Celiac DiseasePhase 1NCT03486990

Study of the Safety, Tolerability and Pharmacokinetics of TIMP-GLIA in Subjects With Celiac Disease

A Phase 1 study testing TIMP-GLIA in people with Celiac Disease, run by Takeda at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Celiac Disease
What is being tested?: TIMP-GLIA
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 23 participants
Where: 4 sitesUnited States
Study dates: 23 Jan 2018to 22 Jul 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

The subject provides written informed consent and is willing and able to comply with study requirements.
At screening the subject has a minimum body mass index (BMI) of 16 kg/m2 and a minimum body weight of 33 kg up to a maximum body weight of 129 kg, inclusive. If subject is considered to be underweight or overweight/obese, the subject is otherwise healthy in the opinion of the investigator.
The subject has celiac disease characterized at Screening Visit by:
a history of biopsy-confirmed celiac disease; and
no known gluten exposure for at least 10 days; and
willingness to maintain a gluten-free diet for the duration of the study; and

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a negative or weak positive transglutaminase (tTG)-specific IgA titer if the subject has a normal total immunoglobulin A (IgA) titer or has a partial IgA deficiency OR
a negative or weak positive deamidated gliadin peptide (DGP)-specific immunoglobulin G (IgG) titer if the subject has IgA deficiency.
The male subject or female subject of childbearing potential will practice medically approved contraception during the study.

Who cannot join

The subject has a history of clinically confirmed immunoglobulin E-mediated reaction and/or anaphylaxis to wheat (i.e., "wheat allergy"), barley or rye.
The subject has a known history of hypersensitivity or allergies to TIMP-GLIA components OR any other known severe hypersensitivity or allergic reaction (resulted in hospitalization [initial or prolonged], congenital anomaly, or disability, or that required medical intervention to prevent permanent impairment or damage) to any other allergens (medications, food or environmental).
The subject has uncontrolled celiac disease and/or complications of celiac disease, or otherwise has experienced celiac symptomology within 10 days of screening, in the opinion of the investigator.
The subject has a history of, or has an active, significant, clinically relevant, comorbidity (including Type 1 and Type 2 diabetes mellitus and other autoimmune disorders, splenectomy) that, in the opinion of the investigator, would make the subject unsuitable for participation in the study and/or could adversely affect interpretation of the study results.
The subject has had significant changes to or anticipates changes to prescription or non-prescription medication used to manage an underlying comorbidity within 30 days prior to first dosing (Day 1).
The subject is currently taking or received systemic biologics 6 months prior to first dosing (Day 1).

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The subject has a compromised immune system, e.g.
known human immunodeficiency virus (HIV) infection or positive for HIV antibodies at Screening or
immunosuppressive medical treatment taken during the 2 months prior to first dosing (Day 1) or
immunosuppressive doses of corticosteroids (more than 20 mg of prednisone given daily for 2 weeks or more within 2 months prior to first dosing (Day 1), or any dose of corticosteroids within 30 days of first dosing (Day 1), or high dose inhaled corticosteroids [>960 µg/day of beclomethasone dipropionate or equivalent]) within 30 days of first dosing Day 1.
The subject has currently untreated or active gastrointestinal disease such as peptic ulcer disease, esophagitis (Los Angeles Classification ≥ Grade C), irritable bowel syndrome, inflammatory bowel disease, or microscopic colitis.
The subject has an active malignancy, or history of malignancy or chemotherapy, within the past 5 years other than history of localized or surgical removal of focal basal cell skin cancer, cervical cancer in situ treated successfully in the past by local treatment (including but not limited to cryotherapy or laser therapy) or by hysterectomy.
The subject has known liver disease or serology positive for hepatitis C infection; positive hepatitis B surface antigen (HBsAg) at Screening Visit.
The subject has a positive test result for drugs of abuse, cannabinoids, or alcohol at Screening Visit or at Check-in.
The subject has a history of any drug or alcohol abuse in the past 5 years or alcohol consumption habits that, in the opinion of the investigator, would interfere with the subject's ability to comply with the study requirements.
The subject has clinically significant laboratory test results (e.g., liver tests) or electrocardiogram (EGC) abnormalities (e.g., cardiac conduction abnormalities) at Screening
The subject received a live or inactive vaccine within 28 days prior or a subunit vaccine within 14 days prior to first dosing/Day 1 or the subject has a planned vaccination during the study.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

