None listed
Conditions
Brief summary
The purpose of this research study is to investigate how safe GIM-407 is when it is administered to adult participants with Coeliac Disease and how this investigational treatment is absorbed and processed by the human body. This study will also look to see if any indicators of the disease are affected by GIM-407. Participants will receive either GIM-407 or a placebo, and be asked to drink a slurry containing a measured amount of gluten each day for several weeks (this is called a 'gluten challenge'), under close medical supervision. The gluten challenge is done to monitor how their body responds to gluten while they are receiving the study treatment.
Interventions
This is a randomized, double-blind, placebo-controlled Phase 2a trial evaluating the safety, tolerability, immune response, and preliminary efficacy of GIM-407 in adults with confirmed coeliac disease by documented duodenal villous atrophy. All participants will receive a standardized daily gluten challenge while taking either GIM-407 or placebo for 6 weeks.
A total of approximately 20 participants are planned to be randomized 3:2 into two cohorts:
Cohort 1: GIM-407, 120 mg twice daily, plus gl
This is a randomized, double-blind, placebo-controlled Phase 2a trial evaluating the safety, tolerability, immune response, and preliminary efficacy of GIM-407 in adults with confirmed coeliac disease by documented duodenal villous atrophy. All participants will receive a standardized daily gluten challenge while taking either GIM-407 or placebo for 6 weeks. A total of approximately 20 participants are planned to be randomized 3:2 into two cohorts: Cohort 1: GIM-407, 120 mg twice daily, plus gluten challenge (n = 12) Cohort 2: Matching placebo twice daily, plus gluten challenge (n = 8) To enable assessment of treatment effect both in the absence and presence of gluten antigen exposure, participants will begin study treatment (GIM-407 or placebo) in the morning of Day 1 (capsules to be taken with meals), with gluten challenge commencing on Day 4. Treatment and the daily gluten challenge will finish on Day 42. Participants will receive the investigational product (GIM-407 capsules or placebo capsules) in the morning and evening, with the morning dose followed by the gluten challenge. Gluten challenge will follow a titration schedule starting with 1 g on Day 4, 2 g on Day 5, and 3 g daily from Day 6 through Day 42. Adherence will be monitored using a subject diary (date/time of each gluten and IP ingestion), weekly in-clinic or telehealth visits to check compliance, regular staff reminders with documentation of re-education, comprehensive dispensation records, and tracking of used/unused gluten packaging returned to site.
Sponsors
Georgiamune Australia Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
• Have a body mass index (BMI) of 18 to 32 kg/m2 (inclusive). • Participants who have adequate hematologic and biological function confirmed by the following lab values at Screening: a. Hemoglobin greater than or equal to 10g/dL b. Platelet Count greater than or equal to 125/L c. Total White Blood Cell Count greater than 3500 cells/mm3 d. AST and ALT less than 2 x upper limit of normal e. eGFR greater than 60ml/min/1.73 m2 based on the Cockcroft-Gault equation • Participants assigned female at birth are eligible to participate if they are not pregnant, not breastfeeding, and at least ONE of the following conditions applies: a. Are a participant of nonchildbearing potential or are a participant of childbearing potential (POCBP) and agree to use a highly effective method of contraception consistently and correctly and have their partner use a barrier method starting from time of Screening until at least 30 days after the last dose of IP. b. Participants assigned male at birth who are sexually active with a female partner of childbearing potential are eligible to participate if they agree to use a condom and have their partner use a highly effective method of contraception from Day 1 until at least 30 days after the last dose of IP. c. Participants must refrain from donating eggs (ova, oocytes) or sperm from Day 1 until at least 90 days after receiving the last dose of the IP. • Documented duodenal villous atrophy in the past when coeliac disease was diagnosed and report adhering to a gluten-free diet for at least 12 months. • A positive Novoleukin-C test • Have a normal IgA anti-tissue transglutaminase or anti-DPG • Are willing to undergo 2 upper gastrointestinal endoscopies required in this study • Willingness to consume a defined amount of gluten for 6 weeks • Are available for weekly telehealth or on-site consultations for the 6-week treatment period
Exclusion criteria
• Has an acute or chronic medical condition that, in the opinion of the Investigator, would render the study procedures unsafe for the participant or may confound the results of the study. • History or presence of any disease that affects IP absorption, distribution, metabolism, or excretion as judged by the Investigator (eg, gastrointestinal dysfunction, peptic ulcer, gastrointestinal surgery, cholecystectomy, etc). a) EXCEPTION: Previous/history of appendectomy is not exclusionary. • Signs of any current active infections, including localized infections, or any recent history of active infections, cough, or fever within 1 week prior to IP administration or any history of recurrent or chronic infections. • Participant has a diagnosis of Refractory Coeliac Disease • Participant has a diagnosis or suspicion of other conditions that may potentially be mis-diagnosed as CeD • Participant has a history of findings of or screening laboratory findings indicative of selective IgA deficiency. • Presence of poorly controlled insulin treated diabetes (T1D or T2D) or clinically significant disease that, in the opinion of the investigator, may put the participant at risk in the study, or influence the results or the participant’s ability to participate in the study. • Known history of significant multiple and/or severe allergies (eg, food, drug, or latex allergy), wheat allergy, or has had an anaphylactic reaction or significant intolerability (ie, systemic allergic reaction) to prescription or nonprescription drugs or food. • History of or current invasive malignancy including hematological malignancies. Participants with a history of basal cell or squamous cell carcinoma or other carcinomas in situ that has been treated with no evidence of recurrence within 1 year prior to Screening will be allowed for inclusion, as judged by the Investigator. • Family history of sudden death or of congenital prolongation of the QT interval corrected for heart rate (QTc) or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval. • Tested positive during the urine drug screen at Screening. a) NOTE: One repeat screen is allowed at the discretion of the Investigator. • Medically uncontrolled hypertension (e.g. Systolic BP >180 or Diastolic BP>110), NYHA Class III or IV cardiac disease, myocardial infarction within prior 6 months, unstable angina pectoris, unstable arrhythmias, or any cardiovascular abnormalities in the investigator’s opinion which would make the subject unsuitable for study participation. • QTcF >450 msec for male participants and >470 msec for female participants per ECG at Screening or on Day–1. • History of significant drug or alcohol abuse during the year prior to study screening as obtained by medical record and/or subject report. • Donated blood (including blood products) or experienced significant loss of blood =450 mL within 30 days prior to Screening, or donated plasma within 7 days of Screening. • Use of any enzyme-inducing, or enzyme-inhibiting drugs (eg. strong CYP450 inducers or inhibitors), biologic drugs, or any drug known to have a well-defined potential for hepatotoxicity (eg, isoniazide, nimesulide, ketoconazole) within 3 months or 5 half-lives of the drug (whichever is longer) prior to first dose of the IP, or their planned use during the study period. • Use of systemic immune suppressants, including systemic steroids ( >10mg prednisone equivalent) within 3 months or 5 half-lives, whichever is longer prior to first dose of the IP, or their planned use during the study period. • Receipt of an investigational drug within 30 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of the IP. • Have received any live vaccines (bacterial or viral) within 30 days prior to the first dose of IP or intend to receive a live vaccine during the study period. EXCEPTIONS: Vaccines allowed by the protocol include inactivated flu and COVID-19 vaccines in all participants. The recommended time intervals for administration of these vaccines are at least 7 days before the first dose of IP or 7 days after the last dose of IP. • Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (drug, vaccine, or invasive medical device). • Pregnant or breastfeeding female participant or who is planning to become pregnant or planning to discontinue contraceptive precautions.
Outcome results
None listed