A Phase 1, First in Human, Randomised, Double-Blind, Placebo-controlled, Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Study to Investigate the Safety, Tolerability and Pharmacokinetics of GB-7624 Administered Subcutaneously in Healthy Adult Participants
This is a randomised, double-blinded, placebo-controlled first in human (FIH) trial to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of GB-7624. The trial will have two parts: a SAD component and a MAD component. Part A (SAD): a total of 24 healthy volunteers are planned to be enrolled across 3 SAD cohorts and will involve the administration of a single subcutaneous (SC) dose of GB-7624 (300 mg, 600 mg, or 1200 mg) or placebo on Day 1 in cohorts A1, A2, and A3. Part B (MAD): a total of 16 healthy volunteers are planned to be enrolled across 2 MAD cohorts and will involve the administration of multiple SC doses of GB-7624 (300 mg on Day 1 and Day 15 or 600 mg on Day1 and Day 15) or placebo in cohorts B1 and B2. The decision to escalate between dose levels in the SAD (Part A) and the MAD (Part B) as well as the decision to proceed from Part A to Part B will be based on safety review committee (SRC) review of prior cohorts, blinded available safety, tolerability and PK data. Study drug will be administered at the study site by trained study site personnel to ensure compliance. The administration of all trial intervention will be recorded in eCRF. Compliance will be assured by direct supervision and witnessing of trial intervention administration.
• Participants must have given written informed consent before any trial-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
• Adults, 18 to 65 years of age (inclusive) at the screening visit.
• Body mass index (BMI) greater than or equal to 18.0 and less than or equal to 32.0 kg/m2 (inclusive)
• Medically healthy as determined by medical history, vital signs, physical examination (no CS findings),ECG and clinical laboratory tests at screening and pre-dose on Day -1 or Day 1. This includes the following:
‣ Systolic blood pressure (BP) in the range of 90 to 140 mmHg (inclusive) and diastolic BP in the range of4050 to 90 mmHg (inclusive) after 5 minutes in seated, semi-recumbent, or supine position
⁃ Heart rate (HR) in the range of 40 to 100 bpm (inclusive) after 5 minutes rest in seated, semi-recumbent, or supine position
⁃ Body temperature, between 35.5°C and 37.5°C (inclusive)
⁃ Electrocardiogram (ECG) without CS abnormalities including QT interval corrected for Fredericia (QTcF) \<450 msec for male participants and \<470 msec for female participants.
⁃ In the opinion of the investigator, no significant findings in serum chemistry, haematology, coagulation and urinalysis tests.
• Female volunteers must:
‣ Be of non-child-bearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 months before the screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or
⁃ A woman of childbearing potential (WOCBP) must have a negative pregnancy test at Screening (blood test) and before the first trial drug administration (Day -1 urine test). They must agree not to attempt to become pregnant or donate ova and to use protocol-defined methods of contraception from one month prior to screening until at least 360 days after the last dose of study drug.
⁃ Women who are currently lactating, breastfeeding, receiving hormone therapy with the intention of having children, planning to donate ova or planning to become pregnant during the trial and within 360days after last dose of trial drug, are excluded from participation.
• Male participants (including vasectomised males and those with documented azoospermia): must agree to not donate sperm and, if engaging in sexual intercourse with a WOCBP, must agree to use a condom in addition to using use protocol-defined methods of contraception and agree to refrain from donating sperm from screening through at least 360 days after the last dose of trial drug. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, agree to use a condom from signing the consent form until at least 360 days after the last dose of study drug.
• Have suitable venous access for blood sampling.
• Be willing and able to comply with all trial assessments and adhere to the protocol schedule and restrictions