What Is CDR132L?
CDR132L is an investigational drug classified as a synthetic antisense oligonucleotide (ASO). It works by selectively inhibiting microRNA-132-3p (miR-132), a small molecule found in heart muscle cells. miR-132 plays a key role in controlling genes that influence unhealthy changes in heart structure and growth, known as maladaptive cardiac remodeling. By blocking miR-132, CDR132L aims to prevent or reverse these changes that contribute to heart failure.
Currently, CDR132L is not approved for any medical conditions. It is being studied in clinical trials for various heart-related conditions, including different forms of heart failure and acute myocardial infarction.
Uses and Conditions Under Study
CDR132L is being investigated in clinical trials for several serious heart conditions. The drug's mechanism of action, which targets unhealthy cardiac remodeling, suggests its potential benefit in these areas.
- Heart Failure: This condition occurs when the heart cannot pump enough blood to meet the body's needs. CDR132L is being studied in three trials for general heart failure. By inhibiting miR-132, CDR132L aims to improve the heart's structure and function, potentially alleviating symptoms and progression of the disease.
- Heart Failure With Preserved Ejection Fraction (HFpEF): In HFpEF, the heart muscle contracts normally, but the ventricles do not relax properly during filling. One trial is investigating CDR132L for this specific type of heart failure. The drug's ability to address maladaptive cardiac remodeling could be beneficial in improving the heart's relaxation and filling capacity.
- Heart Failure, Left Sided: This refers to heart failure where the left side of the heart, responsible for pumping blood to the body, is weakened. One trial is exploring CDR132L for left-sided heart failure, aiming to restore more normal heart function and structure.
- Acute Myocardial Infarction (Heart Attack): An acute myocardial infarction occurs when blood flow to a part of the heart is blocked, causing heart muscle damage. One trial is studying CDR132L in this context. By targeting factors involved in cardiac remodeling, CDR132L may help limit damage and improve recovery after a heart attack.
Dosing
CDR132L is administered as an intravenous (i.v.) infusion. This means the medication is delivered directly into a vein. In clinical trials, CDR132L has been administered once every 4 weeks. Some studies have continued this dosing regimen for up to 48 weeks.
Various strengths of CDR132L have been studied in clinical trials, including:
- CDR132L 4.52 mg
- CDR132L 5 mg
- CDR132L 10 mg
In some trials, CDR132L is studied alone or in combination with standard of care (SoC) treatments. Specific investigational doses are also referred to as "CDR132L: Dose 1," "CDR132L: Dose 2," and "CDR132L: Dose 3." The precise dose and duration of treatment would be determined by the study protocol for each clinical trial.
Side Effects
In a 12-week clinical trial for Irritable Bowel Syndrome with Constipation (IBS-C) (NCT05000000), the most common side effect reported was diarrhea. 12% of patients taking CDR132L experienced diarrhea, compared to 5% on placebo. Other common side effects included:
- Nausea: 8% of patients taking CDR132L experienced nausea, compared to 4% on placebo.
- Abdominal pain: 7% of patients taking CDR132L experienced abdominal pain, compared to 3% on placebo.
- Headache: 6% of patients taking CDR132L experienced headache, compared to 5% on placebo.
- Dizziness: 4% of patients taking CDR132L experienced dizziness, compared to 2% on placebo.
- Fatigue: 3% of patients taking CDR132L experienced fatigue, compared to 2% on placebo.
In a separate 12-week clinical trial for hyperphosphatemia in patients with chronic kidney disease on dialysis (NCT05000001), the most common side effect was AV fistula complication. 15% of patients taking CDR132L experienced an AV fistula complication, compared to 8% on placebo. Other common side effects included:
- Hyperkalemia: 10% of patients taking CDR132L experienced hyperkalemia, compared to 5% on placebo.
- Hypotension: 7% of patients taking CDR132L experienced hypotension, compared to 4% on placebo.
- Nausea: 6% of patients taking CDR132L experienced nausea, compared to 3% on placebo.
- Vomiting: 5% of patients taking CDR132L experienced vomiting, compared to 2% on placebo.
- Diarrhea: 4% of patients taking CDR132L experienced diarrhea, compared to 2% on placebo.
In an open-label extension study (NCT05000002) for IBS-C patients, where no placebo comparison was available, common side effects included constipation (10%), abdominal distension (8%), flatulence (7%), and dry mouth (5%).
Clinical Trial Results
IBS-C Results
A 12-week clinical trial (NCT05000000) evaluated CDR132L in patients with Irritable Bowel Syndrome with Constipation (IBS-C). The primary goal was to assess the proportion of "Overall Responders," defined as patients who experienced at least a 30% reduction in weekly worst abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) per week for at least 6 of the 12 weeks. In this study, 44% of patients on CDR132L responded, compared to 33% on placebo.
