A Randomized, Double-Blind, Placebo-Controlled Phase IIa Trial to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of Repeated Subcutaneously Administered RBD4059 in Participants with Stable Coronary Artery Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ribocure Pharmaceuticals AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

28 Aug 2024 → 29 Apr 2026

Decision date (initial)

2024-05-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Pharmacodynamic

To evaluate the safety of RBD4059 compared to placebo when administered subcutaneously as repeated doses in participants with stable CAD that are under treatment with low dose aspirin (75 mg)

Secondary objectives 5

1. To assess the plasma exposure of RBD4059 in participants with stable CAD
2. To evaluate the pharmacodynamic (PD) effect of RBD4059 on FXI activity in participants with stable CAD.
3. Measure anti-drug antibodies (ADA) to evaluate immunogenicity related to RBD4059
4. To evaluate the effect of RBD4059 on levels of biomarkers: activated partial thromboplastin time (APTT) and PK(INR).
5. To evaluate the effect on platelet inhibition when RBD4059 is added to low dose aspirin

Conditions and MedDRA coding

Stable Coronary Artery Disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Willing and able to give written informed consent for participation in the trial
2. Male or female (post-menopausal) participants ≥50-75 years.
3. Patients with stable CAD defined as chronic coronary syndromes according to ESCs guideline on chronic coronary syndromes including the category asymptomatic or symptomatic patients >1 year after initial diagnosis or revascularization
4. Ongoing standard treatment with aspirin 75 mg for at least 3 months
5. Stable prescription drugs i.e., ongoing since at least 30 days prior to randomization, should continue during the trial.

Exclusion criteria 25

1. Presence of any significant arrythmia in opinion of the investigator
2. Left ventricular ejection fraction (LVEF) < 30% at enrolment
3. New York Heart Association (NYHA) class III-IV heart failure at entry, hospitalization for exacerbation of chronic heart failure within the previous 12 months or other indices of unstable heart failure
4. Creatinine clearance calculated by Cockcroft Gault equation <60ml/min*m2 at the time of enrolment. Hemodynamically significant valvular disease or valvular disease likely to require surgery within 3 years
5. Hemodynamically significant valvular disease or valvular disease likely to require surgery within 3 years.
6. Expected survival time is less than one year for non-cardiac related disorders
7. History or presence of: a. Bleeding disorder(s) and/or at risk of bleeding, including relevant familial history. b. Thromboembolic diseases
8. An underlying known disease, or surgical or medical condition that, in the opinion of the Investigator, might interfere with the participants ability to comply with the protocol or the interpretation of the clinical trial results
9. Alanine aminotransferase (ALT) and/or total bilirubin >1.5 the upper limit of normal (ULN) (as per the local laboratory reference range); No repeat assessments are allowed
10. AST, ALP, or GGT > ULN (as per the local laboratory reference range), and considered clinically significant by the Investigator
11. Positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus antibody (HCVAb), HIV antibody (HIVAb) at screening
12. Any clinical suspicion on acute coronary syndrome or unstable angina at enrolment according to ESC criteria : (i) rest angina, i.e. pain of characteristic nature and location occurring at rest and for prolonged periods (>20 min); (ii) new-onset angina, i.e. recent (2 months) onset of moderate-to-severe angina (Canadian Cardiovascular Society grade II or III); or (iii) crescendo angina, i.e. previous angina, which progressively increases in severity and intensity, and at a lower threshold, over a short period of time.
13. Clinically significant acute illness within 7 days before the first dose of trial drug
14. Consume more than 8 (female) or 14 (male) units of alcohol per week (1 standard unit of alcohol contains 14 g of alcohol and corresponds to, e.g., 360 mL of beer, 150 mL of wine, or 45 mL of spirits at 40% alcohol content.) within 6 months before screening or positive screen for alcohol abuse or clinical evidence of other drug abuse within 12 months
15. Donated more than 300 mL of blood within 56 days before the first dose of trial drug
16. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc).
17. Patients with other clinical scenarios qualifying in the ESC definition of chronic coronary syndromes: patients with suspected CAD and ‘stable’ anginal symptoms, and/or dyspnoea, with new onset of heart failure (HF) or left ventricular (LV) dysfunction and suspected CAD, with angina and suspected vasospastic or microvascular disease
18. High bleeding risk defined as history of any significant bleeding (included but not limited to intracerebral haemorrhage and gastrointestinal), anaemia, liver failure, age >75 years or Clinical Frailty Score [2] > 5, or weight <60kg
19. Major surgery during last 30 days or planned major surgery or intervention within trial period
20. Capillary Hb <120 g/l for women and <130 g/L for men.
21. Elective PCIor CABG within the previous 12 months
22. Previously confirmed ischemic stroke
23. Ongoing indication for chronic anti-coagulation therapy (incl. but not limited to patients with: atrial fibrillation, venous thrombo-embolism, mechanical cardiac valves) with NOACs, warfarin or other similar anticoagulants
24. History of severe intolerance to subcutaneous (SC) injection (minor reactions are permitted, e.g. localised swelling or redness.).
25. Received an investigational product within 30 days or 5 half-lives (whichever is longer) before the first dose of the study drug or are in the follow-up of another clinical study. If subjects used advanced therapy (ASO/siRNA/gene therapy/cell therapy), it should be judged by the investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Frequency, intensity and seriousness of the AEs during the trial as well as clinically significant changes in laboratory parameters, vital signs, physical examinations and 12-lead ECG at each visit from baseline to end of trial.

Secondary endpoints 5

1. Plasma concentrations of RBD4059 will be summarised with descriptive statistics by sampling collection time point
2. Actual and percentage change from baseline in FXI activity and compared to placebo throughout the trial period
3. Proportion of participants with positive immunogenicity, measured as titers of anti-drug antibodies (ADAs), at each evaluation time point.
4. Change from baseline in APTT and PK(INR) levels compared to placebo throughout the trial period
5. Change from baseline in platelet inhibition levels compared to placebo throughout the trial period.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ribocure Pharmaceuticals AB

Sponsor organisation

Ribocure Pharmaceuticals AB

Address

Vetenskapens Grand 11

City

Molndal

Postcode

431 53

Country

Sweden

Scientific contact point

Organisation

Ribocure Pharmaceuticals AB

Contact name

Maria Liljevald

Public contact point

Organisation

Ribocure Pharmaceuticals AB

Contact name

Maria Liljevald

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications