Evaluating DR10624 for treating severe hypertriglyceridemia

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of Subcutaneous Injection of DR10624 in Subjects With Severe Hypertriglyceridemia

This study is testing a new injection called DR10624 to see if it can lower high triglyceride levels in people with severe hypertriglyceridemia.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 17 Years to 75 Years
• Sex: All
• Sponsor: Zhejiang Doer Biologics Co., Ltd. (industry)
• Locations: 1 site (Beijing)
• Trial ID: NCT06555640 on ClinicalTrials.gov

What this trial studies

This clinical investigation aims to assess the efficacy and safety of DR10624, an Fc fusion protein tri-agonist, in reducing fasting serum triglyceride levels in subjects with severe hypertriglyceridemia. Participants will be randomly assigned to receive either the DR10624 injection or a placebo over a 12-week period. The study will measure the impact of the treatment on triglyceride levels and monitor participants for any adverse effects. Each participant will only be enrolled in one cohort throughout the study.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 75 with severe hypertriglyceridemia and a BMI between 19 and 45 kg/m2.

Not a fit: Patients with triglyceride levels outside the specified range or those unable to comply with lifestyle modifications may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly lower triglyceride levels in patients with severe hypertriglyceridemia, potentially reducing their risk of cardiovascular diseases.

How similar studies have performed: While this approach is novel, similar studies targeting triglyceride reduction have shown promise, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* 1.Subjects or their legally acceptable representatives must be able to provide written informed consent, understand the procedures and methods of the study, and agree to comply with all protocol requirements.

  2.Male or female, age of 18 to 75 years (inclusive) at screening.

  3.Subjects must have a BMI of \>19 kg/m2 and BMI of ≤45.0 kg/m2 , and body weight ≥50 Kg at screening.

  4.During screening or within 1 week prior to screening, the TG levels should meet the following criteria: 4.80 mmol/L (425 mg/dL) ≤ fasting TG \< 22.60 mmol/L (2000 mg/dL).

  5.The average fasting TG level of Visit 2 and Visit 3 values must meet: 5.65 mmol/L (500 mg/dL) ≤fasting TG \<22.60 mmol/L(2000 mg/dL); or the average fasting TG level of Visit 3 and Visit 3.1 values must meet the same criteria.

  6.Subjects will able to accept rencommendation on therapeutic lifestyle modificationa and maintain a stable lifestyle for the duration of the study.

  7.Subjects who are receiving statins, cholesterol-absorption inhibitor (CAI), fibrates, niacin ≥500 mg/day, or prescription omega-3 fish oil must have achieved a stable dose for at least 4 weeks before screening.

  8.Subjects diagnosed with type 2 diabetes(T2DM) must have a glycosylated hemoglobin level at screening of\<9.5%(80 mmol/mol）and treated with lifestyle modification or a stable doses of antidiabetic medications for at least 8 weeks prior to screening.

Exclusion Criteria:

* 1.Subjects with known familial hyperchylomicronemia (Fredrickson type 1) ,apo c-II deficiency,or familial β-lipoprotein dyslipidemia (Fredrickson type 3); or subjects with a high suspicion of having this three conditions.

  2.Subjects who have lost ≥5% of body weight within 3 months prior to screening, or who lose ≥5% of body weight during screening, or who plan to lose body weight during the study.

  3.Subjects with type 1 diabetes, or nephrotic syndrome.

  4.Subjects with cirrhosis, alcoholic liver disease, liver failure, liver cancer, or autoimmune hepatitis.

  5.Subjects type 2 diabetes with a duration of less than 12 weeks or with severe complications.

  6.Uncontrolled hypertension at screening, defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg under medication conditions.

  7.Subjects with an active or untreated malignancy or who have been in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for \<5 years prior to screening.

  8.Subjects with a family or personal history of medullary thyroid carcinoma (MTC),multiple endocrine neoplasia syndrome type 2 (MEN2),severe active or unstable major depressive disorder (MDD), or other serious mental disorders (such as schizophrenia, bipolar disorder, or other severe mood or anxiety disorders) or suicidal.

