CARDINAL-HF: Effectiveness of CRD-740 in Heart Failure

• Sponsor: Cardurion Pharmaceuticals, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05409183
• Collaborator: (none)
• Enrollment: 660
• Locations: 100
• Arms: 2
• Anticipated Duration (Months): 19.2
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a two-part study evaluating the effectiveness of CRD-740 in patients with either Heart Failure with Reduced Ejection Fraction (HFrEF) or Heart Failure with Preserved Ejection Fraction (HFpEF) after 12 weeks of treatment. The primary objective in Part A is to assess the effect of CRD-740 compared to placebo in plasma cGMP at Week 4. The primary objective in Part B is to determine whether CRD-740 reduces NT-proBNP compared to placebo at Week 12.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure; Heart Failure With Reduced Ejection Fraction; Heart Failure With Preserved Ejection Fraction; Cardiovascular Diseases; Heart Diseases	Drug: CRD-740; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 660 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Assess the Effectiveness of CRD-740 in Subjects With Chronic Heart Failure (CARDINAL-HF)
• Actual Study Start Date: May 26, 2022
• Anticipated Primary Completion Date: Dec 1, 2023
• Anticipated Study Completion Date: Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CRD-740 Part A: Participants in Part A randomly assigned to this arm will take CRD-740 twice daily at two ascending dose levels over 12 weeks. Part B: Participants in Part B randomly assigned to this arm will take CRD-740 twice daily at a single dose level over 12 weeks.	Drug: CRD-740; Tablets administered orally.
Placebo Comparator: Placebo Part A: Participants in Part A randomly assigned to this arm will take placebo twice daily at two ascending dose levels over 12 weeks. Part B: Participants in Part B randomly assigned to this arm will take placebo twice daily at a single dose level over 12 weeks.	Drug: Placebo; Tablets administered orally.

Outcome Measures

Primary Outcome Measures

1. Part A: The change from baseline (Day -1) in plasma cGMP at Week 4. [Baseline to Week 4]

2. Part B: The change from baseline (Day 1) in NT-proBNP at Week 12. [Baseline to Week 12]

Secondary Outcome Measures

1. Part B: The change from baseline (Day 1) in plasma BNP at Week 12. [Baseline to Week 12]

2. Part B: The change from baseline (Day 1) in plasma cGMP at Week 12. [Baseline to Week 12]

3. Part B: The change from baseline (Day 1) in the KCCQ-23-CS at Week 12. [Baseline to Week 12]

4. Part B: The proportion of subjects with ≥5-point improvement from baseline in the KCCQ-23- CS at Week 12. [Baseline to Week 12]

Other Outcome Measures

1. Part A: The change in NT-proBNP from baseline (Day 1) to Week 2, from Week 2 to Week 4, and from Week 2 to Week 12. [Baseline to Week 12]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males or Females ≥18 years of age, at screening.

2. Diagnosis of clinical heart failure syndrome, New York Heart Association functional class II - III for at least 6 months prior to screening

3. For Part A:

• Ejection Fraction ≤40% by echocardiography at screening.

• NT-proBNP level ≥600 pg/ml at screening. Subjects with atrial fibrillation or flutter at screening are required to have an NT-proBNP level of ≥1000 pg/mL at screening.

1. For Part B:

• For subjects with EF ≤40%:

• Ejection Fraction ≤40% by echocardiography at screening.

• NT-proBNP level ≥600 pg/ml at screening. Subjects with atrial fibrillation or flutter at screening are required to have an NT-proBNP level of ≥1000 pg/mL at screening.

• For subjects with EF >40%:

• EF >40% and left atrial enlargement by echocardiography at screening.

• NT-proBNP level ≥300 pg/ml at screening. Subjects with atrial fibrillation or flutter at screening are required to have an NT-proBNP level of ≥500 pg/mL at screening.

1. Stable doses of guideline-directed heart failure therapy for a minimum of 4 weeks prior to screening that has been individually optimized according to standard practice guidelines and no addition of guideline-directed heart failure therapy within 3 months of screening.

Exclusion Criteria:

1. Documented EF≥60% within 6 months of screening.

2. Recent HF exacerbation defined by hospitalization or requirement for intravenous diuretics within 60 days of screening.

3. Subjects with planned interventions (e.g., percutaneous coronary intervention, devices) etc. occurring during their involvement in this study.

4. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major cardiovascular surgery or carotid angioplasty within 60 days of screening.

