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

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03486990
• Collaborator: COUR Pharmaceutical Development Company, Inc. (Industry)
• Enrollment: 23
• Locations: 4
• Arms: 9
• Actual Duration (Months): 17.9
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Celiac Disease	Drug: TIMP-GLIA	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Single ascending dose followed by repeat dose.Single ascending dose followed by repeat dose.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jan 23, 2018
• Actual Primary Completion Date: May 24, 2019
• Actual Study Completion Date: Jul 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A, Cohort 1: 0.1 mg/kg TIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1.	Drug: TIMP-GLIA; intravenous infusion.; Other Names: TAK-101
Experimental: Part A, Cohort 2: 0.5 mg/kg TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	Drug: TIMP-GLIA; intravenous infusion.; Other Names: TAK-101
Experimental: Part A, Cohort 3: 1.0 mg/kg TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	Drug: TIMP-GLIA; intravenous infusion.; Other Names: TAK-101
Experimental: Part A, Cohort 4: 2.0 mg/kg TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	Drug: TIMP-GLIA; intravenous infusion.; Other Names: TAK-101
Experimental: Part A, Cohort 5: 4.0 mg/kg TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	Drug: TIMP-GLIA; intravenous infusion.; Other Names: TAK-101
Experimental: Part A, Cohort 6: 8.0 mg/kg TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	Drug: TIMP-GLIA; intravenous infusion.; Other Names: TAK-101
Experimental: Part B, Cohort 1: 2.0 mg/kg TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	Drug: TIMP-GLIA; intravenous infusion.; Other Names: TAK-101
Experimental: Part B, Cohort 2: 4.0 mg/kg TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	Drug: TIMP-GLIA; intravenous infusion.; Other Names: TAK-101
Experimental: Part B, Cohort 3: 8.0 mg/kg TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	Drug: TIMP-GLIA; intravenous infusion.; Other Names: TAK-101

Outcome Measures

Primary Outcome Measures

1. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [From Day 1 up to Day 180]

2. Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events [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.

3. Number of Participants With Clinically Significant Physical Examination Findings [From Day 1 up to Day 60]

4. Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings [From Day 1 up to Day 60]

5. Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels [From Day 1 up to Day 60]

6. Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values [From Day 1 up to Day 60]

7. Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 3 [Baseline (Day 1 pre-dose) and Day 3]

   Baseline is defined as Day 1 pre-dose.

8. Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 7 [Baseline (Day 1 pre-dose) and Day 7]

   Baseline is defined as Day 1 pre-dose.

9. Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 8 [Baseline (Day 1 pre-dose) and Day 8]

   Baseline is defined as Day 1 pre-dose.

10. Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 10 [Baseline (Day 1 pre-dose) and Day 10]

    Baseline is defined as Day 1 pre-dose.

11. Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 14 [Baseline (Day 1 pre-dose) and Day 14]

    Baseline is defined as Day 1 pre-dose.

12. Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 38 [Baseline (Day 1 pre-dose) and Day 38]

    Baseline is defined as Day 1 pre-dose.

13. Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 60 [Baseline (Day 1 pre-dose) and Day 60]

    Baseline is defined as Day 1 pre-dose.

14. Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1 [Baseline (Day 1 pre-dose) and 15 minutes (min) post-dose on Day 1]

    Baseline was defined as Day 1 Pre-dose.

15. Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1 [Baseline (Day 1 pre-dose) and 30 min post-dose on Day 1]

    Baseline was defined as Day 1 Pre-dose.

16. Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2 [Baseline (Day 1 pre-dose) and Day 2]

    Baseline was defined as Day 1 Pre-dose.

17. Number of Participants With Clinically Significant Change From Baseline in Hematology, Serum Chemistry, Coagulation, and Urinalysis [From Day 1 up to Day 60]

18. 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 [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]

19. Number of Participants With Clinically Significant Laboratory Abnormalities [From Day 1 up to Day 60]

Secondary Outcome Measures

1. Cmax: Maximum Observed Plasma Concentration For TIMP-GLIA [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]

2. Clast: Last Measurable Observed Plasma Concentration For TIMP-GLIA [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]

3. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TIMP-GLIA [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]

4. AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TIMP-GLIA [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]

5. AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TIMP-GLIA [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]

6. Tlast: Time to Reach the Last Measurable Plasma Concentration for TIMP-GLIA [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]

7. T1/2: Terminal Phase Elimination Half-life (T1/2) for TIMP-GLIA [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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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

• 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.

Exclusion Criteria:

• 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).