Mass General Hospital Translational and Clinical Research Centers
Boston, Massachusetts, 02114
Jacksonville Center For Clinical Research
Jacksonville, Florida, 32216
Mayo Gastroenterology Research Unit
Rochester, Minnesota, 55905
Prism Clinical Research
Saint Paul, Minnesota, 55114

Other trials in United States

About this study

Official title: A Phase 1, First-in-Human, 2-Part, Multicenter Dose Escalation and Repeat Dose Study of the Safety, Tolerability and Pharmacokinetics of TIMP-GLIA in Subjects With Celiac Disease

This study is to characterize the safety and tolerability of an investigational drug called TIMP-GLIA when either one or two intravenous doses are given to subjects with celiac disease. The way the body reacts to TIMP-GLIA is being checked by laboratory tests of the blood and urine, and study subject health will also be monitored by vital signs such as blood pressure, electrocardiogram (ECG), and physical examination.

Read the detailed description

This study is a 2-part, multicenter study. In Part A, eligible subjects will be enrolled into escalating dose cohorts (n = 2/cohort for 2 dose levels followed by n = 3/cohort for 4 dose levels). TIMP-GLIA will be administered as a single intravenous (IV) infusion on Day 1. A staggered dosing strategy will be used in Part A. Subjects will undergo medical observation in the clinic for at least 48 hours after dosing and participate in outpatient follow-up visits. Adverse events (AEs), vital signs, and electrocardiograms (ECGs) and laboratory data (serum chemistry, coagulation, hematology and urinalysis, cytokines) will be assessed by a Safety Committee before the next cohort will be dosed at a higher dose level.

After completion of Part A and confirmation by the Safety Committee to proceed, eligible subjects (n=3) will receive two IV infusions of TIMP-GLIA, 7 days apart, on Day 1 and on Day 8. Each subject in Part B will be observed in clinic for 48 hours after each dose and undergo similar testing and follow-up visits as in Part A.

The safety and pharmacokinetic profile of TIMP-GLIA will be characterized.

Conditions: Celiac Disease
Being tested: TIMP-GLIA
Keywords: safety, tolerability, pharmacokinetics, celiac, gliadin, gluten
Medical subject headings: Celiac Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TIMP-GLIADrug
Also called TAK-101
intravenous infusion.

Study groups in NCT03486990
Study group	Role	What they receive
Part A, Cohort 1: 0.1 mg/kg	Experimental	TIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1. Receives: Drug: TIMP-GLIA
Part A, Cohort 2: 0.5 mg/kg	Experimental	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1. Receives: Drug: TIMP-GLIA
Part A, Cohort 3: 1.0 mg/kg	Experimental	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1. Receives: Drug: TIMP-GLIA
Part A, Cohort 4: 2.0 mg/kg	Experimental	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1. Receives: Drug: TIMP-GLIA
Part A, Cohort 5: 4.0 mg/kg	Experimental	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1. Receives: Drug: TIMP-GLIA
Part A, Cohort 6: 8.0 mg/kg	Experimental	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1. Receives: Drug: TIMP-GLIA
Part B, Cohort 1: 2.0 mg/kg	Experimental	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8. Receives: Drug: TIMP-GLIA
Part B, Cohort 2: 4.0 mg/kg	Experimental	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8. Receives: Drug: TIMP-GLIA
Part B, Cohort 3: 8.0 mg/kg	Experimental	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8. Receives: Drug: TIMP-GLIA

