A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Explore the Efficacy and Safety of BIO89-100 in Subjects with Severe Hypertriglyceridemia
- Conditions
- Severe Hypertriglyceridemia (SHTG)MedDRA version: 20.1Level: LLTClassification code 10020870Term: HypertriglyceridemiaSystem Organ Class: 100000004861Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2020-000641-13-PL
- Lead Sponsor
- 89bio, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 90
1. Subject understands the study design and has been informed of the investigational nature
of the study. Subject has given voluntary, written, informed consent to take part in this
study.
2. Subject agrees to be compliant and is a capable of completing the required study
assessments.
3. Male or female age =21 to =75 years at time of signing informed consent.
4. All subjects (male or female) who are of childbearing potential must agree to use
highly-effective, double contraception (both male and female partners) during the study.
Double contraception is defined as use of a condom by the male partner, combined with
use of 1 of the following forms of highly-effective contraception by the female partner:
a. Oral contraceptive pills
b. Depot or injectable contraceptive
c. Intrauterine device (IUD)
d. Contraceptive patch (e.g., Xulane®) or NuvaRing®
e. Documented evidence of surgical sterilization at least 6 months prior to the
screening visit (i.e., tubal ligation or hysterectomy).
Use of a condom in a male subject who underwent vasectomy is also acceptable as
double contraception. Use of highly-effective, double contraception must continue for
30 days or 5 half-lives (whichever is longer) after the last dose of investigational product.
Female subjects should not donate oocytes during this time. Male subjects must not
donate sperm during this time. Rhythm methods are not considered as highly-effective
methods of birth control. Subject abstinence for the duration of the study and 30 days or
5 half-lives (whichever is longer) after last dose of investigational product is acceptable if
it is the subject’s regular practice.
5. Females of childbearing potential must have a negative serum pregnancy test at screening
V2 and a negative urine pregnancy test on Day 1. Females of childbearing potential must
agree to undergo a urine pregnancy test prior to each administration of investigational
product and at the end of the treatment, and a serum pregnancy test at end of the study.
6. Females not of childbearing potential will be defined for this study as postmenopausal
(defined as cessation of regular menstrual periods for at least 12 months) and confirmed
by follicle-stimulating hormone (FSH) level OR surgically sterile.
7. Serum TG criteria meeting all of the following criteria:
a. A historical documented TG =400 mg/dL (4.52 mmol/L) in the past 5 years from
screening V1, or currently on lipid modifying therapy due to SHTG at
screening V1.
b. Mean of 2 screening fasting serum TGs =500 mg/dL (5.65 mmol/L) and
=2000 mg/dL (22.60 mmol/L). Mean screening fasting serum TG is defined as the
mean of TG at V2 and V3, or V3 and V3.1 if the average of TG at V2 and V3 is
<500 mg/dL, or >2000 mg/dL. The repeat measure of TG is permitted at a
minimum of 7 days apart at V3.1.
c. If 1 of the 2 qualifying TGs is <400 mg/dL, the difference between 2 TG should
be <300 mg/dL.
8. Willing to follow a lifestyle for optimal control of TGs and disease management during
the study e.g., lipid modifying, and approximately isocaloric diet and exercise. At the
screening and subsequent visit, all subjects will receive counseling regarding the National
Cholesterol Education Program Therapeutic Lifestyle Changes Diet.
9. Concomitant medication may include prescription fish oil (including purified
eicosapentaenoic acid [EPA] with or without docosahexaenoic acid [DHA]) and/or statin
with or without ezetimibe (none of which will be supplied as part of study) as long as the
subject ha
1. Females who are pregnant or breastfeeding, or planning to become pregnant, or breastfeed while enrolled in the study or within 30 days or 5 half-lives (whichever is longer) after last dose of investigational product.
2. Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg) at screening V1.
3. Body mass index (BMI) >45 kg/m2 at screening V1.
4. Weight change =5% in 3 months prior to screening V1 or weight change =5% between screening V1 and V3.
5. Central laboratory hemoglobin levels below the lower limit of normal (<12.0 g/dL for males, <11.0 g/dL for females), or dialysis, lipid apheresis, plasma exchange, blood transfusion, or blood donation/blood loss of =400 mL at least a month prior to and during the screening period or anticipation of these procedures during the period of the study and up to 30 days afterwards.
6. A history of symptomatic gallstone disease unless treated with cholecystectomy and/or pancreatitis within 5 years from screening will be excluded from the study.
7. ALT or AST >3× upper limit of normal (ULN) at screening V1.
8. Total bilirubin exceeds ULN at screening V1, unless prior diagnosis and documentation of Gilbert’s syndrome in which case total bilirubin must be =3 mg/dL.
9. Creatine kinase (CK) >3× ULN at screening V1.
10. Risky drinking within the 24 months before screening V1, or had positive alcohol test at screening V1 or at V4. Alcohol intake will be limited to 2 units of alcohol per day for men and 1 unit of alcohol per day for women.
11. Concomitant use of fibrates, PCSK9 inhibitors, niacin, or any supplements, including non-prescription, non-pharmaceutical strength fish oils, used to alter lipid metabolism.
12. Previous long-term (>4 weeks) use of systemic steroid (glucocorticoid) medications such as prednisone within 12 months of screening V1. Inhaled or topical corticosteroids are permitted.
13. Reduced renal function (eGFR =60 mL/min/1.73 m2 calculated using chronic kidney disease epidemiology collaboration [CKD-EPI] equation).
14. Positive for hepatitis b virus (HBV), hepatitis c virus (HCV) or human immunodeficiency virus (HIV). HBV and HCV determined by antibodies first and, if positive, by DNA/ribonucleic acid (RNA).
15. History of drug abuse, or any other substance dependence (with the exception of caffeine) in the past 2 years prior to screening or a positive test for drugs of abuse at screening V1.
16. Participation in a previous clinical trial or exposure to another investigational drug within 12 weeks or 5 half-lives, whichever is longer, prior to screening.
17. Previous exposure to an FGF21 analog or FGFR1 activating product, or known sensitivity to PEG or any of the excipients.
18. Type 1 diabetes mellitus (T1DM).
19. Diagnosis of Type 2 diabetes mellitus (T2DM) <6 months prior to screening.
20. Subjects with T2DM diagnosed =6 months prior to screening must have a HbA1c <9.5%, and, if receiving antidiabetic medications, must be on a stable dose of antidiabetic medications before screening (6 months for glucagon-like peptide 1 analogs or dipeptidyl peptidase IV inhibitor; 3 months for other oral or injectable medications; insulin injection is NOT allowed in this study).
21. History of malignancy within 5 years prior to screening V1, other than successfully treated basal or squamous cell carcinoma or localized cervical carcinoma.
22. Inadequately controlled thyroid disorders. Subjects on thyroid replacement should be on stable doses for at
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the effect of BIO89-100 on serum TG levels in subjects with SHTG (TG =500 mg/dL);Secondary Objective: • To determine the effect of BIO89-100 on selected serum lipids and lipoproteins<br>• To determine the effect of BIO89-100 on highsensitivity C-reactive protein (hsCRP)<br>• To determine the effect of BIO89-100 on metabolic markers<br>• To characterize BIO89-100 pharmacokinetics (PK);Primary end point(s): Percentage change in serum TG from baseline to Week 8;Timepoint(s) of evaluation of this end point: From baseline to Week 8
- Secondary Outcome Measures
Name Time Method