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jacksonville Center For Clinical Research	Jacksonville	Florida	United States	32216
2	Mass General Hospital Translational and Clinical Research Centers	Boston	Massachusetts	United States	02114
3	Mayo Gastroenterology Research Unit	Rochester	Minnesota	United States	55905
4	Prism Clinical Research	Saint Paul	Minnesota	United States	55114

Sponsors and Collaborators

• Takeda
• COUR Pharmaceutical Development Company, Inc.

Investigators

• Study Director: Medical Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Sep 11, 2018
• Statistical Analysis Plan - Oct 9, 2018

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03486990
• Other Study ID Numbers: TGLIA-5.001
• First Posted: Apr 3, 2018
• Last Update Posted: Jun 5, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: safety; tolerability; pharmacokinetics; celiac; gliadin; gluten
• Additional relevant MeSH terms: Celiac Disease

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 5 investigative sites in the United States from 23 January 2018 to 22 July 2019.
Pre-assignment Detail	Participants diagnosed with celiac disease (CD) were enrolled to receive TIMP-GLIA as a single dose escalation of 0.1 milligram per kilogram (mg/kg), 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 4.0 mg/kg, 8.0 mg/kg in Part A; and TIMP-GLIA as a two dose escalation of 2.0 mg/kg, 4.0 mg/kg, 8.0 mg/kg in Part B.

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Period Title: Overall Study
STARTED	2	2	3	3	3	4	2	2	2
COMPLETED	2	2	3	3	3	4	2	2	2
NOT COMPLETED	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	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	Total
Arm/Group Description	TIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	Total of all reporting groups
Overall Participants	2	2	3	3	3	4	2	2	2	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.5 (27.58)	53.5 (20.51)	39.3 (15.57)	38.0 (4.58)	48.3 (14.19)	27.5 (4.65)	42.5 (13.44)	53.5 (7.78)	32.5 (2.12)	40.3 (13.69)
Sex: Female, Male (Count of Participants)
Female	2 100%	1 50%	2 66.7%	2 66.7%	3 100%	3 75%	2 100%	2 100%	1 50%	18 78.3%
Male	0 0%	1 50%	1 33.3%	1 33.3%	0 0%	1 25%	0 0%	0 0%	1 50%	5 21.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	1 25%	0 0%	0 0%	0 0%	1 4.3%
Not Hispanic or Latino	2 100%	2 100%	3 100%	3 100%	3 100%	3 75%	2 100%	2 100%	2 100%	22 95.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	2 100%	2 100%	3 100%	3 100%	3 100%	3 75%	2 100%	2 100%	2 100%	22 95.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	1 25%	0 0%	0 0%	0 0%	1 4.3%
Region of Enrollment (Count of Participants)
United States	2 100%	2 100%	3 100%	3 100%	3 100%	4 100%	2 100%	2 100%	2 100%	23 100%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	3	3	3	4	2	2	2
TEAEs	1 50%	2 100%	3 100%	3 100%	2 66.7%	3 75%	1 50%	1 50%	2 100%
SAEs	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With Grade 3 or Higher TEAEs and Drug-related Adverse Events
Description	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.
Time Frame	From Day 1 up to Day 180

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	3	3	3	4	2	2	2
Grade 3 or Higher TEAEs	0 0%	0 0%	1 33.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Drug-related Adverse Events	1 50%	0 0%	2 66.7%	2 66.7%	2 66.7%	3 75%	0 0%	1 50%	1 50%

3. Primary Outcome

Title	Number of Participants With Clinically Significant Physical Examination Findings
Time Frame	From Day 1 up to Day 60

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	3	3	3	4	2	2	2
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

4. Primary Outcome

Title	Number of Participants With Clinically Significant Electrocardiograms (ECG) Findings
Time Frame	From Day 1 up to Day 60

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	3	3	3	4	2	2	2
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

5. Primary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Arterial Oxygen Saturation Levels
Time Frame	From Day 1 up to Day 60

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	3	3	3	4	2	2	2
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

6. Primary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Vital Signs Values
Time Frame	From Day 1 up to Day 60

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	3	3	3	4	2	2	2
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

7. Primary Outcome

Title	Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 3
Description	Baseline is defined as Day 1 pre-dose.
Time Frame	Baseline (Day 1 pre-dose) and Day 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B, Cohort 1: 2.0 mg/kg	Part B, Cohort 2: 4.0 mg/kg	Part B, Cohort 3: 8.0 mg/kg
Arm/Group Description	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	2
Baseline (Day 1 pre-dose)	2.15 (0.495)	2.85 (0.778)	3.30 (0.990)
Change at Day 3	1.20 (0.000)	0.60 (0.141)	-0.35 (0.071)

8. Primary Outcome

Title	Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 7
Description	Baseline is defined as Day 1 pre-dose.
Time Frame	Baseline (Day 1 pre-dose) and Day 7

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B, Cohort 1: 2.0 mg/kg	Part B, Cohort 2: 4.0 mg/kg	Part B, Cohort 3: 8.0 mg/kg
Arm/Group Description	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	2
Baseline (Day 1 pre-dose)	2.15 (0.495)	2.85 (0.778)	3.30 (0.990)
Change at Day 7	0.75 (0.071)	0.00 (0.000)	0.85 (1.344)

9. Primary Outcome

Title	Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 8
Description	Baseline is defined as Day 1 pre-dose.
Time Frame	Baseline (Day 1 pre-dose) and Day 8

Outcome Measure Data

Analysis Population Description

The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA. The safety analysis population where data at specified time points were available.

Arm/Group Title	Part B, Cohort 1: 2.0 mg/kg	Part B, Cohort 2: 4.0 mg/kg	Part B, Cohort 3: 8.0 mg/kg
Arm/Group Description	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	2
Baseline (Day 1 pre-dose)	2.15 (0.495)	2.85 (0.778)	3.30 (0.990)
Change at Day 8	0.70 (0.141)	0.10 (NA)	1.50 (1.838)

10. Primary Outcome

Title	Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 10
Description	Baseline is defined as Day 1 pre-dose.
Time Frame	Baseline (Day 1 pre-dose) and Day 10

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B, Cohort 1: 2.0 mg/kg	Part B, Cohort 2: 4.0 mg/kg	Part B, Cohort 3: 8.0 mg/kg
Arm/Group Description	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	2
Baseline (Day 1 pre-dose)	2.15 (0.495)	2.85 (0.778)	3.30 (0.990)
Change at Day 10	1.85 (0.778)	1.00 (1.273)	1.25 (1.485)

11. Primary Outcome

Title	Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 14
Description	Baseline is defined as Day 1 pre-dose.
Time Frame	Baseline (Day 1 pre-dose) and Day 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B, Cohort 1: 2.0 mg/kg	Part B, Cohort 2: 4.0 mg/kg	Part B, Cohort 3: 8.0 mg/kg
Arm/Group Description	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	2
Baseline (Day 1 pre-dose)	2.15 (0.495)	2.85 (0.778)	3.30 (0.990)
Change at Day 14	0.90 (0.141)	1.65 (0.495)	1.30 (1.273)

12. Primary Outcome

Title	Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 38
Description	Baseline is defined as Day 1 pre-dose.
Time Frame	Baseline (Day 1 pre-dose) and Day 38

Outcome Measure Data

Analysis Population Description

The safety population, included all participants who signed the study-specific informed consent document and received at least 1 dose of TIMP-GLIA. The safety analysis population where data at specified time points were available.

Arm/Group Title	Part B, Cohort 1: 2.0 mg/kg	Part B, Cohort 2: 4.0 mg/kg	Part B, Cohort 3: 8.0 mg/kg
Arm/Group Description	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	2
Baseline (Day 1 pre-dose)	2.15 (0.495)	2.85 (0.778)	3.30 (0.990)
Change at Day 38	0.30 (NA)	1.50 (1.273)	1.00 (1.980)

13. Primary Outcome

Title	Part B: Change From Baseline (Day 1 Pre-dose) in C1q Binding at Day 60
Description	Baseline is defined as Day 1 pre-dose.
Time Frame	Baseline (Day 1 pre-dose) and Day 60

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B, Cohort 1: 2.0 mg/kg	Part B, Cohort 2: 4.0 mg/kg	Part B, Cohort 3: 8.0 mg/kg
Arm/Group Description	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	2
Baseline (Day 1 pre-dose)	2.15 (0.495)	2.85 (0.778)	3.30 (0.990)
Change at Day 60	0.65 (0.354)	1.15 (1.061)	1.10 (1.838)

14. Primary Outcome

Title	Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 15 Minutes Post-dose on Day 1
Description	Baseline was defined as Day 1 Pre-dose.
Time Frame	Baseline (Day 1 pre-dose) and 15 minutes (min) post-dose on Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B, Cohort 1: 2.0 mg/kg	Part B, Cohort 2: 4.0 mg/kg	Part B, Cohort 3: 8.0 mg/kg
Arm/Group Description	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	2
Baseline (Day 1 pre-dose): C3a level	32.25 (23.264)	16.15 (0.636)	18.65 (17.041)
Change at 15 min post-dose on Day 1: C3a level	45.40 (43.841)	134.90 (104.369)	46.25 (13.930)
Baseline (Day 1 pre-dose): SC5B-9 level	109.5 (17.68)	95.5 (33.23)	112.0 (33.94)
Change at 15 min post-dose on Day 1: SC5B-9 level	59.0 (49.50)	196.0 (193.75)	130.5 (33.23)

15. Primary Outcome

Title	Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at 30 Minutes Post-dose on Day 1
Description	Baseline was defined as Day 1 Pre-dose.
Time Frame	Baseline (Day 1 pre-dose) and 30 min post-dose on Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B, Cohort 1: 2.0 mg/kg	Part B, Cohort 2: 4.0 mg/kg	Part B, Cohort 3: 8.0 mg/kg
Arm/Group Description	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	2
Baseline (Day 1 pre-dose): C3a level	32.25 (23.264)	16.15 (0.636)	18.65 (17.041)
Change at 30 min post-dose on Day 1: C3a level	87.50 (56.569)	144.00 (11.455)	65.65 (34.719)
Baseline (Day 1 pre-dose): SC5B-9 level	109.5 (17.68)	95.5 (33.23)	112.0 (33.94)
Change at 30 min post-dose on Day 1: SC5B-9 level	179.0 (2.83)	307.0 (41.01)	293.0 (185.26)

16. Primary Outcome

Title	Part B: Change From Baseline (Day 1 Pre-dose) in C3a and SC5B-9 Levels at Day 2
Description	Baseline was defined as Day 1 Pre-dose.
Time Frame	Baseline (Day 1 pre-dose) and Day 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Part B, Cohort 1: 2.0 mg/kg	Part B, Cohort 2: 4.0 mg/kg	Part B, Cohort 3: 8.0 mg/kg
Arm/Group Description	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	2
Baseline (Day 1 pre-dose): C3a level	32.25 (23.264)	16.15 (0.636)	18.65 (17.041)
Change at Day 2: C3a level	-6.55 (12.092)	0.90 (0.990)	-6.70 (20.789)
Baseline (Day 1 pre-dose): SC5B-9 level	109.5 (17.68)	95.5 (33.23)	112.0 (33.94)
Change at Day 2: SC5B-9 level	26.0 (14.14)	-12.5 (36.06)	2.0 (22.63)

17. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	3	3	3	4	2	2	2
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

18. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	3	4	2	2	2
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%

19. Primary Outcome

Title	Number of Participants With Clinically Significant Laboratory Abnormalities
Time Frame	From Day 1 up to Day 60

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	2	3	3	3	4	2	2	2
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 50%

20. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) population who received at least 1 dose of TIMP-GLIA and had at least 1 PK parameter reported. The PK analysis population where data at specified time points were available.

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	3	3	3	3	2	2	2
Day 1	91.8 (48.4)	220 (3.0)	457 (17.6)	845 (23.6)	252 (6.7)	529 (22.6)	938 (2.9)
Day 8	NA (NA)	408 (26.8)	735 (11.7)

21. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

The PK population who received at least 1 dose of TIMP-GLIA and had at least 1 PK parameter reported. The PK analysis population where data at specified time points were available.

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	3	3	3	3	2	2	2
Day 1	50.6 (12.2)	63.9 (29.2)	68.6 (27.2)	55.8 (30.2)	77.2 (23.7)	97.9 (85.1)	47.9 (19.0)	111 (5.7)
Day 8	NA (NA)	133 (137.7)	54.4 (19.5)

22. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

The PK population who received at least 1 dose of TIMP-GLIA and had at least 1 PK parameter reported. The PK analysis population where data at specified time points were available.

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	3	3	3	3	2	2	2
Day 1	0.54	0.50	0.50	0.50	2.86	3.21	2.94
Day 8	NA	3.08	2.90

23. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

The PK population who received at least 1 dose of TIMP-GLIA and had at least 1 PK parameter reported. The PK analysis population where data at specified time points were available.

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	3	3	3	3	2	2	2
Day 1	604 (3.4)	3100 (27.0)	3170 (22.8)	8430 (48.9)	NA (NA)	3220 (31.5)	5080 (9.2)
Day 8	NA (NA)	3250 (15.1)

24. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

The PK population who received at least 1 dose of TIMP-GLIA and had at least 1 PK parameter reported. The PK analysis population where data at specified time points were available.

