A phase 1, safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of a subcutaneous injection of BC-006 in adults with obesity-part 2
| ISRCTN | ISRCTN18176375 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18176375 |
| Secondary identifying numbers | CBC006A1101 |
- Submission date
- 12/03/2025
- Registration date
- 16/03/2025
- Last edited
- 14/03/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English Summary
Background and study aims
BC-006 is a type of investigational medication called a small interfering ribonucleic acid (siRNA) which works in the liver to reduce the production of a protein called inhibin subunit beta E (INHBE). Part 1 of the study will investigate the effects of a single ascending doses (SAD) of BC-006 in adult participants with obesity. The purpose of Part 2 of this study is to: evaluate how safe and well tolerated BC-006 is, in adult participants with obesity; measure levels of BC-006 in the blood over time, following a single dose; measure the body’s response to a single dose of BC-006; assess the effect of BC-006 on body composition; and, evaluate the effects of BC-006 on maintaining body weight/body fat loss following a 6-month run-in period with Tirzepatide.
Who can Participate?
Healthy volunteers aged 18 – 65 years old
What does the study involve?
Part 2 of the study requires a minimum 24 week Tirzepatide run-in period with monthly or weekly clinic visits, a 3-night stay at the NZCR research unit and 8 scheduled follow-up clinic visits. Volunteers wishing to participate in this study will be booked in for a consultation with a study doctor (Screening) and asked to sign the consent form before any study assessments can be performed. Study assessments, informed consent, eligibility check, history and demographics, vital signs, height, weight and waist-to-hip circumference, physical examination, electrocardiogram (ECG), pregnancy tests / post-menopausal test, blood samples, urine samples, alcohol breath testing and drug of abuse testing, health and medication check, mental health questionnaires, body composition scan.
What are the possible benefits and risks of participating?
The study is not designed to provide any therapeutic benefits. The information from this study might help to develop better treatments in the future for obesity.
This is the first time that BC-006 is being tested in humans, and as such, there is no human experience available to identify all of the risks of BC-006. Animal studies have been done with BC-006 to try and predict what type of side effects might occur in people. However, animal studies do not always predict human responses to medications. When BC-006 was given to animals at doses higher than the doses that will be given in this study, no adverse (harmful) side effects were seen. The below effects were observed in animal studies:
- Changes in liver cells and function
- Skin reactions at the injection site
The doses planned for this study in people are lower than any of the doses given to animals.
Where is the study run from?
New Zealand Clinical Research- Christchurch
When is the study starting and how long is it expected to run for?
December 2024 to May 2027. Part 2 of the Study is starting to recruit in July 2025 and recruitment is expected to run until November 2026.
Who is funding the study?
BaseCure Therapeutics Inc.
Who is the main contact?
Ms Yvonne Chen, yvonne_chen@basecuretx.com
Contact information
Dr Jane Elizabeth Kerr
Principal Investigator
Principal Investigator
New Zealand Clinical Research, 264 Antigua Street
Christchurch
8011
New Zealand
| Phone | +64033729477 |
|---|---|
| jane.kerr@nzcr.co.nz |
Ms Yvonne Chen
Public
Public
BaseCure Therapeutics Inc, Suite 5-204, 23 Lime tree Bay Avenue P.O. Box 2547
Grand Cayman
KY1-1104
Cayman Islands
| Phone | +12677519392 |
|---|---|
| Yvonne_Chen@basecuretx.com |
Dr Todd Hobbs
Scientific
Scientific
BaseCure Therapeutics Inc, Suite 5-204, 23 Lime tree Bay Avenue P.O. Box 2547
Grand Cayman
KY1-1104
Cayman Islands
| Phone | +12677519392 |
|---|---|
| Todd_Hobbs@basecuretx.com |
Study information
| Study design | Two-part single-center phase 1 first-in-human study including the double-blind placebo-controlled phase of Part 2 |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Pharmaceutical testing facility |
| Study type | Safety, Efficacy |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A phase 1, randomized, double-blind, placebo-controlled, single-dose study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of a subcutaneous injection of BC-006 in adults with obesity- part 2 |
