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 132
- Participant is admitted to hospital and has a positive severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) test by standard reverse transcription-polymerase chain reaction (RT-PCR) assay or equivalent test
- Participant has the presence of any symptom(s) suggestive of moderate or severe systemic illness with COVID-19
Key
- Participant, in opinion of the investigator, is not likely to survive >=48 hours beyond Day 1
- Participant has a diagnosis of asymptomatic COVID-19, mild COVID-19, or critical COVID-19 on Day 1
- Participant has a documented medical history of infection with hepatitis A, B, C, or with human immunodeficiency virus (with a detectable viral load and CD4 count <500 cells per micro liter), or a documented active infection with tuberculosis.
- The Participant has clinically significant electrocardiogram (ECG) abnormalities at screening
Other protocol defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MP1032 MP1032 Participants will receive MP1032 300 milligrams (mg) twice daily (BID) with hospital selected SoC for 28 days. Placebo Placebo Participants will receive placebo matched to MP1032 with hospital selected SoC for 28 days.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Disease Progression Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale at Day 14 At Day 14 Disease progression was defined as the percentage of participants who were not alive or who had respiratory failure. Respiratory failure was defined as participants who had a score of 2, 3 or 4 on the NIAID 8-point ordinal scale: The NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Disease Resolution at Day 14 At Day 14 Disease resolution was defined as participants who were alive and had a score of 6, 7, or 8 on the NIAID 8-point ordinal scale. The NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status.
Percentage of Participants Who Required Invasive Ventilation (Mechanical Ventilator and/ ECMO), or Who Died at Day 14 and Day 28 At Day 14 and Day 28 Percentage of participants who required invasive mechanical ventilation/ECMO or who died by Day 14 and Day 28 were reported.
Time to Discharge by Day 28 and Day 60 Baseline, Day 28 and Day 60 Time to discharge i.e., the total duration of participant hospitalization from baseline to discharge at Day 28 and Day 60 was reported.
Percentage of Participants Who Were Alive and Tested Negative for COVID-19 at Day 14, Day 28, and Day 60 At Day 14, Day 28 and Day 60 Percentage of participants who were alive and tested negative for COVID-19 at Day 14, Day 28, and Day 60 were reported.
Number of Participants With Clinically Significant Change in Vital Sign Day 1 up to Day 60 Vital sign parameters included of systolic and diastolic blood pressure, heart rate, respiration rate, oxygen saturation (SpO2), and body temperature. Any clinically significant change in vital signs were judged by the investigator. Number of participants with clinically significant change in vital sign values were reported.
Area Under the Plasma Concentration-time Curve From Time Zero to Last Non-zero Concentration (AUC0-t) of MP1032 Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 and Day 7 AUC0-t of MP1032 in plasma were reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Percentage of Participants With Disease Resolution at Day 28 At Day 28 Disease resolution was defined as participants who were alive and had a score of 6, 7, or 8 on the NIAID 8-point ordinal scale. The NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status.
All-cause Mortality Rate up to Day 28 Up to Day 28 All-cause mortality rate was the percentage of participants in each treatment group who died by Day 28 were reported.
Change From Baseline in Clinical Status Score Related to COVID-19 According to the NIAID 8-point Ordinal Scale at Day 28 Baseline, Day 28 The NIAID 8-point Ordinal Scale is an assessment of the clinical status on a given study day and the scale was defined as follows: 1=Death, 2=Hospitalized, on invasive ventilation (mechanical ventilator and/or ECMO), 3=Hospitalized, on non-invasive ventilation or high-flow oxygen devices, 4=Hospitalized, requiring supplemental oxygen, 5=Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (COVID-19 related or otherwise), 6=Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care (used if hospitalization was extended for infection-control reasons), 7=Not hospitalized, limitation on activities, and/or requiring home oxygen, 8=Not hospitalized, no limitations on activities. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status.
All-cause Mortality Rate up to Day 14 and Day 60 Up to Day 14 and Day 60 The percentage of participants who died by Day 14 and Day 60 were reported.
Change From Baseline in Clinical Status Score Related to COVID-19 According to the NIAID 8-point Ordinal Scale at Day 14 Baseline, Day 14 The NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status. The change from baseline in NIAID clinical status score related to COVID-19 at Day 14 were reported.
Percentage of Participants With Disease Progression Using NIAID 8-point Ordinal Scale at Day 28 At Day 28 Disease progression was defined as the percentage of participants who were not alive or who had respiratory failure. Respiratory failure was defined as participants who had a score of 2, 3 or 4 on the NIAID 8-point ordinal scale: The NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status.
Change From Baseline in Clinical Status Score of the NIAID 8-point Ordinal Scale at Each Visit Baseline up to Day 60 The NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status. The change from baseline in NIAID clinical status score at each visit were reported.
Percentage of Participants With Clinical Status Improvement of at Least 1 Category From Baseline on the NIAID 8-point Ordinal Scale at Day 14 and Day 28 Baseline, Day 14 and Day 28 NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Higher score = improvement in clinical status. Percentage of Participants with Clinical Status Improvement of at least 1 category from baseline on the NIAID 8-point Ordinal Scale at Day 14 and Day 28 were reported.
