Clinical trial of colchicine to reduce coronary artery inflammation in people with HIV.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Diseases [C] - Virus Diseases [C02]

Decision date (initial)

2025-04-25

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: Efficacy

To assess the impact of colchicine versus placebo in reducing coronary artery inflammation in PWH over 50 years and high cardiovascular risk after 96 weeks

Secondary objectives 14

1. To evaluate the impact of colchicine after 96 weeks on changes in coronary plaque volume and plaque burden
2. To evaluate the impact of colchicine after 96 weeks on changes in plaque morphology
3. To evaluate the impact of colchicine after 96 weeks on changes in the percentage of high-risk plaques
4. To evaluate the impact of colchicine after 96 weeks on changes in serum inflammatory markers
5. To evaluate the impact of colchicine after 96 weeks on changes in the inflammasome markers in extracellular vesicles
6. To evaluate the impact of colchicine after 96 weeks on changes in differential monocytes subpopulations
7. To evaluate the impact of colchicine after 96 weeks on changes in leukocyte count
8. To assess the impact of colchicine after 96 weeks on arterial inflammation in individualised vessels
9. To assess the impact of colchicine after 96 weeks on arterial inflammation in completed analysable vessels
10. To assess the safety and tolerability of colchicine in PWH in comparison with placebo
11. To explore differential inflammatory patterns and treatment responses between males and females
12. To explore differential response patterns to colchicine based on CYP2D6 metabolizer classification
13. To assess differences in major cardiovascular events between treatment groups
14. To assess differences in cardiovascular risk score between treatment groups

Conditions and MedDRA coding

High cardiovascular risk in HIV patients

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. PWH > 50 years old
2. High cardiovascular risk measured by SCORE-2 > 5%
3. Stable antiretroviral therapy (ART) in the previous six months
4. Viral load < 50 copies/mililiter for at least 1 year. One blip is allowed (Viral load between 20-200 copies/mililiter with a previous and after viral load determinations < 20 copies per mililiter.
5. CD4 cell count > 350 cells/mm3
6. Stable dose of an intermediate or high intensity statin in the previous year (statin dose should not be modified throghout the study unless there is a robust clinical indication). In case the participant does not receive statins, all other hypolipemiants (bempedoic acid, ezetimibe) will need to be at a stable dose as well in the previous year.
7. No clinical indication for a change in treatment based on European Society of Cardiology Guidelines
8. Written informed consent obtained according to international guidelines and local laws
9. Ability to understand the nature of the trial and the trial related procedures and to comply with them

Exclusion criteria 15

1. Severe Heart failure defined as LVEF < 35%.
2. Participants with highly elevated hsCRP > 10 mg/dL at screening
3. Women of childbearing potential. - Permanent sterilisation methods including hysterectomy, bilateral salpingectomy and bilateral oophorectomy. - Postmenopausal state, defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. - Male participants are considered fertile after puberty unless permanently sterile by bilateral orchiectomy. To prevent pregnancies in female partners of male participants, they must agree to use highly effective contraceptive methods or have practiced sexual abstinence during the treatment period and until the end of relevant systemic exposure, defined as 5 half-lives of the IMP (9 days approximately).
4. Known hypersensitivity to the active substances or any of the excipients
5. Known iodine contrast allergy with prior history of anaphylaxis
6. Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial
7. Previous MI, stroke or coronary by-pass surgery
8. History of non-cutaneus malignancy prior to enrollment
9. History of inflammatory bowel disease or chronic diarrhoea
10. Renal dysfunctions defined as eGFR < 50 ml/min or serum creatinine levels > 1.7 mg/dL
11. Severe hepatic impairments defined as a Child-Pugh category C
12. Levels of ALT over five times the upper limit of normal OR levels of ALT over three times the upper limit of normal AND bilirrubin levels over one point five times the upper limit of normal
13. Participant is receiving drugs that inhibit the CYP3A4 (e.g. Verapamil, Azithromycin, Clarithromycin, protease inhibitors, cobicistat), CYP2D6 or inhibitors of P-glycoprotein.
14. Participant needs treatment with colchicine for any indication
15. Participants with stomach ulcers or gastrointestinal bleeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change from baseline of the mean Fat Attenuation Index (FAI) score for the 3 coronary arteries (RCA, LAD, LCX), calculated as the average of the analyzable FAI scores (valid baseline and post-baseline FAI score) across the three main coronary arteries

Secondary endpoints 15

1. Changes in plaque volume and plaque burden assessed by CCTA in week 96.
2. Changes in plaque morphology (non-calcified, mixed, calcified) assessed by CCTA in week 96
3. Changes in the percentage of high-risk plaques (positive remodelling, spotty calcium, napky ring sign and low attenuation plaque) assessed by CCTA in week 96
4. Changes in serum inflammatory markers (hsPCR, IL-6, IL-1 beta, IL-18, SuPAR) in week 96
5. Changes in inflammasome markers in extracellular vesicles (NLRP3, ASC, Caspase-1) in week 96
6. Changes in differential monocytes subpopulations (classic CD14++CD16-, non-classic CD14++CD16++ and intermediate CD14+CD16+) in week 96
7. Percentage change of leukocyte count in week 96
8. Solicited and unsolicited AEs in all participants throughout the trial
9. Serious adverse events (SAEs) in all participants
10. Change from baseline for FAI, FAI score (mean absolute change and mean percent change) and FAI score centile in the following vessels: Greatest change in most inflamed vessel, Greatest change in any vessel , RCA only analysis, LAD only analysis, LCX only analysis
11. Mean absolute change from baseline for mean FAI and mean FAI score, defined as the average of the analyzable vessels (with valid baseline FAI and post-baseline FAI) across the three main coronary arteries (RCA, LAD, LCX)
12. Differences in FAI percentage change between males and females in both treatment groups assessed by CCTA in week 96
13. Differences in FAI percentage change by CYP2D6 genotype in the treatment group
14. Differences in MACE between colchicine and placebo groups assessed clinically in week 96
15. Change from baseline for CaRi-Heart risk score (mean absolute change and mean percent change.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz

Sponsor organisation

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz

Address

Paseo De La Castellana 261

City

Madrid

Postcode

28046

Country

Spain

Scientific contact point

Organisation

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz

Contact name

Jose Ignacio Bernardino de la Serna

Public contact point

Organisation

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz

Contact name

Jose Ignacio Bernardino de la Serna

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Results and documents

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

Documents 7 files

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

Application history

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