Study to Evaluate the Safety and Activity of BB3 to Treat Heart Attack

• Sponsor: Angion Biomedica Corp (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01539590
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 5
• Locations: 2
• Arms: 2
• Duration (Months): 16
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The study will evaluate the effect of BB3 to preserve myocardial (heart) tissue and function following myocardial infarction (heart attack).

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction	Drug: BB3; Drug: Normal saline	Phase 2

Detailed Description

Percutaneous coronary intervention (PCI) has become the mainstay for treatment of ST-segment elevation myocardial infarction (STEMI). Whereas early recanalization undoubtedly salvages myocardial tissue, reperfusion following prolonged ischemia can also exacerbate injury. Infarct size needs to be limited, and the conditions favoring adaptive ventricular healing and remodeling optimized because in patients with acute myocardial infarction (AMI) who do not die of out-of-hospital arrhythmias, long-term prognosis is dependent on the amount of myocardium that is lost, and the outcome of ventricular remodeling. Angion Biomedical Corp. has identified BB3, a small molecule mimetic of hepatocyte growth factor/scatter factor (HGF/SF) whose activity is expected to preserve tissue viability and attenuate dysfunction in the setting of organ injury while obviating the logistical difficulties associated with gene or protein therapy. HGF/SF is a naturally occurring cell survival factor that holds significant therapeutic potential. BB3 has been shown to possess HGF/SF activities, including protection against heart injury following myocardial infarction. This study is designed to evaluate clinical efficacy of BB3 in patients presenting with acute ST segment elevation myocardial infarction (A-STEMI) who undergo PCI.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Pilot Study to Evaluate the Safety and Activity of BB3 as an Adjunct to Percutaneous Coronary Intervention (PCI) in Subjects Presenting With Acute ST Segment Elevation Myocardial Infarction (STEMI)
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BB3 Daily intravenous administration of 2 mg/kg BB3 for four (4) days	Drug: BB3; Daily intravenous administration of 2 mg/kg BB3 for four (4) days
Placebo Comparator: Normal Saline Daily intravenous administration for four (4) days	Drug: Normal saline; Daily intravenous administration for four (4) days. The volume of normal saline will vary by estimated weight.

Outcome Measures

Primary Outcome Measures

1. Evaluation of Reduction in Infarct Size [6 month]

   Evaluation of reduction in infarct size by MRI between the BB3 and placebo treatment groups at 6 months based on index of myocardial salvage

2. Evaluation of the Degree of Late Ventricular Remodeling [6 months]

   Evaluation of the degree of late ventricular remodeling between the BB3 and placebo treatment groups at 6 months, as measured by increase in LV end-diastolic volume index (LVEDVI) from initial MR image (day 5±1) to late MR image (6 months).

Secondary Outcome Measures

1. Change in CK-MB and Troponin [6 months]

2. Change in BNP Levels [6 months]

3. Change in Symptoms and Clinical Signs of CHF [6 months]

4. Change in LVEDVI, LVESVI and LV Ejection Fraction (EF) After MI Assessed by Cine MR (SSFP Imaging) [6 months]

5. LVEDVI, LVESVI and LVEF After MI Assessed by 2D and 3D Echocardiography [6 months]

6. Change Between Initial Semi-quantitative Regional Wall Motion Score (17 Segment Model) by Echocardiography [1 and 6 months]

7. Change in Regional Myocardial Radial, Circumferential and Longitudinal Strain [1 and 6 months]

8. Frequency of MACE [6 months]

9. Frequency of New Onset CHF Through 6 Months [6 months]

10. Number of Hospitalizations for CHF Through 6 Months [6 months]

11. Incidence of Complete ST Segment Resolution 60 ± 30 Minutes After Last Angiogram [6 months]

12. Frequency of AE, SAEs [6 months]

13. Frequency of MACCE [6 months]

14. All-cause Mortality [6 months]

15. Development of Ventricular Fibrillation or Other Life-threatening Arrhythmia [6 months]

16. Change From Baseline eCrCl [6 months]

17. Change in Body Weight [6 months]

18. Symptoms and Clinical Signs of CHF [6 months]

    Symptoms and clinical signs of CHF measured by NYHA classification

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. The subject or legally authorized representative has been informed of the nature of the study, agrees to its provisions, and has been provided and signed written informed consent, approved by the Institutional Review Board (IRB), prior to performance of any study related procedure including screening procedure.

2. Subject is male or female

3. Subject is 21 to 80 years of age

4. Estimated body weight < 120 kg and BMI < 40

5. Subject is experiencing clinical symptoms consistent with acute myocardial infarction (AMI) (e.g., chest pain, arm pain, etc.,) >30 minutes duration and unresponsive to nitroglycerin; with ST segment elevation of more than 1 mm in at least two contiguous leads of ECG or new or presumed new onset bundle branch block (BBB)

6. Fulfills clinical center's criteria for primary PCI

7. PCI will be done within 12 hours of onset of STEMI.

8. The subject and his/her physician are willing to comply with the requirements of the study and the specified follow-up evaluations.

