MP1032 Treatment in Patients With Moderate to Severe COVID-19

COVID-19 Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Multicenter, Proof-of-concept, Phase IIA Study of MP1032 Plus Standard of Care vs Standard of Care in the Treatment of Hospitalized Participants With Moderate to Severe COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04932941
• Other study ID #: MP1032-CT05
• Secondary ID: 2021-000344-21
• Status: Completed
• Phase: Phase 2
• Start date: October 19, 2021
• Est. completion date: September 5, 2022

Study information

• Verified date: June 2023
• Source: MetrioPharm AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: September 5, 2022
• Est. primary completion date: July 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• 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 Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• MP1032
Hard gelatin capsules for oral administration.
• Placebo
Placebo capsules matched to MP1032 for oral administration.

Locations

Country	Name	City	State
Bulgaria	MHAT Blagoevgrad AD	Blagoevgrad
Bulgaria	MHAT Sv. Ivan Rilski Kozloduy	Kozloduy
Bulgaria	MHAT Dr. Stamen Iliev AD	Montana
Bulgaria	SHATPD Pernik EOOD	Pernik
Bulgaria	MHAT Dr. Ivan Seliminski AD	Sliven
Bulgaria	Umhatem"N.I.Pirogov"	Sofia
Bulgaria	SHATPPD Sata Zagora EOOD	Stara Zagora
France	Centre Hospitalier Victor Dupouy	Argenteuil
France	CHU de Grenoble Alpes	Grenoble Cedex 9
France	Centre Hospitalier Lyon Sud	Pierre-Benite CEDEX
Hungary	DE KK Infektológiai Klinika	Debrecen
Hungary	Flor Ferenc Hospital of Pest County	Kistarcsa
Italy	Ospedale GB Morgagni	Forlì
Italy	Ospedale SM Goretti	Latina
Italy	ASST-FBF-SACCO - Ospedale Luigi Sacco	Milan
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Policlinico di Napoli	Napoli
Italy	Ospedale "Santo Spirito! Pescara	Pescara
Italy	Policlinico Agostino Gemelli	Roma
Romania	Spitalul Clinic de Boli Infectioase si Tropicale "Dr. Victor Babes"	Bucharest
Romania	Spitalul Municipal Caracal	Caracal
Romania	Spitalul Clinic de Boli Infectioase "Sfanta Parascheva"	Iasi
Romania	Clinica Anestezie si Terapie Intensiva	Timisoara
Spain	Hospital Clinic de Barcelona Hospital Clinic i Provincial	Barcelona
Spain	Hospital Ramon y Cajal, Edificio Central	Madrid
Spain	Hospital Clínico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Marqués de Valdecilla/IDIVAL	Santander
Spain	Hospital Universitario de Valme	Sevilla
Spain	Hospital Álvaro Cunqueiro	Vigo
United States	Snake River Research PLLC	Idaho Falls	Idaho
United States	Richmond University Medical Center	Staten Island	New York

Sponsors (2)

Lead Sponsor	Collaborator
MetrioPharm AG	Syneos Health, LLC

Countries where clinical trial is conducted

United States,  Bulgaria,  France,  Hungary,  Italy,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Disease Progression Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale 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.	At Day 14
Secondary	Percentage of Participants With Disease Progression Using NIAID 8-point Ordinal Scale 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.	At Day 28
Secondary	Percentage of Participants With Disease Resolution 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.	At Day 28
Secondary	All-cause Mortality Rate up to Day 28	All-cause mortality rate was the percentage of participants in each treatment group who died by Day 28 were reported.	Up to Day 28
Secondary	Change From Baseline in Clinical Status Score Related to COVID-19 According to the NIAID 8-point Ordinal Scale at 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.	Baseline, Day 28
Secondary	Percentage of Participants With Disease Resolution 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.	At Day 14
Secondary	All-cause Mortality Rate up to Day 14 and Day 60	The percentage of participants who died by Day 14 and Day 60 were reported.	Up to Day 14 and Day 60
Secondary	Change From Baseline in Clinical Status Score Related to COVID-19 According to the NIAID 8-point Ordinal Scale at 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.	Baseline, Day 14
Secondary	Percentage of Participants Who Required Invasive Ventilation (Mechanical Ventilator and/ ECMO), or Who Died 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.	At Day 14 and Day 28
Secondary	Change From Baseline in Clinical Status Score of the NIAID 8-point Ordinal Scale at Each Visit	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.	Baseline up to Day 60
Secondary	Time to (First) Improvement of at Least 1 Category 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. 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.	Baseline up to Day 28
Secondary	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	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.	Baseline, Day 14 and Day 28
Secondary	Time to Discharge by 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.	Baseline, Day 28 and Day 60
Secondary	Percentage of Participants Who Were Alive and Tested Negative for COVID-19 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.	At Day 14, Day 28 and Day 60
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	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.	Day 1 up to Day 60
Secondary	Number of Participants With Clinically Significant Change in Vital Sign	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.	Day 1 up to Day 60
Secondary	Number of Participants With Clinically Significant Abnormalities in Physical Examinations	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.	Baseline up to Day 60
Secondary	Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Results	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.	Baseline up to Day 60
Secondary	Maximum Observed Plasma Concentration (Cmax) of MP1032	Cmax of MP1032 in plasma were reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.	Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 and Day 7
Secondary	Area Under the Plasma Concentration-time Curve From Time Zero to Last Non-zero Concentration (AUC0-t) of MP1032	AUC0-t of MP1032 in plasma were reported. Geometric mean and geometric coefficient of variation percent (CV%) was reported.	Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 and Day 7
Secondary	Apparent Elimination Rate Constant (Kel) of MP1032	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.	Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1
Secondary	Apparent Body Clearance (CL/F) of MP1032	Cl/F was estimated as Dose/AUC0-inf. CL/F of MP1032 in plasma was reported.	Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1
Secondary	Apparent Volume of Distribution (Vz/F) of MP1032	Vz/F was estimated as Dose/(Kel x AUC0-inf). Vz/F of MP1032 in plasma was reported.	Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1
Secondary	Plasma Concentration Prior to the Next Dose (Ctrough) of MP1032	Ctrough of MP1032 in plasma was reported.	Pre-dose concentration (Day 2, Day 7, and Day 8).
Secondary	Average Observed Plasma Concentration at Steady State of MP1032	Average observed plasma concentration at steady state of MP1032 was reported.	Pre-dose, 0.16, 0.33, 0.5, 1, 2, 8 and 24 hours post-dose at Day 1 and Day 7