None listed
Conditions
Brief summary
This is a first-in-human, multi-centre, randomised, double blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics and immunogenicity of FB102-101 after multiple dose administration in participants with celiac disease. Who is it for? You may be eligible for this study if you are aged 18 to 65 years with a documented diagnosis of celiac disease confirmed by intestinal biopsy and positive celiac serology at least 12 months prior to Screening. Study details: The study will be conducted in a single cohort of participants with biopsy-confirmed, asymptomatic celiac disease who are adhering to a strict gluten free diet, All participants who choose to enrol in this study will receive multiple doses of FB102 or placebo. All participants will have their vital signs checked (heart rate, blood pressure, temperature, etc), and will provide blood and urine samples for testing of celiac disease biomarkers during and following a 16 day gluten challenge. Participants will also have an endoscopy and biopsies done at screening and Day 32. The data generated in this study may inform the design of future clinical studies in patients with autoimmune and inflammatory diseases such as celiac disease.
Interventions
This study will be conducted in a single cohort of participants with biopsy-confirmed, asymptomatic Celiac disease (CeD) who are adhering to a strict gluten-free diet (GFD). It will investigate the safety, tolerability, PK, and immunogenicity following multiple administrations of FB102 and assess the effects of FB102 on CeD and selected biomarkers during and following a 16 day gluten challenge.
Approximately 32 participants will be randomized to FB102 or placebo in a 3:1 ratio, respectively,
This study will be conducted in a single cohort of participants with biopsy-confirmed, asymptomatic Celiac disease (CeD) who are adhering to a strict gluten-free diet (GFD). It will investigate the safety, tolerability, PK, and immunogenicity following multiple administrations of FB102 and assess the effects of FB102 on CeD and selected biomarkers during and following a 16 day gluten challenge. Approximately 32 participants will be randomized to FB102 or placebo in a 3:1 ratio, respectively, to receive 4 weekly intravenous doses of FB102 (10 mg/kg) or placebo to be administered on Days 1, 8, 15, and 22. Participants will initiate the gluten challenge on Day 16 (approximately 24 hours after the 3rd dose of FB102 or placebo). Participants will consume 2 grams of provided gluten on Day 16 (at clinic), 4 grams of provided gluten on Day 17 (at home), 8 grams of provided gluten daily on Days 18 to Day 21 (at home), 8 grams of provided gluten on Day 22 (at clinic) and 8 grams of provided gluten daily on Days 23 to Day 31 (at home). To assess adherence to the gluten challenge participants will be asked to keep all used gluten pouches and to return these to the clinic along with any unused pouches at Day 22 and Day 32, so accountability checks can be performed. Participants will have an end of treatment (EOT) visit done on Day 32. Safety follow-ups will be on Days 70 and 122. Adherence to study interventions will be managed via recording in appropriate drug accountability records. Participants at select sites may consent to an Optional Extension Period that includes a blood assay for celiac disease assessment beginning at the Day 122 visit and continuing approximately every 3 months up to 2 years (approximately Day 750). During the Optional Extension Period, participants must agree to continue adhering to a strict GFD.
Sponsors
Forte Biosciences, Australia Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women aged greater than or equal to 18 to 65 years at screening. 2. Has documented diagnosis of celiac disease confirmed by intestinal biopsy and positive celiac serology at least 12 months prior to Screening (intestinal biopsy and serology do not have to be performed concurrently). 3. Body mass index (BMI) between 16.0 and 32.0 kg/m2, inclusive. 4. Weight greater than or equal to 50 kg and less than or equal to 100 kg for men and greater than or equal to 45 kg and less than or equal to 95 kg for women 5. Self-reported to be on a GFD for at least 12 months prior to Screening and must be willing to remain on a GFD for the duration of study participation, with the exception of the oral gluten challenge administered as a study procedure. 6. Normal or negative celiac serology at Screening defined as follows: a. Measurable total serum immunoglobulin A (IgA), AND b. Negative or weak positive tissue transglutaminase (tTG) immunoglobulin A (IgA) titer, OR c. If IgA deficient, defined by a serum IgA level of less than 3 mg/dL, negative or weak positive DGP-IgG titer. 7. Human leukocyte antigen DQ (HLA-DQ) genotyping compatible with celiac disease (HLA DQ2/DQ8) provided or obtained before baseline EDG with biopsies. 8. Vh:Cd greater than 2.0 on Screening biopsies. Note: EGD with biopsies to be performed only after other initial screening activities are performed that indicate the participant is a candidate for randomization and must be done no later than Day -7 of Screening to allow for biopsy results. 9. If taking a prescription or over the counter medication or supplement with gastrointestinal effects (e.g., laxative, fiber supplements, herbal remedies, etc.), must be at stable regimen for at least 3 months prior to Screening. 10. Men must agree to practice true abstinence; be surgically sterilized (performed at least 6 months prior and documented to no longer produce sperm – verbal confirmation through medical history review acceptable); or agree to use a condom plus effective contraception (i.e. established use of hormonal contraception started at least 30 days prior to Day 1; or placement or an intrauterine device or intrauterine system) for their female partner, if of childbearing potential, from screening and for at least 90 days after dosing and refrain from donating sperm during this period. These contraception requirements do not apply if the male participant is in an exclusively same sex relationship. 11. Women are eligible to participate if they are not pregnant, not breastfeeding, and at least 1 of the following conditions applies: a. Not of childbearing potential, defined as surgically sterile (hysterectomy, bilateral salpingectomy, bilateral tubal ligation or bilateral oophorectomy – verbal confirmation through medical history review is acceptable). b. Postmenopausal (no menses for 12 months and confirmed by FSH level greater than or equal to 40 mlU/mL). c. Of childbearing potential and agree to practice true abstinence or agrees to use a highly effective method of contraception consistently from 30 days prior to Day 1 until the end of study. Must also agree not to donate ova during the study and for 100 days after the end of study. NOTE: Highly effective contraception includes hormonal contraception (oral, injected, implanted or transdermal) plus use of a condom, placement of an intrauterine device or intrauterine system plus use of a condom, or a vasectomized male partner (performed at least 6 months prior) who has been documented to no longer produce sperm – verbal confirmation through medical history review is acceptable. Participants in an exclusively same-sex relationship is acceptable. 12. Willing and able to understand and sign the participant informed consent form (PICF).
Exclusion criteria
1. Uncontrolled CeD and/or active signs/symptoms of CeD, in the opinion of the Investigator. 2. History of or current neuropsychiatric manifestations including ataxia and peripheral neuropathy related to gluten exposure. 3. History of or current diagnosis of any severe complication of celiac disease. such as Refractory Celiac Disease Type l or Type II (RCD-1 or RCD-11). Enteropathy-associated T-cell lymphoma (EATL) ulcerative jejunitis or perforation. 4. History or presence of skin manifestations of CeD such as dermatitis herpetiformis at any time. 5. Diagnosis of any autoimmune disease, other than celiac disease, that might interfere with the conduct of the study or require systemic immunomodulation therapy. 6. Diagnosis of any chronic active gastrointestinal (GI) disease other than celiac disease (e.g., active, untreated peptic ulcer, esophagitis, gastroesophageal reflux disease (GERD); active ulcerative colitis; Crohn’s disease; or irritable bowel syndrome) that might, in the Investigator’s opinion, interfere with assessment of symptoms of abdominal pain, diarrhoea, or other components of CeD. 7. Any other known symptomatic food allergy (e.g., tree nuts, etc.) or intolerance (e.g., lactose intolerance, etc.) that, in the opinion of the Investigator, might interfere with the conduct of the study or result in anaphylaxis. 