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

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ClinicalTrials.gov Identifier: NCT02700529
Recruitment Status : Completed
First Posted : March 7, 2016
Last Update Posted : February 6, 2020
Sponsor:
Information provided by (Responsible Party):
Eiger BioPharmaceuticals

Tracking Information
First Submitted Date  ICMJE February 26, 2016
First Posted Date  ICMJE March 7, 2016
Last Update Posted Date February 6, 2020
Study Start Date  ICMJE June 2016
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2016)
Change in skin thickness of the calf of the most affected leg, measured by skinfold calipers [ Time Frame: Week 24 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2016)
  • Change in lymphedema-specific patient reported outcome measures (Patient-Reported Evaluation of Lymphedema [Leg]) questionnaire results [ Time Frame: Week 24 ]
  • Change in leg volume of the most affected leg [ Time Frame: Week 24 ]
  • Change in extracellular fluid volume of the lower limb, measured by the bioimpedance spectroscopy device. [ Time Frame: Week 24 ]
  • Change in biospy result for dermal thickness [ Time Frame: Week 24 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ubenimex in Adult Patients With Lymphedema of The Lower Limb (ULTRA)
Official Title  ICMJE 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)
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Lymphedema
Intervention  ICMJE
  • Drug: ubenimex
  • Other: placebo
Study Arms  ICMJE
  • Experimental: ubenimex
    ubenimex capsules 150 mg three times a day (TID), administered orally for a total of 24 weeks.
    Intervention: Drug: ubenimex
  • Placebo Comparator: placebo
    matched placebo capsules TID, administered orally for a total of 24 weeks
    Intervention: Other: placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 28, 2017)
46
Original Estimated Enrollment  ICMJE
 (submitted: March 2, 2016)
45
Actual Study Completion Date  ICMJE February 2019
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02700529
Other Study ID Numbers  ICMJE EIG-UBX-003
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eiger BioPharmaceuticals
Study Sponsor  ICMJE Eiger BioPharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Eiger BioPharmaceuticals
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP