Ubenimex in Adult Patients With Lymphedema of The Lower Limb (ULTRA)

Inclusion Criteria

• 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.
• Swelling of at least 1 leg not completely reversed by leg elevation or compression.
• Stage II or greater lymphedema, based on the International Society of Lymphology (ISL) staging system.
• Completion of a full course of complete decongestive therapy (CDT).
• Stable limb volume (within 10% during screening for worse/affected leg) .
• 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.
• Ambulatory status (use of a walking aid is permitted).
• Agree to use a medically acceptable method of contraception, if the possibility of conception exists.

Exclusion Criteria

Exclusions Based on Lymphedema:

• 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)
• Occurrence of significant lymphedema of another body part that is not the lower limb (e.g, upper extremity, trunk, head and neck, genitalia).
• Lymphedema involving all four limbs
• Recent initiation of, or intention to initiate CDT or maintenance physiotherapy for lymphedema.

Exclusions Based on Other Medical Conditions

• Deep venous thrombosis in either lower limb or systemic anticoagulation within 6 months
• Other medical condition that could lead to acute or chronic leg edema.
• Other medical condition that could result in symptoms overlapping those of lymphedema in the affected leg.
• History of clotting disorder (hypercoagulable state).
• Chronic (persistent) infection in either lower limb.
• Cellulitis or other infection in either lower limb or use of antibiotics for cellulitis within 3 months prior to screening.
• Other unstable or severe medical condition requiring active management and/or likely to decompensate/require active management within the next year
• Current evidence of malignancy.
• History of malignancy within the previous 3 years, except for nonmelanoma skin cancer or cervical carcinoma in situ treated with curative intent.
• Currently receiving chemotherapy or radiation therapy.
• Life expectancy < 2 years for any reason.
• Pregnancy or nursing.
• Substance abuse (such as alcohol or drug abuse) within 6 months prior to screening.

Exclusions Based on Concurrent Medication Use

• Regular concurrent use or regular use within 6 months before screening of another leukotriene pathway inhibitor.
• Concurrent antibiotic use.
• Concurrent use of any agent active on the sphingosine-1-phosphate (S1P) pathway.
• Concurrent use of unapproved (including herbal) treatments for lymphedema.

Exclusions Based on Laboratory Values

• Significant or chronic renal insufficiency or requires dialytic support.
• Hepatic dysfunction.
• Absolute neutrophil count <1500 mm3 at screening.
• Hemoglobin concentration <9 g/dL at screening.