Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| P01HL059407 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Terminated by Sponsor for Business Reasons
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
Not provided
Not provided
Not provided
Not provided
This first-in-human study is intended to evaluate the safety and preliminary effectiveness of AAV (Adeno-associated virus)-based liver-directed gene therapy in the treatment of adults with Homozygous Familial Hypercholesterolemia (HoFH).
Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic metabolic disorder characterized by absent or severely reduced capacity to catabolize circulating LDL (Low density lipoprotein) particles by the hepatic LDL receptor. As a consequence, HoFH subjects present abnormal total plasma cholesterol (LDL-C) levels, resulting in severe atherosclerosis often leading to early onset of cardiovascular disease. Early initiation of aggressive treatment for these patients is therefore essential. Unfortunately, despite existing therapies, treated LDL-C (Low density lipoprotein cholesterol) levels could remain well above acceptable levels. Thus, the functional replacement of the defective LDLR via AAV-based liver-directed gene therapy may be a viable approach to treat this disease and improve response to current lipid-lowering treatments. This first-in-human study is intended to evaluate the safety of this gene therapy investigational product and assess preliminary evidence of efficacy using plasma LDL-C levels as a surrogate biomarker for human LDLR transgene expression.
Subjects may be asked to participate in an optional kinetics study to assess the metabolic mechanism by which LDL-C is reduced.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | 2.5E12 (genome copies)/kg (kilogram) body weight (E means the exponential constant) |
|
| Cohort 2 | Experimental | 7.5E12 GC/kg body weight |
|
| Cohort 2 Expansion | Experimental | 7.5E12 GC/kg body weight DSMB (Data Safety Monitoring Board) approved expansion of Dose 2 cohort, 3 additional subjects enrolled and received prophylactic corticosteroids |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AAV directed hLDLR gene therapy | Genetic | AAV directed hLDLR gene therapy is a novel adeno-associated viral (AAV8) vector with human low-density lipoprotein receptor (hLDLR) gene |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With IP (Investigational Product) Related Adverse Events | Physical examinations; Clinical laboratory parameters; and adverse event reporting | Up to 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in LDL-C | Percent change in LDL-C compared to baseline | 18 weeks, 12 weeks for cohort 1 only, compared to baseline |
| Percent Change in Lipid Parameters Compared to Baseline Values |
Not provided
Inclusion Criteria:
Exclusion Criteria
Unwilling to wash out of the following lipid lowering therapies for the pre-specified time period:
History of cirrhosis or chronic liver disease based on documented histological evaluation or non-invasive imaging or testing.
Abnormal liver function tests (LFTs) at screening (AST (Aspartate aminotransferase) or ALT (Alanine aminotransferase) > 2 × upper limit of normal (ULN) and/or Total Bilirubin of > 1.5 × ULN
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Boca Raton location | Boca Raton | Florida | 33434 | United States | ||
| Kansas City Location |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | 2.5E12 GC (genome copies)/kg (kilogram body weight (E means exponential constant) |
| FG001 | Cohort 2 | 7.5E12 GC/kg body weight |
| FG002 | Cohort 2 Expansion | 7.5E12 GC/kg body weight DSMB (Data Safety Monitoring Board) approved expansion of Dose 2 cohort, 3 additional subjects enrolled and received prophylactic corticosteroids |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | 2.5E12 GC/kg body weight Single intravenous (IV) dose of human Low Density Lipoprotein Receptor (LDLR) Gene Therapy AAV directed hLDLR gene therapy: a novel adeno-associated viral (AAV8) vector with human low-density lipoprotein receptor (hLDLR) gene |
