| CTRI Number |
CTRI/2024/12/078408 [Registered on: 20/12/2024] Trial Registered Prospectively |
| Last Modified On: |
01/04/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
A Phase IIb Study of AZD5462 in Patients With Chronic Heart Failure (LUMINARA) |
|
Scientific Title of Study
|
A Phase IIb Two-Cohort, Randomised, Placebo-controlled, Doubleblind,
Multi-centre, Dose-ranging Study of AZD5462 in Stable Patients with
Chronic Heart Failure |
| Trial Acronym |
NIL |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| 2023-510148-19-00 |
EudraCT |
| D9090C00008, v2.0/Local CSP India-2, dated 04-Dec-2024 |
Protocol Number |
| IND155119 |
Other |
| NCT06299826 |
ClinicalTrials.gov |
|
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
|
| Designation |
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| Affiliation |
|
| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
|
| Name |
Dr Annappa Kamath |
| Designation |
Executive Director Project Leadership |
| Affiliation |
PAREXEL International Clinical Research Private Limited |
| Address |
CoWrks, RMZ EcoWorld, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village
Bangalore Rural
KARNATAKA
560103
India |
| Phone |
9902096914 |
| Fax |
918067723001 |
| Email |
Annappa.Kamath@parexel.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Annappa Kamath |
| Designation |
Executive Director Project Leadership |
| Affiliation |
PAREXEL International Clinical Research Private Limited |
| Address |
CoWrks, RMZ EcoWorld, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village
KARNATAKA
560103
India |
| Phone |
9902096914 |
| Fax |
918067723001 |
| Email |
Annappa.Kamath@parexel.com |
|
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Source of Monetary or Material Support
|
| Astrazeneca UK Limited, 1 Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge-CB20AA, England |
|
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Primary Sponsor
|
| Name |
AstraZeneca AB |
| Address |
151 85 Sodertalje, Sweden |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
Details of Secondary Sponsor
Modification(s)
|
| Name |
Address |
| PAREXEL International Clinical Research Private Limited |
CoWrks, EcoWorld, Ground Floor, Bay Area Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village, BENGALURU - 560103, Karnataka, INDIA |
|
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Countries of Recruitment
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Bulgaria
Czech Republic
Denmark
Hungary
India
Japan
Netherlands
Poland
Slovakia
United States of America |
|
Sites of Study
|
| No of Sites = 4 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Sankar Chandra Mondal |
IPGMER and SSKM Hospital Clinical Research |
Department of Cardiology, Room, 1st Floor, IPGMER and SSKM Hospital, 244, AJC Bose Road
Kolkata
WEST BENGAL |
9433009582
drscmandal5@gmail.com |
| Dr Jabir Abdullakutty |
LISIE hospital |
Department of Cardiovascular Clinical Research, 5th floor, P.B no.3053, st. Antonys block,
Ernakulam
KERALA |
04842402084
04842403877
drjabi@yahoo.co.in |
| Dr Nirav Chandulal Bhalani |
Rhythm Heart Institute, A Unit of Synergy Lifecare Pvt Ltd |
Clinical Research Department,
1st Floor, Near Siddharth Bunglows, Sama-Savli Road
Vadodara
GUJARAT |
9979841924
drpanchaninirav@gmail.com |
| Dr Atul Damodar Abhyankar |
Shri B.D. Mehta Mahavir Heart Institute |
Department of Cardiac, OPD no-01
Shree Mahavir Health Campus, Athwa gate,
Ring road, OPD area
Surat
GUJARAT |
02612290000
02612290000
atulda@hotmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 4 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee, LISIE Hospital |
Approved |
| IPGMER Research Oversight Committee |
Approved |
| Rhythm Heart Institute Ethics Committee |
Approved |
| Shri B. D. Mehta Mahavir Heart Institute Ethics Committee |
Approved |
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Regulatory Clearance Status from DCGI
Modification(s)
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|
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: I501||Left ventricular failure, unspecified, (2) ICD-10 Condition: I509||Heart failure, unspecified, (3) ICD-10 Condition: I110||Hypertensive heart disease with heart failure, (4) ICD-10 Condition: I130||Hypertensive heart and chronic kidney disease with heart failure and stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease, (5) ICD-10 Condition: I132||Hypertensive heart and chronic kidney disease with heart failure and with stage 5 chronic kidney disease, or end stage renal disease, |
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Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Intervention |
AZD5462 |
Participants will receive low, medium and high doses of film-coated tablets of AZD5462 OD orally and duration of treatment will be 24 weeks |
| Comparator Agent |
Placebo to AZD5462 |
Placebo matching to AZD5462 film-coated tablets will be given orally and duration of treatment will be 24 weeks |
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Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
85.00 Year(s) |
| Gender |
Both |
| Details |
Participant must be 18 years (or the legal age of consent in the jurisdiction in which the study is taking place) to 85 years of age, inclusive, at the time of signing the ICF
Participants must have a pre-existing diagnosis of HF NYHA FC II to III
Participants must be on stable HF standard of care medication for at least 4 weeks prior to consent and during the Screening period
Minimum body mass index (BMI) of 18 kilograms per meter square (kg/m2) at Screening
For female participants, the participant must not be pregnant or lactating and must be of non-childbearing potential
All male participants should refrain from fathering a child or donating sperm until 3 months after the final study Follow-up Visit. Non-sterilised male participants should avoid fathering a child either by true abstinence or use of a condom for all sexual intercourse with a female partner of childbearing potential from the first dose until 3 months after the final Follow-up Visit |
|
| ExclusionCriteria |
| Details |
Historical or current evidence of a clinically significant disease or disorder including, but not limited to:
1. Myocardial infarction, stroke, transient ischaemic attack, coronary artery bypass grafting, or percutaneous coronary intervention within 12 weeks prior to Screening or transcatheter structural heart interventions or cardiac valve surgery within 6 months prior to Screening
2. Sarcoidosis, restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, or hypertrophic (obstructive) cardiomyopathy
3. History of untreated clinically significant valve disease or a Screening confirmation of severe aortic stenosis, severe mitral stenosis, moderate or severe aortic insufficiency or severe mitral insufficiency