9. If female, either surgically sterile or post-menopausal or using acceptable contraception and agree to use effective birth control regimen during the study period. Men must agree to use condoms during the study period. Women of child bearing potential must have a negative urine or serum pregnancy test.

10. In the opinion of the Investigator, the subject is capable of understanding and complying with the protocol.

Exclusion Criteria:

1. Pregnant or nursing subjects and those who plan pregnancy in the period up to 6 months following index procedure.

2. Cardiogenic shock (Killip class 4) or cardiac arrest

3. History of prior myocardial infarction or pre-existing Q waves on ECG

4. An elective surgical procedure is planned that would necessitate interruption of anti-platelet agents during the first six months post enrollment;

5. Any contraindication to undergo MRI imaging. This will include any of the following exclusions:

6. Cardiac pacemaker or implantable defibrillator;

7. Non-MRI-compatible aneurysm clip;

8. Neural stimulator (e.g., TENS-Unit);

9. Any implanted or magnetically activated device (e.g., insulin pump);

10. Any type of non-MRI-compatible metallic ear implant;

11. Metal shavings in the orbits;

12. Any metallic foreign body, shrapnel, or bullet in a location which the physician feels would present a risk to the subject;

13. Any history indicating contraindication to MRI, including claustrophobia or allergy to gadolinium;

14. Inability to follow breathhold instructions or to maintain a breathhold for >15 seconds;

15. Irregular cardiac rhythm not expected to resolve after treatment of the acute cardiac condition (e.g., chronic atrial fibrillation)

16. Known hypersensitivity or contraindication to gadolinium contrast.

17. Subject has active bleeding or a history of bleeding diathesis or coagulopathy (including heparin induced thrombocytopenia), or refusal to receive blood transfusions if necessary;

18. Subjects presenting with cardiogenic shock (SBP <80 mmHg for >30 minutes, or requiring IV pressors or emergency IABP for hypotension treatment) or cardiopulmonary resuscitation prior to randomization;

19. History of intracerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke; stroke or transient ischemic attack within the past 6 months, or any permanent residual neurologic defect; known preceding cardiac ventricular arrhythmia

20. Impaired renal function (eGFR of ≤30 ml/min/1.73m2, as estimated by the MDRD4v equation) or on dialysis.

21. Impaired hepatic function (ALT > 2x upper limit of normal, or a total bilirubin greater than 1.5 x upper limit of normal).

22. Currently participating in or has participated in an investigational drug or medical device study within 30 days or 5 half-lives, whichever is longer, prior to enrollment into this study

23. Have an active malignancy or history of solid, metastatic, or hematologic malignancy with the exception of basal or squamous cell carcinoma of the skin that has been removed

24. History of positive human immunodeficiency virus (HIV) test

25. History of rheumatoid arthritis

26. History of proliferative retinopathy or laser surgery for retinopathy

27. Subjects who require cytochrome P450 1A2 (CYP1A2) inhibitors, ciprofloxacin and/or fluvoxamine (Luvox®)

28. Subject has other medical illness or known history of substance abuse (alcohol, cocaine, heroin etc.) that may cause non-compliance with the protocol, confound the data interpretation or is associated with a limited life expectancy of less than 6 months,

29. Any significant medical condition which in the Investigator's opinion may interfere with the subject's optimal participation in the study;

30. Subject has a known hypersensitivity or allergy to stainless steel, nickel, cobalt chromium, nitinol, titanium or known hypersensitivity or allergy to contrast media (e.g. rash) that cannot effectively be controlled by premedication with steroids and/or diphenhydramine. Subjects with hypersensitivity or allergy to any of the components of the device (structural, drug or polymer components) and subjects with true prior anaphylaxis to contrast media should not be enrolled

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota	United States	55417-1139
2	Yale University Medical Center	New Haven	New York	United States	06520

Sponsors and Collaborators

• Angion Biomedica Corp
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Study Director: Weizhong Cai, Sponsor GmbH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Angion Biomedica Corp
• ClinicalTrials.gov Identifier: NCT01539590
• Other Study ID Numbers: 001-10; 5R44HL091699
• First Posted: Feb 27, 2012
• Last Update Posted: Nov 21, 2014
• Last Verified: Nov 1, 2014

• Keywords provided by Angion Biomedica Corp: hepatocyte growth factor mimetic; hepatocyte growth factor(HGF); Myocardial Infarction; Acute ST Segment Elevation Myocardial Infarction (STEMI); Percutaneous Coronary Intervention (PCI)
• Additional relevant MeSH terms: Myocardial Infarction; ST Elevation Myocardial Infarction; Infarction

Study Results

Participant Flow

Arm/Group Title	BB3, 4 Daily Doses	Placebo; 4 Daily Doses
Arm/Group Description	BB3: Daily intravenous administration of 2 mg/kg BB3 for four (4) days ; 10 to 12 minutes; small molecule mimetic of hepatocyte growth factor	Placebo: Normal saline; Daily intravenous administration for four (4) days. The volume of normal saline will vary by estimated weight.
Period Title: Overall Study
STARTED	3	2
Complete Study Treatment	1	2
COMPLETED	0	2
NOT COMPLETED	3	0

