A randomized, placebo-controlled, parallel-group, investigator- and participant-blinded Phase 2a study to investigate the efficacy, safety, and tolerability of DFV890 and MAS825 for inflammatory marker reduction in an adult population with coronary heart disease and Clonal Hematopoiesis of Indeterminate Potential (CHIP)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

16 Feb 2024 → 5 Nov 2024

Decision date (initial)

2024-02-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacogenetic, Efficacy, Others, Pharmacokinetic, Safety

To evaluate the effect of various dose levels of DFV890 versus placebo to reduce circulating levels of inflammatory markers in participants with coronary heart disease and CHIP

To evaluate the effect of MAS825 versus placebo to reduce circulating levels of inflammatory markers in participants with coronary heart disease and CHIP

Secondary objectives 3

1. To evaluate the safety and tolerability of DFV890 and MAS825 in participants with coronary heart disease and CHIP
2. To assess the pharmacokinetics of DFV890 in participants with coronary heart disease and CHIP
3. To assess the pharmacokinetics of MAS825 in participants with coronary heart disease and CHIP

Conditions and MedDRA coding

Atherosclerotic cardiovascular disease

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male and female participants aged between 18 - 80 years (inclusive) at the start of screening will be included.
2. Participants must have a body mass index (BMI) within the range of 18 - 40 kg/m2 at screening. BMI = Body weight (kg) / [Height (m)]2.
3. Documented spontaneous myocardial infarction (MI) (diagnosed according to the universal MI criteria with or without evidence of ST segment elevation) at least 30 days before the start of screening (Thygesen et al 2007).
4. Known presence of CHIP, restricted to driver mutations in TET2 or DNMT3A with a VAF ≥2%, as documented in the participant's medical history.
5. For participants on statin therapy (HMG-CoA reductase inhibitor) as clinically indicated, participants must be on a stable regimen (at least 4 weeks before randomization), with no planned statin dose changes over the course of the trial treatment period. Unplanned statin dose changes during the trial treatment period may occur.

Exclusion criteria 8

1. Patients receiving concomitant medications that are known to be strong or moderate inducers of cytochrome CYP2C9 enzyme and/or strong inducers of CYP3A, strong inhibitors of CYP2C9 and/or strong or moderate inhibitors of CYP3A and the treatment cannot be discontinued or switched to a different medication within 5 half-lives or 1 week (whichever is longer) prior to Day 1 and for the duration of the study.
2. At screening, pre-malignant clonal cytopenias or clonal cytopenia of unknown significance (CCUS).
3. History of ongoing, chronic, or major recurrent infectious disease, at the discretion of the Investigator, at the start of screening.
4. Patients with suspected or proven immunocompromised state at screening.
5. Use of any biologic drugs targeting the immune system within 26 weeks of Day 1.
6. Multi-vessel coronary artery bypass graft (CABG) surgery within the past 3 years prior to the start of screening.
7. Planned coronary revascularization (percutaneous coronary intervention (PCI) or CABG) or any other major surgical procedure during the study (until End of Study (EOS)).
8. Symptomatic Class IV heart failure (New York Heart Association [NYHA]) at the start of screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Serum levels of IL-6 and IL-18 at 3 weeks after the start of a DFV890 dosing period
2. Serum level of IL-6 at 3 weeks after a single s.c. dose of MAS825

Secondary endpoints 3

1. Adverse events, and parameters from safety assessments, including vital signs, electrocardiograms (ECGs), and laboratory assessments (urine and blood)
2. Plasma trough concentrations (Ctrough) of DFV890 at steady-state
3. Serum concentrations of MAS825 after a single s.c. dose of MAS825

Investigational products

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

Test 3

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 12

Locations

1 EU/EEA country · 4 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 11 files

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

Application history

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