Efficacy and Safety Evaluation of RBD5044 Sodium in Patients with Mixed Dyslipidemia: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial
- Trial ID
- 2023-510369-92-00
- Protocol
- RC02T001
- Sponsor
- Ribocure Pharmaceuticals AB
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this randomized, double-blind, placebo-controlled, parallel-group, Phase 2 trial is to evaluate the **efficacy** of RBD5044 in participants with **mixed dyslipidemia**. This is clinically relevant as mixed dyslipidemia is associated with an increased risk of cardiovascular diseases, and effective management of lipid levels is crucial in reducing this risk.
Secondary objectives include:
- Evaluating the **safety** and tolerability of RBD5044 when administered subcutaneously as repeated doses in trial participants.
- Assessing the **plasma exposure** of RBD5044 in trial participants.
- Evaluating the efficacy of RBD5044 on levels of **apolipoprotein-CIII (apoC-III)**.
- Evaluating the efficacy of RBD5044 on various **lipid parameters**: low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglyceride-rich lipoprotein cholesterol (TRL-C), apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), and lipoprotein(a) (Lp(a)).
Participants
The clinical trial involves participants diagnosed with **mixed dyslipidemia**, aiming to evaluate the efficacy of RBD5044. The study population includes both male and female participants aged between 18 and 80 years. Participants are required to have a fasting triglyceride (TG) level of ≥ 150 mg/dL and <499 mg/dL, and fasting levels at screening of non-HDL-C ≥ 100 mg/dL, or low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL after at least 4 weeks of stable diet and optimal statin therapy. The body mass index (BMI) of participants must be between 18 and 40 kg/m². The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on their willingness to comply with the protocol, including visit schedules and requirements, and to provide written informed consent. Lifestyle considerations include maintaining a stable diet and, for female participants of childbearing potential, practicing abstinence or using highly effective contraception methods. Male participants are required to practice sexual abstinence or use condoms to prevent pregnancy and drug exposure of a female partner.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study** to evaluate the efficacy and safety of RBD5044 in patients with **mixed dyslipidemia**. The trial will involve the administration of RBD5044 Sodium via subcutaneous injection, with a placebo group receiving a clear, colorless sterile solution formulated with a 25 mM phosphate buffer. The trial is expected to commence recruitment on January 13, 2025, and conclude by June 30, 2026, with a total duration of approximately 48 weeks for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, fasting triglyceride levels, and body mass index. Following successful screening, participants will be randomized to receive either the investigational product or placebo. The primary endpoint is the percent change from baseline in triglyceride levels at week 16. Secondary endpoints include the frequency and intensity of adverse events, changes in laboratory parameters, and various lipid parameters at multiple time points throughout the study.
Study visits will occur at regular intervals, including follow-up visits at weeks 4, 8, 12, 20, 24, 32, 40, and 48, to monitor safety and efficacy outcomes. The end-of-study visit will mark the completion of the trial for each participant. The expected length of participant involvement is approximately 48 weeks, with conditions for early termination including non-compliance with the protocol, withdrawal of consent, or the occurrence of significant adverse events. The trial aims to provide comprehensive data on the efficacy and safety of RBD5044 in managing mixed dyslipidemia, contributing to the understanding of its potential therapeutic benefits.
Treatment
The clinical trial involves the administration of **RBD5044 Sodium**, an experimental medication developed by Ribocure Pharmaceuticals AB. This investigational product is formulated as an **injection** and is classified as a small interfering RNA. The pharmaceutical form is a subcutaneous injection, which is administered to participants in the study. The dosing schedule is designed to ensure the maximum treatment period does not exceed 12 weeks. The specific dosage in milligrams is not disclosed, but the administration is carefully monitored to ensure compliance with the study protocol. The active substance, RBD5044 Sodium, originates from nucleic acid, highlighting its innovative approach in targeting mixed dyslipidemia.
In addition to the experimental treatment, the study includes a **placebo** control group. The placebo, referred to as RBD3000 Placebo Injection, is a clear, colorless sterile solution intended for subcutaneous injection. It is formulated with a 25 mM phosphate buffer to match the administration route and appearance of the experimental medication. The placebo serves as a comparator to evaluate the efficacy and safety of RBD5044 Sodium in a double-blind, randomized, and controlled manner. The use of a placebo is critical in maintaining the integrity of the trial's design, ensuring that any observed effects can be attributed to the investigational product rather than external factors.
Efficacy
The efficacy of RBD5044 in patients with mixed dyslipidemia will be assessed through a randomized, double-blind, placebo-controlled, parallel-group, Phase 2 clinical trial. The primary endpoint for evaluating efficacy is the percent change from baseline in triglyceride (TG) levels at week 16. Secondary endpoints include the percent change from baseline in TG levels at multiple timepoints: weeks 4, 8, 12, 20, 24, 32, 40, and 48. Additionally, the percent change from baseline in apolipoprotein C-III (apoC-III) levels will be measured at weeks 4, 8, 12, 16, 20, 24, 32, 40, and 48. Other lipid parameters such as total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglyceride-rich lipoprotein cholesterol (TRL-C), apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), and lipoprotein(a) [Lp(a)] will also be evaluated for percent change from baseline at the same timepoints.
