Study of the Safety of BMS-986259 in Participants With Post-Acute Decompensated Heart Failure

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04318093
• Collaborator: (none)
• Enrollment: 25
• Locations: 18
• Arms: 2
• Actual Duration (Months): 8.4
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of the study is to assess the safety of BMS-986259 in stable participants hospitalized for acute decompensated heart failure.

Condition or Disease	Intervention/Treatment	Phase
Acute Decompensated Heart Failure	Drug: BMS-986259; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blinded, Placebo-Controlled, Study to Evaluate the Safety and Tolerability of BMS-986259 in Stabilized Patients Hospitalized for Acute Decompensated Heart Failure
• Actual Study Start Date: Nov 6, 2020
• Actual Primary Completion Date: Jul 19, 2021
• Actual Study Completion Date: Jul 19, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BMS-986259	Drug: BMS-986259; Specified dose on specified days
Placebo Comparator: Placebo	Other: Placebo; Specified dose on specified days

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Experiencing Clinically Relevant Hypotension [From first dose to 30 days following first dose]

   Clinically Relevant Hypotension is defined as occurrence of any of the following: Supine Systolic Blood Pressure (SBP) <85 mmHg (confirmed by repeat measurement within 30 minutes), regardless of symptoms of hypotension Supine SBP <90 mmHg (confirmed by repeat measurement within 30 minutes) AND symptoms of hypotension (eg, dizziness, lightheadedness, etc).

Secondary Outcome Measures

1. Maximum Observed Serum Concentration (Cmax) [Day 1 and Day 5 of study treatment]

2. Time of Maximum Observed Serum Concentration (Tmax) [Day 1 and Day 5 of study treatment]

3. Area Under the Concentration-Time Curve Within a Dosing Interval (AUC(TAU)) [Day 1 and Day 5 of study treatment]

4. Trough Concentration (Ctrough) [Day 2 through Day 14 of study treatment (with the exception of Day 11, for which data is not available)]

Eligibility Criteria

Criteria

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

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Participants currently hospitalized for acute decompensated heart failure (ADHF)

• Participants must be hemodynamically stable, as assessed by the investigator

• Men must agree to follow specific methods of contraception, if applicable, while participating in the trial

• Women participants must have documented proof that they are not of childbearing potential

Exclusion Criteria:

• Acute cardiovascular condition other than heart failure (HF) decompensation

• Cardiogenic shock at presentation to emergency room (ER) or at any time before randomization

• Recipient of ventricular assist devices or use of any cardiac extracorporeal devices, within 12 weeks of study randomization

• Participants with contraindications to vasodilator therapy such as restrictive or obstructive cardiomyopathy, severe mitral or aortic stenosis

Other protocol-defined inclusion/exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution - 0009	Ciudad de Buenos Aires	Buenos Aires	Argentina	1180
2	Local Institution - 0007	Alberdi	Cordoba	Argentina	5000
3	Local Institution - 0010	Córdoba	Cordoba	Argentina	X5000EPU
4	Local Institution	Ciudad Autónoma de Buenos Aires	Distrito Federal	Argentina	C1093AAS
5	Local Institution - 0028	Cordoba	Provincia DE Cordoba	Argentina	5000
6	Local Institution - 0025	Cordoba		Argentina	5006
7	Local Institution - 0020	Praha 2		Czechia	12808
8	Nemocnice Slany-Interna - kardiologicka ambulance	Slany		Czechia	274 01
9	Local Institution - 0011	Athens		Greece	11527
10	Local Institution - 0022	Athens		Greece	142 33
11	Local Institution - 0014	Tel Aviv	Tell Abīb	Israel	6423906
12	Local Institution	Jerusalem		Israel	912001
13	Local Institution	Petah Tikva		Israel	4941492
14	Local Institution - 0034	Bialystok		Poland	15 276
15	Local Institution - 0030	Wrocaw		Poland	50-556
16	Local Institution - 0027	Wroclaw		Poland	54-049
17	Local Institution	Edinburgh		United Kingdom	EH16 4SA
18	Local Institution	Swindon		United Kingdom	SN3 6BB

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 28, 2020

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls
• Investigator Inquiry Form

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT04318093
• Other Study ID Numbers: CV019-010; 2019-004186-40
• First Posted: Mar 23, 2020
• Last Update Posted: Aug 4, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bristol-Myers Squibb: Heart failure
• Additional relevant MeSH terms: Heart Failure

Study Results

Participant Flow

Pre-assignment Detail	25 participants were randomized and treated.

