Severe Hypertriglyceridemia (SHTG) MedDRA version: 20.1 Level: LLT Classification code 10020870 Term: Hypertriglyceridemia System Organ Class: 100000004861
Conditions
Interventions
Product Name: BIO89-100
Product Code: BIO89-100
Pharmaceutical Form: Solution for injection
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: BIO89-100
Other descriptive name: BIO89-100
Con
Sponsors
89bio, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 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
Exclusion criteria
Exclusion criteria: 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 (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 le
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 • To determine the effect of BIO89-100 on highsensitivity C-reactive protein (hsCRP) • To determine the effect of BIO89-100 on metabolic markers • 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
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Achieve TG <500 mg/dL at Week 8 • Percentage change in very low density lipoprotein cholesterol (VLDL-C) , low density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (non-HDL-C), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein triglycerides (VLDL-TG), apolipoprotein B100 (ApoB), remnant lipoprotein cholesterol (RLP-C) from baseline to Week 8 • Percentage change in hsCRP from baseline to Week 8 • Percentage change in fasting plasma glucose, adiponectin, and body weight from baseline to Week 8 • Serum BIO89-100 concentration • PK parameters in Intensive PK subgroup o Maximal observed serum concentrations (Cmax) within a dosing interval o Area under the serum drug concentration by time curve within a dosing interval (AUC0-tau) o Time to achieve Cmax (tmax) o Terminal elimination half-life (t½) • Additional PK parameters may be calculated if also deemed appropriate.;Timepoint(s) of evaluation of this end point: • Week 8 • From baseline to Week 8 | — |
Countries
Czech Republic, Hungary, Poland, United States
Contacts
Public ContactProject Manager
89bio, Inc.
Outcome results
None listed