| Study hypothesis | This first-in-human, 2-part study is designed to provide initial single-dose safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of SC administered BC-006 in adults with obesity. The study will be conducted in 2 parts. Part 1 will be a single-ascending-dose (SAD) study of BC-006. This record is Part 2 which will be comprised of an initial open-label Tirzepatide (TZP) run-in period followed by a double-blind, placebo-controlled BC-006 treatment phase. An SRC will oversee dose escalation decisions in Part 1 (SAD) and will be responsible for determining the BC-006 doses to be used in Part 2 based on emerging data from Part 1. Analysis of urine and plasma concentrations will characterize the single dose PK of BC-006 and its metabolites. Pharmacodynamic, immunogenicity and exploratory samples, as well as preliminary markers of efficacy, will be analyzed to further characterize the effects of single dose BC-006 exposure. The results of this study will be used to refine dosing strategies for future studies. |
| Ethics approval(s) |
Approved 24/02/2025, Northern B Health and Disability Ethics Committee (Ministry of Health, 133 Molesworth Street, PO Box 5013, Wellington, 6011, New Zealand; +64 (0)800 855 066; hdecs@health.govt.nz), ref: 2025 FULL 22086 |
| Condition | Diet and Nutrition |
| Intervention | This is a single-center Phase 1, first-in-human, 2-part study to evaluate the safety, tolerability, Pharmacokinetics, Pharmacodynamic, and preliminary efficacy of BC-006 administered subcutaneous (SC) injection in adults with obesity. The study will be conducted in 2 parts. Part 2 of the study will assess the safety, tolerability and evaluate the effect of BC-006 on maintenance of body weight/body fat loss following at least 6 months of Tirzepatide (TZP) administration. The Safety Review committee (SRC) will review all the available blinded safety and tolerability data from part 1 before making a recommendation of dose selection for part 2 BC-006 doses. In no case will the Part 2 BC-006 doses exceed the highest dose administered in Part 1 (SAD) and no case will the double-blind, placebo-controlled phase of Part 2 commence before this Safety Review Committee review. The TZP run-in period may commence any time after the Safety Review Committee review of Part 1 Cohort B data. In Part 2 of the study, approximately 60 obese subjects will initially be enrolled to receive open-label TZP for a minimum 168-day run-in period. Randomization is performed by the Randomization and Trial Supply Management (RTSM) computer program. The pharmacist will be able to randomize manually if required, based on the randomization schedule provided to them (as a Back-up). At least 36 subjects who have achieved at least 10% body weight reduction since screening will be randomized into the double-blind, placebo-controlled BC-006 treatment period to receive a single subcutaneous (SC) injection dose of placebo, or 1 of 2 dose levels of BC-006 (doses to determine by the Safety Review Committee) at a 1:1:1 ratio (12 placebo: 12 low dose BC-006: 12 high dose BC-006). Post treatment follow-up phase (85 days following BC-006 dosing). Assess pharmacokinetics, pharmacodynamics, subcutaneous doses of BC-006 and effect of BC-006 on body composition. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Pharmacodynamic |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | BC-006, tirzepatide |
| Primary outcome measure | 1. Incidence and severity of Adverse Events (AEs) measured using event reporting from the time of BC-006 dosing through End of Study (EOS, day 85 post-dose) 2. Incidence of laboratory abnormalities measured using hematology, serum chemistry, coagulation, and urinalysis test results 12-lead ECG parameter. Vital signs measurements. Part 2 ECG done on day -196 -169 (screening), day -1 (check-in), and day 85 (End of Study (EOS, day 85 post-dose)/ early termination (ET). Clinical Laboratory Assessments Physical examination: day -196 -169 (screening) day -1 (check-in), day 3,8,15,22,29,36,43,57 and 85 post -dose. 3. Physical examination measured on day -196 -169 (screening) day -1 (check-in), day 3 and 85 post dose 4. Suicide risk measured using the Columbia-Suicide Severity Rating Scale (C-SSRS) on Day 1 (dose), 29,57 and Day 85 post-dose |
| Secondary outcome measures | 1. Characterize the pharmacokinetics (PK) of SC doses of BC-006 in adults with obesity. Assessment pharmacokinetics (PK) parameters of BC-006, including but not limited to: AUCinf, AUClast, Cmax, tmax, Kel, t1/2, CL/F, and Vz/F in plasma Ae0-24, Fe%, and CLR in urine. Part 2 timepoints Day 1 (dose), Day 15, Day 29, Day 57 and Day 85 (post-dose). 2. Assess the pharmacodynamic (PD) response following SC doses of BC006 in adults with obesity. Change from baseline of circulating biomarker proteins. Part 2 timepoints Day 1 (dose), Day 15, Day 29, Day 57 and Day 85 post-dose. 3. Characterize the Pharmacokinetics (PK) of BC-006 metabolites following SC doses of BC-006 in adults with obesity. Pharmacokinetics (PK) parameters of BC-006 metabolites, including but not limited to: AUCinf, AUClast, Cmax, tmax, Kel, t1/2, CL/F, and Vz/F in plasma, Ae0-24, Fe%, and calculation of renal clearance (CLR) in urine. Part 2 timepoints Day 1 (dose), Day 2, Day 8, and Day 15 post-dose. 4. Evaluate the effect of BC-006 on maintenance body weight following at least 6 months of Tirzepatide (TZP) administration. Assessed by percent change from baseline in body weight will be analyzed by mixed model for repeated measurements. Body weight assessed by digital scales and BMI body mass index. Part 2 timepoints screening, Day 1 (check-in), and Day 85 post dose (EOS/ET). 5. Evaluate the effect of BC-006 on maintenance of body fat loss following at least 6 months of Tirzepatide (TZP) administration. Assessed by body composition, including fat mass (FM), fat-free mass (FFM), visceral adipose tissue (VAT), and appendicular lean mass (ALM) will be measured using whole body dual-energy x-ray absorptiometry (DX) scans. Waist circumference and waist-to-hip ratio will be recorded in centimeters (cm) using a stretch-resistant tape. Part 2 timepoints screening, Day 1 (check-in) 29, 57 and 85 (EOS/ET) post dose. |
