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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01796171




Registration number
NCT01796171
Ethics application status
Date submitted
19/02/2013
Date registered
21/02/2013
Date last updated
21/06/2024

Titles & IDs
Public title
A Phase 1/2 Study of Betalutin for Treatment of Relapsed Non-Hodgkin Lymphoma
Scientific title
A Phase 1/2 Study of Lutetium (177Lu)-Lilotomab Satetraxetan (Betalutin®) Antibody-radionuclide-conjugate for Treatment of Relapsed Non-Hodgkin Lymphoma.
Secondary ID [1] 0 0
EudraCT: 2011-000033-36
Universal Trial Number (UTN)
Trial acronym
LYMRIT-37-01
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Hodgkin Lymphoma 0 0
Follicular Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Part A, Arm 1: 10 MBq/kg Betalutin with lower dose lilotomab pre-dosing - 10 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing

Experimental: Part A, Arm 1: 15 MBq/kg Betalutin with lower dose lilotomab pre-dosing - 15 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing

Experimental: Part A, Arm 1: 20 MBq/kg Betalutin with lower dose lilotomab pre-dosing - 20 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing

Experimental: Part A, Arm 2: 10 MBq/kg Betalutin with no pre-dosing - 10 MBq/kg (based on body weight) Betalutin without pre-dosing

Experimental: Part A, Arm 2: 15 MBq/kg Betalutin with no pre-dosing - 15 MBq/kg (based on body weight) Betalutin without pre-dosing

Experimental: Part A, Arm 3: 15 MBq/kg Betalutin with rituximab pre-dosing - 15 MBq/kg (based on body weight) Betalutin with rituximab pre-dosing

Experimental: Part A, Arm 4: 15 MBq/kg Betalutin with higher dose lilotomab pre-dosing - 15 MBq/kg (based on body weight) Betalutin with 100 mg/m2 (based on body surface area) lilotomab pre-dosing

Experimental: Part A, Arm 4: 20 MBq/kg Betalutin with higher dose lilotomab pre-dosing - 20 MBq/kg (based on body weight) Betalutin with 100 mg/m2 (based on body surface area) lilotomab pre-dosing

Experimental: Part A, Arm 5: 20 MBq/kg Betalutin with intermediate dose lilotomab pre-dosing - 20 MBq/kg (based on body weight) Betalutin with 60 mg/m2 (based on body surface area) lilotomab pre-dosing

Experimental: Part B, Arm 1: 15 MBq/kg Betalutin with lower dose lilotomab pre-dosing - 15 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing

Experimental: Part B, Arm 2: 20 MBq/kg Betalutin with higher dose lilotomab pre-dosing - 20 MBq/kg (based on body weight) Betalutin with 100 mg/m2 (based on body surface area) lilotomab pre-dosing

Experimental: Part B, Arm 3: 12.5 MBq/kg Betalutin with lower dose lilotomab pre-dosing - 12.5 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing

Experimental: Part C: 15 MBq/kg Betalutin with lower dose lilotomab pre-dosing - 15 MBq/kg (based on body weight) Betalutin with 40 mg lilotomab pre-dosing
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A, Phase I
Timepoint [1] 0 0
12 weeks
Primary outcome [2] 0 0
Part A, Phase IIa
Timepoint [2] 0 0
5 years
Primary outcome [3] 0 0
Part B, Phase IIb
Timepoint [3] 0 0
up to 5 years

Eligibility
Key inclusion criteria
Part A and Part C:



1. Histologically confirmed (by World Health Organization [WHO] classification) relapsed incurable non-Hodgkin B-cell lymphoma of following subtypes; follicular grade I-IIIA (for Part C, this excludes patients meeting Part B criteria, who should enter Part B), marginal zone, small lymphocytic, lymphoplasmacytic, mantle cell.
2. Age = 18 years.
3. Part A: A pre-study WHO performance status of 0-1; Part C: WHO performance status of 0-2.
4. Life expectancy should be =3 months.
5. <25% tumour cells in bone marrow biopsy (biopsy taken from a site not previously irradiated).
6. Measurable disease by radiological methods.
7. Women of childbearing potential must:

1. understand that the study medication is expected to have teratogenic risk.
2. have a negative pregnancy test.
3. agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study medication, throughout study medication therapy and for 12 months after end of study medication therapy, even if she has amenorrhoea.
8. Male patients must agree to use condoms during intercourse throughout study medication therapy and the following 12 months.
9. Patients previously treated with native rituximab are eligible.
10. The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow up visits and examination.
11. The patient has been fully informed about the study and has signed the informed consent form.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Medical contraindications, including uncontrolled infection, severe cardiac, pulmonary, neurologic, psychiatric or metabolic disease, uncontrolled asthma/allergy requiring systemic steroids, known to be human immunodeficiency virus (HIV) positive.