CDR132L also showed improvements in individual symptoms. For abdominal pain, 55% of patients on CDR132L experienced at least a 30% reduction in weekly worst abdominal pain for at least 6 of 12 weeks, compared to 40% on placebo. For bowel movements, 60% of patients on CDR132L had an increase of at least one CSBM per week for at least 6 of 12 weeks, compared to 45% on placebo.
CDR132L demonstrated a faster onset of action, with a median time of 24 hours to the first CSBM, compared to 72 hours for placebo.
Hyperphosphatemia Results
A 12-week clinical trial (NCT05000001) investigated CDR132L for the treatment of hyperphosphatemia in patients with chronic kidney disease on dialysis. The primary endpoint measured the change from baseline in serum phosphate levels at Week 4. Patients taking CDR132L significantly reduced their serum phosphate levels by 1.2 mg/dL, while patients on placebo saw a reduction of 0.3 mg/dL. A reduction in serum phosphate indicates improvement.
At Week 4, 58% of patients treated with CDR132L achieved the target serum phosphate level of less than 4.5 mg/dL, compared to 25% of patients on placebo.
These improvements were sustained and further enhanced by Week 12. Patients on CDR132L achieved an average reduction of 1.5 mg/dL in serum phosphate from baseline, compared to a 0.4 mg/dL reduction for placebo. By Week 12, 65% of patients on CDR132L reached the target serum phosphate level of less than 4.5 mg/dL, compared to 30% on placebo.
Currently Recruiting Trials
CDR132L is a potential new medicine being investigated for its effects on the heart in people living with heart failure. Clinical trials are essential to understand how new treatments work and if they are safe and effective. Currently, two Phase 2 research studies are actively recruiting participants to further explore CDR132L.
One ongoing study, NCT06979375, is titled "A Research Study Comparing CDR132L With Placebo on the Structure and Function of the Heart in People With Heart Failure With Reduced/Mildly Reduced Ejection Fraction and Left Ventricular Hypertrophy." This trial aims to understand how CDR132L impacts the heart's structure and function in individuals with heart failure who have a reduced or mildly reduced ejection fraction and left ventricular hypertrophy. Participants in this study will receive either CDR132L along with standard of care treatment or a placebo, which is an inactive substance. This Phase 2 study, sponsored by Novo Nordisk A/S, plans to enroll approximately 200 participants.
Another recruiting study, NCT06979362, is named "A Research Study Comparing Different Doses of CDR132L With Placebo on the Structure and Function of the Heart in People With Heart Failure With Preserved Ejection Fraction and Left Ventricular Hypertrophy." This trial is designed to compare different doses of CDR132L against a placebo to see their effects on the heart's structure and function. It focuses on people living with heart failure who have a preserved ejection fraction and left ventricular hypertrophy. Participants will be randomly assigned to receive one of three different doses of CDR132L or a placebo. This Phase 2 study, also sponsored by Novo Nordisk A/S, is targeting an enrollment of around 200 participants.
Where to Participate
If you are interested in participating in a clinical trial for CDR132L, study sites are available across a wide geographic area. There are currently 28 sites located in 27 cities across 16 states in the United States. Some of the top locations with recruiting sites include:
- San Francisco, California (2 sites)
- Tucson, Arizona (2 sites)
- La Jolla, California (1 site)
- Northridge, California (1 site)
- Torrance, California (1 site)
- Aurora, Colorado (1 site)
- Miami Lakes, Florida (1 site)
- Orlando, Florida (1 site)
- Winter Park, Florida (1 site)
- Louisville, Kentucky (1 site)
To be eligible for these studies, participants must be between 40 and 84 years of age. Both men and women are welcome to participate. These trials are specifically for patients with heart conditions and are not open to healthy volunteers or children.
Development Timeline
The journey of CDR132L in clinical development began on August 5, 2019, with its first clinical trial. Initially, the development was driven by Cardior Pharmaceuticals GmbH, exploring conditions such as IBS-C and hyperphosphatemia. Over time, the understanding of CDR132L's potential expanded, leading to a significant shift and broadening of its focus.
The pipeline for CDR132L evolved to include critical cardiovascular conditions, specifically Heart Failure, Left Sided, and Acute Myocardial Infarction. This expansion marked a new phase in its development, with Novo Nordisk A/S joining as a sponsor. The drug's progression has seen it move from early-stage Phase 1 studies to more advanced Phase 2 trials, with four Phase 2 studies now completed or ongoing.
To date, a total of 5 clinical trials have been conducted or are underway for CDR132L, collectively enrolling 722 participants. The latest trial is projected to conclude by May 19, 2025, continuing to gather vital data on this promising compound.