Clinical trial NCT05656495: Efficacy and Safety of Ambervin® and Standard Therapy in Hospitalized Patients With COVID-19
Official title: An Open Randomized Multicenter Comparative Study to Evaluate the Efficacy, Safety and Tolerability of the Use of Ambervin® for Intramuscular Administration and for Inhalation in Patients Hospitalized With COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Keywords: SARS-CoV-2
Ambervin
Lead sponsor: Promomed, LLC
Sponsor class: OTHER
First posted: 2022-12-19
Enrollment: 313
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is open-labe randomized multicenter comparative Phase III study conducted in 8 medical facilities. The objective of the study is to assess the efficacy, safety and tolerability of Ambervin for intramuscular and inhaled administration in complex therapy COVID-19 compared with the Standard of care (SOC) in hospitalized patients with moderate COVID-19.

Detailed description: Upon signing the informed consent form and screening, 313 eligible patients hospitalized with COVID-19 were randomized at a 1:1:1 ratio to receive either Ambervin intramuscular 1mg 1 times a day for 10 days or Ambervin inhaled 10mg 1 times a day for 10 days or SOC.

Eligibility criteria: Inclusion Criteria:

1. Availability of the Informed Consent Form of thePatient Information Leaflet (PIL) signed and dated bypatient.
2. Men and women aged 18 to 80 years inclusive at thetime of signing the Informed Consent Form in PIL.
3. Confirmed case of COVID-19 at the time ofscreening based on SARS-CoV-2 RNA test usingnucleic acid amplification (NAA) method. It isacceptable to include a patient with a presumptiveCOVID-19 diagnosis prior to receiving the results ofSARS-CoV-2 RNA test made at the screening stage.
4. Hospital admission due to COVID-19.
5. Moderate severity infection with SARS-CoV-2: Clinical signs (the presence of at least 2 of the following criteria):

   * body temperature \> 38 °C;
   * RR \> 22/min;
   * CT pattern typical of a viral lesion
   * shortness of breath on exertion;
   * SpO2 \< 95%;
   * Serum CRP \> 10 mg/L.
6. Lesion volume is minimal or moderate; CT 1-2.
7. Patient's consent to use reliable contraceptive methods through out the study and within 1 month for women and 3 months for men after its completion. Reliable means of contraception are: sexualabstinence, use of condom in combination withspermicide.

Women incapable of childbearing may also participate inthe study (with past history of: hysterectomy, tubal ligation,infertility, menopause for more than 2 years), as well asmen with infertility or a history of vasectomy

Exclusion Criteria:

1. Hypersensitivity to components of the study drug.
2. Impossibility of CT procedure (for example, gypsumdressing or metal structures in the field of imaging).
3. Obstacles or inability to perform intramuscular injections and / or inhalations
4. Arterial hypotension (a decrease in blood pressure (BP) below 100/60 mm Hg) at the time of screening and / or a history of hypotensive crises.
5. The need for the use of drugs from the list of prohibited therapies.
6. Availability of criteria for severe and extremely severe disease at the time of screening
7. Presence within 6 months prior to screening of a probable or confirmed case of moderate COVID-19
8. History of presumptive or confirmed COVID-19 caseof moderate, severe and extremely severe course ofthe disease.
9. Vaccination less than 4 weeks prior to screening.
10. The need for treatment in the intensive care unit at the time of screening.
11. Impaired liver function (AST and/or ALT ≥ 2 UNLand/or total bilirubin ≥ 1.5 UNL) at the time ofscreening.
12. Renal impairment (GFR \< 60 ml/min) at the time of screening.
13. Positive testing for HIV, syphilis, hepatitis B and/or C.
14. Chronic heart failure FC III-IV according to New York Heart Association (NYHA) functional classification.
15. Malignancies in the past medical history.
16. Alcohol, pharmacological and/or drug addiction in the past medical history and/or at the time of screening.
17. Epilepsy in history.
18. Schizophrenia, schizoaffective disorder, bipolardisorder, or other history of mental pathology orsuspicion of their presence at the time of screening.
19. Severe, decompensated or unstable somatic diseases (any disease or condition that threaten thepatient's life or impair the patient's prognosis, and also make it impossible for him/her to participate in the clinical study).
20. Any history data that the investigating physician believes could lead to complication in the interpretation of the study results or create an additional risk to the patient as a result of his/her participation in the study.
21. Patient's unwillingness or inability to comply with procedures of the Study Protocol (in the opinion of physician investigator).
22. Pregnant or nursing women or women planning pregnancy.
23. Participation in another clinical study for 3 monthsprior to inclusion in the study.
24. Other conditions that, according to the physicianinvestigator, prevent the patient from being includedin the study.

