NAN-101 in Patients With Class III Heart Failure (NAN-CS101)
Primary Purpose
Congestive Heart Failure, Heart Failure, Heart Disease, Ischemic
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
3 x 10e13vg NAN-101
Sponsored by
About this trial
This is an interventional treatment trial for Congestive Heart Failure
Eligibility Criteria
Inclusion criteria:
- Age >18 years of age
- Chronic non-ischemic cardiomyopathy
- LVEF ≤ 30% by transthoracic echocardiography (TTE) within 6 months prior to enrollment
NYHA Class III HF for a minimum of 6 months HF despite appropriate medical therapy (defined below):
- Treatment with appropriate HF therapy as tolerated, including, but not limited to:
- Beta blocker therapy and angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) or sacubitril/valsartan combination therapy (Entresto) for ≥ 90 days prior to enrollment. May also receive aldosterone antagonist therapy. Doses of the above medications must be stable for ≥ 30 days prior to enrollment; and
- Cardiac resynchronization therapy (CRT), if clinically indicated, must have been implanted ≥ 90 days prior to enrollment. Internal cardioverter defibrillator (ICD) must be implanted, if clinically indicated ≥ 30 days prior to enrollment
- Females of childbearing potential must use at least one of the following acceptable birth control methods throughout the study and for 6 months after IP administration:
- Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) 6 months minimum prior to IP administration
- Intrauterine device in place for at least 90 days prior to receiving IP
- Barrier methods (diaphragm plus spermicide or condom) starting at least 30 days prior to receiving IP
- Abstinence (the subject must be willing to remain abstinent from screening to 6 months after receiving IP). Females are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject
- Surgical sterilization of the partner(s) (vasectomy) for >180 days prior to IP administration
- Hormonal contraceptives starting > 90 days prior to IP. If hormonal contraceptives are started less than 90 days prior to receiving IP, subjects must agree to use a barrier method (diaphragm plus spermicide or condom) from screening through 90 days after initiation of hormonal contraceptives
- Males subjects capable of fathering a child:
- Must agree to use a condom from IP administration through 6 months after the time of IP administration
- Must agree not to donate sperm for 6 months after time of receiving IP
- Documented evidence of vasectomy in males for 180 days minimum prior to receiving IP is an acceptable form of contraception
- Males who claim abstinence as their method of contraception are allowed provided they agree to use barrier methods should they become sexually active from screening through 6 months after receiving IP. Males are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject
- Ability to sign Informed Consent Form (ICF) and Release of Medical Information Form
- Appropriate candidate for protocol-specified intracoronary infusion in the judgment of the infusing interventional cardiologist
Exclusion Criteria:
- Chronic ischemic cardiomyopathy
- Intravenous (IV) inotropic therapy, intra-aortic balloon pump (IABP) or percutaneous cardiac assist device therapy within 30 days prior to enrollment
- Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or dyskinetic LV aneurysm
- Cardiac surgery or percutaneous coronary intervention (PCI) within 30 days prior to enrollment
- Third degree heart block
- Clinically significant myocardial infarction (MI) in the judgment of the subject's physician (e.g., ST elevation MI [STEMI] or large non-STEMI) within 6 months prior to enrollment
- Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), surgically implanted LVAD or cardiac shunt
- Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LV reduction surgery, heart transplant, conventional revascularization procedure, or valvular repair within 3 months of IP dosing
- Known hypersensitivity to contrast dyes used for angiography; history of, or likely need for, high-dose steroid pretreatment prior to contrast angiography
- Expected survival < 1 year in the judgment of the investigator
- Active or suspected infection within 48 hours prior to enrollment as evidenced by fever or positive culture
- Known intrinsic liver disease (e.g., cirrhosis, hepatitis A, chronic hepatitis B or hepatitis C virus infection). If serology is positive and PCR is negative, subject may be eligible (confirm with medical monitor).
- Liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase) > 2x upper limit of normal (ULN) within 30 days prior to enrollment.
- Renal Failure, dialysis dependent or serum creatinine > 2.5 mg/dl within 30 days prior to enrollment
- Bleeding diathesis or thrombocytopenia defined as platelets <50,000 platelets/μL within 30 days prior to enrollment
- Anemia defined as hemoglobin <10 g/dL or transfusion dependent within 30 days prior to enrollment
- Neutropenia defined as absolute neutrophils <1500 mm3 within 30 days prior to enrollment
- Known AIDS or HIV-positive status, or a previous diagnosis of immunodeficiency with an absolute neutrophil count <1000 cells/mm3
- Previous participation in a study of gene transfer
- Receiving investigational intervention or participating in another clinical study within 30 days or within 5 half-lives of another investigational drug administration prior to administration of NAN-101 that may impact the therapeutic potential of NAN-101.
- Pregnancy or breastfeeding at the time of screening
Sites / Locations
- Minneapolis Heart Foundation InstituteRecruiting
- The Linder Center for Education and Research at The Christ HospitalRecruiting
- The Ohio State UniversityRecruiting
- University of Wisconsin at MadisonRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
3 x 10e13vg NAN-101
1 x 10e14vg NAN-101
3 x 10e14 vg NAN-101
Arm Description
Intracoronary Infusion of NAN-101 at 3 x 10e13vg up to 4 subjects
Intracoronary Infusion of NAN-101 1 x 10e14vg up to 4 subjects
Intracoronary Infusion of NAN-101 3 x 10e14 vg up to 4 subjects
Outcomes
Primary Outcome Measures
Observed and change from baseline in Peak VO2
Cardiopulmonary exercise testing using a modified Bruce protocol
Observed and change from baseline in Echocardiographic assessment in Left Ventricular Ejection Fraction
Echocardiography LVEF measurement
Secondary Outcome Measures
Observed and change from baseline in 6-minute walk test distance
Analysis of Percent predicted in heart failure subjects compared to normal subjects
Full Information
NCT ID
NCT04179643
First Posted
September 6, 2019
Last Updated
March 15, 2023
Sponsor
Asklepios Biopharmaceutical, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04179643
Brief Title
NAN-101 in Patients With Class III Heart Failure
Acronym
NAN-CS101
Official Title
Phase 1 Open Label, Dose Escalation Trial of Intracoronary Infusion of NAN-101 in Subjects With NYHA Class III Heart Failure
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 20, 2019 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Asklepios Biopharmaceutical, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase 1, prospective, multi-center, open-label, sequential dose escalation study to explore the safety, feasibility, and efficacy of a single intracoronary infusion of BNP116.sc-CMV.I1c in patients with NYHA Class III heart failure. Patients with symptomatic congestive heart failure will be enrolled until up to 12 subjects have received infusions of investigational product. All patients will be followed until 12 months post treatment intervention, and then undergo long-term follow-up via semi-structured telephone questionnaires every 6 months for an additional 24 months (+/- 30 days).
