CLINICAL TRIAL / NCT05353985
A Study of TAK-062 in Treatment of Active Celiac Disease in Participants Attempting a Gluten-Free Diet
- Interventional
- Recruiting
- NCT05353985
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of TAK-062 for the Treatment of Active Celiac Disease in Subjects Attempting a Gluten-Free Diet
The main aim is to see how TAK-062 works to reduce celiac-related symptoms and improve small intestinal damage due to gluten exposure, in participants with celiac disease (CeD) attempting to maintain a gluten-free diet (GFD) in treated participants versus placebo controls.
The drug being tested in this study is called TAK-062. TAK-062 is designed to break down
gluten in the stomach and is being tested to treat people who have active CeD, attempting
to maintain a GFD.
The study will enroll approximately 357 patients. Participants will be randomly assigned
(by chance, like flipping a coin) to one of the two treatment groups in Cohort 1:
1. Cohort 1 (Age 18 and older): TAK-062 Placebo + SIGE Gluten-Bar
2. Cohort 1 (Age 18 and older): TAK-062 Dose 1 + SIGE Gluten-Bar
After the interim analysis (IA), Cohort 1 data will be reviewed by an external
independent data monitoring committee (DMC), and based on the Sponsor's decision,
adolescent participants will be enrolled in Cohort 2. Adult participants, 18 years and
older will be enrolled into Cohort 2 once Cohort 1 has completed enrolment. Adult
participants will be randomly assigned to one of the five study drug and SIGE treatment
groups (Groups a-e), and approximately 21 adolescent participants will be enrolled and
randomly assigned to Groups d, e, and f (adolescents only). Adolescents in Cohort 2 will
receive only gluten-free SIGE bars.
1. Cohort 2 (Age 18 and older): TAK-062 Placebo + SIGE Gluten-Bar
2. Cohort 2 (Age 18 and older): TAK-062 Dose 2 + SIGE Gluten-Bar
3. Cohort 2 (Age 18 and older): TAK-062 Dose 3 + SIGE Gluten-Bar
4. Cohort 2 (Age 12 and older): TAK-062 Placebo + Gluten-free SIGE Bar
5. Cohort 2 (Age 12 and older): TAK-062 Dose 1 + Gluten-free SIGE Bar
6. Cohort 2 (Age 12-17): TAK-062 Dose 2 + Gluten-free SIGE Bar
This multi-center trial will be conducted in the United States (US), Canada, United
Kingdom and the European Union. The overall time to participate in this study is
approximately 36 weeks.
Gender
All
Age Group
12 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
1. Has an adequate comprehension of a gluten-free diet (GFD) assessed by the site
investigator after review of responses to a knowledge test. The final determination
of a participant's adequate comprehension of a GFD is at the discretion of the
investigator.
2. Has at least 1 CeD-related GI symptom of moderate or greater severity, as measured
by the CDSD, on at least 3 days out of any consecutive 7-day period during the
screening period (Week -8 visit until Week -4 visit), felt by the investigator to be
related to gluten exposure. The CeD-related symptom(s) may vary day by day as long
as the severity of at least 1 symptom is moderate or greater. The participants must
meet symptom criteria to undergo esophagogastroduodenoscopy (EGD)/video capsule
endoscopy (VCE).
3. Has been attempting to maintain a GFD for at least 12 months as self-reported by the
participant.
4. Has small intestinal villous atrophy on duodenal biopsy defined as Vh:Cd <2.5 at
Week -4.
5. The participant is human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8 positive.
6. The participant is in a good general state of health according to clinical history
and physical examination, in the opinion of the investigator.
7. Have a body mass index (BMI) between 16 and 45 kilogram per meter square (kg/m^2),
inclusive.
Note: Individuals with BMI of 40 to 45 should be discussed with the medical monitor
and confirmed to be appropriate for endoscopy according to local site guidelines.
8. The participant is willing and able to continue any current dietary and/or medical
regimens (including gastric acid suppression) in effect at the first visit (Visit
1).
There should be no changes to diet, medications (prescription or over-the-counter) or
supplements during study participation.
Exclusion Criteria:
1. Has the presence of other inflammatory GI disorders or systemic autoimmune diseases
that either have the potential to cause persistent GI symptoms similar to CeD or are
not well controlled without the use of excluded medication.
- Examples of conditions that are exclusionary include inflammatory bowel
disease, eosinophilic esophagitis, gastroenteritis or colitis, microscopic
colitis diagnosed at screening or requiring treatment in the 6 months before
screening.
- Examples of conditions that may be permissible after discussion with the
medical monitor include systemic autoimmune disease such as scleroderma,
psoriatic or rheumatoid arthritis, or lupus that is stable and without GI
involvement; well controlled autoimmune thyroid disease; well-controlled type 1
diabetes; or proton pump inhibitor (PPI) responsive eosinophilic esophagitis in
symptomatic and histologically confirmed remission.
