Celiac Disease
Conditions
Keywords
Drug Therapy
Brief summary
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.
Detailed description
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.
Interventions
DRUGTAK-062
TAK-062 tablets.
DIETARY_SUPPLEMENTSimulated Inadvertent Gluten Exposure (SIGE) Gluten-Bar
SIGE gluten bars.
DRUGTAK-062 Placebo
TAK-062 placebo-matching tablets.
DIETARY_SUPPLEMENTSimulated Inadvertent Gluten Exposure (SIGE) Gluten-free Bar
SIGE gluten-free bars.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Weekly Celiac Disease Symptom Diary (CDSD) Gastrointestinal (GI) Symptom Severity Score From Baseline to Week 12 | Baseline (Week -1) to Week 12 | CDSD GI symptom severity score is an average of the daily GI symptom severity scores during the week. The daily GI symptom severity score is the average of the severity score for diarrhea, abdominal pain, bloating and nausea, ranging from 0 to 4. Symptom severity is evaluated using 5-point Likert-type scales (none, mild, moderate, severe, and very severe). Higher scores indicate more severe symptoms. Results are reported as least squares (LS) mean change from baseline at Week 12, determined using a mixed-effect model for repeated measures (MMRM). A negative change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Villous Height to Crypt Depth Ratio (Vh:Cd) From Baseline to Week 24 | Baseline (Week -4, Run-in Period) to Week 24 | The Vh:Cd ratio represents mucosal architectural changes and a lower Vh:Cd ratio indicates more severe intestinal injury characterized by a flattening of the mucosa. Results are reported as least squares (LS) mean change from baseline at Week 24, determined using an analysis of covariance (ANCOVA) model. A negative change from baseline indicates worsening disease. |
| Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE), Serious Treatment-Emergent Adverse Events (Serious TEAEs) and Treatment-Related TEAEs | Up to Week 28 | Adverse event(AE)=any untoward medical occurrence in clinical investigation participant administered a drug; it does not necessarily have to have causal relationship with this treatment.AE can therefore be any unfavorable&unintended sign(e.g.,clinically significant abnormal laboratory value, electrocardiogram\[ECG\] value,or vital sign measurement),symptom,or disease temporally associated with use of drug whether or not it is considered related to drug.TEAE=new onset or worsening AEs after first dose of study treatment regardless of relationship to study drug.SAE=any untoward medical occurrence at any dose that results in death,is life threatening,requires inpatient hospitalization/prolongation of existing hospitalization,results in persistent/significant disability/incapacity,leads to a congenital anomaly/birth defect/is important medical event. TEAEs considered related to study drug as assessed by investigator were reported.Percentages were rounded off to nearest single decimal place. |
| Number of Participants With Positive Antidrug Antibodies (ADA) in Serum for TAK-062 | Up to Week 28 | A positive ADA participant was defined as a participant who had at least 1 positive ADA result during the study and was further categorized as: Transiently positive- defined as participants with confirmed positive ADA in at least 1 sample and no consecutive samples; Persistently positive- defined as participants with confirmed positive ADA in 2 or more consecutive positive ADA samples. |
Countries
Belgium, Canada, France, Italy, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at various investigative sites globally from 30 June 2022 to 06 November 2024.
Pre-assignment details
Participants with a diagnosis of celiac disease were enrolled and randomly assigned to receive either TAK-062 Placebo + simulated inadvertent gluten exposure (SIGE) Gluten-Bar or pre-determined amount of TAK-062 + SIGE Gluten-Bar in Cohort 1. 153 participants were enrolled in the trial but 1 participant out of 153 was randomized but not treated. Cohort 2 of the trial was not initiated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + SIGE Gluten-Bar Participants received TAK-062 placebo-matching tablets and SIGE gluten bar, orally for up to 24 weeks. | 76 |
| TAK-062 + SIGE Gluten-Bar Participants received pre-determined amount of TAK-062 tablets and SIGE gluten bar, orally, for up to 24 weeks. | 77 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 7 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Randomized in Error & Not Treated | 0 | 1 |
| Overall Study | Reason Not Specified | 1 | 0 |
| Overall Study | Withdrawal by Subject | 13 | 17 |
Baseline characteristics
| Characteristic | TAK-062 + SIGE Gluten-Bar | Total | Placebo + SIGE Gluten-Bar |
|---|---|---|---|
| Age, Continuous | 46.8 years STANDARD_DEVIATION 12.95 | 46 years STANDARD_DEVIATION 14.16 | 45.2 years STANDARD_DEVIATION 15.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 12 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 70 Participants | 139 Participants | 69 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) White | 71 Participants | 145 Participants | 74 Participants |
| Sex: Female, Male Female | 58 Participants | 115 Participants | 57 Participants |
| Sex: Female, Male Male | 19 Participants | 38 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 76 | 0 / 76 |
| other Total, other adverse events | 13 / 76 | 24 / 76 |
| serious Total, serious adverse events | 4 / 76 | 1 / 76 |
Outcome results
Primary
Change in Weekly Celiac Disease Symptom Diary (CDSD) Gastrointestinal (GI) Symptom Severity Score From Baseline to Week 12
CDSD GI symptom severity score is an average of the daily GI symptom severity scores during the week. The daily GI symptom severity score is the average of the severity score for diarrhea, abdominal pain, bloating and nausea, ranging from 0 to 4. Symptom severity is evaluated using 5-point Likert-type scales (none, mild, moderate, severe, and very severe). Higher scores indicate more severe symptoms. Results are reported as least squares (LS) mean change from baseline at Week 12, determined using a mixed-effect model for repeated measures (MMRM). A negative change from baseline indicates improvement.
Time frame: Baseline (Week -1) to Week 12
Population: The FAS-SIGE included all randomized participants who were randomized to receive gluten-containing SIGE. Overall number of participants analyzed is the number of participants with data available for analysis. Cohort 2 of the trial was not initiated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + SIGE Gluten-Bar | Change in Weekly Celiac Disease Symptom Diary (CDSD) Gastrointestinal (GI) Symptom Severity Score From Baseline to Week 12 | -0.128 score on a scale | Standard Error 0.083 |
| TAK-062 + SIGE Gluten-Bar | Change in Weekly Celiac Disease Symptom Diary (CDSD) Gastrointestinal (GI) Symptom Severity Score From Baseline to Week 12 | -0.111 score on a scale | Standard Error 0.082 |
p-value: =0.84795% CI: [-0.162, 0.197]MMRM
Secondary
Change in Villous Height to Crypt Depth Ratio (Vh:Cd) From Baseline to Week 24
The Vh:Cd ratio represents mucosal architectural changes and a lower Vh:Cd ratio indicates more severe intestinal injury characterized by a flattening of the mucosa. Results are reported as least squares (LS) mean change from baseline at Week 24, determined using an analysis of covariance (ANCOVA) model. A negative change from baseline indicates worsening disease.
Time frame: Baseline (Week -4, Run-in Period) to Week 24
Population: The FAS-SIGE included all randomized participants who were randomized to receive gluten-containing SIGE. Overall number of participants analyzed is the number of participants with data available for analysis. Cohort 2 of the trial was not initiated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + SIGE Gluten-Bar | Change in Villous Height to Crypt Depth Ratio (Vh:Cd) From Baseline to Week 24 | -0.006 unitless ratio | Standard Error 0.1 |
| TAK-062 + SIGE Gluten-Bar | Change in Villous Height to Crypt Depth Ratio (Vh:Cd) From Baseline to Week 24 | -0.338 unitless ratio | Standard Error 0.099 |
p-value: <0.00195% CI: [-0.481, -0.181]ANCOVA
Secondary
Number of Participants With Positive Antidrug Antibodies (ADA) in Serum for TAK-062
A positive ADA participant was defined as a participant who had at least 1 positive ADA result during the study and was further categorized as: Transiently positive- defined as participants with confirmed positive ADA in at least 1 sample and no consecutive samples; Persistently positive- defined as participants with confirmed positive ADA in 2 or more consecutive positive ADA samples.