4. Amyloidosis, Fabry disease, or haemochromatosis.
5. Pericardial disease (i.e., visually significant white pericardium on echocardiogram)
6. Known coagulation disorders
7. Current diagnosis of active hepatitis
8. Severe pulmonary disease that is not expected to improve over time, as assessed by the investigator
9. Decompensated HF or any cardiopulmonary hospitalisation within 4 weeks prior to Screening
History of active malignancy within 2 years, except for fully excised or treated basal cell carcinoma, or less than or equal to 2 squamous cell carcinomas of the skin and participants who are under investigation for breast or cervical cancer, including participants with a pap smear of grade greater than or equal to 3
History of hypersensitivity to drugs with a similar chemical structure or class to AZD5462 or any component of AZD5462 drug product
Known history of drug or alcohol abuse within 24 months of Screening
Congenital long QT syndrome or history of QT prolongation associated with other medications that required discontinuation of that medication
Cardiac ventricular arrhythmia that requires treatment
History of or anticipated heart transplant.
Current or planned cardiac resynchronization therapy or bi ventricular pacemaker or mechanical assist device implantation.
Any planned highly invasive cardiovascular procedure (eg, coronary revascularisation, ablation of atrial fibrillation/flutter etc).
Positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody at Screening
Known to have historically tested positive for Human immunodeficiency virus
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Method of Generating Random Sequence
|
Computer generated randomization |
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Method of Concealment
|
Centralized |
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Blinding/Masking
|
Participant and Investigator Blinded |
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Primary Outcome
|
| Outcome |
TimePoints |
| To evaluate the effect of AZD5462 after treatment in participants with HF |
From Baseline to Week 25 |
|
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Secondary Outcome
|
| Outcome |
TimePoints |
| To evaluate the effect and dose response of AZD5462 and effect on echocardiographic markers related to structural, systolic and diastolic function after treatment in participants with HF |
From Baseline to Week 13 and Week 25 |
To evaluate the effect of AZD5462 on HF health status in participants with HF.
The KCCQ is a validated questionnaire developed for patients with congestive HF. It is a 23-item, self-administered health status measure that quantifies physical limitations, symptoms, social interference, self-efficacy, and quality of life. Results for each domain are summarized and transformed to a score of 0 to 100 with higher scores indicating better health status
|
From Baseline to Weeks 3, 5, 13, and 25 |
To evaluate the effect of AZD5462 on HF health status in participants with HF.
The NYHA Functional Classification is a system to measure the severity of symptoms of heart failure. It places patients in four categories based on limitations of physical activity, from Class I with no limitation, progressing to Class IV with severe limitations
|
Baseline and Week 25 |
| To evaluate the effect of AZD5462 on biomarkers of cardiac function in treatment participants with HF |
From Baseline to Weeks 5, 13, and 25 |
| To evaluate the PK of AZD5462 after repeat OD oral dosing in participants with HF |
Day 15 (Week 3), Day 29 (Week 5) and Day 85 (Week 13) |
| To evaluate the safety and tolerability of AZD5462 as compared to placebo in participants with HF |
From Baseline to Week 29 (Day 197) |
|
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Target Sample Size
|
Total Sample Size="360"
Sample Size from India="36"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
10/01/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
10/06/2024 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="2"
Months="0"
Days="0" |
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Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
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Publication Details
|
N/A |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
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Brief Summary
|
The purpose of this study is to measure
efficacy and safety of AZD5462 compared to placebo in adult participants with
HF
The study will include 3 periods and
approximately 12 study visits: Screening period of up to 4 weeks, with at least one
study visit Treatment period of 24 weeks, with 8 study visits Follow-up period of 4
weeks, with 3 study visits |