Plasma concentrations of RBD5044 will be summarized using descriptive statistics at each sampling collection time point. The frequency, intensity, and seriousness of adverse events (AEs) will be monitored throughout the trial, along with clinically significant changes in laboratory parameters, vital signs, physical examinations, and 12-lead ECGs from baseline to week 48. These assessments will be conducted at each visit to ensure comprehensive monitoring of the participants' health and the investigational product's impact. The trial is designed to provide robust data on the efficacy and safety of RBD5044 in the target population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Willingness to comply with protocol required visit schedule and visit requirements and provide written informed consent.
- Male or female participants, aged 18 to 80 years inclusive.
- Fasting TG level of ≥ 150 mg/dL (≥ 1.69 mmol/L) and <499 mg/dL (5.61 mmol/L).
- Fasting levels at screening of non-HDL-C ≥ 100 mg/dL (2.59 mmol/L), or low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (1.8 mmol/L) after at least 4 weeks of stable diet and stable optimal statin therapy (+ or – ezetimibe) if indicated
- Body mass index between 18 and 40 kg/m2.
- Female participants of childbearing potential must also be willing to practice abstinence from heterosexual intercourse (only allowed when this is the preferred and usual lifestyle of the participant) or be willing to use a highly effective method of contraception (i.e., with a failure rate of < 1%/year) to prevent pregnancy from at least 2 weeks prior to the first administration of IMP to 4 weeks after the last administration of IMP. The following are considered highly effective contraceptive methods: • Combined (oestrogen and progestogen-containing) or progestogen-only hormonal contraception associated with the inhibition of ovulation (oral, transdermal, intravaginal, injectable, or implantable). • Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS). Female participants of non-childbearing potential are defined as pre-menopausal females who have undergone any of the following surgical procedures; hysterectomy, bilateral salpingectomy or bilateral oophorectomy, or who are post-menopausal defined as 12 months of amenorrhoea (in questionable cases a blood sample with detection of follicle stimulating hormone [FSH] >25 IU/mL will be confirmatory). Male participants must be willing, unless they have undergone vasectomy, to practice sexual abstinence from heterosexual intercourse (only allowed when this is the preferred and usual lifestyle of the participant) or use condoms from the first administration of IMP and until 4 weeks after the last administration of IMP to prevent pregnancy and drug exposure of a female partner.
Exclusion Criteria
- Any uncontrolled or serious disease, or any medical or surgical condition, that may interfere with participation in the clinical trial and/or put the participant at significant risk (according to the investigator’s judgment) if he/she participates in the clinical trial.
- Donated more than 500 mL of blood within 56 days before the first dose of the trial drug.
- History of severe intolerance to subcutaneous (SC) injection (minor reactions are permitted, e.g. localized swelling or redness.).
- Any conditions which would make the participant unsuitable for enrollment or could interfere with the participant’s participation in or completion of the trial in the opinion of the investigator
- Uncontrolled hypertension (blood pressure >160/100 mmHg at screening). (If untreated, participant may be re-screened once hypertension is treated and controlled).
- Active or history of serious mental illness or psychiatric disorder, including but not limited to schizophrenia, bipolar disorder, or severe depression, which require current pharmacological intervention. Participants with a history of severe depression who are no longer on medication.
- Any of the following laboratory values at screening: - Hepatic: ALT or AST >2× ULN at screening, - eGFR <30 mL/min/1.73 m2 (using the Modification of Diet in Renal Disease [MDRD] equation) at screening, - HbA1c >9.0% (or >75 mmol/mol International Federation of Clinical Chemistry [IFCC] units) at screening.
- Received an investigational product within 30 days or 5 half-lives (whichever is longer) before the first dose of the trial drug or are in the follow-up of another clinical trial.
- Patients with a diagnosis of HBV, HCV or HIV at screening.
- Clinically significant illness within 7 days before the first dose of the trial drug.
- Consume more than 10 units of alcohol per week for male and female (unit: 1 glass of wine (125 mL) = 1 measure of spirits = ½ pint of beer) within the 12 months before screening or positive screen for excessive alcohol consumption (defined as b-PEth >0.30 µmol/l).
- History or clinical evidence of drug abuse within the 12 months before screening or positive screen for drug abuse. Drug abuse is defined as compulsive, repetitive, and/or chronic use of drugs or other substances with or without problems related to their use and/or where stopping or a dose reduction will lead to withdrawal symptoms.
- Women of childbearing potential who are pregnant, breastfeeding, or planning to become pregnant during the course of the trial.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Poland | Recruiting | 13 Jan 2025 | 40 |
 Sweden | Recruiting | 13 Jan 2025 | 120 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
RBD3000 Placebo Injection is a clear, colorless sterile solution for subcutaneous injection, which is formulated by 25 mM phosphate buffer | Placebo | N/A | — | — | — | N/A |