Apparent Elimination Rate Constant (Kel) of MP1032 Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 Kel was calculated using negative of the estimated slope of the linear regression of the ln-transformed plasma concentration versus time profile in the terminal elimination phase. Kel of MP1032 in plasma were reported.
Apparent Body Clearance (CL/F) of MP1032 Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 Cl/F was estimated as Dose/AUC0-inf. CL/F of MP1032 in plasma was reported.
Apparent Volume of Distribution (Vz/F) of MP1032 Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 Vz/F was estimated as Dose/(Kel x AUC0-inf). Vz/F of MP1032 in plasma was reported.
Plasma Concentration Prior to the Next Dose (Ctrough) of MP1032 Pre-dose concentration (Day 2, Day 7, and Day 8). Ctrough of MP1032 in plasma was reported.
Average Observed Plasma Concentration at Steady State of MP1032 Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 and Day 7 Average observed plasma concentration at steady state of MP1032 was reported.
Time to (First) Improvement of at Least 1 Category on the NIAID 8-point Ordinal Scale Baseline up to Day 28 The NIAID scale is an assessment of clinical status on a given study day and was defined as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or ECMO; 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Participants who did not improve at least 1 category on the NIAID scale or died before Day 28 were censored at Day 28. The total score range was 1 to 8 where, higher score indicates improvement in the clinical status.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs Day 1 up to Day 60 An Adverse Event (AE) was any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at screening, worsens during the study, regardless of the suspected cause of the event. TEAE was defined as any adverse event which starts or worsens at any time after initiation of study drug until the end of the follow-up period at Day 60. An SAE was any untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. Number of participants with TEAEs and Serious TEAEs were reported.
Number of Participants With Clinically Significant Abnormalities in Physical Examinations Baseline up to Day 60 Physical examination included examination of respiratory, cardiovascular, dermatological, neurological, and gastrointestinal system. Any clinically significant abnormalities in physical examination were judged by the investigator. Number of participants with clinically significant abnormalities in physical examinations findings were reported.
Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Results Baseline up to Day 60 Clinical laboratory tests included biochemistry, hematology and urinalysis. Any clinically significant abnormalities in clinical laboratory results were judged by the investigator. Number of participants with clinically significant abnormalities in laboratory results were reported.
Maximum Observed Plasma Concentration (Cmax) of MP1032 Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 and Day 7 Cmax of MP1032 in plasma were reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.
Trial Locations
- Locations (31)
MHAT Sv. Ivan Rilski Kozloduy
🇧🇬Kozloduy, Bulgaria
Snake River Research PLLC
🇺🇸Idaho Falls, Idaho, United States
Richmond University Medical Center
🇺🇸Staten Island, New York, United States
MHAT Blagoevgrad AD
🇧🇬Blagoevgrad, Bulgaria
MHAT Dr. Ivan Seliminski AD
🇧🇬Sliven, Bulgaria
SHATPD Pernik EOOD
🇧🇬Pernik, Bulgaria
MHAT Dr. Stamen Iliev AD
🇧🇬Montana, Bulgaria
Umhatem"N.I.Pirogov"
🇧🇬Sofia, Bulgaria
Centre Hospitalier Lyon Sud
🇫🇷Pierre-Benite CEDEX, France
Flor Ferenc Hospital of Pest County
🇭🇺Kistarcsa, Hungary
Centre Hospitalier Victor Dupouy
🇫🇷Argenteuil, France
CHU de Grenoble Alpes
🇫🇷Grenoble Cedex 9, France
DE KK Infektológiai Klinika
🇭🇺Debrecen, Hungary
Ospedale GB Morgagni
🇮🇹Forlì, Italy
Ospedale SM Goretti
🇮🇹Latina, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
ASST-FBF-SACCO - Ospedale Luigi Sacco
🇮🇹Milan, Italy
Policlinico di Napoli
🇮🇹Napoli, Italy
Ospedale "Santo Spirito! Pescara
🇮🇹Pescara, Italy
Policlinico Agostino Gemelli
🇮🇹Roma, Italy
Spitalul Municipal Caracal
🇷🇴Caracal, Romania
Spitalul Clinic de Boli Infectioase si Tropicale "Dr. Victor Babes"
🇷🇴Bucharest, Romania
Spitalul Clinic de Boli Infectioase "Sfanta Parascheva"
🇷🇴Iaşi, Romania
Hospital Clinic de Barcelona Hospital Clinic i Provincial
🇪🇸Barcelona, Spain
Hospital Universitario Marqués de Valdecilla/IDIVAL
🇪🇸Santander, Spain
Hospital Clínico Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Álvaro Cunqueiro
🇪🇸Vigo, Spain
Hospital Universitario de Valme
🇪🇸Sevilla, Spain
SHATPPD Sata Zagora EOOD
🇧🇬Stara Zagora, Bulgaria
Hospital Ramon y Cajal, Edificio Central
🇪🇸Madrid, Spain
Clinica Anestezie si Terapie Intensiva
🇷🇴Timişoara, Romania