2. Laboratory values within 15 days pre-registration:

1. Absolute neutrophil counts (ANC) =1.5×109/L.
2. Part A: Platelet count =150×109/L; Part C: Platelet count <150×109/L. For Part C, criteria 2a and 2b must be satisfied within 72 hours of the administration of rituximab
3. Total bilirubin =30 mmol/L (Part A only). Total bilirubin > 1.5×ULN (except patients with documented Gilbert's syndrome [=3.0 mg/dL]) (Part C only).
4. Alkaline phosphatase (ALP) and alanine transaminase (ALT) =4×normal level (Part A only).

Aspartate transaminase (AST), ALT or ALP >2.5×ULN (or >5.0×ULN with liver involvement by primary disease). (Part C only).
5. Creatinine =115 µmol/L (men), 97 µmol/L (women) (Part A only). Serum creatinine =1.5×ULN (Part C only).
6. Haemoglobin <9.0 g/dL (Part C only). 3. Known central nervous system (CNS) involvement of lymphoma. 4. Previous total body irradiation. 5. Positive test for human anti-murine antibody (HAMA) at screening. 6. Chemotherapy or immunotherapy received within the last 4 weeks prior to start of study treatment. Pre treatment with rituximab is allowed.

7. Pregnant or lactating women. 8. Previous hematopoietic stem cell transplantation (autologous and allogenic). 9. Part A: Previous treatment with radioimmunotherapy. Part C: Not applicable. 10. Actively participating in another study or received an IMP within 4 weeks prior to enrolment.

11. Receipt of live-attenuated vaccine within 30 days prior to enrolment. 12. Part A and Part C: Test positive for hepatitis B (HBsAg and anti-HBc). Part C only: Test positive for hepatitis C and human immunodeficiency virus (HIV).

13. A known hypersensitivity to rituximab, lilotomab, Betalutin or murine proteins or any excipient used in rituximab, lilotomab, or Betalutin.

Part B:

Inclusion Criteria:

Histologically confirmed (by WHO classification) relapsed non-Hodgkin B-cell FL (grade I IIIA).

2. Male or female aged =18 years. 3. Received at least 2 prior systemic anti-neoplastic or immunotherapy-based regimens (maintenance therapy following a CR/PR is not considered to be a separate line of therapy). Systemic regimens including agents such as idelalisib or other PI3K inhibitors qualify as a prior line of therapy.

4. Prior therapy must have included a rituximab/anti-CD20 agent and an alkylating agent - which may be been administered in separate regimens.

5. Patients must be refractory to any at least one previous regimen that contained rituximab or an anti CD20 agent, with refractoriness defined as:

i. no response (no CR or PR) during therapy, or ii. a response (CR/PR) lasting less than 6 months after the completion of a regimen including rituximab/anti-CD20 therapy (including occurrence of progressive disease (PD) during rituximab/anti-CD20 maintenance therapy, or within 6 months of completion of maintenance therapy).

6. WHO performance status of 0-2. 7. Life expectancy of =3 months. 8. Bone marrow tumour infiltration <25% (in biopsy taken from a site not previously irradiated).

9. Measurable disease by CT or MRI: longest diameter (LDi) >1.5 cm for nodal lesion, LDi >1.0 cm for extra nodal lesion on an assessment performed during the screening period.

Criteria 10 and 11 must be satisfied within 72 hours of the administration of rituximab:

10. ANC =1.5×109/L. 11. Platelet count =100×109/L.

Criteria 12 to 15 must be verified at time of eligibility review within 2 weeks prior to rituximab administration:

12. Haemoglobin =9.0 g/dL. 13. Total bilirubin =1.5×upper limit of normal (ULN) (except patients with documented Gilbert's syndrome [<3.0 mg/dL]).