Arm/Group Title	Placebo	BMS-986259 3 mg
Arm/Group Description	Placebo matching BMS-986259	BMS-986259 administered subcutaneously QD for 14 days
Period Title: Overall Study
STARTED	13	12
COMPLETED	10	9
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	Placebo	BMS-986259 3 mg	Total
Arm/Group Description	Placebo matching BMS-986259	BMS-986259 administered subcutaneously QD for 14 days	Total of all reporting groups
Overall Participants	13	12	25
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 30.8%	6 50%	10 40%
>=65 years	9 69.2%	6 50%	15 60%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	65.1 (12.18)	63.1 (15.65)	64.1 (13.69)
Sex: Female, Male (Count of Participants)
Female	4 30.8%	3 25%	7 28%
Male	9 69.2%	9 75%	18 72%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	13 100%	12 100%	25 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Experiencing Clinically Relevant Hypotension
Description	Clinically Relevant Hypotension is defined as occurrence of any of the following: Supine Systolic Blood Pressure (SBP) <85 mmHg (confirmed by repeat measurement within 30 minutes), regardless of symptoms of hypotension Supine SBP <90 mmHg (confirmed by repeat measurement within 30 minutes) AND symptoms of hypotension (eg, dizziness, lightheadedness, etc).
Time Frame	From first dose to 30 days following first dose

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Placebo	BMS-986259 3 mg
Arm/Group Description	Placebo matching BMS-986259	BMS-986259 administered subcutaneously QD for 14 days
Measure Participants	13	12
Number [Percent of participants]	15.4 118.5%	16.7 139.2%

2. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax)
Time Frame	Day 1 and Day 5 of study treatment

Outcome Measure Data

Analysis Population Description

All participants receiving study drug with available measurements

Arm/Group Title	BMS-986259 3 mg
Arm/Group Description	BMS-986259 administered subcutaneously QD for 14 days
Measure Participants	12
Day 1	105 (49)
Day 5	268 (31)

3. Secondary Outcome

Title	Time of Maximum Observed Serum Concentration (Tmax)
Time Frame	Day 1 and Day 5 of study treatment

Outcome Measure Data

Analysis Population Description

All participants receiving study drug with available measurements

Arm/Group Title	BMS-986259 3 mg
Arm/Group Description	BMS-986259 administered subcutaneously QD for 14 days
Measure Participants	12
Day 1	11.0
Day 5	7.97

4. Secondary Outcome

Title	Area Under the Concentration-Time Curve Within a Dosing Interval (AUC(TAU))
Time Frame	Day 1 and Day 5 of study treatment

Outcome Measure Data

Analysis Population Description

All participants receiving study drug with available measurements

Arm/Group Title	BMS-986259 3 mg
Arm/Group Description	BMS-986259 administered subcutaneously QD for 14 days
Measure Participants	9
Day 1	1778 (40)
Day 5	5156 (36)

5. Secondary Outcome

Title	Trough Concentration (Ctrough)
Time Frame	Day 2 through Day 14 of study treatment (with the exception of Day 11, for which data is not available)

Outcome Measure Data

Analysis Population Description

All participants receiving study drug with available measurements

Arm/Group Title	BMS-986259 3 mg
Arm/Group Description	BMS-986259 administered subcutaneously QD for 14 days
Measure Participants	11
Day 2	79.9 (36.0)
Day 3	145 (32.3)
Day 4	181 (28.9)
Day 5	185 (32.4)
Day 6	210 (27.3)
Day 7	260 (41.3)
Day 8	226 (69.4)
Day 9	252 (48.1)
Day 10	259 (49.7)
Day 12	229 (22.9)
Day 13	248 (50.5)
Day 14	246 (7.53)

Adverse Events

Time Frame	All-cause mortality was assessed from first dose to study completion date (up to approximately 8 months). SAEs and NSAEs were assessed from first dose to 30 days following first dose.
Arm/Group Title	Placebo		BMS986259 3 mg
Arm/Group Description	Placebo matching BMS-986259		BMS-986259 administered subcutaneously QD for 14 days
All Cause Mortality
	Placebo		BMS986259 3 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/13 (15.4%)		0/12 (0%)
Serious Adverse Events
	Placebo		BMS986259 3 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/13 (38.5%)		2/12 (16.7%)
Cardiac disorders
Cardiac failure	1/13 (7.7%)		0/12 (0%)
Cardiac failure chronic	1/13 (7.7%)		0/12 (0%)
Cardiogenic shock	1/13 (7.7%)		0/12 (0%)
Ventricular tachycardia	1/13 (7.7%)		0/12 (0%)
Infections and infestations
COVID-19	0/13 (0%)		1/12 (8.3%)
COVID-19 pneumonia	1/13 (7.7%)		1/12 (8.3%)
Renal and urinary disorders
Acute kidney injury	1/13 (7.7%)		0/12 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/13 (7.7%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		BMS986259 3 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/13 (23.1%)		8/12 (66.7%)
Blood and lymphatic system disorders
Haemoconcentration	1/13 (7.7%)		0/12 (0%)
Cardiac disorders
Sinus tachycardia	0/13 (0%)		1/12 (8.3%)
Gastrointestinal disorders
Diarrhoea	1/13 (7.7%)		0/12 (0%)
Infections and infestations
Pneumonia	1/13 (7.7%)		0/12 (0%)
Injury, poisoning and procedural complications
Procedural haemorrhage	0/13 (0%)		1/12 (8.3%)
Investigations
Blood creatinine increased	1/13 (7.7%)		0/12 (0%)
Metabolism and nutrition disorders
Hyperkalaemia	0/13 (0%)		1/12 (8.3%)
Hypokalaemia	0/13 (0%)		1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Muscle spasms	0/13 (0%)		1/12 (8.3%)
Nervous system disorders
Dizziness	1/13 (7.7%)		0/12 (0%)
Reproductive system and breast disorders
Genital haemorrhage	0/13 (0%)		1/12 (8.3%)
Vascular disorders
Hypotension	1/13 (7.7%)		3/12 (25%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.