| BG001 | Cohort 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With IP (Investigational Product) Related Adverse Events | Physical examinations; Clinical laboratory parameters; and adverse event reporting | Posted | Count of Participants | Participants | Up to 24 weeks |
|
up to 104 weeks
regular investigator assessment
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 | 2.5E12 GC/kg body weight Single intravenous (IV) dose of human Low Density Lipoprotein Receptor (LDLR) Gene Therapy AAV directed hLDLR gene therapy: A novel adeno-associated viral (AAV) vector with human low-density lipoprotein receptor (hLDLR) gene |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| device failure | Product Issues | Systematic Assessment | acute failure of prosthetic aortic valve |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina Pectoris | Cardiac disorders | Systematic Assessment |
Due to early termination of the program for business reasons, planned efficacy analysis was not possible.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Development Lead | Regenxbio Inc. | 240-552-8968 | srastogi@regenxbio.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 14, 2018 | Mar 24, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 14, 2020 | Mar 24, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000090542 | Homozygous Familial Hypercholesterolemia |
| D006938 | Hyperlipoproteinemia Type II |
| D008659 | Metabolic Diseases |
| D035583 | Rare Diseases |
| D030342 | Genetic Diseases, Inborn |
| D050197 | Atherosclerosis |
| D002318 | Cardiovascular Diseases |
| ID | Term |
|---|---|
| D008052 | Lipid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006951 | Hyperlipoproteinemias |
Not provided
Not provided
dose escalation
Not provided
Not provided
Not provided
Not provided
total cholesterol (TC); non-high density lipoprotein cholesterol (non-HDL-C); HDL-C; fasting triglycerides (TG); overflow density lipoprotein cholesterol (VLDL-C); lipoprotein(a) (Lp(a)); apolipoprotein B (apoB) and apolipoprotein A-I (apo A-I)
| 18 weeks, 12 weeks for cohort 1 only, compared to baseline |
| Number of Participants With IP Related Adverse Events | Physical examinations; Clinical laboratory parameters; and adverse event reporting | up to 104 weeks |
| Amount of Vector Shedding, Urine | Amount of virus secreted in urine | up to 104 weeks |
| Amount of Vector Shedding, Plasma | Amount of virus secreted in plasma | up to 104 weeks |
| Kansas City |
| Kansas |
| 66160 |
| United States |
| Portland location | Portland | Oregon | 97239 | United States |
| Philadelphia Location | Philadelphia | Pennsylvania | 19104 | United States |
| Nashville location | Nashville | Tennessee | 37232 | United States |
| Montreal location | Montreal | Quebec | H1T1C8 | Canada |
| Palermo location | Palermo | PA | 90127 | Italy |
| Rome location | Roma | RM | 00161 | Italy |
| Rotterdam location | Rotterdam | 3015 CE | Netherlands |
7.5E12 GC/kg body weight Single intravenous (IV) dose of human Low Density Lipoprotein Receptor (LDLR) Gene Therapy AAV directed hLDLR gene therapy: a novel adeno-associated viral (AAV8) vector with human low-density lipoprotein receptor (hLDLR) gene |
| BG002 | Cohort 2 Expansion | 7.5E12 GC/kg body weight DSMB (Data Safety Monitoring Board) approved expansion of Dose 2 cohort, 3 additional subjects enrolled and received prophylactic corticosteroids Single intravenous (IV) dose of human Low Density Lipoprotein Receptor (LDLR) Gene Therapy AAV directed hLDLR gene therapy: a novel adeno-associated viral (AAV8) vector with human low-density lipoprotein receptor (hLDLR) gene |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG002 | Cohort 2 Expansion | 7.5E12 GC/kg body weight DSMB (Data Safety Monitoring Board) approved expansion of Dose 2 cohort, 3 additional subjects enrolled and received prophylactic corticosteroids Single intravenous (IV) dose of human Low Density Lipoprotein Receptor (LDLR) Gene Therapy AAV directed hLDLR gene therapy: A novel adeno-associated viral (AAV8) vector with human low-density lipoprotein receptor (hLDLR) gene |