Primary outcomes:
measure: Prevalence of patients with category 0-1 as per categorical ordinal clinical improvement WHO scale
timeFrame: From baseline to Visit 4 (days 14-15)
Secondary outcomes:
measure: Prevalence of patients with clinical status less than 4 points on the categorical ordinal WHO scale of clinical improvement
timeFrame: From baseline to Visit 3 (days 11-12) and 4 (days 14-15)
measure: Frequency of improvement in clinical status on a categorical ordinal WHO scale of clinical improvement of 2 or more categories
timeFrame: From baseline to Visit 3 (days 11-12) and 4 (days 14-15)
measure: Time to improve clinical status on a categorical ordinal scale of clinical improvement by ≥ 1 point.
timeFrame: From baseline to Visit 6 (study completion, day 28±1)
measure: Prevalence of patients eligible for discharge to continue outpatient treatment according to BMR
timeFrame: From baseline to Visit 2 (days 6-7), 3 (days 11-12)
measure: Prevalence of patients with RR < 22/min
timeFrame: From baseline to Visit 2 (days 6-7), 3 (days 11-12)
measure: Prevalence of patients with CRP level < 10 mg/l
timeFrame: From baseline to Visit 2 (days 6-7), 3 (days 11-12)
measure: Prevalence of patients with blood lymphocytes > 1.2 x 10(9)/L
timeFrame: From baseline to Visit 2 (days 6-7), 3 (days 11-12)
measure: Assessment of the degree of lung damage according to CT
timeFrame: From baseline to Visit 4 (days 14-15)
measure: Prevalence of patients with SpO2 ≥ 95% on 2 consecutive days
timeFrame: From baseline to Visit 2 (days 6-7), 3 (days 11-12), 4 (days 14-15)
measure: The frequency of transfer of patients to the intensive care unit and intensive care
timeFrame: From baseline to Visit 6 (study completion, day 28±1)
measure: The frequency of cases of the use of high flow oxygen therapy, non-invasive and invasive ventilation of lung, ECMO
timeFrame: From baseline to Visit 6 (study completion, day 28±1)
measure: The frequency of cases of ARDS
timeFrame: From baseline to Visit 6 (study completion, day 28±1)
measure: The frequency of patients with a fatal outcome
timeFrame: From baseline to Visit 6 (study completion, day 28±1)
Other outcomes:
Locations:
city: Cheboksary
country: Russian Federation
facility: Budgetary institution of the Chuvash Republic "Emergency Hospital"
city: Moscow
country: Russian Federation
facility: City clinical Hospital №24
city: Moscow
country: Russian Federation
facility: Infectious Clinical Hospital No.1
city: Moscow
country: Russian Federation
facility: State Budgetary Healthcare Institution City Clinical Hospital named after S. I. Spasokukotskiy of Moscow Healthcare Department
city: Ryazan
country: Russian Federation
facility: Regional Clinical Hospital
city: Ryazan
country: Russian Federation
facility: Ryazan State Medical University named after academician I.P. Pavlov of Ministry of Health of the Russian Federation
city: Saransk
country: Russian Federation
facility: Ogarev Mordova State University of Ministry of Health of the Russian Federation
city: Sestroretsk
country: Russian Federation
facility: City Hospital No. 40 Kurortny District
city: Smolensk
country: Russian Federation
facility: Regional State Budget Healthcare Institution "Clinical hospital No. 1"
city: Voronezh
country: Russian Federation
facility: Voronezh Regional Clinical Hospital No.1
Study officials:
affiliation: Moscow State Clinical Hospital №50
name: Dmitriy Pushkar
role: PRINCIPAL_INVESTIGATOR
References:
citation: L.A. Balykova, O.A. Radaeva, K.Ya. Zaslavskaya, P.A. Bely, V.F. Pavelkina, N.A. Pyataev, A.Yu. Ivanova, G.V. Rodoman, N.E. Kostina, V.B. Filimonov, E.N. Simakina, D.A. Bystritsky, A.S. Agafina, K.N. Koryanova, D.Yu. Pushkar. Efficacy and safety of original drug based on hexapeptide succinate in complex COVID-19 therapy in adults hospitalized patients. Pharmacy & Pharmacology. 2022;10(6):573-588. DOI: 10.19163/2307-9266-2022-10-6-573-588