Clinical trial NCT02549170: A Study of HyQvia and Gammagard Liquid (Kiovig) in Adults With Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Official title: A Phase III Study to Evaluate the Efficacy, Safety, and Tolerability of Immune Globulin Infusion 10% (Human) With Recombinant Human Hyaluronidase (HYQVIA/HyQvia) and Immune Globulin Infusion (Human), 10% (GAMMAGARD LIQUID/KIOVIG) for the Treatment of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Keywords: Autoimmune Diseases
Polyneuropathies
Nervous System Diseases
Peripheral Nervous System Diseases
Polyradiculoneuropathy
Autoimmune Diseases of the Nervous System
Immunoglobulins
Immune System Diseases
Demyelinating Diseases
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Neuromuscular Diseases
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2015-09-15
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to learn more about the following treatment options in adults with CIDP:

* Subcutaneous self-infusion with HyQvia.
* Intravenous infusion with Gammagard/Kiovig. Gammagard and Kiovig are the brand names for the same immunoglobulin compound.

The study is in two parts. In Part 1, participants receive either HyQvia or a placebo subcutaneously. In Part 2 (only for participants who have a CIPD relapse during Part 1), participants will receive Gammagard Liquid/Kiovig intravenously. US participants will receive Gamunex-C.

The first SC infusion will be given in the study clinic. The remaining SC infusions may be given in the study clinic or the participant's home. This will be decided by the study doctor and whether the participant or their caregiver can do the self-infusion.


Eligibility criteria: Inclusion Criteria:

1. Males or females of age greater than or equal to (\>=)18 years old at the time of screening.
2. Participant has a documented diagnosis of definite or probable Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) (focal atypical CIDP and pure sensory atypical CIDP will be excluded), as confirmed by a neurologist specializing/experienced in neuromuscular diseases to be consistent with the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 criteria (European Federation of Neurological Societies, 2010). Fulfillment of electrodiagnostic criteria must be confirmed by an independent qualified/experienced central reader.
3. Participant has responded to IgG treatment in the past (partial or complete resolution of neurological symptoms and deficits), and must currently be on stable doses of IGIV treatment within the dose range equivalent to a cumulative monthly dose of 0.4 to 2.4 gram per kilogram (g/kg) BW (inclusive) administered intravenously for at least 12 weeks prior to screening. The dosing interval of IGIV treatment must be between 2 and 6 weeks (inclusive). Variations in the dosing interval of up to ± 7 days or monthly dose amount of up to ± 20% between participant's pre-study Immunoglobulin G (IgG) infusions are within acceptable limits.
4. INCAT disability score between 0 and 7 (inclusive). Participants with INCAT scores of 0, 1 (whether from upper or lower extremities), or 2 (if at least 1 point is from an upper extremity) at screening and/or baseline will be required to have a history of significant disability as defined by an INCAT disability score of 2 (must be exclusively from the lower extremities) or greater documented in the medical record. Participants will be eligible if one of the below eligibility criteria are met:

   Screening and Baseline INCAT disability score of between 3 and 7 inclusive.
   1. Screening and/or Baseline INCAT disability score of 2 (both points are from lower extremities).
   2. Screening and/or Baseline INCAT disability score of 2 (both points are not from lower extremities) AND has at least a score of 2 or greater documented in the medical record prior to screening. If a score was greater than 2 documented in the medical record prior to screening at least 2 points must be from lower extremities.
   3. Screening and/or Baseline INCAT disability score of 0 or 1 AND has at least a score of 2 or greater (both from lower extremities) documented in the medical record prior to screening, at least 2 points must be from lower extremities.
5. If female of childbearing potential, the participant must have a negative pregnancy test at screening and agree to employ a highly effective contraceptive measure throughout the course of the study and for at least 30 days after the last administration of investigational product (IP).
6. Participant is willing and able to sign an Informed Consent Form (ICF).
7. Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