| Overall study start date | 05/12/2024 |
| Overall study end date | 05/05/2027 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | 60 |
| Participant inclusion criteria | 1. Male and female subjects aged 18 to 65 years, inclusive, at the time of signing the informed consent. 2. Subjects who are in good general health according to the judgment of the investigator per local guidance, eg, with no clinically relevant abnormalities based on medical history, physical examinations, neurological examinations, clinical laboratory evaluations (hematology, serum chemistry, coagulation, urinalysis), and 12-lead ECG that, in the opinion of the investigator would affect subject safety. Subjects may have well-controlled hypertension providing they have been on stable treatment for at least 3 months before screening. 3. Subjects with a BMI of greater than or equal to 30 to less than 40 kg/m at screening. 4. Self-reported stable body weight (plus or minus 5%) for at least 3 months prior to screening. 5. Male subjects are eligible to participate if they are permanently sterile by vasectomy (at least 6 months before screening, and confirmed by post-surgical sperm count [verbal confirmation by subject is acceptable]), or agree to the following during the study and for at least 90 days after the last dose of study drug: 5.1. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or 5.2. Agree to use a male condom (contraception/barrier) and be advised of the benefit for a female partner to use an acceptable, highly effective method of contraception as a condom may break or leak when having sexual intercourse. 6. Female subjects are eligible to participate if they are not pregnant or breastfeeding, subject to 1 of the following during the study and for at least 90 days after the last dose of study drug: 6.1. WOCBP, defined as women physiologically capable of becoming pregnant, must have a negative serum pregnancy test at screening and Day -1; women of childbearing potential (WOCBP) must agree to be abstinent as their preferred or usual lifestyle or use an acceptable, highly effective contraceptive method (implant contraceptive or intrauterine device) from screening. WOCBP using an effective form of contraception (injectable contraceptive or oral contraceptive pill) must also agree to use a barrier method of contraception (male condom, female condom, or female diaphragm) OR 6.2. Menopausal women (amenorrhea for greater than 12 months) must have an elevated serum FSH level at screening (greater than or equal to 40 mIU/mL); if the FSH is not elevated, they are considered to be of childbearing potential (unless permanently surgically sterile by hysterectomy, tubal ligation, etc.). 7. Agree to abstain from sperm or egg donation through 90 days after last dose of study drug. 8. Legally and ethically capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. |
| Participant exclusion criteria | 1. Clinically significant infection and/or cardiovascular, hematological, renal, hepatic, pulmonary, endocrine, gastrointestinal, immunological, dermatological, neurological, or psychiatric disease which could interfere with, or the treatment for which might interfere with, the conduct of the study or which would, in the opinion of the investigator, unacceptably increase the subject’s risk if he/she were to participate in the study. 2. Diagnosed with diabetes (Type 1, 2 or other forms of diabetes mellitus, excluding a history of gestational diabetes). 3. Have at least 1 laboratory value suggestive of diabetes during screening, including 1 or more of HbA1c greater than or equal to 6.5% (48 mmol/mol), fasting serum glucose greater than or equal to 126 mg/dL (7.0 mmol/L), or random glucose greater than or equal to 200 mg/dL (11.1 mmol/L). Participants with prediabetes are permitted. 4. If liver function tests (alanine aminotransferase, aspartate aminotransferase, or total bilirubin) and serum creatinine are 2.0 times ULN at screening; or if creatinine phosphokinase is 3 times ULN at screening; except subjects with Gilbert’s syndrome at screening who are permitted if all other criteria are met. 5. History of renal disease at any time in the past or abnormal kidney function tests at screening (glomerular filtration rate less than 60 mL/min/1.73 m2 as estimated using the CKD-EPI 2009 equation). 