  9.Subjects with a known clinically significant gastric emptying abnormality (e.g. severe diabetic gastroparesis), and who have undergone or plan to undergo gastric bypass surgery or gastric banding surgery during the study, or those who chronically take drugs that directly affect GI motility.

  10.New York Heart Association Functional Classification III or IV CHF.

  11.In the opinion of the investigator, the subjects are likely to require concurrent treatment with systemic glucocorticoids during the trial due to comorbidities.

  12.Subjects with a history of acute pancreatitis within 1 year prior to screening, or a history of chronic pancreatitis, or symptomatic of gallbladder disease (e.g. choledocholithiasis, gallbladder multiple stones, unless treated with cholecystectomy).

  13.Subjects with any of the following cardiovascular (CV) conditions within 6 months prior to screening: acute myocardial infarction, cerebral hemorrhage or cerebral infarction (except lacunar infarction), or hospitalization due to CHF, unstable angina pectoris or transient ischemic attack, or cardiac surgery such as percutaneous coronary intervention and coronary artery bypass grafting,or subjects who have been treated with GLP-1R agonists, or have participated in a clinical study involving GLP-1R and received the study drug within 6 months prior to screening.

  14.Subjects who have undergone large-sized surgery,have been treated with GCGR or multiple target point and agonists containing FGF-21R targets;have been treated with SiRNA type and monoclonal antibody type of PCSK9 inhibitors;or who have participated in a clinical study related to above all the types of drug within 3 months prior to screening.

  15.Subjects with severe trauma, severe infection who have not recoveredwithin 4 weeks prior to screening,who have been treated with DPP-4 inhibitors, or have participated in a clinical study related to DPP-4 inhibitors and received the study product;who have undergone lipid apheresis or plasma exchange treatment within the last 4 weeks or plan to undergo apheresis or plasma exchange during the study period.

  16.Subjects with hyperthyroidism or hypothyroidism who have the stable dose of therapeutic drugs less than 3 months prior to screening.

  17.Subjects with Cushing's syndrome or who have continuously or cumulatively used systemic glucocorticoids for more than 14 days within 6 months before screening, Inhaled or topical corticosteroids are permitted.

  18.Subjects who do not agree to discontinue medications, supplements, or nutraceuticals that have lipid-altering effects other than those specified in the protocol.

  19.Subjects who are taking insulin or second-generation antipsychotics and cannot stop taking them.

  20.Serum calcitonin ≥20 ng/L (pg/mL) in subjects with eGFR≥60 mL/min/1.73 m2 , or serum calcitonin ≥35 ng/L (pg/mL) in subjects with eGFR \<60 mL/min/1.73 m2.

  21.Alanine aminotransferase\>3.0 × upper limit of normal value (ULN) and/or aspartate aminotransferase\>3.0 × ULN and/or total bilirubin\>1.5 × ULN.

  22.Glomerular filtration rate eGFR \< 45 mL/min/1.73 m2

  23.TSH \> upper normal limit or \< lower normal limit.

  24.Serum amylase or lipase \> 2.0 × ULN.

  25.Hemoglobin \< 110 g/L (males) or \< 100 g/L (females).

  26.Test positive for Human Immunodeficiency Virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV), HBV and HCV determined by antibodies first and, if positive, by DNA/ribonucleic acid (RNA).

  27.Clinically significant 12-lead electrocardiogram (ECG) abnormalities at the time of screening.

  28.History of drug abuse or excessive alcohol consumption within 3 months prior to screening.

  29.Presence of potential allergies to the study drug, its ingredients, or drugs of the same class.

  30.Pregnant or lactating women;as well as men and women of childbearing potential who are unwilling to prevent pregnancy throughout the study and within the specified time after the study.

  31.Blood donation and/or blood loss ≥400 mL, or bone marrow donation within 3 months prior to screening.

  32.Subjects in which the investigator deems to that there are any other factors may affect the efficacy or safety evaluation of this study(including medical, psychological, social, or geographical considerations) .

Where this trial is running

Beijing

• Peking University First Hospital — Beijing, China (RECRUITING)

Study contacts

• Study coordinator: Senior Clinical Operations Director

Conditions: Severe Hypertriglyceridemia