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	3	3	3	3	2	2	2
Day 1	119 (210.7)	503 (12.1)	1690 (88.1)	2920 (21.6)	2870 (501.3)	932 (65.2)	2930 (30.6)	4590 (9.6)
Day 8	NA (NA)	1410 (107.1)	3050 (14.7)

25. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

The PK population who received at least 1 dose of TIMP-GLIA and had at least 1 PK parameter reported. The PK analysis population where data at specified time points were available.

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	3	3	3	3	2	2	2
Day 1	2.49	4.00	12.17	12.00	12.00	7.99	18.10	12.00
Day 8	NA	8.01	12.08

26. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

The PK population who received at least 1 dose of TIMP-GLIA and had at least 1 PK parameter reported. The PK analysis population where data at specified time points were available.

Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.	TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.	TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
Measure Participants	2	3	3	3	3	2	2	2
Day 1	NA	1.81	4.38	3.03	4.36	NA	4.60	3.03
Day 8	NA	2.51

Adverse Events

Time Frame	TEAEs are adverse events that started after the first dose of study drug up to Day 180
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	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
Arm/Group Description	TIMP-GLIA 0.1 mg/kg, infusion, intravenously, once on Day 1.		TIMP-GLIA 0.5 mg/kg, infusion, intravenously, once on Day 1.		TIMP-GLIA 1.0 mg/kg, infusion, intravenously, once on Day 1.		TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Day 1.		TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Day 1.		TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Day 1.		TIMP-GLIA 2.0 mg/kg, infusion, intravenously, once on Days 1 and 8.		TIMP-GLIA 4.0 mg/kg, infusion, intravenously, once on Days 1 and 8.		TIMP-GLIA 8.0 mg/kg, infusion, intravenously, once on Days 1 and 8.
All Cause Mortality
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Serious Adverse Events
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		2/2 (100%)		3/3 (100%)		3/3 (100%)		2/3 (66.7%)		3/4 (75%)		1/2 (50%)		1/2 (50%)		2/2 (100%)
Blood and lymphatic system disorders
Leukopenia	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Cardiac disorders
Sinus tachycardia	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Eye disorders
Visual impairment	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Gastrointestinal disorders
Abdominal distension	0/2 (0%)		0/2 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Abdominal pain	1/2 (50%)		0/2 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/4 (25%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Colitis	0/2 (0%)		0/2 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Diarrhoea	0/2 (0%)		0/2 (0%)		0/3 (0%)		2/3 (66.7%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Nausea	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Tongue geographic	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Vomiting	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
General disorders
Chills	0/2 (0%)		0/2 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Cyst	0/2 (0%)		0/2 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Fatigue	0/2 (0%)		0/2 (0%)		1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Medical device site erythema	0/2 (0%)		0/2 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Vessel puncture site haemorrhage	0/2 (0%)		0/2 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Infections and infestations
Bronchitis	0/2 (0%)		0/2 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Upper respiratory tract infection	0/2 (0%)		0/2 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Urinary tract infection	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		1/2 (50%)		0/2 (0%)
Injury, poisoning and procedural complications
Contusion	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Infusion related reaction	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		1/4 (25%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Meniscus injury	0/2 (0%)		0/2 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Sunburn	0/2 (0%)		0/2 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Investigations
Alanine aminotransferase increased	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		1/2 (50%)
Blood creatine phosphokinase increased	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		1/2 (50%)
Fibrin D dimer increased	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Metabolism and nutrition disorders
Gluten sensitivity	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/2 (50%)		0/2 (0%)		0/2 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/2 (50%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Back pain	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		2/4 (50%)		0/2 (0%)		1/2 (50%)		1/2 (50%)
Muscle tightness	0/2 (0%)		1/2 (50%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Myalgia	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Neck pain	0/2 (0%)		0/2 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Pain in extremity	0/2 (0%)		0/2 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Plantar fasciitis	0/2 (0%)		0/2 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Nervous system disorders
Disturbance in attention	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Headache	0/2 (0%)		1/2 (50%)		1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		1/2 (50%)		1/2 (50%)		1/2 (50%)
Paraesthesia	1/2 (50%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Reproductive system and breast disorders
Vulvovaginal discomfort	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		1/2 (50%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/2 (0%)		0/2 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Oropharyngeal pain	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/2 (0%)		1/2 (50%)		0/2 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact	0/2 (0%)		1/2 (50%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Vascular disorders
Flushing	0/2 (0%)		0/2 (0%)		0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		2/4 (50%)		0/2 (0%)		0/2 (0%)		0/2 (0%)
Hypotension	0/2 (0%)		0/2 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/2 (0%)		0/2 (0%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda's sole discretion.