LymphedemaPhase 2NCT02700529
Ubenimex in Adult Patients With Lymphedema of The Lower Limb (ULTRA)
A Phase 2 study testing ubenimex in people with Lymphedema, run by Eiger BioPharmaceuticals at 4 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Lymphedema
- What is being tested?
- ubenimex
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Jun 2016to Feb 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 29Show fewer
- 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.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States3 sites
The Ohio State University Wexner Medical Center James Cancer Hospital
Columbus, Ohio, 43210
Orlando Health, Inc.
Orlando, Florida, 32806
Stanford University
Stanford, California, 94305
Australia1 site
Macquarie University Hospital (MUH)
Sydney, New South Wales, 2109
About this study
Official 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)
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.
Read the detailed description
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
- Conditions
- Lymphedema
- Being tested
- ubenimex, placebo
- Medical subject headings
- Lymphedema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ubenimexDrug
Also called UBX
placeboOther
| Study group | Role | What they receive |
|---|---|---|
| ubenimex | Experimental | ubenimex capsules 150 mg three times a day (TID), administered orally for a total of 24 weeks. Receives: Drug: ubenimex |
| placebo | Placebo comparator | matched placebo capsules TID, administered orally for a total of 24 weeks Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Skin Thickness of the Calf of the Most Affected Leg, Measured by Skinfold Calipers
Change from baseline to Week 24 in skin thickness of the calf of the most affected leg, measured by skinfold calipers in the Skin-Thickness Intent-to-Treat (ST-ITT) population (patients with skin thickness >/= 10 mm at baseline) which comprised of 36 patients (16 ubenimex, 20 placebo).
Measured: Baseline through Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2016 (estimated)
- Study startJun 2016
- Primary completionOct 2018
- Study completionFeb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphedemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eiger BioPharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02700529
- Sponsor's protocol ID
- EIG-UBX-003
- Status last verified
- Dec 2022
- First submitted
- 26 Feb 2016
- Last updated
- 18 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
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.
PubMed 1846352
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT02700529
- Acronym / sponsor ID
- EIG-UBX-003
- Conditions
- Lymphedema
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Eiger BioPharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jun 2016
- Primary completion
- Oct 2018 (actual)
- Study completion
- Feb 2019 (actual)
- First posted
- 7 Mar 2016 (estimated)
- Results
- Posted 18 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ubenimex | Experimental | Drug: ubenimexubenimex capsules 150 mg three times a day (TID), administered orally for a total of 24 weeks. |
| placebo | Placebo comparator | Other: placebomatched placebo capsules TID, administered orally for a total of 24 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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) .
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ubenimexAlso: UBX | Drug | ubenimex |
| placebo | Other | placebo |
Primary outcome
Change in Skin Thickness of the Calf of the Most Affected Leg, Measured by Skinfold Calipers
Time frame: Baseline through Week 24
Change from baseline to Week 24 in skin thickness of the calf of the most affected leg, measured by skinfold calipers in the Skin-Thickness Intent-to-Treat (ST-ITT) population (patients with skin thickness >/= 10 mm at baseline) which comprised of 36 patients (16 ubenimex, 20 placebo).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 1846352Orning 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ubenimex in people with Lymphedema, run by Eiger BioPharmaceuticals at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Skin Thickness of the Calf of the Most Affected Leg, Measured by Skinfold Calipers (time frame: Baseline through Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02700529, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2023.