Trial of Acebilustat for the Treatment of Upper Arm Lymphedema (HEAL)

A Pilot Placebo-Controlled Trial of Acebilustat (CTX-4430) for the Treatment of Human Upper Extremity Lymphedema

This study is designed to investigate the response of unilateral upper extremity (arm) lymphedema, during pharmacologic treatment of lymphedema with oral placebo and oral acebilustat. Participants will receive "study drug" (Acebilustat or placebo), for 9 months. For 3 of these months, the participant will receive placebo; for 6 of these months, the participant will receive active ingredient, acebilustat. The study is blinded which means that the participant will not be told which study pill they are taking.

Study Overview

• Status: Recruiting
• Conditions: Lymphedema of Upper Arm
• Intervention / Treatment: Drug: Acebilustat; Drug: Placebo

Detailed Description

To enter this study, participants will have to meet requirements that will be evaluated during screening, Visit 1. If eligible, and if they choose to continue, Visit 2, treatment start, will take place 2-7 days later. Study visits are every (approximately) 90 days. Physical exam, including limb measurements and skin measurements (with tape measure and dermal ultrasound) are performed. Phlebotomy for research samples and clinical labs will be performed at study start and end of study.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shayne Hargis; Phone Number: 650-725-9820; Email: heal-lymphedema-study@stanford.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94305
      • Recruiting
      • Stanford University
      • Sub-Investigator: Mark Nicolls, MD
      • Sub-Investigator: Wen Tian, PhD
      • Sub-Investigator: Xinguo Jiang, MD
      • Contact: Shayne Hargis; Phone Number: 650-725-9820; Email: heal-lymphedema-study@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Upper arm lymphedema, single arm, stage 2, greater than 6 months duration
• Male or female.
• Ages 18-75.
• Prior imaging by lymphoscintigraphy or magnetic resonance lymphangiography that confirms the presence of lymphedema in the affected limb OR, at screening, an affected:unaffected limb volume ratio of ≥1.1 with significant history of lymphedema
• Consistent use of an appropriately sized compression garment for daytime use.
• Willing to maintain a stable regimen of self-care from screening to end-of-study.
• If a potential participant has undergone prior microvascular (vascular lymph node transfer, lymphaticovenous anastomosis) or debulking surgical intervention, at least one year must have elapsed prior to screening AND, at screening, an affected: unaffected limb volume ratio of ≥1.1.
• Lymphedema therapy must be completed at least 8 weeks prior to screening.
• Has received Covid-19 vaccine (Pfizer, Moderna or Johnson & Johnson)
• Ability to understand and the willingness to sign a written informed consent document.
• . If the possibility of conception exits, agrees to use a medically acceptable method of contraception (both male and female) from the signing of the informed consent form through the entire study period; men or women who are surgically sterile (> 6 months after surgery) or women who have been postmenopausal for at least 1 year are not considered to be of childbearing potential.

Exclusion Criteria:

• Concurrent participation in a clinical trial of any other investigational drug or therapy
• Other medical condition that could lead to acute limb edema (e.g. acute blood clot) or other medical condition that could result in symptoms overlapping those of lymphedema (e.g. frozen shoulder).
• History of clotting disorder.
• Chronic (persistent) infection in the affected limb.
• Active cancer treatment or history of cancer treatment within the past 2 years, except for non-melanoma skin cancer or cervical cancer in-situ.
• Chronic kidney disease
• Liver disease
• Pregnancy or nursing.
• Substance abuse (e.g., alcohol or drug abuse) within 6 months prior to screening.
• Any current use of non-steroidal anti-inflammatory drug (NSAID), e.g. ibuprofen, ketoprofen) or prior therapeutic use of ketoprofen.
• Any current use of immunosuppressive or immunomodulatory drugs (e.g., immunosuppressants, anticancer drugs, interleukins, interleukin antagonists or interleukin receptor blockers) or leukotriene pathway inhibitor (zileuton), leukotriene receptor antagonist (e.g montelukast).
• Personal or family history of prolonged QT syndrome
• Any reason (in addition to those listed above) that, in the opinion of the investigator, precludes full participation in the study.
• Any current use of statin drugs. The use of any statin drug should be discontinued at least 2 weeks prior to the trial enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo and acebilustat; Participants will take acebilustat and placebo over a period of 9 months.	Drug: Acebilustat; By mouth, once a day, 100 mg capsule; Drug: Placebo; Placebo to match acebilustat by mouth, once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in ultrasonographic measurement of dermal thickness in the affected upper extremity	Dermal thickness will be derived from an ultrasonographic examination of the skin of the forearm using a Terason 3200T device.	Baseline through week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in caliper measurement of dermal thickness in the affected upper extremity	Dermal thickness will be derived from a caliper measurement of the skin of the forearm.	Baseline through week 36

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Celltaxis LLC
• Investigators: Principal Investigator: Stanley Rockson, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2022
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: January 10, 2022
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 24, 2022

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lymphatic Diseases; Lymphedema
• Other Study ID Numbers: IRB-62051; NCI-2022-09343 (Other Identifier: CTRP); BRS0140 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No