Baseline Characteristics

Arm/Group Title	BB3, 4 Daily Doses	Placebo	Total
Arm/Group Description	BB3: Daily intravenous administration of 2 mg/kg BB3 for four (4) days	Normal saline. Daily intravenous administration for four (4) days.	Total of all reporting groups
Overall Participants	3	2	5
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	61	57.5	59
Sex: Female, Male (Count of Participants)
Female	1 33.3%	0 0%	1 20%
Male	2 66.7%	2 100%	4 80%
Region of Enrollment (participants) [Number]
United States	3 100%	2 100%	5 100%

Outcome Measures

1. Primary Outcome

Title	Evaluation of Reduction in Infarct Size
Description	Evaluation of reduction in infarct size by MRI between the BB3 and placebo treatment groups at 6 months based on index of myocardial salvage
Time Frame	6 month

Outcome Measure Data

Analysis Population Description

Five subjects were enrolled into the study; 3 subjects were randomized to BB3 and 2 subjects to placebo. Of the 3 subjects randomized to BB3, 1 completed study treatment; all three subjects discontinued the study prematurely. The two subjects randomized to placebo completed study treatment and neither discontinued the study prematurely.

Arm/Group Title	BB3, 4 Daily Doses	Placebo, 4 Daily Doses
Arm/Group Description	BB3: Daily intravenous administration of 2 mg/kg BB3 for four (4) days	Normal saline. Daily intravenous administration for four (4) days.
Measure Participants	0	0

2. Primary Outcome

Title	Evaluation of the Degree of Late Ventricular Remodeling
Description	Evaluation of the degree of late ventricular remodeling between the BB3 and placebo treatment groups at 6 months, as measured by increase in LV end-diastolic volume index (LVEDVI) from initial MR image (day 5±1) to late MR image (6 months).
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Change in CK-MB and Troponin
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Change in BNP Levels
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Change in Symptoms and Clinical Signs of CHF
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Change in LVEDVI, LVESVI and LV Ejection Fraction (EF) After MI Assessed by Cine MR (SSFP Imaging)
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	LVEDVI, LVESVI and LVEF After MI Assessed by 2D and 3D Echocardiography
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Change Between Initial Semi-quantitative Regional Wall Motion Score (17 Segment Model) by Echocardiography
Time Frame	1 and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Change in Regional Myocardial Radial, Circumferential and Longitudinal Strain
Time Frame	1 and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Frequency of MACE
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Frequency of New Onset CHF Through 6 Months
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Number of Hospitalizations for CHF Through 6 Months
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Secondary Outcome

Title	Incidence of Complete ST Segment Resolution 60 ± 30 Minutes After Last Angiogram
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Secondary Outcome

Title	Frequency of AE, SAEs
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

15. Secondary Outcome

Title	Frequency of MACCE
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

16. Secondary Outcome

Title	All-cause Mortality
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

17. Secondary Outcome

Title	Development of Ventricular Fibrillation or Other Life-threatening Arrhythmia
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

18. Secondary Outcome

Title	Change From Baseline eCrCl
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

19. Secondary Outcome

Title	Change in Body Weight
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

20. Secondary Outcome

Title	Symptoms and Clinical Signs of CHF
Description	Symptoms and clinical signs of CHF measured by NYHA classification
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	BB3 Small Molecule Mimetic of Hepatocyte Growth Factor		Placebo
Arm/Group Description	small molecule mimetic of hepatocyte growth factor/scatter factor BB3: Daily intravenous administration of 2 mg/kg BB3 for four (4) days		Normal saline Placebo: Daily intravenous administration for four (4) days. The volume of normal saline will vary by estimated weight.
All Cause Mortality
	BB3 Small Molecule Mimetic of Hepatocyte Growth Factor		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	BB3 Small Molecule Mimetic of Hepatocyte Growth Factor		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	BB3 Small Molecule Mimetic of Hepatocyte Growth Factor		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		1/2 (50%)
Cardiac disorders
bradycardia	1/3 (33.3%)		0/2 (0%)
ventricular tachycardia	1/3 (33.3%)		0/2 (0%)
Ear and labyrinth disorders
tinnitus	0/3 (0%)		1/2 (50%)
Gastrointestinal disorders
nausea and vomiting	1/3 (33.3%)		0/2 (0%)
General disorders
headache	0/3 (0%)		1/2 (50%)
hyperhidrosis	1/3 (33.3%)		0/2 (0%)
dizziness	1/3 (33.3%)		0/2 (0%)
fatigue	0/3 (0%)		1/2 (50%)
Infections and infestations
sinusitis	0/3 (0%)		1/2 (50%)
Surgical and medical procedures
infusion site pain	1/3 (33.3%)		0/2 (0%)
Vascular disorders
hypotension	1/3 (33.3%)		0/2 (0%)

Limitations/Caveats

Five subjects were enrolled into the study; 3 subjects were randomized to BB3 and 2 subjects to placebo. All the 3 subjects randomized to BB3 discontinued the study prematurely. The 2 subjects randomized to placebo completed study treatment.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.