14. Liver enzymes: AST; ALT or ALP =2.5×ULN (or =5.0×ULN with liver involvement by primary disease).

15. Adequate renal function as demonstrated by a serum creatinine <1.5×ULN. 16. Women of childbearing potential must:

1. understand that the study medication is expected to have teratogenic risk.
2. have a negative serum beta human-chorionic gonadotropin (ß-HCG) pregnancy test at screening.
3. commit to continued abstinence from heterosexual intercourse (excluding periodic abstinence or the withdrawal method) or begin a highly effective method of birth control with a Pearl-Index <1%, without interruption, from 4 weeks before starting study medication, throughout study medication therapy and for 12 months after end of study medication therapy, even if she has amenorrhoea. Apart from abstinence, highly effective methods of birth control are: i. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal).

ii. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) iii. Intrauterine device (IUD). iv. Intrauterine hormone-releasing system (IUS). v. Bilateral tubal occlusion. vi. Vasectomised partner. 17. Male patients must agree to use condoms during intercourse throughout study treatment administration and for 12 months following administration of Betalutin.

18. The patient is willing and able to comply with the protocol, and agrees to return to the hospital for follow up visits and examination.

19. The patient has been fully informed about the study and has signed the informed consent form.

20. Negative HAMA test at screening. 21. Negative test at screening for Hepatitis B (negative HBsAg and anti-HBc), Hepatitis C and HIV.

Exclusion Criteria

1. Prior hematopoietic allogenic stem cell transplantation.
2. Patients with a prior autologous SCT are excluded unless at least two years have elapsed since transplantation.
3. Evidence of histological transformation from FL to diffuse large B-cell lymphoma (DLBCL) at time of screening (transformation to grade IIIB that was successfully treated with recurrence of grade I-IIIA initial clone is accepted).
4. Previous total body irradiation.
5. Prior anti-lymphoma therapy (chemotherapy, immunotherapy or other systemic agent including any investigational agent) within 4 weeks prior to start of study treatment (corticosteroid treatment at doses of = 20 mg/day, topical or inhaled corticosteroids, granulocyte colony-stimulating factor [G-CSF] or granulocyte-macrophage colony-stimulating factor [GM-CSF] are permitted up to 2 weeks prior to start of rituximab)..
6. Patients who are receiving any other investigational medicinal products.
7. Patients with known or suspected CNS involvement of lymphoma.
8. History of malignancy other than FL within 5 years prior to screening( i.e. patients with cancer diagnosed within 5 years prior to screening or who were diagnosed prior to 5 years and were not in CR or were on treatment within 5 years prior to screening), with the exception of malignancies with a negligible risk of metastasis or death (e.g. 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localised prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.

.9. Pregnant or breastfeeding women. 10. Exposure to another CD37 targeting drug. 11. A known hypersensitivity to rituximab, lilotomab, Betalutin or murine proteins or any excipient used in rituximab, lilotomab, or Betalutin.

12. Has received a live-attenuated vaccine within 30 days prior to enrolment. 13. Evidence of severe or uncontrolled systemic diseases:

1. Uncontrolled infection including evidence of ongoing systemic bacterial, fungal, or viral infection (excluding viral upper respiratory tract infections) at the time of initiation of study treatment.
2. Pulmonary conditions e.g. unstable or uncompensated respiratory disease.
3. Hepatic, renal, neurological, or metabolic conditions - which in the opinion of the investigator would compromise the protocol objectives.
4. Psychiatric conditions e.g. patients unlikely to comply with the protocol, e.g. mental condition rendering the patient unable to understand the nature, scope, and possible consequences of participating in the study.
5. History of erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome.
6. Cardiac conditions in the previous 24 weeks (before date of consent), including

i. history of acute coronary syndromes (including unstable angina). ii. class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.

iii. known uncontrolled arrhythmias (except sinus arrhythmia).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/10/2022
Sample size
Target
Accrual to date
Final
191
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 0 0
7000 - Hobart
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
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United States of America
State/province [4] 0 0
Illinois
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United States of America
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Kentucky
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United States of America
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Louisiana
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Oregon
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United States of America
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Pennsylvania
Country [11] 0 0
United States of America
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Texas
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Austria
State/province [12] 0 0
Innsbruck
Country [13] 0 0
Austria
State/province [13] 0 0
Wien
Country [14] 0 0
Belgium
State/province [14] 0 0
Gent
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Belgium
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La Louvière
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Belgium
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Leuven
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Canada
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London
Country [18] 0 0
Canada
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Sault Ste Marie
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Canada
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Toronto
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Croatia
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Zagreb
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Czechia
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Olomouc
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Czechia
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Ostrava-Poruba
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Denmark
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Aarhus
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Denmark
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Odense
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Finland
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Helsinki
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Finland
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Jyväskylä
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France
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Bordeaux
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France
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Grenoble
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France
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Paris
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France
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Pierre-Bénite
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France
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Tours
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Hungary
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Budapest
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Ireland
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Dublin
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Ireland
State/province [34] 0 0
Galway
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Israel
State/province [35] 0 0
Afula
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Israel
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Be'er Ya'aqov
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Tel Aviv
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Italy
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Alessandria
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Italy
State/province [41] 0 0
Bologna
Country [42] 0 0
Italy
State/province [42] 0 0
Firenze
Country [43] 0 0
Italy
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Meldola
Country [44] 0 0
Italy
State/province [44] 0 0
Milano
Country [45] 0 0
Italy
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Napoli
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Italy
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Reggio Emilia
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Italy
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Torino
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Korea, Republic of
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Jeonju
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Korea, Republic of
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Seoul
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Korea, Republic of
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Ulsan
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Netherlands
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Groningen
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Norway
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Bergen
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Norway
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Oslo
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Norway
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Trondheim
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Poland
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Gdynia
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Poland
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Krakow
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Poland
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Warszawa
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Singapore
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Singapore
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Spain
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Barcelona
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Spain
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Cadiz
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Spain
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Majadahonda
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Spain
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Ourense
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Spain
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Pamplona
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Spain
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Salamanca
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Spain
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Seville
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Spain
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Valencia
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Sweden
State/province [67] 0 0
Umeå
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Switzerland
State/province [68] 0 0
Chur
Country [69] 0 0
Turkey
State/province [69] 0 0
Adana
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Turkey
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Ankara
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Turkey
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Eskisehir
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Turkey
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Fatih
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Turkey
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Izmir
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Turkey
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Manisa
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Turkey
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Samsun
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Turkey
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Sehitkamil
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Dorset
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United Kingdom
State/province [78] 0 0
Bristol
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United Kingdom
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Edinburgh
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United Kingdom
State/province [80] 0 0
Glasgow
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United Kingdom
State/province [81] 0 0
London
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United Kingdom
State/province [82] 0 0
Manchester
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United Kingdom
State/province [83] 0 0
Plymouth
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Nordic Nanovector
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
ICON Clinical Research
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Chris Freitag
Address 0 0
Nordic Nanovector
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol https://cdn.clinicaltrials.gov/large-docs/71/NCT01796171/Prot_000.pdf
Statistical analysis plan Statistical Analysis Plan: Part A main SAP https://cdn.clinicaltrials.gov/large-docs/71/NCT01796171/SAP_001.pdf
Statistical analysis plan Statistical Analysis Plan: Part A SAP addendum https://cdn.clinicaltrials.gov/large-docs/71/NCT01796171/SAP_002.pdf
Statistical analysis plan Statistical Analysis Plan: Part B and C SAP https://cdn.clinicaltrials.gov/large-docs/71/NCT01796171/SAP_003.pdf
Study protocol https://cdn.clinicaltrials.gov/large-docs/71/NCT01796171/Prot_000.pdf
Statistical analysis plan Statistical Analysis Plan: Part A main SAP https://cdn.clinicaltrials.gov/large-docs/71/NCT01796171/SAP_001.pdf
Statistical analysis plan Statistical Analysis Plan: Part A SAP addendum https://cdn.clinicaltrials.gov/large-docs/71/NCT01796171/SAP_002.pdf
Statistical analysis plan Statistical Analysis Plan: Part B and C SAP https://cdn.clinicaltrials.gov/large-docs/71/NCT01796171/SAP_003.pdf



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01796171