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Measured: From Day 1 up to Day 180
Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events
AE Grades will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), version 4.0. Grade 1 scaled as Mild; Grade 2 scaled as Moderate; Grade 3 scaled as severe or medically significant but not immediately life-threatening; Grade 4 scaled as life-threatening consequences; and Grade 5 scaled as death related to AE. Drug-related adverse events are those that the investigator assessed as possibly or probably related to the study treatment.
Measured: From Day 1 up to Day 180
Number of Participants With Clinically Significant Physical Examination Findings
Measured: From Day 1 up to Day 60
Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings
Measured: From Day 1 up to Day 60
Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels
Measured: From Day 1 up to Day 60
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values
Measured: From Day 1 up to Day 60
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 3
Baseline is defined as Day 1 pre-dose.
Measured: Baseline (Day 1 pre-dose) and Day 3
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 7
Baseline is defined as Day 1 pre-dose.
Measured: Baseline (Day 1 pre-dose) and Day 7
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 8
Baseline is defined as Day 1 pre-dose.
Measured: Baseline (Day 1 pre-dose) and Day 8
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 10
Baseline is defined as Day 1 pre-dose.
Measured: Baseline (Day 1 pre-dose) and Day 10
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 14
Baseline is defined as Day 1 pre-dose.
Measured: Baseline (Day 1 pre-dose) and Day 14
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 38
Baseline is defined as Day 1 pre-dose.
Measured: Baseline (Day 1 pre-dose) and Day 38
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 60
Baseline is defined as Day 1 pre-dose.
Measured: Baseline (Day 1 pre-dose) and Day 60
Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1
Baseline was defined as Day 1 Pre-dose.
Measured: Baseline (Day 1 pre-dose) and 15 minutes (min) post-dose on Day 1
Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1
Baseline was defined as Day 1 Pre-dose.
Measured: Baseline (Day 1 pre-dose) and 30 min post-dose on Day 1
Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2
Baseline was defined as Day 1 Pre-dose.
Measured: Baseline (Day 1 pre-dose) and Day 2
Number of Participants With Clinically Significant Change From Baseline in Hematology, Serum Chemistry, Coagulation, and Urinalysis
Measured: From Day 1 up to Day 60
Part A (Greater Than or Equal to [>=] 4.0 mg/kg) and Part B: Number of Participants With Clinically Significant Change From Baseline in Gliadin-Specific T-cell Proliferation and Cytokine Release Markers
Measured: Part A (>=4.0 mg/kg): Day 1 pre-dose up to 144 hours post-dose on Day 7; Part B: Day 8 pre-dose up to 144 hours post-dose on Day 14
Number of Participants With Clinically Significant Laboratory Abnormalities
Measured: From Day 1 up to Day 60

Secondary outcomes (7)

Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA
Measured: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA
Measured: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TIMP-GLIA
Measured: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TIMP-GLIA
Measured: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA
Measured: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA
Measured: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
T1/2: Terminal Phase Elimination Half-life (T1/2) for TIMP-GLIA
Measured: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Jan 201822 Jul 2019

First posted3 Apr 2018
Study start23 Jan 2018
Primary completion24 May 2019
Study completion22 Jul 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Celiac DiseaseStudies of the same condition, open and under way.
More trials run by TakedaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Model description: Single ascending dose followed by repeat dose.
Masking: None (open label)
Enrolment: 23 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03486990
Sponsor's protocol ID: TGLIA-5.001
Status last verified: May 2020
First submitted: 21 Mar 2018
Last updated: 5 Jun 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Publications

Kelly CP, Murray JA, Leffler DA, Getts DR, Bledsoe AC, Smithson G, First MR, Morris A, Boyne M, Elhofy A, Wu TT, Podojil JR, Miller SD; TAK-101 Study Group. TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in Celiac Disease: A Randomized, Double-Blind, Placebo-Controlled Study. Gastroenterology. 2021 Jul;161(1):66-80.e8. doi: 10.1053/j.gastro.2021.03.014. Epub 2021 Mar 17.
PubMed 33722583

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 5 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, First-in-Human, 2-Part, Multicenter Dose Escalation and Repeat Dose Study of the Safety, Tolerability and Pharmacokinetics of TIMP-GLIA in Subjects With Celiac Disease
ClinicalTrials.gov ID: NCT03486990
Acronym / sponsor ID: TGLIA-5.001
Conditions: Celiac Disease
Keywords: safety, tolerability, pharmacokinetics, celiac, gliadin, gluten
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 23 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Collaborators: COUR Pharmaceutical Development Company, Inc.
Study start: 23 Jan 2018 (actual)
Primary completion: 24 May 2019 (actual)
Study completion: 22 Jul 2019 (actual)
First posted: 3 Apr 2018 (actual)
Results: Posted 5 Jun 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The safety and pharmacokinetic profile of TIMP-GLIA will be characterized.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 9
Model description: Single ascending dose followed by repeat dose.

Arm	Type	Receives
Part A, Cohort 1: 0.1 mg/kg	Experimental	Drug: TIMP-GLIATIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1.
Part A, Cohort 2: 0.5 mg/kg	Experimental	Drug: TIMP-GLIATIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.
Part A, Cohort 3: 1.0 mg/kg	Experimental	Drug: TIMP-GLIATIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.
Part A, Cohort 4: 2.0 mg/kg	Experimental	Drug: TIMP-GLIATIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.
Part A, Cohort 5: 4.0 mg/kg	Experimental	Drug: TIMP-GLIATIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.
Part A, Cohort 6: 8.0 mg/kg	Experimental	Drug: TIMP-GLIATIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.
Part B, Cohort 1: 2.0 mg/kg	Experimental	Drug: TIMP-GLIATIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Part B, Cohort 2: 4.0 mg/kg	Experimental	Drug: TIMP-GLIATIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Part B, Cohort 3: 8.0 mg/kg	Experimental	Drug: TIMP-GLIATIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

The subject provides written informed consent and is willing and able to comply with study requirements.
At screening the subject has a minimum body mass index (BMI) of 16 kg/m2 and a minimum body weight of 33 kg up to a maximum body weight of 129 kg, inclusive. If subject is considered to be underweight or overweight/obese, the subject is otherwise healthy in the opinion of the investigator.
The subject has celiac disease characterized at Screening Visit by:
a history of biopsy-confirmed celiac disease; and
no known gluten exposure for at least 10 days; and

Key exclusion criteria (17 listed)

The subject has a history of clinically confirmed immunoglobulin E-mediated reaction and/or anaphylaxis to wheat (i.e., "wheat allergy"), barley or rye.
The subject has a known history of hypersensitivity or allergies to TIMP-GLIA components OR any other known severe hypersensitivity or allergic reaction (resulted in hospitalization [initial or prolonged], congenital anomaly, or disability, or that required medical intervention to prevent permanent impairment or damage) to any other allergens (medications, food or environmental).
The subject has uncontrolled celiac disease and/or complications of celiac disease, or otherwise has experienced celiac symptomology within 10 days of screening, in the opinion of the investigator.
The subject has a history of, or has an active, significant, clinically relevant, comorbidity (including Type 1 and Type 2 diabetes mellitus and other autoimmune disorders, splenectomy) that, in the opinion of the investigator, would make the subject unsuitable for participation in the study and/or could adversely affect interpretation of the study results.
The subject has had significant changes to or anticipates changes to prescription or non-prescription medication used to manage an underlying comorbidity within 30 days prior to first dosing (Day 1).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TIMP-GLIAAlso: TAK-101intravenous infusion.	Drug	Part A, Cohort 1: 0.1 mg/kg, Part A, Cohort 2: 0.5 mg/kg, Part A, Cohort 3: 1.0 mg/kg, Part A, Cohort 4: 2.0 mg/kg, Part A, Cohort 5: 4.0 mg/kg, Part A, Cohort 6: 8.0 mg/kg, Part B, Cohort 1: 2.0 mg/kg, Part B, Cohort 2: 4.0 mg/kg, Part B, Cohort 3: 8.0 mg/kg

Primary outcome

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From Day 1 up to Day 180
Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events
Time frame: From Day 1 up to Day 180
AE Grades will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), version 4.0. Grade 1 scaled as Mild; Grade 2 scaled as Moderate; Grade 3 scaled as severe or medically significant but not immediately life-threatening; Grade 4 scaled as life-threatening consequences; and Grade 5 scaled as death related to AE. Drug-related adverse events are those that the investigator assessed as possibly or probably related to the study treatment.
Number of Participants With Clinically Significant Physical Examination Findings
Time frame: From Day 1 up to Day 60
Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings
Time frame: From Day 1 up to Day 60
Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels
Time frame: From Day 1 up to Day 60
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values
Time frame: From Day 1 up to Day 60
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 3
Time frame: Baseline (Day 1 pre-dose) and Day 3
Baseline is defined as Day 1 pre-dose.
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 7
Time frame: Baseline (Day 1 pre-dose) and Day 7
Baseline is defined as Day 1 pre-dose.
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 8
Time frame: Baseline (Day 1 pre-dose) and Day 8
Baseline is defined as Day 1 pre-dose.
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 10
Time frame: Baseline (Day 1 pre-dose) and Day 10
Baseline is defined as Day 1 pre-dose.
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 14
Time frame: Baseline (Day 1 pre-dose) and Day 14
Baseline is defined as Day 1 pre-dose.
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 38
Time frame: Baseline (Day 1 pre-dose) and Day 38
Baseline is defined as Day 1 pre-dose.
Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 60
Time frame: Baseline (Day 1 pre-dose) and Day 60
Baseline is defined as Day 1 pre-dose.
Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1
Time frame: Baseline (Day 1 pre-dose) and 15 minutes (min) post-dose on Day 1
Baseline was defined as Day 1 Pre-dose.
Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1
Time frame: Baseline (Day 1 pre-dose) and 30 min post-dose on Day 1
Baseline was defined as Day 1 Pre-dose.
Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2
Time frame: Baseline (Day 1 pre-dose) and Day 2
Baseline was defined as Day 1 Pre-dose.
Number of Participants With Clinically Significant Change From Baseline in Hematology, Serum Chemistry, Coagulation, and Urinalysis
Time frame: From Day 1 up to Day 60
Part A (Greater Than or Equal to [>=] 4.0 mg/kg) and Part B: Number of Participants With Clinically Significant Change From Baseline in Gliadin-Specific T-cell Proliferation and Cytokine Release Markers
Time frame: Part A (>=4.0 mg/kg): Day 1 pre-dose up to 144 hours post-dose on Day 7; Part B: Day 8 pre-dose up to 144 hours post-dose on Day 14
Number of Participants With Clinically Significant Laboratory Abnormalities
Time frame: From Day 1 up to Day 60

7 secondary outcomes

Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA
Time frame: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA
Time frame: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TIMP-GLIA
Time frame: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TIMP-GLIA
Time frame: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA
Time frame: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA
Time frame: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose
T1/2: Terminal Phase Elimination Half-life (T1/2) for TIMP-GLIA
Time frame: Parts A and B, Day 1: pre-dose and at multiple time points (up to 144 hours) post-dose; Part B, Day 8: pre-dose and at multiple time points (up to 144 hours) post-dose

Results and safety

Results posted to the registry on 5 Jun 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A, Cohort 1: 0.1 mg/kg	2	2
Part A, Cohort 2: 0.5 mg/kg	2	2
Part A, Cohort 3: 1.0 mg/kg	3	3
Part A, Cohort 4: 2.0 mg/kg	3	3
Part A, Cohort 5: 4.0 mg/kg	3	3
Part A, Cohort 6: 8.0 mg/kg	4	4
Part B, Cohort 1: 2.0 mg/kg	2	2
Part B, Cohort 2: 4.0 mg/kg	2	2
Part B, Cohort 3: 8.0 mg/kg	2	2

Primary outcome: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time frame: From Day 1 up to Day 180. Count of participants. Unit: Participants

Measure	Part A, Cohort 1: 0.1 mg/kg n = 2	Part A, Cohort 2: 0.5 mg/kg n = 2	Part A, Cohort 3: 1.0 mg/kg n = 3	Part A, Cohort 4: 2.0 mg/kg n = 3	Part A, Cohort 5: 4.0 mg/kg n = 3	Part A, Cohort 6: 8.0 mg/kg n = 4	Part B, Cohort 1: 2.0 mg/kg n = 2	Part B, Cohort 2: 4.0 mg/kg n = 2	Part B, Cohort 3: 8.0 mg/kg n = 2
TEAEs	1	2	3	3	2	3	1	1	2
SAEs	0	0	0	0	0	0	0	0	0

Population analysed: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.