1. Participants with Focal atypical CIDP or pure sensory atypical CIDP.
2. Any neuropathy of other causes, including:

   1. Hereditary demyelinating neuropathies, such as hereditary sensory and motor neuropathy (HSMN) (Charcot-Marie-Tooth \[CMT\] disease), and hereditary sensory and autonomic neuropathies (HSANs).
   2. Neuropathies secondary to infections, disorders, or systemic diseases such as Borrelia burgdorferi infection (Lyme disease), diphtheria, systemic lupus erythematosus, POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome, osteosclerotic myeloma, diabetic and non-diabetic lumbosacral radiculoplexus neuropathy, lymphoma, and amyloidosis.
   3. Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM).
   4. Multifocal motor neuropathy (MMN).
   5. Drug-, biologic-, chemotherapy-, or toxin-induced peripheral neuropathy.
3. Immunoglobulin M (IgM) paraproteinemia, including IgM monoclonal gammopathy with high titer antibodies to myelin-associated glycoprotein.
4. Prominent sphincter disturbance.
5. Central demyelinating disorders (eg, multiple sclerosis).
6. Any chronic or debilitating disease, or central nervous disorder that causes neurological symptoms or may interfere with assessment of CIDP or outcome measures (eg, arthritis, stroke, Parkinson's disease, and diabetic peripheral neuropathy) (Participants with clinically diagnosed diabetes mellitus who do not have diabetic peripheral neuropathy, who have adequate glycemic control with Hemoglobin A1C; also known as glycosylated or glycated hemoglobin (HbA1C) of less than (\<) 7.5% at screening, and who agree to maintain adequate glycemic control during the study are allowed).
7. Congestive heart failure (New York Heart Association \[NYHA\] Class III/IV), unstable angina, unstable cardiac arrhythmias, or uncontrolled hypertension (ie, diastolic blood pressure greater than (\>) 100 millimeter of mercury (mmHg) and/or systolic blood pressure \>160 mmHg).
8. History of deep vein thrombosis or thromboembolic events (eg, cerebrovascular accident, pulmonary embolism) in the past 12 months.
9. Condition(s) which could alter protein catabolism and/or IgG utilization (eg, protein-losing enteropathies, nephrotic syndrome).
10. Known history of chronic kidney disease, or glomerular filtration rate (GFR) of \<60 milliliter per minute per 1.73 square meter (mL/min/1.73m\^2) estimated based on CKD-EPI equation (Levey et al., 2009) at the time of screening.
11. Participant with active malignancy requiring chemotherapy and/or radiotherapy, or history of malignancy with less than 2 years of complete remission prior to screening. Exceptions are: adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and stable prostate cancer not requiring treatment.
12. Clinically significant anemia or hemoglobin (Hgb) level of less than (\<) 10.0 grams per deciliter (g/dL) at screening.
13. Hypersensitivity or adverse reactions (AR's) (eg, urticaria, breathing difficulty, severe hypotension, or anaphylaxis) to human blood products such as human IgG, albumin, or other blood components.
14. Known allergy to hyaluronidase of human (including recombinant human hyaluronidase) or animal origin (such as bee or wasp venom).
15. Known history of or immunoglobulin A (IgA) deficiency (\<8 milligram per deciliter \[mg/dL\]) at screening.
16. Abnormal laboratory values at screening:

    1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \> 2.5\* upper limit of normal (ULN)
    2. Platelet count \<100,000 cells per microliter (cells/mcL).
    3. Absolute neutrophil count (ANC) \<1000 cells/mcL.
17. Ongoing/active infection with hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) Type 1/2 infection.
18. The participant has received or is currently receiving treatment with immunomodulatory/ immunosuppressive agents within 6 months prior to screening.
19. Participant has received or is currently receiving treatment with corticosteroids dose within 8 weeks prior to screening, regardless of indication.
20. Participant has undergone plasma exchange (PE) within 3 months prior to screening.
21. The participant has any disorder or condition that in the investigator's judgment may impede the participant's participation in the study, pose increased risk to the participant, or confound the results of the study.
22. The participant is nursing or intends to begin nursing during the course of the study.
23. Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment, or is scheduled to participate in another clinical study (with the exception of the HYQVIA/HyQvia extension study in CIDP) involving an IP or investigational device during the course of this study.
24. The participant is a family member or employee of the investigator.
25. Participants with acquired or inherited thrombophilic disorders. These will include the specific types of acquired or inherited thrombophilic disorders that could put participants at risk of develop thrombotic events. Examples include:

    a. Hereditary Thrombophilias i. Factor V Leiden mutation. ii. Prothrombin 20210A mutation. iii. Protein C deficiency. iv. Protein S deficiency. v. Antithrombin deficiency. b. Acquired thrombophilias i. Antiphospholipid antibody syndrome. ii. Activated protein C Resistance acquired. iii. Homocystinemia.