Detailed Description
The primary endpoint for this study is safety as measured by the following which will be assessed over the 12 month follow-up period as indicated in the Data Collection Table:
Adverse Events
All-cause Mortality
Heart failure (HF) Hospitalization
Secondary Endpoints
The secondary safety endpoints assessed will include the following:
Echocardiographic assessments at 4 weeks +/- 3 days post-administration of BNP116.sc-CMV.I1c including
Echocardiographic assessments of LVEF, LVEVD, LVEDVI, VLESV, LVEVI, SpI and GLSand degree of mitral regurgitation o
The secondary efficacy endpoints will explore efficacy. Functional endpoints will be assessed as changes from baseline to 6 and 12 months following investigational product administration as indicated. These endpoints include:
Functional Status & Hospitalizations
Peak VO2 assessed by cardiopulmonary exercise testing
6-minute walk test
New York Heart Association (NYHA) Classification
Total number of days alive out-of-hospital (as well as total days out-of-hospital as a % of total days alive post study intervention)
Physiologic Assessments at 6 and 12 months compared to baseline
Echocardiographic assessments of LVEF, LVEVD, LVEDVI, VLESV, LVEVI, SpI and GLSand degree of mitral regurgitation
NT-proBNP level
Quality of Life at 6 and 12 months compared to baseline
o Health related quality of life as assessed by Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
The following endpoints will also be measured over the 12 month follow-up period and long-term follow-up period (until month 36 post-intervention):
Survival
Cardiac transplantation
Left ventricular assist device (LVAD) implantation
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congestive Heart Failure, Heart Failure, Heart Disease, Ischemic, Cardiovascular Diseases, Heart Failure, Systolic, Heart Failure,Congestive, Heart Arrhythmia, Heart Failure, Diastolic, Heart; Complications
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
3 x 10e13vg NAN-101
Arm Type
Experimental
Arm Description
Intracoronary Infusion of NAN-101 at 3 x 10e13vg up to 4 subjects
Arm Title
1 x 10e14vg NAN-101
Arm Type
Experimental
Arm Description
Intracoronary Infusion of NAN-101 1 x 10e14vg up to 4 subjects
Arm Title
3 x 10e14 vg NAN-101
Arm Type
Experimental
Arm Description
Intracoronary Infusion of NAN-101 3 x 10e14 vg up to 4 subjects
Intervention Type
Biological
Intervention Name(s)
3 x 10e13vg NAN-101
Intervention Description
There are 2 components to NAN-101. The first is an active I-1 transgene (AA 1-65 with T35D), and the second is the vector, BNP116, which delivers the gene selectively to the heart after intracoronary administration.
Primary Outcome Measure Information:
Title
Observed and change from baseline in Peak VO2
Description
Cardiopulmonary exercise testing using a modified Bruce protocol
Time Frame
Measured at screening, month 6 and month 12
Title
Observed and change from baseline in Echocardiographic assessment in Left Ventricular Ejection Fraction
Description
Echocardiography LVEF measurement
Time Frame
Measured at screening, 18-24 hours post intervention, week 4, Month 6 and Month 12
Secondary Outcome Measure Information:
Title
Observed and change from baseline in 6-minute walk test distance
Description
Analysis of Percent predicted in heart failure subjects compared to normal subjects
Time Frame
Measured at screening, Month 6 and month 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Age >18 years of age
Chronic non-ischemic cardiomyopathy
LVEF ≤ 30% by transthoracic echocardiography (TTE) within 6 months prior to enrollment
NYHA Class III HF for a minimum of 6 months HF despite appropriate medical therapy (defined below):
Treatment with appropriate HF therapy as tolerated, including, but not limited to:
Beta blocker therapy and angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) or sacubitril/valsartan combination therapy (Entresto) for ≥ 90 days prior to enrollment. May also receive aldosterone antagonist therapy. Doses of the above medications must be stable for ≥ 30 days prior to enrollment; and
Cardiac resynchronization therapy (CRT), if clinically indicated, must have been implanted ≥ 90 days prior to enrollment. Internal cardioverter defibrillator (ICD) must be implanted, if clinically indicated ≥ 30 days prior to enrollment
Females of childbearing potential must use at least one of the following acceptable birth control methods throughout the study and for 6 months after IP administration:
Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) 6 months minimum prior to IP administration
Intrauterine device in place for at least 90 days prior to receiving IP
Barrier methods (diaphragm plus spermicide or condom) starting at least 30 days prior to receiving IP
