Treatment of Women With Lipedema Involving Substantial Fat Knee of Women and Men With Nodular Dercum's Disease

An Open Label, Phase 2a Clinical Trial for the Evaluation of Safety and Efficacy of RZL-012 for the Treatment of Women With Lipedema Involving Substantial Fat Above the Knee or of Women and Men With Nodular Dercum's Disease

This is an open label, 2 cohort, clinical trial in women with lipedema with substantial fat above the knee and men with Dercum's disease. Each cohort will have 6 subjects who will receive RZL-012.

Study Overview

• Status: Completed
• Conditions: Dercum Disease; Lipedema
• Intervention / Treatment: Drug: RZL-012

Detailed Description

This is an open label, 2 cohort, clinical trial in women with lipedema with substantial fat above the knee and men with Dercum's disease.

• The 1st cohort will be comprised of subjects with Dercum's disease.
• The 2nd cohort will be comprised of subjects with lipedema with substantial fat above the knee

Within each cohort dosing of the subjects will progress consecutively from one individual to the other with a minimum 7 days between subjects to asses safety. The study design will allow the physicians to monitor safety for at least 7 days prior to dosing the next subject. Cohort 2 will be conducted in a dose escalation manner and the decision to proceed to the next dose level will be made after reviewing all safety data collected by Day 14 within 2+/-1 day of the last dosed subject. The trial will proceed within a cohort provided that no more than one subject experience intolerable side effects in a cohort, and based on the decision made by the Principal Investigator (PI) and the medical monitor.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Post-menopausal (at least 2 years) women no more than 65 years old, with lipedema involving substantial fat above the knee or nodular Dercum's disease in such women and in men 20 - 65 years with nodular Dercum's disease.
2. For Dercum's disease subjects - at least 2 nodules to be injected of at least 2cm diameter each, as determined by ultrasound
3. For lipedema subjects - Significant subcutaneous fat above the knee as determined by circumference of 50cm
4. Generally considered healthy according to medical history, physical examination, ECG and laboratory evaluation with a special emphasis on metabolic parameters (fasting glucose concentration < 100 mg, normal blood pressure).
5. Subjects must be able to adhere to the visit schedule and protocol requirements and be available to complete the study.
6. Subjects must sign an informed consent indicating that they are aware of the investigational nature of the study.

Exclusion Criteria:

1. Unable to tolerate subcutaneous injection.
2. Subjects with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric disorders, that in the opinion of the investigator, put the subject at significant risk, are not eligible.
3. Positive blood screen for Hepatitis B surface antigen (HbSAg), Hepatitis C virus (HCV), or Human immunodeficiency virus (HIV), or positive urine screen for alcohol or drugs of abuse (unless prescribed by a physician).
4. Subjects with a clinical history of primary or secondary immunodeficiency, autoimmune disease or subjects taking immunosuppressive drugs such as corticosteroids are ineligible.
5. As a result of medical review, physical examination, the PI (or medically qualified nominee) considers the subject unfit for the study.
6. Known sensitivity to components of the injection formulation.
7. Prior wound, tattoo or infection in the treated area.
8. Prior invasive treatment such as surgery or injectable drug at the RZL-012 injected area.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cohort 1 - Dercum's Disease; Nodular size - diameter (cm) 2-2.9, 3-3.9, 4-8 Total dose of RZL-012(mg) 10 15 20 Dose per NOAEL 1/25th , 1/18.75th, 1/12.5th Number of injections: 2,3,4	Drug: RZL-012; The dosing regimen will be a single dose treatment injection of RZL-012 in multiple sites
Active Comparator: Cohort 2 - Lipedema; Total dose of RZL-012 (mg) 60 , 80 Dose per NOAEL: 1/4.6888, 1/3.125 Number of injections: 12, 16	Drug: RZL-012; The dosing regimen will be a single dose treatment injection of RZL-012 in multiple sites

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Incidence of Any Grade 3 or Greater Event Intolerable Side Effect Experienced in a Cohort	Trial will proceed as long as no more than one subject experiences an intolerable side effect in a cohort	0-14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
For lipedema subjects - The reduction of fat above the knee in the injection site region	Evaluated by measurement of leg circumference above the knee compared to baseline.	0-56 days
For Dercum's disease subjects - The reduction in local subcutaneous fat in the injection site region.	Evaluated by the reduction in nodules size and/or n number of nodules as assessed by ultrasound compared to baseline	0-56 days
Extended duration of the fat reduction effect	Assessed by leg circumference measurement that will be followed for 56 days	0-56 days
Elucidation of the tissue changes	Assessed by nodular quality at the injection site by ultrasound and compared to baseline	0-56 days
Improvement in local pain	Assessed by the Comparative Pain Scale and compared to baseline. Comparative Pain Scale ranges are: 1-3 Minor pain, 4-6 Moderate pain, 7-10 Severe pain. Higher values represent worst outcome.	0-56 days
Improvement in pain	Assessed by reduction in the use of analgesics and compared to baseline.	0-56 days
Improvement in physical function in lipedema subjects	Assessed by The Lower Extremity Functional Scale (LEFS). LEFS is used to assess if the patient has difficulties in their physical function activities. For each physical function activity the range is 1-4 when higher values are considered worse outcome. Subscales are combined to compute a total score. The percentage of physical function is calculated by dividing the total score by 80.	0-56 days
For lipedema subjects - The reduction in local subcutaneous fat in the injection site region	Assessed by ultrasound images that will be followed for 56 days	0-56 days

Collaborators and Investigators

• Sponsor: Raziel Therapeutics Ltd.
• Collaborators: University of Arizona
• Investigators: Principal Investigator: Karen Herbst, MD, University of Arizona

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2018
• Primary Completion (Actual): May 2, 2019
• Study Completion (Actual): May 2, 2019

Study Registration Dates

• First Submitted: February 19, 2018
• First Submitted That Met QC Criteria: April 8, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: January 15, 2024
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Skin Diseases; Connective Tissue Diseases; Lipid Metabolism Disorders; Lipomatosis; Lipedema; Adiposis Dolorosa
• Other Study ID Numbers: RZL-012-FD-P2aUS-001.70

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