Primary outcomes:
measure: Epoch 1: Relapse Rate
timeFrame: Week 32 End of Epoch 1 Treatment (EOET1)/Unscheduled relapse visit assessment (UV)/Early Termination (ET)
measure: Epoch 2: Responder Rate
timeFrame: Up to 6 Months post-Epoch 1 (End of Epoch 2 Treatment [EOE2T])/Unscheduled visit assessment (UV)/Early Termination
Secondary outcomes:
measure: Epoch 1: Percentage of Participants Who Experience a Worsening of Functional Disability
timeFrame: Week 32 (EOET1)/UV/ET
measure: Time to Relapse
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Change From Pre-Subcutaneous (SC) Treatment Baseline in Rasch-built Overall Disability Scale (R-ODS)
timeFrame: Pre-subcutaneous (SC) treatment baseline, end of Epoch 1 treatment (approximately 7.3 months)
measure: Epoch 1: Number of Participants Experiencing Any Treatment-Emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs), Regardless of Causality
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Number of Participants Experiencing Causally Related Serious and/or Non-Serious Adverse Events (SAEs and/or AEs)
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Number of Participants With Serious and/or Non-serious Adverse Reactions (ARs) Plus Suspected ARs
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Number of Treatment-emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions Regardless of Causality
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Number of Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Number of Adverse Events (AEs) Temporally Associated With Infusions
timeFrame: During an infusion or within 72 hours after completion of an infusion (up to Week 32)
measure: Epoch 1: Number of Serious and/or Non-serious Adverse Reactions (ARs) Plus Suspected ARs Associated With Infusions
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Number of Treatment-emergent Systemic Adverse Events (AEs) Associated With Infusions
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Number of Treatment-emergent Local Infusion Site Reactions Associated With Infusions
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Number of Infusions in Participants for Which the Infusion Rate Was Reduced And/Or the Infusion Was Interrupted or Stopped Due to Intolerability And/Or Adverse Events (AEs)
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Infusion
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Participant
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per 1000 Participant-year
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Infusion
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Participant
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events Per Participant-year
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) Plus Suspected ARs, Expressed as Number of Events Per Infusion
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) Plus Suspected ARs, Expressed as Number of Events Per Participant
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Rates of Systemic and Local Adverse Reactions (ARs) Plus Suspected ARs, Expressed as Number of Events Per 1000 Participant-Year
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 1: Number of Participants Who Develop Binding and/or Neutralizing Antibodies to Recombinant Human Hyaluronidase (rHuPH20)
timeFrame: Week 32 (EOET1)/UV/ET
measure: Epoch 2: Number of Participants Experiencing Any Treatment-emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs), Regardless of Causality
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Number of Participants Experiencing Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs)
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Number of Participants With Serious and/or Non-serious Adverse Reactions (ARs) Plus Suspected ARs
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Number of Treatment-emergent Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions Regardless of Causality
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Number of Causally Related Serious and/or Non-serious Adverse Events (SAEs and/or AEs) Associated With Infusions
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Number of Adverse Events (AEs) Temporally Associated With Infusions
timeFrame: During an infusion or within 72 hours after completion of an infusion (up to Week 32)
measure: Epoch 2: Number of Serious and/or Non-serious Adverse Reactions (ARs) Plus Suspected ARs Associated With Infusions
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Number of Treatment-emergent Systemic Adverse Events (AEs) Associated With Infusions
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Number of Treatment-emergent Local Infusion Site Reactions Associated With Infusions
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Number of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped Due to Intolerability and/or Adverse Events (AEs)
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Infusion
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per Participant
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Rates of Systemic and Local Adverse Events (AEs), Regardless of Causality, Expressed as Number of Events Per 1000 Participant-year
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed As Number of Events Per Infusion
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events Per Participant
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Rates of Causally Related Systemic and Local Adverse Events (AEs), Expressed as Number of Events Per Participant-Year
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) Plus Suspected Ars, Expressed as Number of Events Per Infusion
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) Plus Suspected ARs, Expressed as Number of Events Per Participant
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Rates of Systemic and Local Adverse Reactions (ARs) Plus Suspected ARs, Expressed as Number of Events Per 1000 Participant-Year
