Status and phase
Conditions
Treatments
About
The goal of this clinical trial is to learn if BB-TL1A-VIAL-HLE is safe in healthy adults and is safe and effective in treating adults with moderate-to-severe ulcerative colitis. The main questions it aims to answer are:
Is the intervention safe in healthy adults and in adults with moderate-to-severe ulcerative colitis? Is the intervention effective in treating adults with moderate-to-severe ulcerative colitis? Researchers will compare the Phase 1b arm to a historical treatment arm to see if the study drug is at least as effective as a relevant benchmark.
Participants will:
Full description
This is a Phase 1a/b integrated clinical investigation. Phase 1a is an open-label, single-ascending dose (SAD) study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of BB-TL1A-VIAL-HLE in healthy volunteers. Phase 1b is a single-arm, open-label study evaluating the safety, PK, PD, immunogenicity, and efficacy of a single dose of BB-TL1A-VIAL-HLE in patients with moderate-to-severe ulcerative colitis.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria (Phase 1a):
Written informed consent to participate in the study and the ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures is provided.
Aged 18 to 55 years old (inclusive).
A weight of ≥50 kg and a body mass index between 18 and 32 kg/m2 (inclusive).
Considered healthy by the investigator, based on a detailed medical history, full physical examination, clinical laboratory tests, 12-lead ECG, and vital signs.
Women of childbearing potential (WOCBP) may be considered if the participant is following the contraception guidance below in 5a. The participant will be questioned at each visit where there is a potential pregnancy. Similarly, male participants must follow the contraception guidance below in 5b.
Female participants meet this criterion if they are:
Postmenopausal for at least 1 year before the first dose of study drug, including a serum FSH level of >40 mIU/mL to be reported to confirm menopause.
OR
Surgically sterile (documented hysterectomy [by self-disclosure] or bilateral oophorectomy ≥90 days prior to enrollment).
OR
Abstinent from heterosexual intercourse as per usual lifestyle (self-reported).
OR
Using effective contraceptive methods for at least 6 weeks prior to enrollment and agree to continue effective contraceptive methods throughout study participation and up to 81 weeks (t1/2 x 5) after the last dose of the study drug.
Male participants meet this criterion if they agree to:
Practice effective barrier contraception from the time of enrollment throughout study participation and up to 81 weeks (t1/2 x 5) after the last dose of the study drug.
OR
Be abstinent from heterosexual intercourse as per usual lifestyle (self-reported).
AND
Refrain from donating sperm during study participation and up to 81 weeks (t1/2 x 5) after the last dose of the study drug.
Non-smoker. If participant is a social smoker (up to 10 cigarettes per week), participant is willing to abstain during confinement.
Exclusion Criteria (Phase 1a):
Allergy to the investigational drug or any of its components or clinically significant allergies (excluding mild seasonal allergies), in the opinion of the investigator.
Use of drugs with the same target and mechanism of action as the investigational product (TL1A targeting antibodies) within 30 days or 5 half-lives (whichever is longer) prior to screening.
History of tuberculosis (TB) or active, latent or inadequately treated TB infection. TB testing to be conducted at screening using QuantiFERON-TB Gold. Refer to a general practitioner for X-rays, etc. if required.
Clinically relevant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, drug hypersensitivity, or medication history making implementation of the protocol or interpretation of the study results difficult, or that would put the participant at risk by participating in the study in the opinion of the Investigator. History or fully resolved childhood asthma with no hospitalizations, that has had no recurrence as an adult are allowed.
Use of prescription medications, medical devices (other than hormonal contraception [e.g., oral contraceptive pills, long-acting implantable hormones, or injectable hormones], vaginal ring, or IUD) within 30 days prior to enrollment, or use of any over-the-counter (OTC) medications, herbal remedies, supplements, or vitamins within 30 days prior to enrollment and during the course of the study without prior approval of the Investigator and the independent Medical Monitor. Use of simple analgesics (e.g., paracetamol, a nonsteroidal anti-inflammatory drug [NSAID]) and antihistamines may be permitted at the discretion of the Investigator.
Evidence of malignancy or other clinically relevant abnormality in the opinion of the investigator at screening or within 5 years prior to Day 1, with the exception of squamous cell or basal cell carcinomas.
Known or suspected autoimmune disorder.
Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C antibody (HCV Ab).
Administered a live attenuated vaccine within 28 days of enrollment (participants must also abstain from taking any live vaccines until at least 12 weeks after study completion).
A hospital admission or major surgery within 30 days prior to screening.
Participation in any other investigational drug trial within 30 days prior to screening or 5 half-lives, whichever is longer.
Confirmed or suspected COVID-19 infection within 14 days of any screening procedures.
Substance use disorder (SUD) and/or alcohol use disorder (AUD).
Other conditions that may affect compliance in the opinion of the investigator, or who is unable to participate in the study on his/her own.
The possible sites of injection (abdomen, front of thighs) have tattoos, scars, or significant dermatological disorders that prohibit the clear assessment of injection site reactions.
Blood donation ≤30 days prior to screening.
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) >3 times the upper limit of normal (ULN) at baseline.
Serum total bilirubin >2 times ULN at baseline.
Neutrophil count below 1,000 cells/µL at baseline.
Urea or serum creatinine >1.5 times ULN at baseline.
Employees or related personnel of the investigator, study site, or sponsor.
Inclusion Criteria (Phase 1b):
Participant meets all inclusion criteria defined for Phase 1a.
Moderately-to-severely active ulcerative colitis at screening/baseline (defined as a modified Mayo score [mMS] of 5-9 and an endoscopic subscore of at least 2).
If the participant is concomitantly taking 5-aminosalicylates, the participant must be on a stable dose for at least 4 weeks before enrollment.*
If the participant is concomitantly taking low-dose oral/rectal corticosteroids (≤20mg per day), the participant must be on a stable dose for at least 2 weeks before enrollment.*
If the participant is concomitantly taking thiopurines, the participant must be on a stable dose for at least 8 weeks before enrollment.*
Exclusion Criteria (Phase 1b):
Participant does not meet any exclusion criteria defined in Phase 1a (except for Phase 1a exclusion criterion #5 and criterion #7 in the case of ulcerative colitis).
Use of Janus kinase (JAK) inhibitors within 7 days of enrollment or 5 half-lives, whichever is longer.*
Use of biologics (antibody therapies) within 12 weeks of enrollment or 5 half-lives, whichever is longer.*
Use of any injected corticosteroids OR oral/rectal corticosteroids >20mg per day within 2 weeks of enrollment.*
Use of methotrexate or calcineurin inhibitors within 30 days of enrollment or 5 half-lives, whichever is longer.*
*All applicable washout/dose stabilization periods must be completed before the daily symptom collection (stool frequency & rectal bleeding) and endoscopy (flexible sigmoidoscopy) are performed during the screening period.
Primary purpose
Allocation
Interventional model
Masking
54 participants in 5 patient groups
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Central trial contact
Associate, Clinical Development; General Manager, Therapeutics Operations
Data sourced from clinicaltrials.gov
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