A randomized double-blind, placebo-controlled, multicenter trial assessing the impact of lipoprotein(a) lowering with pelacarsen (TQJ230) on the progression of calcific aortic valve stenosis [Lp(a)FRONTIERS CAVS]

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

18 Jul 2024 → ongoing

Decision date (initial)

2024-05-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2022-502135-19-00

ClinicalTrials.gov

NCT05646381

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacogenetic, Therapy

To demonstrate the superiority of pelacarsen (TQJ230) versus placebo in slowing the progression of calcific aortic valve stenosis by evaluating the change from baseline to month 36 in peak aortic jet velocity by echocardiography and,
To demonstrate the superiority of pelacarsen (TQJ230) vs. placebo in slowing the progression of calcific aortic valve stenosis by evaluating the change from baseline to month 36 in aortic valve calcium score by computed tomography

Secondary objectives 4

1. To assess the effect of pelacarsen (TQJ230) versus placebo on the reduction of lipoprotein(a) levels from baseline to month 12
2. To assess the effect of pelacarsen (TQJ230) vs. placebo in slowing the progression of calcific aortic valve stenosis by evaluating the change from baseline to month 36 in fibrocalcific thickening of the aortic valve by contrast computed tomography
3. To assess the effect of pelacarsen (TQJ230) vs. placebo in reducing the risk of composite clinical endpoint
4. Safety and tolerability of Lp(a) lowering therapy with pelacarsen (TQJ230)

Conditions and MedDRA coding

Calcific Aortic Valve Stenosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Male and female ≥50 to <80 years of age
2. Lipoprotein(a) ≥175 nmol/L, measured at the central laboratory
3. Mild or moderate calcific aortic valve stenosis, as assessed by the core laboratory
4. At the randomization visit, participant must be optimally treated for existing CV risk factors

Exclusion criteria 8

1. Severe calcific aortic valve stenosis as assessed by the core laboratory
2. History of hemorrhagic stroke or other major bleeding
3. Platelet count <140,000 per mm3
4. Active liver disease or hepatic dysfunction
5. Significant kidney disease
6. Pregnant or nursing women
7. Uncontrolled hypertension
8. History of malignancy of any organ system

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change in peak aortic jet velocity from baseline to month 36
2. Change in aortic valve calcium score from baseline to month 36

Secondary endpoints 4

1. Change in lipoprotein(a) levels from baseline to month 12
2. Change in fibrocalcific thickening of the aortic valve from baseline to month 36
3. Time from randomization to first occurrence of composite clinical endpoint event, defined as reaching either: • Unplanned CAVS related hospital admission • Aortic valve intervention • Death related to calcific aortic valve stenosis
4. Safety endpoints (including adverse events/serious adverse events, safety laboratory parameters, vital signs) collected from baseline to end of study

Investigational products

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

Test 1

Placebo 1

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 22

Locations

10 EU/EEA countries · 69 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 105 files

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

Application history

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