Dercum's Disease Lipomas
Conditions
Brief summary
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
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).
Interventions
DRUGRZL-012
small synthetic molecule for the treatment of Dercum's Disease lipomas
DRUGVehicle
Vehicle of RZL-012 drug product
Sponsors
Raziel Therapeutics Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy - Change in Lipomas Dimensions | 0-84 days | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Key Secondary Outcome - Efficacy - Improvement in Pain Assessment of Individual Lipomas | 0-84 days | 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 |
| Safety Number of Participants With One or More Abnormal Laboratory Values up to Day 28 | 0-28 days | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory | 0-84 Days | Improvement in Quality of Life - QOL questionnaire. Improvement will be measured for active vs. placebo at Day 0 and Day 84 following treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RZL-012 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).
RZL-012: small synthetic molecule for the treatment of Dercum's Disease lipomas | 20 |
| Vehicle of RZL-012 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.
Vehicle: Vehicle of RZL-012 drug product | 18 |
| Total | 38 |
Baseline characteristics
| Characteristic | RZL-012 | Total | Vehicle of RZL-012 |
|---|---|---|---|
| Age, Continuous | 52.3 years STANDARD_DEVIATION 11.4 | 50.15 years STANDARD_DEVIATION 11.9 | 48 years STANDARD_DEVIATION 12.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 36 Participants | 17 Participants |
| Region of Enrollment United States | 20 participants | 38 participants | 18 participants |
| Sex: Female, Male Female | 15 Participants | 29 Participants | 14 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 18 |
| other Total, other adverse events | 20 / 20 | 18 / 18 |
| serious Total, serious adverse events | 0 / 20 | 0 / 18 |
Outcome results
Primary
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
Time frame: 0-84 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RZL-012 | Efficacy - Change in Lipomas Dimensions | -15.13 percentage of change from baseline | Standard Deviation 25.56 |
| Vehicle of RZL-012 | Efficacy - Change in Lipomas Dimensions | -15.92 percentage of change from baseline | Standard Deviation 23.96 |
Secondary
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
Time frame: 0-84 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RZL-012 | Key Secondary Outcome - Efficacy - Improvement in Pain Assessment of Individual Lipomas | -56.15 percentage of change from baseline | Standard Deviation 35.77 |
| Vehicle of RZL-012 | Key Secondary Outcome - Efficacy - Improvement in Pain Assessment of Individual Lipomas | -34.34 percentage of change from baseline | Standard Deviation 40.15 |
Secondary
Safety Number of Participants With One or More Abnormal Laboratory Values up to Day 28
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.
Time frame: 0-28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RZL-012 | Safety Number of Participants With One or More Abnormal Laboratory Values up to Day 28 | 0 Participants |
| Vehicle of RZL-012 | Safety Number of Participants With One or More Abnormal Laboratory Values up to Day 28 | 0 Participants |
Other Pre-specified
Exploratory
Improvement in Quality of Life - QOL questionnaire. Improvement will be measured for active vs. placebo at Day 0 and Day 84 following treatment.
Time frame: 0-84 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RZL-012 | Exploratory | 0 Participants |
| Vehicle of RZL-012 | Exploratory | 0 Participants |