A phase 2, randomised, double-blind, placebo-controlled trial to evaluate safety and local tolerability of four weekly administrations of A24110He in subjects with elevated triglyceride plasma concentrations
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 26
- 试验地点
- 6
- 主要终点
- Physical examination
研究概览
简要总结
To evaluate the safety and local tolerability of A24110He in a multiple dose trial in subjects with elevated plasma triglyceride concentrations
研究设计
- 分配方式
- Randomized
- 主要目的
- Placebo-controlled trial evaluating safety
- 盲法
- Double (Monitor, Subject, Analyst, Investigator)
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Provision of signed and dated, written informed consent prior to any trial specific procedures.
- •Access to proper venous access as per Investigator discretion.
- •Willing to comply with CTP procedures and restrictions.
- •Age 18-78 years (both inclusive).
- •Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and must be using a highly effective contraceptive method. All details that need to be applied are noted in the main body text of the CTP. A woman is considered of childbearing potential if she is not surgically sterile or is less than 1 year since last menstrual period. Male subjects who are sexually active and not surgically sterile must have undergone a vasectomy or be willing to use condom or practice sexual abstinence (only allowed when this is the preferred and usual lifestyle of the subject) to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the date of dosing until 6 months after last dosing with A24110He. Their female partner of childbearing potential must use contraception methods with a failure rate of < 1% to prevent pregnancy during the trial and until 180 days after the last dose of A24110He.
- •Body mass index (BMI) <38 kg/m
- •Body weight ≥ 56 kg.
- •History of hypertriglyceridemia prior to screening. Any lipid-lowering therapy must have been stable for at least 1 month prior to screening (visit 1) and be kept stable until randomisation (visit 4). Stable treatment is defined as unchanged in terms of dose and compound. Change of product is allowed if active substance is the same.
- •Fasting TGpl levels ≥ 1.7 mmol/L at Visit
- •Subjects with type 2 diabetes mellitus must be on stable glucose-lowering treatment (metformin, sulfonylurea, glitazones, DPP4-inhibitors, GLP-1 agonists, SGLT2-inhibitors, repaglinide) for 3 months prior to screening (visit 1) and be kept stable until randomisation (Visit 4). Stable treatment is defined as unchanged in terms of dose and compound. Change of product is allowed if active substance is the same. The subject´s glucose control must be acceptable in terms of safety, based on the Investigator´s discretion.
排除标准
- •Unstable body weight, defined as more than 5% self-reported change in body weight in the period from 30 days prior to Visit
- •Intention of losing body weight within 6 months from screening.
- •Active malignancy within the past 5 years except for in situ removal of basal cell carcinoma or non-melanoma skin cancer.
- •Participation in a clinical trial involving administration of an investigational or a marketed medicine within 3 months or five half-lives of the investigational medicine, whichever is longer, prior to Visit
- •Previous enrolment in the present trial, defined as having participated in any visit beyond Visit
- •Acute coronary syndrome < 3 months prior to Visit 1, stroke < 6 months prior to Visit 1, or symptomatic congestive heart failure.
- •Any significant medical/surgical procedure or trauma within 4 weeks of the first administration of IMP, at the discretion of the Investigator.
- •Any planned major surgery within the duration of the trial.
- •Uncontrolled or previously unknown hypertension; SBP ≥150 mmHg, or DBP ≥95 mmHg. Antihypertensive treatment must have been stable for at least 4 weeks prior to Visit
- •Involved in the planning and/or conduct of the trial.
- •Treatment within 6 months prior to Visit 4 with therapeutic oligonucleotides. mRNA vaccines are allowed.
- •Women who are pregnant, lactating or planning to become pregnant during the trial period, or women of childbearing potential who are not using acceptable contraceptive methods.
- •Current alcohol or drug addiction as judged by the Investigator or high-risk alcohol consumption. High-risk alcohol consumption is defined as more than 14 standard drinks for men and 9 standard drinks for women per week.
- •Treatment with insulin or insulin derivatives during the last 3 months prior to Visit
- •Start of any medication not previously used by the subject within 2 weeks prior to Visit
- •> 1 hypoglycaemic episode during last month prior to Visit
- •Plasma donation within 1 month of Visit 1 or any blood donation or corresponding blood loss during 3 months prior to Visit
- •Overt hypothyroidism, or other conditions potentially affecting plasma triglyceride levels.
- •Any history of acute pancreatitis related to hypertriglyceridaemia (according to investigator judgment) or any other pancreatitis episode during the last 2 years.
- •ASAT, ALAT, ALP or GGT > 2.5 times upper limit of normal (ULN) or bilirubin >1.5 times ULN at Visit
- •S-Creatinine > 1.5 x ULN at Visit
- •HbA1c >70 mmol/mol at Visit
- •Clinically significant disease, or in any other way unsuitable for participation in this trial, which in the opinion of the Investigator might interfere with the interpretation of results and/or safety of the subject.
- •Active inflammatory skin disease or contact dermatitis at Visit 1.
结局指标
主要结局
Physical examination
Physical examination
Assessment of local tolerability
Assessment of local tolerability
Vital signs: systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, body temperature
Vital signs: systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, body temperature
12- lead ECG
12- lead ECG
Safety laboratory tests - Clinical chemistry: creatinine (eGFR), cystatin C (eGFR), ASAT, ALAT, bilirubin, GGT, alkaline phosphatase, albumin, bicarbonate, chloride, phosphate, urea, potassium, calcium, sodium, fasting plasma glucose (FPG), f-insulin, HbA1c, C-reactive protein (CRP), TSH, LDH
Safety laboratory tests - Clinical chemistry: creatinine (eGFR), cystatin C (eGFR), ASAT, ALAT, bilirubin, GGT, alkaline phosphatase, albumin, bicarbonate, chloride, phosphate, urea, potassium, calcium, sodium, fasting plasma glucose (FPG), f-insulin, HbA1c, C-reactive protein (CRP), TSH, LDH
Safety laboratory tests - Haematology: haemoglobin, EVF, MCV, MHC, MCHC, erythrocyte count, platelet count, leucocyte count with differential count, haptoglobin
Safety laboratory tests - Haematology: haemoglobin, EVF, MCV, MHC, MCHC, erythrocyte count, platelet count, leucocyte count with differential count, haptoglobin
Safety laboratory tests - Coagulation: APTT, INR
Safety laboratory tests - Coagulation: APTT, INR
Safety laboratory tests - Urinalysis: erythrocytes, glucose, ketones, leucocytes, nitrite, pH, protein, hCG (women of childbearing potential only), albumin, creatinine, urinary albumin/creatinine ratio
Safety laboratory tests - Urinalysis: erythrocytes, glucose, ketones, leucocytes, nitrite, pH, protein, hCG (women of childbearing potential only), albumin, creatinine, urinary albumin/creatinine ratio
Frequency, seriousness, intensity of adverse events (AEs)
Frequency, seriousness, intensity of adverse events (AEs)
次要结局
- Plasma concentrations and PK parameters of A24110He. PK parameters to be determined: a) Maximum plasma concentration (Cmax); b) Time to Cmax (Tmax); c) Terminal half-life (t½) after the fourth dose. Cmax and Tmax will be evaluated in sampling frame up to 4 hours after dosing.
- Fasting triglyceride levels (clinical routine enzymatic assay)
- Triglyceride-glucose (TyG) index based on fasting triglyceride and glucose levels
研究者
Lipigon contact point
Scientific
Lipigon Pharmaceuticals AB