Time frame: Up to Week 28
Population: Immunogenicity Analysis Set included all randomized participants who received any TAK-062 and had the baseline and at least 1 postbaseline immunogenicity sample assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo + SIGE Gluten-Bar | Number of Participants With Positive Antidrug Antibodies (ADA) in Serum for TAK-062 | At least 1 Positive ADA | 27 Participants |
| Placebo + SIGE Gluten-Bar | Number of Participants With Positive Antidrug Antibodies (ADA) in Serum for TAK-062 | Transiently Positive | 19 Participants |
| Placebo + SIGE Gluten-Bar | Number of Participants With Positive Antidrug Antibodies (ADA) in Serum for TAK-062 | Persistently Positive | 8 Participants |
| TAK-062 + SIGE Gluten-Bar | Number of Participants With Positive Antidrug Antibodies (ADA) in Serum for TAK-062 | At least 1 Positive ADA | 67 Participants |
| TAK-062 + SIGE Gluten-Bar | Number of Participants With Positive Antidrug Antibodies (ADA) in Serum for TAK-062 | Transiently Positive | 8 Participants |
| TAK-062 + SIGE Gluten-Bar | Number of Participants With Positive Antidrug Antibodies (ADA) in Serum for TAK-062 | Persistently Positive | 59 Participants |
Secondary
Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE), Serious Treatment-Emergent Adverse Events (Serious TEAEs) and Treatment-Related TEAEs
Adverse event(AE)=any untoward medical occurrence in clinical investigation participant administered a drug; it does not necessarily have to have causal relationship with this treatment.AE can therefore be any unfavorable&unintended sign(e.g.,clinically significant abnormal laboratory value, electrocardiogram\[ECG\] value,or vital sign measurement),symptom,or disease temporally associated with use of drug whether or not it is considered related to drug.TEAE=new onset or worsening AEs after first dose of study treatment regardless of relationship to study drug.SAE=any untoward medical occurrence at any dose that results in death,is life threatening,requires inpatient hospitalization/prolongation of existing hospitalization,results in persistent/significant disability/incapacity,leads to a congenital anomaly/birth defect/is important medical event. TEAEs considered related to study drug as assessed by investigator were reported.Percentages were rounded off to nearest single decimal place.
Time frame: Up to Week 28
Population: The Safety Analysis Set (SAF) included all randomized participants who received at least 1 dose of study drug. Cohort 2 of the trial was not initiated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + SIGE Gluten-Bar | Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE), Serious Treatment-Emergent Adverse Events (Serious TEAEs) and Treatment-Related TEAEs | TEAEs | 64.5 percentage of participants |
| Placebo + SIGE Gluten-Bar | Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE), Serious Treatment-Emergent Adverse Events (Serious TEAEs) and Treatment-Related TEAEs | Serious TEAEs | 5.3 percentage of participants |
| Placebo + SIGE Gluten-Bar | Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE), Serious Treatment-Emergent Adverse Events (Serious TEAEs) and Treatment-Related TEAEs | Treatment-Related TEAEs | 5.3 percentage of participants |
| TAK-062 + SIGE Gluten-Bar | Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE), Serious Treatment-Emergent Adverse Events (Serious TEAEs) and Treatment-Related TEAEs | TEAEs | 73.7 percentage of participants |
| TAK-062 + SIGE Gluten-Bar | Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE), Serious Treatment-Emergent Adverse Events (Serious TEAEs) and Treatment-Related TEAEs | Serious TEAEs | 1.3 percentage of participants |
| TAK-062 + SIGE Gluten-Bar | Percentage of Participants Experiencing at Least One Treatment-Emergent Adverse Event (TEAE), Serious Treatment-Emergent Adverse Events (Serious TEAEs) and Treatment-Related TEAEs | Treatment-Related TEAEs | 13.2 percentage of participants |