Abstinence (the subject must be willing to remain abstinent from screening to 6 months after receiving IP). Females are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject
Surgical sterilization of the partner(s) (vasectomy) for >180 days prior to IP administration
Hormonal contraceptives starting > 90 days prior to IP. If hormonal contraceptives are started less than 90 days prior to receiving IP, subjects must agree to use a barrier method (diaphragm plus spermicide or condom) from screening through 90 days after initiation of hormonal contraceptives
Males subjects capable of fathering a child:
Must agree to use a condom from IP administration through 6 months after the time of IP administration
Must agree not to donate sperm for 6 months after time of receiving IP
Documented evidence of vasectomy in males for 180 days minimum prior to receiving IP is an acceptable form of contraception
Males who claim abstinence as their method of contraception are allowed provided they agree to use barrier methods should they become sexually active from screening through 6 months after receiving IP. Males are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject
Ability to sign Informed Consent Form (ICF) and Release of Medical Information Form
Appropriate candidate for protocol-specified intracoronary infusion in the judgment of the infusing interventional cardiologist
Exclusion Criteria:
Chronic ischemic cardiomyopathy
Intravenous (IV) inotropic therapy, intra-aortic balloon pump (IABP) or percutaneous cardiac assist device therapy within 30 days prior to enrollment
Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or dyskinetic LV aneurysm
Cardiac surgery or percutaneous coronary intervention (PCI) within 30 days prior to enrollment
Third degree heart block
Clinically significant myocardial infarction (MI) in the judgment of the subject's physician (e.g., ST elevation MI [STEMI] or large non-STEMI) within 6 months prior to enrollment
Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), surgically implanted LVAD or cardiac shunt
Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LV reduction surgery, heart transplant, conventional revascularization procedure, or valvular repair within 3 months of IP dosing
Known hypersensitivity to contrast dyes used for angiography; history of, or likely need for, high-dose steroid pretreatment prior to contrast angiography
Expected survival < 1 year in the judgment of the investigator
Active or suspected infection within 48 hours prior to enrollment as evidenced by fever or positive culture
Known intrinsic liver disease (e.g., cirrhosis, hepatitis A, chronic hepatitis B or hepatitis C virus infection). If serology is positive and PCR is negative, subject may be eligible (confirm with medical monitor).
Liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase) > 2x upper limit of normal (ULN) within 30 days prior to enrollment.
Renal Failure, dialysis dependent or serum creatinine > 2.5 mg/dl within 30 days prior to enrollment
Bleeding diathesis or thrombocytopenia defined as platelets <50,000 platelets/μL within 30 days prior to enrollment
Anemia defined as hemoglobin <10 g/dL or transfusion dependent within 30 days prior to enrollment
Neutropenia defined as absolute neutrophils <1500 mm3 within 30 days prior to enrollment
Known AIDS or HIV-positive status, or a previous diagnosis of immunodeficiency with an absolute neutrophil count <1000 cells/mm3
Previous participation in a study of gene transfer
Receiving investigational intervention or participating in another clinical study within 30 days or within 5 half-lives of another investigational drug administration prior to administration of NAN-101 that may impact the therapeutic potential of NAN-101.
Pregnancy or breastfeeding at the time of screening
Facility Information:
Facility Name
Minneapolis Heart Foundation Institute
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jake Jensen
Phone
612-863-3818
Email
jacob.jensen@allina.com
First Name & Middle Initial & Last Name & Degree
Jay Traverse, MD
Facility Name
The Linder Center for Education and Research at The Christ Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Denise Krabbe, RN
Phone
513-585-1790
Email
dkrabbe@thechristhospital.com
First Name & Middle Initial & Last Name & Degree
Timothy D Henry, MD
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shawna Oxier, RN
Phone
614-247-6797
Email
shawna.oxier@osumc.edu
First Name & Middle Initial & Last Name & Degree
Konstantinos Boudoulas, MD
Facility Name
University of Wisconsin at Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Soni VanderArk, MD
Phone
608-265-0612
Email
cav@medicine.wisc.edu
First Name & Middle Initial & Last Name & Degree
David Murray, MD
12. IPD Sharing Statement
Plan to Share IPD
No
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NAN-101 in Patients With Class III Heart Failure
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