2. Has ongoing systemic immunosuppressant, systemic corticosteroid treatment excluding
medication given for the endoscopies, or treatment with systemic immunosuppressants
or systemic corticosteroids in the 12 weeks before Screening.
• The participant is receiving immunosuppressive doses of corticosteroids: 3 mg per
day or more of budesonide for more than 3 consecutive days within 3 months before
Screening, more than 20 mg of prednisone given daily or on alternative days for 2
weeks or more within 90 days before the first dose, any dose of oral or intravenous
(IV) corticosteroids within 30 days of the first dose, or high-dose inhaled
corticosteroids (>960 micrograms per day [μg/day] of beclomethasone dipropionate or
equivalent), or other systemic immunosuppressive agents.
3. Has ongoing use of over-the-counter digestive enzymes or digestive supplements,
other than lactase, including those for gluten digestion. Probiotics are allowable
if they were started before Screening and not discontinued or changed in dose or
type during the study.
4. Has completed the CDSD on ≤75% of the evaluable days during the run-in period until
randomization.
5. Has active microscopic colitis requiring treatment in the 6 months before Screening.
• Microscopic colitis detected at screening if sigmoidoscopy is performed would
exclude the participant.
6. Has known or suspected type 2 refractory CeD or ulcerative jejunitis.
7. Has ongoing chronic use (defined as >7 days continuous use) of a nonsteroidal
anti-inflammatory drug aside from <100 mg aspirin, daily, for prophylactic use.
8. Has ongoing use, or use in the 3 months before screening, of medications known to
cause villous abnormalities (e.g., mycophenolate mofetil, angiotensin receptor
blockers, colchicine).
9. Has used treatments for GI symptoms including antiemetics, antidiarrheals,
antispasmodics, medical marijuana, (use of medical marijuana indicated for non-GI
conditions is not exclusionary) within 2 weeks of Screening and during the run-in
period. Participants on stable dose (i.e., more than 4 weeks) of an osmotic,
bulking-forming or emollient (surface active agent) laxative are eligible, provided
symptoms are considered not related to CeD in the opinion of the investigator.
10. Has a known or suspected severe enteric infection (viral, bacterial, or parasitic)
within 6 months before randomization. Severe enteric infection is defined as
requiring emergency room visit or hospitalization or treatment with antibiotics or
anti-infectives due to infection. Non enteric viral infections, either resolved or
well-controlled are not exclusionary.
11. Has a contraindication to endoscopy with duodenal biopsy.
--Contraindication to VCE (strictures, anastomoses, etc) is not an exclusion if the
participant is able to complete the other aspects of the study.
12. Has additional food allergies (tapioca syrup, oats, almonds, rice crisp, chocolate,
almond, butter, wheat gluten, cocoa butter, oat flour, glycerin, sunflower lecithin,
salt, and natural flavors) to nongluten ingredients in the SIGE bar study food or
significant symptoms upon ingestion of the gluten-free SIGE bar during screening.
13. Has a history of intolerance, hypersensitivity, or idiosyncratic reaction to an
aminoglycoside.
14. Has a known human immunodeficiency virus (HIV) infection or positive tests for
hepatitis B or C. The participant has a known clinically significant chronically
active hepatopathy of any origin, including cirrhosis, and participants with
persistent positive hepatitis B virus surface antigen and quantitative hepatitis B
virus polymerase chain reaction (PCR), or positive serology for hepatitis C virus
(HCV) and quantitative HCV PCR within 6 months before the screening visit.
15. Is positive for severe acute respiratory syndrome coronavirus 2 at the time of
screening and exhibits symptoms that, in the opinion of the investigator, may
interfere with study compliance, completion, or accurate assessment of study
outcomes or safety.
16. Has a known hypersensitivity reaction and/or allergy, including anaphylaxis, to
wheat and/or gluten.
17. Has known history of hypersensitivity, idiosyncratic reaction, or intolerance to any
ingredients or excipients in TAK-062 and/or placebo.
18. The participant has a current diagnosis of active malignancy or is receiving
treatment for active malignancy (hormone therapy alone is not exclusionary).
Participants with fully resected Stage 0 (carcinoma in situ) or Stage 1 tumor
without signs of recurrence may participate. All other individuals with malignancies
diagnosed in the 5 years prior to screening are excluded.
Region-specific Exclusion Criteria:
18. Participant enrolling in a study in France is not affiliated to a social security
scheme or a beneficiary of such a scheme.
19. Participant enrolling in a study in France is deprived of their liberty by a
judicial or administrative decision.