5. Subjects with clinical suspicion of infiltrative cardiomyopathy (e.g., amyloid, sarcoid), hypertrophic cardiomyopathy (obstructive or non-obstructive), or HF secondary to severe valvular disease, active myocarditis, active pericarditis, or clinically significant congenital heart disease.

6. Prior or planned orthotopic heart transplantation.

7. Presence of or plan for mechanical circulatory support.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardurion Investigative Site	Alexander City	Alabama	United States	35010
2	Cardurion Investigative Site	Birmingham	Alabama	United States	35211
3	Cardurion Investigative Site	Fairhope	Alabama	United States	36532
4	Cardurion Investigative Site	Torrance	California	United States	90502
5	Cardurion Investigative Site	Miami	Florida	United States	33169
6	Cardurion Investigative Site	Naples	Florida	United States	34102
7	Cardurion Investigative Site	Tampa	Florida	United States	33612
8	Cardurion Investigative Site	Zephyrhills	Florida	United States	33541
9	Cardurion Investigative Site	Atlanta	Georgia	United States	30303
10	Cardurion Investigative Site	Eatonton	Georgia	United States	31024
11	Cardurion Investigative Site	Hazel Crest	Illinois	United States	60429
12	Cardurion Investigative Site	Winfield	Illinois	United States	60190
13	Cardurion Investigative Site	Wichita	Kansas	United States	67207
14	Cardurion Investigative Site	Alexandria	Louisiana	United States	71301
15	Cardurion Investigative Site	Bossier City	Louisiana	United States	71111
16	Cardurion Investigative Site	Detroit	Michigan	United States	48202
17	Cardurion Investigative Site	New York	New York	United States	10029
18	Cardurion Investigative Site	Greensboro	North Carolina	United States	27405
19	Cardurion Investigative Site	Pittsburgh	Pennsylvania	United States	15212
20	Cardurion Investigative Site	Blagoevgrad		Bulgaria	2700
21	Cardurion Investigative Site	Haskovo		Bulgaria	6300
22	Cardurion Investigative Site	Haskovo		Bulgaria	6304
23	Cardurion Investigative Site	Kyustendil		Bulgaria	2500
24	Cardurion Investigative Site	Pleven		Bulgaria	5806
25	Cardurion Investigative Site	Plovdiv		Bulgaria	4002
26	Cardurion Investigative Site	Plovdiv		Bulgaria	4003
27	Cardurion Investigative Site	Smolyan		Bulgaria	4700
28	Cardurion Investigative Site	Sofia		Bulgaria	1202
29	Cardurion Investigative Site	Sofia		Bulgaria	1407
30	Cardurion Investigative Site	Sofia		Bulgaria	1510
31	Cardurion Investigative Site	Sofia		Bulgaria	1527
32	Cardurion Investigative Site	Sofia		Bulgaria	1606
33	Cardurion Investigative Site	Sofia		Bulgaria	1709
34	Cardurion Investigative Site	Edmonton	Alberta	Canada	T6G 2H7
35	Cardurion Investigative Site	Vancouver	British Columbia	Canada	V5Z 1M9
36	Cardurion Investigative Site	Victoria	British Columbia	Canada	V8R 1B2
37	Cardurion Investigative Site	Winnipeg	Manitoba	Canada	R2H 2A6
38	Cardurion Investigative Site	Saint John's	Newfoundland and Labrador	Canada	A1B 3V6
39	Cardurion Investigative Site	Halifax	Nova Scotia	Canada	B3H 3A7
40	Cardurion Investigative Site	Brampton	Ontario	Canada	L6Z 4N5
41	Cardurion Investigative Site	Oshawa	Ontario	Canada	L1J 2K1
42	Cardurion Investigative Site	Montréal	Quebec	Canada	H1T 1C8
43	Cardurion Investigative Site	Montréal	Quebec	Canada	H3G 1A4
44	Cardurion Investigative Site	Québec	Quebec	Canada	G1V 4G5
45	Cardurion Investigative Site	Sherbrooke	Quebec	Canada	J1G 2E8
46	Cardurion Investigative Site	Brandýs Nad Labem-Stará Boleslav		Czechia	25001
47	Cardurion Investigative Site	Prague		Czechia	12800
48	Cardurion Investigative Site	Prague		Czechia	15030
49	Cardurion Investigative Site	Příbram		Czechia	26101
50	Cardurion Investigative Site	Balatonfüred		Hungary	8230
