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Trial registered on ANZCTR


Registration number
ACTRN12624000974505
Ethics application status
Approved
Date submitted
25/07/2024
Date registered
12/08/2024
Date last updated
12/08/2024
Date data sharing statement initially provided
12/08/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of FB102 after multiple dose administration in participants with celiac disease.
Scientific title
A multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of FB102 after multiple dose administration in participants with celiac disease.
Secondary ID [1] 312536 0
FB102-101
Universal Trial Number (UTN)
Trial acronym
Linked study record
This is a patient extension study of ACTRN12623001199606 to evaluate FB102 in Celiac disease patients.

Health condition
Health condition(s) or problem(s) studied:
autoimmune and inflammatory diseases 334408 0
Coeliac disease 334639 0
Condition category
Condition code
Inflammatory and Immune System 331046 331046 0 0
Autoimmune diseases
Oral and Gastrointestinal 331221 331221 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.

Adherence to study interventions will be managed via recording in appropriate drug accountability records.
Intervention code [1] 329049 0
Treatment: Drugs
Comparator / control treatment
Placebo will be formulated the same as the Investigational Product (IP) in 25mM L-Histidine, 9% sucrose, 0.1% polysorbate 80 without the antibody.
Control group
Placebo

Outcomes
Primary outcome [1] 338811 0
To assess the safety and tolerability of multiple IV doses of FB102 in participants with celiac disease.
Timepoint [1] 338811 0
Adverse events - will be graded using the most current version of the Common Terminology Criteria for Adverse Events (CTCAE) (Version 5) and assessed continuously as they are reported or observed and reviewed daily through to end of study.

Electrocardiogram (ECG) - single 12-lead ECG recordings will be obtained at screening, Days 1, 8, 15, 22, 32 and Day 70 post commencement of intervention.

Vital signs - Blood pressure and heart rate is measured using sphygmomanometer, respiratory rate by manual breath count and temperature by thermometer. Measured at screening and Day 1, 8, 15, 22, 32 and Day 70 post commencement of intervention.

Clinical laboratory evaluations (haematology, serum chemistry and urinalysis) - blood and urine samples will be collected from screening, pre-dose on Days 1, 8, 15, 22, 32, and Day 70 post commencement of intervention.

Physical examinations will be conducted at screening and then symptom-directed examinations conducted as required daily on Days 1, 8, 15, 22, 32, and Day 70 post commencement of intervention.
Secondary outcome [1] 437558 0
To characterize the PK of multiple IV doses of FB102 in participants with celiac disease.
Timepoint [1] 437558 0
Blood serum samples will be collected Day 1 pre-dose and 5 min, 1 hr and 4 hrs post-dose, pre-dose Day 8 and 15, Day 22 pre-dose and 5 min, 1 hr and 4 hrs post-dose. Days 32 and 70 at any time during the visit.
Secondary outcome [2] 437559 0
To evaluate the immunogenicity of FB102 following multiple IV doses of FB102 in participants with celiac disease.
Timepoint [2] 437559 0
Blood serum samples will be collected pre-dose Day 1 and 15, then at any time during visits on Day 32 and Day 70.
Secondary outcome [3] 437560 0
Exploratory: To assess the effect of FB102 on attenuation of the effects of an oral gluten challenge in adults with celiac disease at Day 32.
Timepoint [3] 437560 0
Biopsy tissue samples will be collected at screening after other initial screening activities are performed and must be at least 10 days prior to Day 1 and up to 5 days post Day 32
Secondary outcome [4] 437561 0
Exploratory: To assess the effects of FB102 on a biomarker of disease activity.
Timepoint [4] 437561 0

Blood samples to measure IL-2 will be collected on Day 16 pre consumption of the gluten challenge and 2, 4 and 8 hours post consumption of gluten challenge, and on Day 22 pre-dose which will also be prior to taking the required gluten for the day
Secondary outcome [5] 437562 0
Exploratory: To assess the effects of FB102 on celiac disease signs and symptoms before and during an oral gluten challenge as documented in the celiac disease Symptom Diary.
Timepoint [5] 437562 0
Participants will be provided with a celiac disease symptom diary to record their symptoms at screening and Days 1, through 31, Day 32 and Day 70

