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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02700529




Registration number
NCT02700529
Ethics application status
Date submitted
26/02/2016
Date registered
7/03/2016
Date last updated
6/02/2020

Titles & IDs
Public title
Ubenimex in Adult Patients With Lymphedema of The Lower Limb (ULTRA)
Scientific title
Ubenimex in Adult Patients With Lymphedema of The Lower Limb: a Phase 2, RAndomized, Double-blind, Placebo-controlled Study of Efficacy, Safety, and Pharmacokinetics (ULTRA)
Secondary ID [1] 0 0
EIG-UBX-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphedema 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ubenimex
Other interventions - placebo

Experimental: ubenimex - ubenimex capsules 150 mg three times a day (TID), administered orally for a total of 24 weeks.

Placebo Comparator: placebo - matched placebo capsules TID, administered orally for a total of 24 weeks


Treatment: Drugs: ubenimex


Other interventions: placebo


Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in skin thickness of the calf of the most affected leg, measured by skinfold calipers
Timepoint [1] 0 0
Week 24
Secondary outcome [1] 0 0
Change in lymphedema-specific patient reported outcome measures (Patient-Reported Evaluation of Lymphedema [Leg]) questionnaire results
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Change in leg volume of the most affected leg
Timepoint [2] 0 0
Week 24
Secondary outcome [3] 0 0
Change in extracellular fluid volume of the lower limb, measured by the bioimpedance spectroscopy device.
Timepoint [3] 0 0
Week 24
Secondary outcome [4] 0 0
Change in biospy result for dermal thickness
Timepoint [4] 0 0
Week 24

Eligibility
Key inclusion criteria
1. Has a diagnosis of secondary leg lymphedema, based on a positive lymphoscintigraphy
(LSG) study of the affected leg OR has a diagnosis of primary lymphedema not of
congenital onset affecting one or both lower limbs, based on positive LSG.

2. Swelling of at least 1 leg not completely reversed by leg elevation or compression.

3. Stage II or greater lymphedema, based on the International Society of Lymphology (ISL)
staging system.

4. Completion of a full course of complete decongestive therapy (CDT).

5. Stable limb volume (within 10% during screening for worse/affected leg) .

6. If patient has had a lymphatic vascularization procedure (lymphovenous bypass or lymph
node transfer) or liposuction for lymphedema in the affected limb, then procedure must
have been performed at least 1 year (12 months) prior to Screening AND affected limb
must be clinically stable over the 3 months prior to Screening AND significant
residual disease must be present.

7. Ambulatory status (use of a walking aid is permitted).

8. Agree to use a medically acceptable method of contraception, if the possibility of
conception exists.
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusions Based on Lymphedema:

1. A diagnosis of primary lymphedema with congenital onset. Primary lymphedema is defined
as lymphedema with onset prior to or without an inciting event (e.g, surgery, trauma,
radiation)

2. Occurrence of significant lymphedema of another body part that is not the lower limb
(e.g, upper extremity, trunk, head and neck, genitalia).

3. Lymphedema involving all four limbs

4. Recent initiation of, or intention to initiate CDT or maintenance physiotherapy for
lymphedema.

Exclusions Based on Other Medical Conditions

5. Deep venous thrombosis in either lower limb or systemic anticoagulation within 6
months

6. Other medical condition that could lead to acute or chronic leg edema.

7. Other medical condition that could result in symptoms overlapping those of lymphedema
in the affected leg.

8. History of clotting disorder (hypercoagulable state).

9. Chronic (persistent) infection in either lower limb.

10. Cellulitis or other infection in either lower limb or use of antibiotics for
cellulitis within 3 months prior to screening.

11. Other unstable or severe medical condition requiring active management and/or likely
to decompensate/require active management within the next year

12. Current evidence of malignancy.

13. History of malignancy within the previous 3 years, except for nonmelanoma skin cancer
or cervical carcinoma in situ treated with curative intent.

14. Currently receiving chemotherapy or radiation therapy.

15. Life expectancy < 2 years for any reason.

16. Pregnancy or nursing.

17. Substance abuse (such as alcohol or drug abuse) within 6 months prior to screening.

Exclusions Based on Concurrent Medication Use

18. Regular concurrent use or regular use within 6 months before screening of another
leukotriene pathway inhibitor.

19. Concurrent antibiotic use.

20. Concurrent use of any agent active on the sphingosine-1-phosphate (S1P) pathway.

21. Concurrent use of unapproved (including herbal) treatments for lymphedema.

Exclusions Based on Laboratory Values

22. Significant or chronic renal insufficiency or requires dialytic support.

23. Hepatic dysfunction.

24. Absolute neutrophil count <1500 mm3 at screening.

25. Hemoglobin concentration <9 g/dL at screening.

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Macquarie University Hospital (MUH) - Sydney
Recruitment postcode(s) [1] 0 0
2109 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eiger BioPharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Leukotriene B4 (LTB4) inhibits lymphangiogenesis in the mouse tail model of lymphedema and is
elevated in tissue in patients with lymphedema. Ubenimex is an inhibitor of leukotriene A4
hydrolase (LTA4H), the biosynthetic enzyme for LTB4. This proof-of-concept study is designed
as a randomized, double-blind, placebo-controlled study comparing ubenimex at 150 mg, 3 times
daily (total daily dose of 450 mg) with placebo for 6 months treatment period in patients
with leg lymphedema. The primary objectives for the study are:

- To evaluate the efficacy of ubenimex in patients with leg lymphedema

- To evaluate the safety and tolerability of ubenimex in patients with leg lymphedema
Trial website
https://clinicaltrials.gov/show/NCT02700529
Trial related presentations / publications
Orning L, Krivi G, Fitzpatrick FA. Leukotriene A4 hydrolase. Inhibition by bestatin and intrinsic aminopeptidase activity establish its functional resemblance to metallohydrolase enzymes. J Biol Chem. 1991 Jan 25;266(3):1375-8.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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

Summary results
Other publications