51	Cardurion Investigative Site	Budapest		Hungary	1051
52	Cardurion Investigative Site	Budapest		Hungary	1122
53	Cardurion Investigative Site	Budapest		Hungary	1134
54	Cardurion Investigative Site	Debrecen		Hungary	4032
55	Cardurion Investigative Site	Gyöngyös		Hungary	3200
56	Cardurion Investigative Site	Kaposvár		Hungary	7400
57	Cardurion Investigative Site	Kistarcsa		Hungary	2143
58	Cardurion Investigative Site	Nyíregyháza		Hungary	4400
59	Cardurion Investigative Site	Zalaegerszeg		Hungary	8900
60	Cardurion Investigative Site	Ashkelon		Israel	7830604
61	Cardurion Investigative Site	Be'er Ya'aqov		Israel	70300
62	Cardurion Investigative Site	Haifa		Israel	31096
63	Cardurion Investigative Site	Haifa		Israel	31999
64	Cardurion Investigative Site	Kfar Sava		Israel	4428164
65	Cardurion Investigative Site	Nahariya		Israel	2210001
66	Cardurion Investigative Site	Reẖovot		Israel	76100
67	Cardurion Investigative Site	Tiberias		Israel	15208
68	Cardurion Investigative Site	Pozzilli	Isernia	Italy	86077
69	Cardurion Investigative Site	Rozzano	Milan	Italy	20089
70	Cardurion Investigative Site	Bergamo		Italy	24127
71	Cardurion Investigative Site	Milan		Italy	20138
72	Cardurion Investigative Site	Palermo		Italy	90127
73	Cardurion Investigative Site	Pavia		Italy	27100
74	Cardurion Investigative Site	Sassari		Italy	07100
75	Cardurion Investigative Site	Wrocław	Dolnoslaskie	Poland	50-556
76	Cardurion Investigative Site	Chrzanów	Malopolskie	Poland	32-500
77	Cardurion Investigative Site	Krakow	Malopolskie	Poland	30-076
78	Cardurion Investigative Site	Grodzisk Mazowiecki	Mazowieckie	Poland	30-076
79	Cardurion Investigative Site	Tychy	Silesia	Poland	43-100
80	Cardurion Investigative Site	Jasło	Woj. Podkarpackie	Poland	38-200
81	Cardurion Investigative Site	Kraków		Poland	30-363
82	Cardurion Investigative Site	Lublin		Poland	20078
83	Cardurion Investigative Site	Poznań		Poland	61-144
84	Cardurion Investigative Site	Wrocław		Poland	50-981
85	Cardurion Investigative Site	Wrocław		Poland	51-162
86	Cardurion Investigative Site	Łódź		Poland	92-213
87	Cardurion Investigative Site	Łódź		Poland	93-513
88	Cardurion Investigative Site	Brezno	Banskobystricky	Slovakia	97701
89	Cardurion Investigative Site	Lučenec	Banskobystricky	Slovakia	98401
90	Cardurion Investigative Site	Lučenec	Banskobystricky	Slovakia	98439
91	Cardurion Investigative Site	Trebišov	Kosice	Slovakia	07501
92	Cardurion Investigative Site	Prešov	Presovsky	Slovakia	08001
93	Cardurion Investigative Site	Svidník	Presovsky	Slovakia	08901
94	Cardurion Investigative Site	Bardejov		Slovakia	08501
95	Cardurion Investigative Site	High Wycombe	Buckinghamshire	United Kingdom	HP11 2TT
96	Cardurion Investigative Site	Airdrie	Lanarkshire	United Kingdom	ML6 8LL
97	Cardurion Investigative Site	Isleworth	Middlesex	United Kingdom	TW7 6AF
98	Cardurion Investigative Site	Clydebank		United Kingdom	G81 4DY
99	Cardurion Investigative Site	Dundee		United Kingdom	DD1 4HN
100	Cardurion Investigative Site	Glasgow		United Kingdom	G4 0SF

Sponsors and Collaborators

• Cardurion Pharmaceuticals, Inc.

Investigators

• Study Director: Pirouz Shamszad, MD, Executive Director, Clinical Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Cardurion Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT05409183
• Other Study ID Numbers: CRD-740-201; 2021-005768-23
• First Posted: Jun 8, 2022
• Last Update Posted: Jun 8, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Cardurion Pharmaceuticals, Inc.: PDE9; Heart Failure; CRD-740; HFpEF; HFrEF
• Additional relevant MeSH terms: Heart Failure; Cardiovascular Diseases; Heart Diseases

Study Results

No Results Posted as of Jun 8, 2022