Dalcetrapib for Heart Attack

(dal-GenE-2 Trial)

Recruiting at 53 trial locations

Overseen By Therese Heinonen, DVM

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: DalCor Pharmaceuticals

Must be taking: Lipid-lowering drugs

Disqualifiers: Pregnancy, Heart failure, Hypertension, Liver disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Average of 30 months

2000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Dalcetrapib for individuals who have recently experienced a heart attack. Researchers aim to determine if Dalcetrapib can improve heart health by comparing it to a placebo (a pill with no medicine). Participants must have been hospitalized for a heart attack within the last three months and possess a specific genetic profile. The trial seeks to establish whether Dalcetrapib can benefit those with the appropriate genetic makeup. As a Phase 3 trial, it represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking advancements in heart health.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does require that you have evidence of guidelines-based management of LDL-C, which includes medical and dietary treatment. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that dalcetrapib is generally well-tolerated. In one 48-week study, patients taking dalcetrapib experienced good safety outcomes. Most side effects were mild, such as headaches or slight increases in blood pressure, with few serious issues. Another study involving patients with various heart conditions also demonstrated positive safety results. Dalcetrapib increased "good" cholesterol levels without major safety concerns. Overall, research suggests that dalcetrapib is safe, but ongoing studies continue to monitor its effects closely. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for heart attacks, which primarily focus on reducing cholesterol levels or preventing blood clots, Dalcetrapib works differently by targeting the CETP (cholesteryl ester transfer protein). This unique mechanism of action is designed to increase the levels of "good" HDL cholesterol, potentially offering a novel way to protect the heart after a heart attack. Researchers are excited about Dalcetrapib because it could provide an additional protective benefit beyond what current medications offer, potentially improving outcomes for heart attack patients.

What evidence suggests that Dalcetrapib could be an effective treatment for heart attack?

Research shows that dalcetrapib, which participants in this trial may receive, might help lower the risk of heart attacks in some patients. In earlier studies, patients with a certain genetic profile who took dalcetrapib had fewer heart problems compared to those who took a placebo, a pill with no active medicine. This suggests dalcetrapib could work well for people recently hospitalized for acute coronary syndrome (ACS), if they have the right genes. Previous trials have found dalcetrapib to be safe and easy to tolerate, making it a possible choice for those who meet the genetic requirements. ^{1 2 3 4 6}

Who Is on the Research Team?

David Kallend, MBBS

Principal Investigator

DalCor

Are You a Good Fit for This Trial?

This trial is for adults over 45 who've been hospitalized with Acute Coronary Syndrome (ACS) within the last 3 months, are stable, and have a specific AA genotype. They must be on LDL-C management and not pregnant or breastfeeding. Excluded are those with severe kidney/liver disease, uncontrolled hypertension, certain heart failures, recent other trials participation or life expectancy under 3 years.

Inclusion Criteria

Are you 45 years or older?

Have you had a Heart Attack in the past 2-3 months?

Have you been diagnosed with Myocardial Infarction in the past 2-3 months?

Exclusion Criteria

Have you undergone coronary artery bypass graft (CABG) surgery in the past 2-3 months?

Timeline for a Trial Participant

Pre-screening

Initial pre-screening genetic testing for AA genotype

Not specified

Screening

Participants are screened for eligibility to participate in the trial

Up to 12 weeks

Treatment

Participants receive either Dalcetrapib or placebo and are monitored for cardiovascular events

Average of 30 months

Every 3 months (virtual or clinic visits)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Not specified

What Are the Treatments Tested in This Trial?

Interventions

• Dalcetrapib
• Placebo

Trial Overview The study tests Dalcetrapib's effect on cardiovascular risk in patients with a recent ACS event and a particular genetic profile. It's randomized (patients assigned by chance), double-blind (neither researchers nor participants know who gets what treatment), comparing Dalcetrapib against a placebo.

How Is the Trial Designed?

Group I: Dalcetrapib Experimental Treatment 1 Intervention

Dalcetrapib 600 mg (two 300 mg tablets) orally once daily

Group II: Placebo Placebo Group 1 Intervention

Matching dalcetrapib placebo tablets (2 tablets) orally once per day

Who Is Running the Clinical Trial?

DalCor Pharmaceuticals

Lead Sponsor

Trials

3

Recruited

8,400+

The Montreal Health Innovations Coordinating Center (MHICC)

Collaborator

Trials

14

Recruited

10,900+

Published Research Related to This Trial

A network meta-analysis of 15 randomized controlled trials involving 55,798 patients with acute coronary syndrome (ACS) found that de-escalating dual antiplatelet therapy (DAPT) to clopidogrel or low-dose prasugrel significantly reduced the risk of bleeding events without compromising cardiovascular safety outcomes.