Eligibility
Key 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).
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomized 3:1 to receive FB102 or placebo. The unblinded CRO biostatistician will prepare the study randomization schedule and treatment assignment list and distribute to the site’s unblinded pharmacy team to be kept in an area with restricted access per institutional guidelines. Emergency unblinding codes will be stored securely by the unblinded pharmacy at the research facility. The randomization schedule and corresponding treatment assignment will be generated by the CRO’s biostatistics department per CRO standard operating procedures (SOPs).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Participant disposition and demographic characteristics will be summarized using descriptive statistic for the safety Population. All participants administered any amount of study drug will be included in the safety analyses.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
26/08/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
32
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 26804 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [2] 26805 0
Sunshine Coast University Private Hospital - Birtinya
Recruitment hospital [3] 26806 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 26807 0
The Wesley Hospital - Auchenflower
Recruitment postcode(s) [1] 42855 0
2560 - Campbelltown
Recruitment postcode(s) [2] 42856 0
4575 - Birtinya
Recruitment postcode(s) [3] 42857 0
5000 - Adelaide
Recruitment postcode(s) [4] 42858 0
4066 - Auchenflower
Recruitment outside Australia
Country [1] 26429 0
New Zealand
State/province [1] 26429 0

Funding & Sponsors
Funding source category [1] 316960 0
Commercial sector/Industry
Name [1] 316960 0
Forte Biosciences, Australia Pty Ltd
Country [1] 316960 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Forte Biosciences, Australia Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 319218 0
Commercial sector/Industry
Name [1] 319218 0
Avance Clinical Pty Ltd
Address [1] 319218 0
Country [1] 319218 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315715 0
Bellberry Human Research Ethics Committee A
Ethics committee address [1] 315715 0
https://bellberry.com.au/
Ethics committee country [1] 315715 0
Australia
Date submitted for ethics approval [1] 315715 0
26/07/2024
Approval date [1] 315715 0
Ethics approval number [1] 315715 0
Ethics committee name [2] 315724 0
Central Adelaide Local Health Network HREC
Ethics committee address [2] 315724 0
https://www.rah.sa.gov.au/research/for-researchers/central-adelaide-local-health-network-human-research-ethics-committee
Ethics committee country [2] 315724 0
Australia
Date submitted for ethics approval [2] 315724 0
16/07/2024
Approval date [2] 315724 0
Ethics approval number [2] 315724 0
Ethics committee name [3] 315725 0
Central Health and Disability Ethics Committee
Ethics committee address [3] 315725 0
https://ethics.health.govt.nz/about/central-health-and-disability-ethics-committee/
Ethics committee country [3] 315725 0
New Zealand
Date submitted for ethics approval [3] 315725 0
13/06/2024
Approval date [3] 315725 0
19/07/2024
Ethics approval number [3] 315725 0

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 135582 0
Dr Vincent Ho
Address 135582 0
Level 10, Gastroenterology Clinical Trials Unit, Building A, Campbelltown Hospital, Therry Road, Campbelltown, NSW 2560
Country 135582 0
Australia
Phone 135582 0
+61 02 46344001
Fax 135582 0
Email 135582 0
[email protected]
Contact person for public queries
Name 135583 0
Vincent Ho
Address 135583 0
Level 10, Gastroenterology Clinical Trials Unit, Building A, Campbelltown Hospital, Therry Road, Campbelltown, NSW 2560
Country 135583 0
Australia
Phone 135583 0
+61 02 46344001
Fax 135583 0
Email 135583 0
[email protected]
Contact person for scientific queries
Name 135584 0
Vincent Ho
Address 135584 0
Level 10, Gastroenterology Clinical Trials Unit, Building A, Campbelltown Hospital, Therry Road, Campbelltown, NSW 2560
Country 135584 0
Australia
Phone 135584 0
+61 02 46344001
Fax 135584 0
Email 135584 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.