RZL-012 for Dercum's Disease Lipomas

Study Overview
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Brief Summary
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Thirty-eight (38) subjects will be included in the study. Subjects will be randomized in a ration of 1:1 to be treated with RZL-012 or placebo. Subjects will be injected with a different doses of RZL-012 according to their lipomas sizes. The total of 38 subjects will be enrolled in 3 clinical sites.

Detailed Description
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This is a multi-center, randomized, double blind, placebo controlled clinical trial in DD subjects having lipomas. Subjects will be randomized, in a 1:1 ratio, into two groups injected with either RZL-012 or vehicle. Once the study ends and codes are opened, 84 days after dosing, placebo-treated subjects will be offered the option of receiving treatment with RZL-012 and followed up for an additional 84 days. At least 4 lipomas/nodules, preferably 6, and no more than 8, will be injected per subject, two of which will be medium (4-5.9 cm), large (6-7.9 cm) or extra-large (8-10 cm) in diameter. Dosing will be according to lipoma size, where the total injected dose will not exceed 240 mg per patient (48 injections at 5mg/injection).

Official Title
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A Double Blind, Randomized, Multi-Center, Placebo-Controlled Phase 2B Clinical Trial for the Evaluation of Efficacy and Safety of RZL-012 in Subjects Having Dercum's Disease Lipomas

Conditions
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Dercum's Disease Lipomas

Intervention / Treatment
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* Drug: RZL-012
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 4 painful lipomas of appropriate size to be injected on a background of Dercum's Disease. Generally considered healthy according to medical history, physical examination, electrocardiogram (ECG) and laboratory evaluation with an emphasis on metabolic parameters (fasting glucose concentration < 200 mg/dL). Subjects must be able to adhere to the visit schedule and protocol requirements and be capable of completing the study. Males or females in the age of fertility are willing to refrain from sexual activity or agree to use a double-barrier contraceptive device (e.g., condom and spermicide) for 4 weeks after treatment with RZL 012. Subjects must sign an informed consent indicating they are aware of the investigational nature of the study. Exclusion Criteria: Unable to tolerate subcutaneous injections. Pregnant women. Subjects with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric disorders, that in the opinion of the investigator places the subject at significant risk. Positive blood screen for Hepatitis B surface antigen (HbSAg), Hepatitis C virus (HCV), or Human immunodeficiency virus (HIV). Subjects with a clinical history of active primary or secondary immunodeficiency, autoimmune disease or subjects taking immunosuppressive drugs such as corticosteroids Subjects with dysfunctional gallbladder activity, e.g. underwent cholecystectomy or cholecystitis. As a result of medical review and physical examination, the PI (or medically qualified nominee) considers the subject unfit for the study. Known sensitivity to components of the injection formulation. Prior wound, tattoo or infection in the treated area. Prior invasive treatment such as surgery or injectable drug at the RZL-012 injected area. Subjects treated chronically at least 3 months prior to study entry with systemic steroids or immunosuppressive drugs. Subjects treated chronically at least one week prior to study entry with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Current participation or participation within 3 months prior to the start of this study in a drug or other investigational research study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RZL-012<br>A single-treatment injection, multiple subcutaneous injections of RZL-012 administered into 4-8 lipomas in each subject, preferably 6. Dosing will be done according to lipomas size, as will be determined by Ultrasound. Each injection contains 0.1mL RZL-012 (5mg). Lipomas in the size of: 2-3.9 cm will be dozed with 0.4mL RZL-012 (20mg). 4-5.9 cm will be dozed with 0.8mL RZL-012 (80mg). 6-7.9 cm will be dozed with 1 mL RZL-012 (100mg). 8-10 cm will be dozed with 1.2 mL RZL-012 (120mg). | Drug: RZL-012<br>* small synthetic molecule for the treatment of Dercum's Disease lipomas<br>|
| Placebo Comparator: Vehicle of RZL-012<br>A single-treatment injection, multiple subcutaneous injections of vehicle administered into 4-8 lipomas in each subject, preferably 6. Dosing will be done according to lipomas size, as will be determined by Ultrasound. Each injection contains 0.1mL vehicle. Lipomas in the size of: 2-3.9 cm will be dozed with 0.4mL vehicle. 4-5.9 cm will be dozed with 0.8mL vehicle. 6-7.9 cm will be dozed with 1 mL vehicle. 8-10 cm will be dozed with 1.2 mL vehicle. | Drug: Vehicle<br>* Vehicle of RZL-012 drug product<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - Change in lipomas dimensions | Evaluation of the efficacy of RZL-012 following injection into lipomas/nodules of Dercum's Disease (DD) subjects. Efficacy will be determined by ultrasound assessment of the lipoma/nodule dimensions after treatment vs baseline. Lipomas Dimensions will be measured for active vs. placebo at days 28,56,84 | 0-84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Key secondary outcome - efficacy - Improvement in pain assessment of individual lipomas | Assessment of lipoma/nodule associated pain using the Comparative Pain Scale. 0 is no pain and 10 is worst pain. Pain measured for active vs. placebo at days 28,56,84 | 0-84 days | 
| Safety change from baseline in clinical laboratory tests | Safety will be assessed by by change-from-baseline values for clinical laboratory tests. measured for active vs. placebo at days 1 and 28 following injection. Number of subjects with abnormal laboratory values will be compared in both study arms. | 0-28 days |