Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Ulcerative Colitis

NCT ID: NCT03616821

Last Updated: 2023-11-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

242 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-08-07

Study Completion Date

2023-10-23

Brief Summary

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The present study (D5272C00001/Legacy #3151-201-008) aims to evaluate the efficacy and safety of brazikumab in patients with moderately to severely active UC and will include assessments of clinical responses as demonstrated by improvement of symptoms and of colonic mucosal appearance as observed on endoscopy

Detailed Description

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Conditions

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Ulcerative Colitis IBD

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Global, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Brazikumab Dose 1

Intravenous brazikumab on day 1, day 15, and day 43 followed by Subcutaneous brazikumab every 4 weeks beginning on day 71 through week 50

Group Type EXPERIMENTAL

Brazikumab

Intervention Type DRUG

Intravenous brazikumab on day 1, day 15, and day 43 followed by Subcutaneous brazikumab every 4 weeks beginning on day 71 through Week 50

Brazikumab Dose 2

Intravenous brazikumab on day 1, day 15, and day 43 followed by Subcutaneous brazikumab every 4 weeks beginning on day 71 through Week 50

Group Type EXPERIMENTAL

Brazikumab

Intervention Type DRUG

Intravenous brazikumab on day 1, day 15, and day 43 followed by Subcutaneous brazikumab every 4 weeks beginning on day 71 through Week 50

Placebo

Intravenous placebo on day 1, day 15, and day 43 followed by Subcutaneous every 4 weeks beginning on day 71 through Week 50.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Intravenous placebo on day 1, day 15, and day 43 followed by Subcutaneous placebo every 4 weeks beginning on Day 71 through Week 50.

Interventions

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Brazikumab

Intravenous brazikumab on day 1, day 15, and day 43 followed by Subcutaneous brazikumab every 4 weeks beginning on day 71 through Week 50

Intervention Type DRUG

Placebo

Intravenous placebo on day 1, day 15, and day 43 followed by Subcutaneous placebo every 4 weeks beginning on Day 71 through Week 50.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Ability to provide informed consent
2. Aged 18 to 80 years of age
3. Diagnosis of UC with an onset of symptoms for a minimum of 3 months prior to Screening
4. Evidence of UC extending proximal to the rectum (≥ 15 cm of involved colon)
5. Moderately to severely active UC as defined by:

1. Average daily mMS Stool Frequency subscore ≥ 1 AND Average daily mMS Rectal Bleeding subscore ≥ 1
2. Modified Mayo endoscopic subscore of ≥ 2 based on a full colonoscopy within 14 days prior to randomization.
6. Participant had an inadequate response or intolerance to intervention with conventional treatment or prior biological treatment or demonstrated CS dependence for the treatment of UC. For participants who have previously used biological treatment, a participant may have failed up to 3 biologics that include up to 2 different mechanisms of action.
7. Participants taking 5-aminosalicylates, oral prednisone (or equivalent), oral budesonide, or immunomodulators must be at a stable dose or discontinued. Topical (rectal) aminosalicylic acid or topical (rectal) steroids should be discontinued.
8. Female participants of childbearing potential must have a negative urine pregnancy test prior to administration of study intervention and must agree to use a highly effective method of birth control throughout the study and for at least 18 weeks after the last dose of study intervention.
9. Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal.
10. Non sterilized males who are sexually active with a female partner of childbearing potential should use condoms during treatment and until the end of relevant systemic exposure in the male participant, plus a further 18 weeks.
11. No known history of active TB or latent TB without completion of appropriate intervention and negative QFT-TB during Screening.

Exclusion Criteria

1. Participant has UC limited to the rectum (ie, not beyond 15 cm of the anal verge).
2. Current diagnosis of fulminant colitis, a diagnosis of CD or indeterminate colitis, presence or history of a fistula consistent with CD, primary sclerosing cholangitis, celiac disease, or untreated bile acid malabsorption. Participants with a history of toxic megacolon within 12 months of screening are excluded.
3. History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, ileostomy, or other prior colonic resection, or need for surgical intervention for control of UC anticipated within 6 months.
4. Participant has received the following treatment:

1. Infliximab: within 8 weeks prior to randomization.
2. Adalimumab, certolizumab pegol, or golimumab: within 8 weeks prior to randomization.
3. Vedolizumab or ustekinumab within 12 weeks of randomization.
4. Other prohibited medication, biologic or small molecule treatment within 5 half-lives prior to randomization.
5. Fecal microbiota transplantation: within 8 weeks prior to randomization.
5. Criterion deleted as part of Amendment 5 v6.0
6. Except for ustekinumab, prior exposure to any biologic agent targeting IL-12 or IL-23.
7. Known history of allergy to the study intervention formulation or any of its excipients or components of the delivery device, or to any other biologic therapy.
8. Participant received cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, tacrolimus (FK-506), or tofacitinib within 2 weeks prior to Screening.
9. Participants who received IV or intramuscular steroids within 2 weeks prior to Screening.
10. Participant is currently enrolled in another investigational device or drug study, or is within 35 days or 5 half-lives, whichever is longer, since ending another investigational device or drug study(s), or receiving other investigational agent(s).
11. Participant received a transfusion of blood, plasma, or platelets within 30 days prior to Screening.
12. Participant received a Bacille Calmette-Guérin vaccination within 12 months of randomization or any other live vaccine less than 4 weeks prior to randomization.
13. Participant has any of the following criteria related to infections:

1. Evidence of a recent systemic fungal infection, requiring inpatient hospitalization, and/or antifungal treatment.
2. Any infection requiring hospitalization or treatment with IV anti-infectives within 4 weeks of Screening.
3. Cytomegalovirus or Epstein-Barr virus infection that has not resolved within 8 weeks prior to Screening.
4. Clinically significant chronic infection that has not resolved within 8 weeks of Screening.
5. Nonserious infection requiring oral anti-infectives within 2 weeks prior to randomization must be further discussed with study medical monitor.
6. Clinical evidence of or suspected to have an abscess during Screening.
7. Any underlying condition that predisposes the participant to infections.
8. Participant had previous allogenic bone marrow transplant or history of organ or cell-based transplantation.
9. Clinically significant active infection or signs/symptoms of infection that has the potential to worsen with immunosuppressive therapy.
10. Signs or symptoms of ongoing infection due to intestinal pathogens.
14. Participant has known or suspected history of chronic use of NSAIDs and/or opiates, drug, or alcohol abuse.
15. History of cancer with the following exceptions: history of basal cell carcinoma and/or squamous cell carcinoma of the skin OR carcinoma in situ of the cervix; with apparent successful curative therapy, greater than 12 months prior to Screening.
16. Clinically significant cardiovascular conditions.
17. Prolonged QTcF interval or conditions leading to additional risk for QT prolongation.
18. Clinically significant kidney disease
19. Abnormal laboratory results at Screening as defined in the study protocol
20. Participant is pregnant or breastfeeding or plans to become pregnant during the study.
21. Participant has other known, pre-existing, clinically significant medical conditions that are not associated with UC and are uncontrolled with standard treatment.
22. Participant has any disorder that may compromise the ability of the participant to give written informed consent and/or to comply with all required study procedures.
23. Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kathy Bohannon

Role: STUDY_DIRECTOR

AstraZeneca

Locations

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Little Rock, Arkansas, United States

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Chula Vista, California, United States

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Lancaster, California, United States

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Lincoln, California, United States

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Mission Hills, California, United States

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Poway, California, United States

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Colorado Springs, Colorado, United States

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Clearwater, Florida, United States

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Inverness, Florida, United States

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Kissimmee, Florida, United States

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Lakeland, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami Lakes, Florida, United States

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Naples, Florida, United States

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New Port Richey, Florida, United States

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Tampa, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Gurnee, Illinois, United States

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Oak Lawn, Illinois, United States

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Brownsburg, Indiana, United States

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Evansville, Indiana, United States

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Shawnee Mission, Kansas, United States

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Topeka, Kansas, United States

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Baton Rouge, Louisiana, United States

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Marrero, Louisiana, United States

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Shreveport, Louisiana, United States

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Wyoming, Michigan, United States

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Biloxi, Mississippi, United States

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Las Vegas, Nevada, United States

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Las Vegas, Nevada, United States

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New York, New York, United States

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Sunnyside, New York, United States

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Morehead City, North Carolina, United States

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Beachwood, Ohio, United States

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Springfield, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Uniontown, Pennsylvania, United States

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Amarillo, Texas, United States

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Carrollton, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Humble, Texas, United States

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Pflugerville, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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North Chesterfield, Virginia, United States

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Chicoutimi, Quebec, Canada

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Brno, , Czechia

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České Budějovice, , Czechia

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Hradec Králové, , Czechia

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Ostrava, , Czechia

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Hamburg, , Germany

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Kiel, , Germany

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Ulm, , Germany

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Debrecen, , Hungary

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Bangalore, , India

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Hyderabad, , India

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Jaipur, , India

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New Delhi, , India

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Rajkot, , India

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Surat, , India

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Haifa, , Israel

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Jerusalem, , Israel

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Petah Tikva, , Israel

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Milan, , Italy

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Negrar, , Italy

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Rho, , Italy

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Roma, , Italy

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Asahikawa-shi, , Japan

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Chiba, , Japan

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Fukuoka, , Japan

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Fukuyama-shi, , Japan

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Hakodate-shi, , Japan

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Kasama-shi, , Japan

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Kashiwa-shi, , Japan

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Koshigaya-shi, , Japan

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Kure-shi, , Japan

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Minatoku, , Japan

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Nagaoka-shi, , Japan

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Onga-gun, , Japan

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Sapporo, , Japan

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Takarazuka-shi, , Japan

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Bydgoszcz, , Poland

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Chojnice, , Poland

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Częstochowa, , Poland

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Gdansk, , Poland

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Krakow, , Poland

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Ksawerów, , Poland

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Piaseczno, , Poland

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Poznan, , Poland

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Rzeszów, , Poland

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Sopot, , Poland

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Torun, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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San Juan, , Puerto Rico

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Aramil, , Russia

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Izhevsk, , Russia

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Moscow, , Russia

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Novosibirsk, , Russia

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Perm, , Russia

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Tomsk, , Russia

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Košice, , Slovakia

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Bloemfontein, , South Africa

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Cape Town, , South Africa

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Cape Town, , South Africa

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Plumstead, , South Africa

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Busan, , South Korea

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Daegu, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Wŏnju, , South Korea

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Valencia, , Spain

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Taichung, , Taiwan

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Taipei, , Taiwan

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Kyiv, , Ukraine

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Vinnytsia, , Ukraine

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West Bromwich, , United Kingdom

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Countries

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United States Canada Czechia Germany Hungary India Israel Italy Japan Poland Puerto Rico Russia Slovakia South Africa South Korea Spain Taiwan Ukraine United Kingdom

Other Identifiers

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Legacy #3151-201-008

Identifier Type: OTHER

Identifier Source: secondary_id

2018-001605-93

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D5272C00001

Identifier Type: -

Identifier Source: org_study_id

NCT04718818

Identifier Type: -

Identifier Source: nct_alias

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