Ubenimex in Adult Patients With Lymphedema of The Lower Limb (ULTRA)
Condition: Lymphedema
MeSH terms: Lymphedema
Intervention: ubenimex; placebo
Intervention MeSH terms: Ubenimex
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.

        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.