Clinical Trial of Dimolegin (DD217) in Prevention of Thrombotic Complications in Patients With COVID-19

NCT05185804 | Completed Phase 3 DMC

• 1 other identifier: АМ217-03
• Study Type: interventional
• Target: 399
• Locations: 1 country
• Sites: 6

Brief Summary

Study purpose was to study the safety and efficacy of Dimolegin - DD217 as a drug for prevention of thrombotic complications compared to Clexane (enoxaparin sodium) - the standard therapy currently prescribed to patients hospitalized with COVID-19. Patients who met all inclusion criteria and no exclusion criteria were randomized into two therapy groups:

• Group 1 - test drug Dimolegin - DD217 (60 mg orally, 1 time per day);
• Group 2 - reference drug Clexane (40 mg subcutaneously, 1 time per day). The study drugs were taken once a day until:
• the discharge from the hospital due to recovery or positive dynamics;
• or up to 30 days of the patient's stay in the hospital;
• or until the Investigator decides to discontinue the therapy for other reasons. Planned: screening of up to 450 patients, randomization: 430 (215 per group). The required number of patients is 200 per group as a result of the entire study.

Conditions

COVID-19; Venous Thromboembolism

Keywords

Dimolegin; Dioxaban; DD217; factor Xa Inhibitor; anticoagulant; therapeutic anticoagulation; thromboprophylaxis; anticoagulation; venous thromboembolism; deep venous thrombosis; arterial thromboembolism; pulmonary embolism

Outcome Measures

Primary Outcomes (5)

• The frequency of DVT

  The frequency of DVT during the study therapy (maximum - 30 days)

  30 Days

• The frequency of PE

  The frequency of PE during the study therapy (maximum - 30 days)

  30 Days

• The frequency of ischemic stroke

  The frequency of ischemic stroke during the study therapy (maximum - 30 days)

  30 Days

• The frequency of AMI

  The frequency of AMI during the study therapy (maximum - 30 days)

  30 Days

• The frequency of arterial thrombotic complication

  The frequency of arterial thrombotic complication (thrombosis of mesenteric arteries, renal arteries, spleen, upper and lower extremities) during the study therapy (maximum - 30 days)

  30 Days

Secondary Outcomes (9)

• The proportion of patients transferred to the ICU

  30 Days

• The all-cause mortality rate

  30 Days

• The all-cause mortality rate during the study

  90 Days

• The proportion of patients who stayed in the hospital more than 30 days

  30 Days

• The number of days the patient spent in the hospital before discharge due to recovery or positive dynamics, including outpatient follow-up before 30 days expire

  30 Days

Other Outcomes (5)

• The frequency of major and clinically significant minor bleedings

  30 Days

• The total frequency of all hemorrhagic complications

  30 Days

• The frequency of clinical signs of severe thrombocytopenia

  30 Days

Study Arms (2)

Group DD217

EXPERIMENTAL

Study drug Dimolegin - DD217, 60 mg orally, 1 time per day

Drug: Dimolegin

Group Clexane

ACTIVE COMPARATOR

Reference drug Clexane, 40 mg subcutaneously, 1 time per day

Drug: Clexane

Interventions

Dimolegin DRUG

60 mg orally, 1 time per day

Also known as: DD217

Group DD217

Clexane DRUG

40 mg subcutaneously, 1 time per day

Also known as: Enoxaparin sodium

Group Clexane

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who have signed a written consent to participate in the study
• Hospitalized patients with a diagnosis: COVID-19 coronavirus disease confirmed by laboratory testing regardless of the severity of clinical signs no later than 72 hours before screening (U07.1 - virus was identified), or COVID-19 coronavirus disease, when the infection is diagnosed clinically or epidemiologically no later than 72 hours before screening, but laboratory tests are inconclusive or unavailable (U07.2 - virus was not identified), moderate form. To be classified as a moderate form, the patient must have at least one of the following criteria: Body temperature \> 38 °C; respiratory rate (RR) \> 22/min; shortness of breath during physical exertion; CT (radiography) findings typical of viral lesion (minimal or average lesion volume, Grade 1-2 on CT); SpO2\<95 %; serum C reactive protein (CRP) \> 10 mg/L
• Males and non-pregnant females (negative pregnancy test or human chorionic gonadotropin (HCG) blood test (for females with childbearing potential)) at the age of 18 to 85 years
• Patients who are able to comply with all the requirements of the study protocol;
• Patients who agreed to use adequate methods of contraception during the entire study and for at least 7 days after the end of the study

You may not qualify if:

• The need to prescribe anticoagulants to the patient at therapeutic doses
• Active bleeding currently or within 6 months prior to screening, high risk of bleeding
• Severe anemia
• Severe thrombocytopenia
• Congenital thrombophilia (deficiency of antithrombin III, protein C, protein S, Leiden mutation of coagulation factor V, increased level of coagulation factor VIII, mutation of prothrombin G20210A, etc.)
• Other coagulation disorders and indications when anticoagulants is impossible to use according to the Investigator
• It is necessary to monitor and to treat in the ICU
• Disease with the life expectancy of \<3 months
• Surgery on the brain or spinal cord, spine, ophthalmic or major surgery or injury in the last 90 days
• Gastrointestinal tract disorders that can disrupt the absorption of the study drug (Crohn's disease, ulcerative colitis, irritable bowel syndrome, etc.)
• Acute gastric or duodenal ulcer, erosive gastritis with increased risk of bleeding
• Active liver disease (viral hepatitis B or C, cirrhosis of the liver) and biliary tract disease, with the exception of non-alcoholic steatohepatitis with normal levels of hepatic transaminases
• Nephrotic syndrome, significant kidney diseases with the nephrotic syndrome events
• Severe renal failure (creatinine clearance \< 30 mL/min)
• Active cancer (excluding non-melanoma skin cancer), defined as cancer without remission or requiring active chemotherapy or additional treatments such as immunotherapy or radiation therapy

Sponsors & Collaborators

• PharmaDiall Ltd.: lead

Study Sites (6)

Regional budgetary healthcare institution Ivanovskaya clinical hospital named after Kuvaevs

Ivanovo, 153025, Russia

Location

State Budgetary Institution of Healthcare Research Institute - Regional Clinical Hospital No. 1 named after Professor S.V. Ochapov Ministry of Health of the Krasnodar Territory

Krasnodar, 350086, Russia

Location

Federal State Budgetary Educational Institution of Higher Education Ryazan State Medical University named after academician I.P. Pavlova of the Ministry of Health of the Russian Federation

Ryazan, 390026, Russia

Location

State Healthcare Institution Saratov City Clinical Hospital No. 2 named after IN AND. Razumovsky

Saratov, 410028, Russia

Location

St. Petersburg State Budgetary Healthcare Institution City Hospital No. 40 of Kurortny District

Sestroretsk, 197706, Russia

Location

State budgetary institution of health care of the Yaroslavl region Yaroslavl Regional Clinical Hospital of War Veterans - International Center for the Problems of the Elderly Healthy Longevity

Yaroslavl, 150047, Russia

Location

Related Publications (2)

• Tovbin DG, Tarasov DN, Malakhov DV, Tserkovnikova NA, Aybush AV, Drozd NN. The Development of New Low-Molecular-Weight Factor Xa Inhibitors that are Potential Anticoagulants. Curr Drug Discov Technol. 2022;19(1):e010921191770. doi: 10.2174/1568009621666210224104940.

  PMID: 33655836 BACKGROUND

• Tarasov DN, Tovbin DG, Malakhov DV, Aybush AV, Tserkovnikova NA, Savelyeva MI, Sychev DA, Drozd NN, Savchenko AY. The Development of New Factor Xa Inhibitors Based on Amide Synthesis. Curr Drug Discov Technol. 2018;15(4):335-350. doi: 10.2174/1570163815666180215114732.

  PMID: 29468977 BACKGROUND

MeSH Terms

Conditions

COVID-19; Venous Thromboembolism; Venous Thrombosis; Pulmonary Embolism

Interventions

(+-)-(1'R*,2'S*,6'R*)-(2-hydroxy-4,6-dimethoxyphenyl)(3'-methyl-2'-(3''-methylbut-2''-enyl)-6-phenylcyclohex-3'-enyl)methanone; Enoxaparin; enoxaparin sodium

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thrombosis; Embolism

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Dmitry A Napalkov, Professor

  Department of Faculty Therapy No. 1 of the Sechenov University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, randomized, prospective, open-label clinical trial

Study Record Dates

• First Submitted: December 29, 2021
• First Posted: January 11, 2022
• Study Start: February 8, 2021
• Primary Completion: August 6, 2021
• Study Completion: October 29, 2021
• Last Updated: January 11, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

RU (6)