|
|
| Secondary | Percent Change in LDL-C | Percent change in LDL-C compared to baseline | Posted | Mean | Standard Deviation | percentage of change from baseline | 18 weeks, 12 weeks for cohort 1 only, compared to baseline |
|
|
|
| Secondary | Percent Change in Lipid Parameters Compared to Baseline Values | total cholesterol (TC); non-high density lipoprotein cholesterol (non-HDL-C); HDL-C; fasting triglycerides (TG); overflow density lipoprotein cholesterol (VLDL-C); lipoprotein(a) (Lp(a)); apolipoprotein B (apoB) and apolipoprotein A-I (apo A-I) | Posted | Mean | Standard Deviation | percentage of change from baseline | 18 weeks, 12 weeks for cohort 1 only, compared to baseline |
|
|
|
| Secondary | Number of Participants With IP Related Adverse Events | Physical examinations; Clinical laboratory parameters; and adverse event reporting | Posted | Count of Participants | Participants | up to 104 weeks |
|
|
|
| Secondary | Amount of Vector Shedding, Urine | Amount of virus secreted in urine | Posted | Mean | Standard Deviation | GC/12 μL (microliter) specimen) (urine) | up to 104 weeks |
|
|
|
| Secondary | Amount of Vector Shedding, Plasma | Amount of virus secreted in plasma | Posted | Mean | Standard Deviation | GC/ μg (microgram) DNA | up to 104 weeks |
|
|
|
| 0 |
| 3 |
| 2 |
| 3 |
| 2 |
| 3 |
| EG001 | Cohort 2 | 7.5E12 GC/kg body weight Single intravenous (IV) dose of human Low Density Lipoprotein Receptor (LDLR) Gene Therapy AAV directed hLDLR gene therapy: A novel adeno-associated viral (AAV) vector with human low-density lipoprotein receptor (hLDLR) gene | 0 | 3 | 1 | 3 | 3 | 3 |
| EG002 | Cohort 2 Expansion | 7.5E12 GC/kg body weight DSMB (Data Safety Monitoring Board) approved expansion of Dose 2 cohort, 3 additional subjects enrolled and received prophylactic corticosteroids Single intravenous (IV) dose of human Low Density Lipoprotein Receptor (LDLR) Gene Therapy AAV directed hLDLR gene therapy: A novel adeno-associated viral (AAV) vector with human low-density lipoprotein receptor (hLDLR) gene | 1 | 3 | 1 | 3 | 2 | 3 |
|
| cardiac arrest | Cardiac disorders | Systematic Assessment |
|
| pnuemonia | Infections and infestations | Systematic Assessment |
|
| acute respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | acute lung failure |
|
| acute coronary syndrome | Cardiac disorders | Systematic Assessment |
|
| dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | shortness of breath |
|
| hypotension | Vascular disorders | Systematic Assessment |
|
| Angina pectoris | Cardiac disorders | Systematic Assessment | worsening of angina |
|
| chest pain | General disorders | Systematic Assessment | chest pain unknown etiology |
|
| appendicitis | Infections and infestations | Systematic Assessment |
|
| hepatic enzyme increased | Investigations | Systematic Assessment | elevated liver enzymes |
|
| Acute left ventricular failure | Cardiac disorders | Systematic Assessment | acute on chronic diastolic heart failure |
|
| Acute Coronary Syndrome | Cardiac disorders | Systematic Assessment |
|
| Palpitations | Cardiac disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Chest Pain | General disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Pyrexia | General disorders | Systematic Assessment |
|
| Swelling Face | General disorders | Systematic Assessment |
|
| Hepatic Enzyme Increased | Investigations | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Restlessness | Psychiatric disorders | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
Not provided
Not provided
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
|
| overflow density lipoprotein cholesterol (VLDL-C) |
|
| fasting triglycerides (TG) |
|
| HDL-C |
|
| non-high density lipoprotein cholesterol (non-HDL-C) |
|
| lipoprotein(a) (Lp(a)) |
|
| apolipoprotein A-I (apo A-I) |
|