De-escalation therapy was associated with a lower risk of major and minor bleeding compared to standard doses of other P2Y12 inhibitors, while maintaining similar efficacy in preventing cardiovascular death, myocardial infarction, and stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De-Escalation of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndromes. Shoji, S., Kuno, T., Fujisaki, T., et al.[2022]

In a study of 3,691 patients with stable coronary artery disease, 24% were treated with dual-antiplatelet therapy (DAPT), with factors like persistent angina and prior myocardial infarction influencing its use.

The study found no significant difference in the rates of cardiovascular events between patients on DAPT (5.5%) and those on single-antiplatelet therapy (SAPT) (4.6%) over two years, suggesting that prolonged DAPT does not provide additional benefits in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual antiplatelet therapy in patients with stable coronary artery disease in modern practice: prevalence, correlates, and impact on prognosis (from the Suivi d'une cohorte de patients COROnariens stables en region NORd-Pas-de-Calais study). Lemesle, G., Lamblin, N., Meurice, T., et al.[2014]

In a study of 120 patients undergoing transcatheter aortic valve implantation (TAVI), single antiplatelet therapy (aspirin only) was found to be as safe as dual antiplatelet therapy (DAPT) without increasing morbidity or mortality over a 6-month follow-up period.

Patients receiving single antiplatelet therapy experienced fewer vascular complications at 30 days compared to those on DAPT, suggesting that DAPT may not be necessary for TAVI procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAT-TAVI (single antiplatelet therapy for TAVI) study: a pilot randomized study comparing double to single antiplatelet therapy for transcatheter aortic valve implantation. Stabile, E., Pucciarelli, A., Cota, L., et al.[2022]

In a study of 16,237 patients with their first myocardial infarction, 4.4% were identified as having myocardial infarction with non-obstructive coronary artery disease (MINOCA), and 55% of these patients were discharged on dual antiplatelet therapy (DAPT).

Factors such as being male, being an active smoker, having a history of previous percutaneous intervention, experiencing ST elevation myocardial infarction, and being in sinus rhythm at admission were identified as independent predictors for the use of DAPT in MINOCA patients, suggesting these groups may be at higher risk for thrombotic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual antiplatelet therapy in myocardial infarction with non-obstructive coronary artery disease - insights from a nationwide registry. Montenegro Sá, F., Carvalho, R., Santos, L., et al.[2021]

In a study of 100 patients undergoing transcatheter aortic valve implantation (TAVI), clopidogrel platelet reactivity testing before and after the procedure was found to be a significant predictor of in-hospital bleeding, with specific cut-off values indicating increased risk.

The results suggest that monitoring clopidogrel response is crucial, as a significant drop in platelet reactivity during the procedure correlates with higher bleeding risk, while aspirin response did not show the same predictive value.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of platelet reactivity assessment in dual antiplatelet prophylaxis after transcatheter aortic valve implantation. Czerwińska-Jelonkiewicz, K., Witkowski, A., Dąbrowski, M., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2821630/

Safety and tolerability of dalcetrapib (RO4607381/JTT-705) Safety and tolerability of dalcetrapib (RO4607381/JTT-705): results from a 48-week trial. Evan A Stein. Evan A Stein. 1Metabolic and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3585985/

Dalcetrapib: JTT 705; JTT-705; R 1658; R1658 Favorable safety and efficacy results were reported from phase II trials of dalcetrapib in patients with dyslipidemia, coronary heart disease (CHD), or CHD ...

3. researchgate.net researchgate.net/publication/41123092_Safety_and_tolerability_of_dalcetrapib_RO4607381JTT-705_Results_from_a_48-week_trial

Safety and tolerability of dalcetrapib (RO4607381/JTT-705) Dalcetrapib 900 mg administered for up to 48 weeks showed no clinically relevant changes in lymph nodes, BP, or other safety parameters.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00658515

A Study of RO4607381 in Stable Coronary Heart Disease ... This study will evaluate the potential of RO4607381 to reduce cardiovascular morbidity and mortality in stable coronary heart disease patients with recent ...

5. academic.oup.com academic.oup.com/eurheartj/article/43/39/3947/6646961

Pharmacogenetics-guided dalcetrapib therapy after an acute ... A total of 6147 patients were randomly assigned to receive dalcetrapib 600 mg or placebo daily. The primary endpoint was the time from ...

6. iro.uiowa.edu iro.uiowa.edu/esploro/outputs/journalArticle/Safety-and-tolerability-of-dalcetrapib-RO4607381JTT-705/9984364421902771

Safety and tolerability of dalcetrapib (RO4607381/JTT-705) Lipid changes and safety parameters were assessed. Mesenteric lymph nodes were evaluated by magnetic resonance imaging. Dalcetrapib increased HDL-C (33.4%, Week ...