Primary outcome: Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events

Time frame: From Day 1 up to Day 180. Count of participants. Unit: Participants

Measure	Part A, Cohort 1: 0.1 mg/kg n = 2	Part A, Cohort 2: 0.5 mg/kg n = 2	Part A, Cohort 3: 1.0 mg/kg n = 3	Part A, Cohort 4: 2.0 mg/kg n = 3	Part A, Cohort 5: 4.0 mg/kg n = 3	Part A, Cohort 6: 8.0 mg/kg n = 4	Part B, Cohort 1: 2.0 mg/kg n = 2	Part B, Cohort 2: 4.0 mg/kg n = 2	Part B, Cohort 3: 8.0 mg/kg n = 2
Grade 3 or Higher TEAEs	0	0	1	0	0	0	0	0	0
Drug-related Adverse Events	1	0	2	2	2	3	0	1	1

Population analysed: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.

Primary outcome: Number of Participants With Clinically Significant Physical Examination Findings

Time frame: From Day 1 up to Day 60. Count of participants. Unit: Participants

Measure	Part A, Cohort 1: 0.1 mg/kg n = 2	Part A, Cohort 2: 0.5 mg/kg n = 2	Part A, Cohort 3: 1.0 mg/kg n = 3	Part A, Cohort 4: 2.0 mg/kg n = 3	Part A, Cohort 5: 4.0 mg/kg n = 3	Part A, Cohort 6: 8.0 mg/kg n = 4	Part B, Cohort 1: 2.0 mg/kg n = 2	Part B, Cohort 2: 4.0 mg/kg n = 2	Part B, Cohort 3: 8.0 mg/kg n = 2
Value	0	0	0	0	0	0	0	0	0

Population analysed: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.

Primary outcome: Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings

Time frame: From Day 1 up to Day 60. Count of participants. Unit: Participants

Measure	Part A, Cohort 1: 0.1 mg/kg n = 2	Part A, Cohort 2: 0.5 mg/kg n = 2	Part A, Cohort 3: 1.0 mg/kg n = 3	Part A, Cohort 4: 2.0 mg/kg n = 3	Part A, Cohort 5: 4.0 mg/kg n = 3	Part A, Cohort 6: 8.0 mg/kg n = 4	Part B, Cohort 1: 2.0 mg/kg n = 2	Part B, Cohort 2: 4.0 mg/kg n = 2	Part B, Cohort 3: 8.0 mg/kg n = 2
Value	0	0	0	0	0	0	0	0	0

Population analysed: The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: TEAEs are adverse events that started after the first dose of study drug up to Day 180. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A, Cohort 1: 0.1 mg/kg	0 of 2 (0%)	1 of 2 (50%)	0 of 2
Part A, Cohort 2: 0.5 mg/kg	0 of 2 (0%)	2 of 2 (100%)	0 of 2
Part A, Cohort 3: 1.0 mg/kg	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Part A, Cohort 4: 2.0 mg/kg	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Part A, Cohort 5: 4.0 mg/kg	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Part A, Cohort 6: 8.0 mg/kg	0 of 4 (0%)	3 of 4 (75%)	0 of 4
Part B, Cohort 1: 2.0 mg/kg	0 of 2 (0%)	1 of 2 (50%)	0 of 2
Part B, Cohort 2: 4.0 mg/kg	0 of 2 (0%)	1 of 2 (50%)	0 of 2
Part B, Cohort 3: 8.0 mg/kg	0 of 2 (0%)	2 of 2 (100%)	0 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33722583Kelly CP, Murray JA, Leffler DA, Getts DR, Bledsoe AC, Smithson G, First MR, Morris A, Boyne M, Elhofy A, Wu TT, Podojil JR, Miller SD; TAK-101 Study Group. TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in Celiac Disease: A Randomized, Double-Blind, Placebo-Controlled Study. Gastroenterology. 2021 Jul;161(1):66-80.e8. doi: 10.1053/j.gastro.2021.03.014. Epub 2021 Mar 17.
Individual participant dataSharing planned: Yes. Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Takeda

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TIMP-GLIA in people with Celiac Disease, run by Takeda at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (time frame: From Day 1 up to Day 180). The study lists 19 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03486990, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2020.