8. History of a severe reaction to wheat or gluten exposure (anaphylaxis, hospitalization, prolonged moderate or severe symptoms greater than 3 days after a single exposure). 9. Participant not a good candidate or is at increased risk to undergo two EGDs with associated biopsies during the course of the study, as assessed by the Investigator. 10. Severe infection within the three months prior to Day 1. 11. Positive for hepatitis B surface antigen (HbsAg), anti-hepatitis C virus (HCV) antibodies or anti-human immunodeficiency virus (HIV) 1 and 2 antibodies at Screening. 12. Received a live vaccine within 4 weeks of Screening. 13. Use of systemic immune suppressants (including corticosteroids) within 3 months or 5 half-lives, whichever is longer, prior to Day 1. Inhaled corticosteroids for respiratory diseases such as asthma. and topical corticosteroids are permitted. 14. Use of oral pharmaceutical presentations (e.g., capsules, powders) of probiotic or prebiotic supplements less than or equal to 7 days prior to Day 1 (foods such as yogurt or kefir are acceptable). 15. History or presence of any form of cancer within the 5 years prior to screening, with the exception of excised basal cell or squamous cell carcinoma of the skin, or carcinoma in situ such as cervical or breast carcinoma that has been excised or resected completely and is without evidence of local recurrence or metastasis. 16. Must not have the following laboratory criteria during Screening: a. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 2.5 x the upper limit of normal. b. Total bilirubin greater than 1.5x the upper limit of normal (ULN). Participants with a bilirubin greater than 2x ULN that have a documented diagnosis of Gilbert’s syndrome may be enrolled at the Investigator’s discretion. c. Serum creatinine greater than 2.0 mg/dL or creatinine clearance less than 60 m L/ min measured or calculated by Cockroft-Gault equation. d. Screening neutrophil count less than 3.5 x 109/L. e. Screening platelet count less than 125 x 109/L. f. Screening haemoglobin (Hgb) less than 10.0 g/dL. g. Glycosylated haemoglobin (HbA1C) greater than 7% (greater than 53 mmol/mol) in participants with Type I or Type II Diabetes Mellitus. 17. History or presence of any medical condition (acute or chronic illness) that is uncontrolled or, in the opinion of the Investigator, could jeopardize or would compromise the participant’s ability to safely participate in this study such as but not limited to: a. Cardiovascular disease (e.g., uncontrolled hypertension defined as office systolic blood pressure [BP] equal to or greater than 180 mmHg or office diastolic BP equal or greater than 110 mm/Hg, unstable angina, congestive heart failure worse than NYHA Class II, coronary angioplasty or myocardial infarction within the last 6 months, uncontrolled atrial or ventricular cardiac arrhythmias, clinically significant pleural or pericardial effusion or ascites); b. Hepatic, renal (e.g. impaired renal function), pulmonary (e.g. severe chronic pulmonary disease); haematological (e.g., presence or history of any significant haemorrhage, thromboembolic diseases or diatheses such as hypercoagulability, platelet disorder, or erythrocytosis), gastrointestinal, endocrine (e.g. poorly controlled diabetes mellitus or thyroid disease), immunologic, dermatological, neurological, metabolic, psychological, musculoskeletal disease, significant allergies (except for untreated, asymptomatic seasonal allergies at the time of dosing), immunosuppressive conditions or medications, recent or recurrent infections, or any other clinically significant disease, as assessed by the Investigator. 18. Type I Diabetes Mellitus 19. Any history of alcohol abuse or current average intake of greater than 14 units of alcohol per week for women and greater than 21 units of alcohol per week for men (1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine, or 35 mL of spirits). 20. Drug (including cannabis products) as defined by local guidance and / or positive drug screen (cannabinoids, amphetamines, opiates, methadone, cocaine, benzodiazepines, barbiturates, and tricyclic antidepressants) at Screening. Repeats are allowed at the Investigator’s discretion if there is reason to warrant a repeat. 21. Donation or loss of more than 100 mL of blood or blood products within 60 days of screening, or plasma donations in the last 30 days prior to screening. 22. Treatment with any other investigational agent, device, or procedure, within 30 days (or 5 half-lives, whichever is greater) of Day 1. 23. Participation in an oral gluten challenge within 6 months prior to Day 1. 24. Any condition, laboratory abnormality, social circumstance or other reason that, in the investigator’s opinion, could adversely affect the safety of the participant, impair the assessment of study results, or preclude compliance with the study. 25. Unwilling to comply with study procedures including follow-up as specified by the protocol or unwilling to cooperate fully with the Principal Investigator. 26. Known allergies, hypersensitivity, or intolerance to any of the investigational product (including placebo) or excipients (excluding gluten).
Outcome results
None listed