6. History of acute or chronic pancreatitis from any etiology, including but not limited to gallstone pancreatitis, at any time in the past. 7. Clinically significant allergy to any type of drug (anesthetics, antibiotics) at the discretion of the investigator, or allergy to any constituents of BC-006. If there is any history of anaphylaxis/hospitalization due to drug reaction in the past, the site should discuss further with the medical monitor, if needed. 8. Any of the following abnormalities on triplicate 12-lead ECG at screening: 8.1. PR (PR interval) greater than or equal to 210 msec 8.2. QRS (QRS complex) greater than or equal to 120 msec 8.3. QTcF (Fridericia’s corrected QT interval) greater than 450 msec (males) and greater than 470 msec (females) 8.4. In addition to the above, any clinically significant abnormality on an ECG, at the Investigator’s discretion. 9. Sitting or semi-supine (for at least 5 minutes) systolic blood pressure less than 145 mmHg at screening, confirmed by repeat. 10. Sitting or semi-supine (for at least 5 minutes) diastolic blood pressure greater than 95 mmHg at screening, confirmed by repeat. 11. Clinically significant history of orthostatic hypotension at any time in the past. 12. Presence of birthmarks, tattoos, wounds, scars, blemishes, heavy hair, or other skin conditions (such as eczema) at the planned dosing site/s that could be expected to obscure the observation of injection site reactions. 13. Use of prescription drugs (other than anti-hypertension therapy and hormonal contraceptives), over-the-counter drugs (other than paracetamol and ibuprofen), food supplements, statins, fish oil supplements, or herbal medications within 7 days or 5 half–lives, whichever is longer, prior to BC-006 dosing on Day 1, and antibiotics and systemic steroids within 30 days prior to BC-006 dosing on Day 1. Anti-hypertension therapy must be stable for at least 3 months prior to screening; more than 1 anti-hypertension therapy is permitted at Investigator’s discretion. The sponsor may allow exceptions only if the medication’s administration is deemed unlikely to impact the PK results. 14. Use of any GLP-1-based therapy within 12 months of screening. 15. Smoking greater than 5 cigarettes per day (or nicotine equivalent) at the time of screening or anticipated use during the study, and unable to abstain completely from smoking/vaping during the inpatient stay. 16. Any vaccination within 14 days prior to screening or anticipated live vaccination while participating in the study. 17. Receipt of an investigational product or device, or participation in a drug research study, within a period of 60 days (or 5 half-lives of the drug, whichever is longer) before dosing on Day 1 for Part 1 18. Prior exposure to BC-006 at any time in the past. 19. Positive screen for hepatitis B surface antigen (HbsAg), hepatitis C antibody (if positive, amplification may be performed to confirm; cured hepatitis C can be enrolled), or HIV antibody. 20. Positive alcohol breath test or positive urine drugs of abuse screen at screening or Day -1. 21. Past or current history or evidence of drug or alcohol abuse, regular use of more than 3 units of alcohol per day (1 unit of alcohol = 150 mL of wine, 360 mL of beer, or 45 mL of alcohol 40%). Use of any illicit drugs (eg, amphetamines, benzodiazepines, cocaine, methamphetamine, opioids, cannabis, and synthetic cannabinoids) within 6 months of screening (brief use of benzodiazepines and opiates with appropriate medical history is permitted at Investigator discretion). 22. Donation of more than 500 mL of blood or plasma within 8 weeks prior to screening or planned blood or plasma donation through 90 days after last dose of study drug. 23. Any positive responses in the C-SSRS at Day -1 that indicate the subject may be at increased risk by participating in this study or may cause potential interference with study conduct or results, at Investigator discretion. 24. Known hypersensitivity or allergy to TZP or other GLP-1-based therapy. 25. History of failure to lose weight on, or intolerance to TZP or other GLP-1-based therapy. 26. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2. |
| Recruitment start date | 28/07/2025 |
| Recruitment end date | 08/11/2026 |
Locations
Countries of recruitment
- New Zealand
Study participating centre
New Zealand Clinical Reseach
264 Antigua Street
Christchurch
8011
New Zealand
Christchurch
8011
New Zealand
Sponsor information
BaseCure Therapeutics Inc.
Industry
Industry
Suite 5-204,23 Lime Tree Bay Avenue P.O. Box 2547
Grand Cayman
KY1-1104
New Zealand
| Phone | +12677519392 |
|---|---|
| Jing_yang@basecuretx.com |
Funders
Funder type
Industry
BaseCure Therapeutics Inc.
No information available
Results and Publications
| Intention to publish date | 05/05/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | There is no plan to publish |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to confidentiality |
Editorial Notes
13/03/2025: Study's existence confirmed by the Northern B Health and Disability Ethics Committee