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
measure: Epoch 2: Percentage of Participants With Clinically Meaningful Improvement in Functional Ability
timeFrame: Throughout Epoch 2, up to 6 months post-Epoch 1
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Phoenix
country: United States
facility: Arizona Neuromuscular Research Center
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Neurology
state: Arizona
city: Orange
country: United States
facility: University of California-Irvine
state: California
city: San Francisco
country: United States
facility: Forbes Norris Mda/als Ctr
state: California
city: Aurora
country: United States
facility: Regents of the University of colorado
state: Colorado
city: Centennial
country: United States
facility: Immunoe Research Centers
state: Colorado
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute, Inc.
state: Kansas
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Las Vegas
country: United States
facility: Neurology Center of Las Vegas
state: Nevada
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Austin
country: United States
facility: Austin Neuromuscular Center
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital Research Institute
state: Texas
city: Houston
country: United States
facility: University Texas Physicians CAR
state: Texas
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Italiano
state: Buenos Aires
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Complejo Medico de la Policia Federal Argentina Churruca Visca
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Instituto de Investigaciones Neurologicas Raul Carrea, FLENI
city: Curitiba
country: Brazil
facility: Instituto de Neurologia de Curitiba - Hospital Ecoville
state: Paraná
city: Niterói
country: Brazil
facility: HUAP - UFF - Hospital Universitario Antonio Pedro - Universidade Federal Fluminense
state: Rio Do Janeiro
city: Campinas
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da UNICAMP
state: Sao Paulo
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clínicas FMRP-USP
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Hospital Sao Paulo
state: Sao Paulo
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: London
country: Canada
facility: LHSC - University Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Medellin
country: Colombia
facility: Institucion Prestadora de Servicios de Salud de la Universidad de Antioquia "IPS UNIVERSITARIA"
city: Rijeka
country: Croatia
facility: Clinical Hospital Centre Rijeka
city: Zagreb
country: Croatia
facility: Clinical Hospital Centar Zagreb
city: Zagreb
country: Croatia
facility: University Hospital Centre "Sestre Milosrdnice"
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Ostrava - Poruba
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Aarhus
country: Denmark
facility: Århus Universitetshospital
city: Nice Cedex 1
country: France
facility: CHU de Nice Hôpital Pasteur 2
state: Alpes Maritimes
city: Marseille cedex 5
country: France
facility: Hôpital de la Timone
state: Bouches-du-Rhône
city: Bordeaux Cedex
country: France
facility: Groupe Hospitalier Pellegrin - Hôpital Pellegrin
state: Gironde
city: Bron cedex
country: France
facility: Hopital Neurologique Pierre Wertheimer
state: Rhone
city: Göttingen
country: Germany
facility: Universitaetsmedizin Goettingen
state: Niedersachsen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
state: Nordrhein Westfalen
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig AoeR
state: Sachsen
city: Patras
country: Greece
facility: University Hospital of Patra
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo della Sofferenza
state: Foggia
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
city: Rome
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Tor Vergata
state: Roma
city: Genova
country: Italy
facility: Azienda Ospedaliero Universitaria San Martino
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico G. Martino
city: Milano
country: Italy
facility: Casa di Cura del Policlinico
city: Pavia
country: Italy
facility: Fondazione Istituto Neurologico Casimiro Mondino
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
city: Torino
country: Italy
facility: Azienda Ospedaliera Città della Salute e della Scienza di Torino
city: Udine
country: Italy
facility: Azienda Ospedaliero-Universitaria Santa Maria della Misericordia
city: Mexico
country: Mexico
facility: Instituto Nacional de Ciencias Médicas y Nutricion Dr. Salvador Zubiran
state: Distrito Federal
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Ullevål
city: Gdansk
country: Poland
facility: COPERNICUS Podmiot Leczniczy Sp. z o. o.,
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
city: Łódź
country: Poland
facility: Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Nis
country: Serbia
facility: Clinical Center Nis
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava Nemocnica ak. L. Derera, II. Neurologicka klinika
city: Nitra
country: Slovakia
facility: Fakultna nemocnica Nitra
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Halmstad
country: Sweden
facility: Hallands sjukhus
city: Denizli
country: Turkey
facility: Pamukkale Uni. Med. Fac.
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
city: Izmir
country: Turkey
facility: Dokuz Eylul University Faculty of Medicine
city: Konya
country: Turkey
facility: Selcuk Universitesi Selcuklu Tip Fakultesi Hastanesi
city: Manisa
country: Turkey
facility: Celal Bayar University Medical Faculty
city: Bristol
country: United Kingdom
facility: Southmead Hospital
state: Avon
city: London
country: United Kingdom
facility: King's College Hospital
state: Greater London
city: Liverpool
country: United Kingdom
facility: The Walton Centre
state: Merseyside
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: