A Study to Evaluate the Efficacy and Safety of CBL-514 Compared to Placebo in Participants With Dercum's Disease Lipomas

Dercum's Disease Clinical Trial

Official title:

A Single-Blind, Placebo-Control, Randomized Phase 2 Study to Evaluate the Efficacy and Safety of CBL-514 in Participants With Dercum's Disease Lipomas

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06303570
• Other study ID #: CBL-0202DD
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 28, 2024
• Est. completion date: May 23, 2025

Study information

• Verified date: February 2024
• Source: Caliway Biopharmaceuticals Co., Ltd.
• Contact: Sandy Liu
• Phone: +886 2 26971355
• Email: cr[@]caliway.com.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single-blind, placebo-controlled, randomized phase 2 study to evaluate the efficacy and safety of CBL-514 injections in participants with Dercum's Disease lipomas.

Description:

This is a phase 2 study to evaluate the efficacy and safety of CBL-514 injections in participants with Dercum's disease lipomas.

A total of approximately 30 participants will be randomized. Eligible participants will be randomized (1:1) to receive either CBL-514 or placebo once every 4 weeks for up to 5 treatments for each selected lipoma. This means that there will be 15 participants in each dose group (CBL-514 group and placebo group). Eligible participants must have at least 4 and up to 10 painful individual lipomas. The injection volume per lipoma will depend on the lipoma size (as determined by ultrasound).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: May 23, 2025
• Est. primary completion date: May 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

1. Male or female, aged 18 years to 64 years old (at screening), inclusive.

2. Body mass index (BMI) >18.5 kg/m2 at screening and Day 1.

3. Has confirmed DD and/or fulfills the following clinical criteria of DD in localized nodular form. The final diagnosis of disease is in the opinion of the Investigator.

1. Chronic pain (>3 months) in the adipose tissue specific to the presence of lipomas and/or

2. Pain in and around multiple lipomas.

4. Has at least 4 and up to 10 painful and well-defined lipomas with dimension of =10 mm and =50 mm as measured by ultrasound (read by the Investigator) at screening. The selected lipomas to be treated must meet the following conditions at screening.

1. At least 4 lipomas among the 10 lipomas should have greatest dimension of = 20 mm but =50 mm.

2. Pain level is =4 scores as assessed by Comparative Pain Scale.

3. Excluding lipomas in proximity to vulnerable anatomic structures, including the salivary glands, lymph nodes, muscles, and along the anatomic landmarks of the marginal mandibular nerve.

4. Isolated form and not connected with other lipoma(s).

5. Generally considered healthy according to medical history, physical examination, ECG, and laboratory evaluation.

6. Voluntarily signs the informed consent form (ICF) and, in the opinion of the Investigator or designee, is physically and mentally capable of participating in the study, and willing to adhere to study procedures.

Exclusion Criteria:

1. Female participant of childbearing potential who is not willing to commit to an acceptable contraceptive regimen from the time of screening and throughout study participation until 90 days after the last IP dose, or who is currently pregnant or lactating. Female participant of childbearing potential who is breastfeeding or anticipates breastfeeding from the time of screening and throughout study participation until 90 days after the last IP dose. Male participant who is not willing to commit to using of a condom and refraining from sperm donation from the time of the first dose of IP, throughout study participation until 90 days after the last IP dose.

Note: Participants who are not of childbearing potential are not required to use contraception. Females not of childbearing potential are defined as those who have been surgically sterilized (hysterectomy or bilateral oophorectomy) or who are postmenopausal (defined as at least 50 years of age with =12 months of amenorrhea with a follicle stimulating hormone >30 IU/L).

2. Unable to tolerate SC injections.

3. Diagnosed with another disorder with similar characteristics as DD as follows.

1. Madelung's disease: multiple symmetric lipomatosis only localized in the upper body ie, shoulders, neck, or head.

2. Panniculitis: inflammation of the SC adipose tissue, characterized by tender nodules and systemic signs.

3. Proteus syndrome: disproportionate and asymmetric overgrowth of skin, and fatty and connective tissue.

4. PTEN hamartoma syndrome: multiple hamartomas which includes segmental overgrowth, lipomatosis, arteriovenous malformation, and epidermal nevus.

5. Gardner syndrome: multiple digestive adenomas with osteomas and multiple skin and soft tissue tumors.

4. Diagnosed with coagulation disorders or is receiving anticoagulant/antiplatelet therapy or medications or dietary supplements, which inhibit coagulation or platelet aggregation.

5. Has fasting glucose concentration >200 mg/dL, delayed wound healing, bleeding risk, or any diabetic risks which, in the opinion of the Investigator or designee, is inappropriate to participate in the study.

6. Any clinically significant cardiac, hepatic, renal or neurologic/psychiatric disorders that in the opinion of the Investigator places the participant at significant risk, including but not limited to any of the following:

1. Participants with cirrhosis or with inadequate liver function at screening defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or total bilirubin >3.0 upper limit of normal (ULN).

2. Participants with renal impairment, defined as both serum creatinine and blood urea nitrogen >1.5× ULN, or estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2, or who are currently on dialysis.

Note: Participant with an eGFR =60 and <90 mL/min/1.73 m2 at screening should be evaluated by the Investigator for pre-existing renal disease or associated dysfunction. If mild decrease in eGFR is deemed not clinically significant or not related to dysfunction by the Investigator, the participant will not be excluded unless the Investigator deems it necessary.

7. Participant with a history of human immunodeficiency virus (HIV)-1 infection or participant with active HIV infection at screening with positive HIV antigen/antibody (Ag/Ab) combo test.

8. Participant is undergoing chronic steroid or immunosuppressive therapy, with the exception of oral steroid inhalation indicated for asthma management or topical steroid application for skin conditions that are not directly applied to or indirectly affect the treatment area.

9. Participant with active or prior history of malignancies within 5 years before screening or currently being evaluated for a possible malignancy, with the exception of adequately treated basal cell carcinoma of skin and in situ squamous cell carcinoma of skin at Investigator's discretion.

10. Abnormal skin, local skin conditions, or body modifications at the treatment area, which in the opinion of the Investigator, is inappropriate for participation in the study, including but not limited to any of the following:

1. Prior wound, scar tissue, or infection in the treated area.

2. Tattoo in the treated area.

11. Use of any analgesic including Cannabis within 14 days prior to Screening

12. Requiring continual use of any medication that is known to strongly inhibit or induce CYP1A2 enzymes, sensitive CYP1A2 substrates or drugs with narrow therapeutic index during the study that, in the opinion of the Investigator, may affect the evaluation of the study product or place the participant at undue risk.

Note: If a participant needs to use the above mentioned therapeutic agents during the study for any reason, these therapeutic agents should not be used at least for 2 days prior to dosing and until 1 day postdose.

13. Participant who has undergone the following procedures:

1. Liposuction or aesthetic surgery to the region to be treated before screening or during the study,

2. Aesthetic procedure for body contouring, eg, cryolipolysis, ultrasonic lipolysis, low level laser therapy, lipolysis injection to the region to be treated within 12 months before screening or during the study.

14. Unable to receive local anesthesia.

15. Known allergies or sensitivities to the study drug or its components.

16. Use of other investigational drug or device within 12 weeks prior to screening.

Related Conditions & MeSH terms

• Dercum's Disease

Intervention

Drug:
• CBL-514 injection
The total injection volume per lipoma will based on the lipoma size,as determined by ultrasound. Dosing scheme is presented as below: Lipoma diameter of >0mm and <10mm - total injection volume per lipoma: 1 mL ; total of 5 mg CBL-514. Lipoma diameter of =10mm and =20mm - total injection volume per lipoma: 3 mL ; total of 15 mg CBL-514. Lipoma diameter of >20mm and =30mm - total injection volume per lipoma: 6 mL ; total of 30 mg CBL-514. Lipoma diameter of >30mm and =40mm - total injection volume per lipoma: 10 mL ; total of 50 mg CBL-514. Lipoma diameter of >40mm and =50mm - total injection volume per lipoma: 20 mL ; total of 100 mg CBL-514.
• 0.9% Sodium chloride
The total injection volume per lipoma will based on the lipoma size,as determined by ultrasound. Dosing scheme is presented as below: Lipoma diameter of >0mm and <10mm - total injection volume per lipoma: 1 mL. Lipoma diameter of =10mm and =20mm - total injection volume per lipoma: 3 mL. Lipoma diameter of >20mm and =30mm - total injection volume per lipoma: 6 mL. Lipoma diameter of >30mm and =40mm - total injection volume per lipoma: 10 mL. Lipoma diameter of >40mm and =50mm - total injection volume per lipoma: 20 mL.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Caliway Biopharmaceuticals Co., Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To estimate the treatment effect, as measured by Complete Response (CR), between CBL-514 and placebo at Week 12 in participants with Dercum's disease (DD).	Percentage of lipomas with CR as measured by ultrasound (read by central reviewer) after treatment with CBL-514 at Week 12 compared to placebo.	Week 12
Secondary	To estimate the treatment effect, as measured by pain, between CBL-514 and placebo at Week 12 in participants with DD.	Percentage of lipomas which achieve at least 3-score improvement as assessed by the Comparative Pain Scale after treatment with CBL-514 at Week 12 compared to placebo.	Week 12
Secondary	To estimate the treatment effect, as measured by CR, between CBL-514 and placebo, at Weeks 4, 8, 16, 20, and 24.	Percentage of lipomas with CR as measured by ultrasound (read by central reviewer) after treatment with CBL-514 at Weeks 4, 8, 16, 20, and 24 compared to placebo.	Up to Week 24
Secondary	To estimate the treatment effect, as measured by CR, between CBL-514 and placebo, at Weeks 4, 8, 16, 20, and 24.	Percentage of lipomas with CR lasting for at least 4 weeks as measured by ultrasound (read by central reviewer) after treatment with CBL-514 compared to placebo.	Up to Week 24
Secondary	To estimate the treatment effect, as measured by CR, between CBL-514 and placebo, at Weeks 4, 8, 16, 20, and 24.	Percentage of lipomas with CR lasting for at least 8 weeks as measured by ultrasound (read by central reviewer) after treatment with CBL-514 compared to placebo.	Up to Week 24
Secondary	To estimate the treatment effect, as measured by CR, between CBL-514 and placebo, at Weeks 4, 8, 16, 20, and 24.	Duration of CR as measured by ultrasound (read by central reviewer) on the lipomas after treatment.	Up to Week 24
Secondary	To estimate the treatment effect, as measured by CR, between CBL-514 and placebo, at Weeks 4, 8, 16, 20, and 24.	Percentage of participants with CR of one or more lipomas after treatment with CBL-514 compared to placebo.	Up to Week 24
Secondary	To estimate the treatment effect, as measured by partial response, between CBL-514 and placebo, at Weeks 4, 8, 12, 16, 20, and 24.	Percentage of lipomas with partial response as measured by ultrasound (read by central reviewer) after treatment with CBL-514 at Weeks 4, 8, 12, 16, 20, and 24 compared to placebo.	Up to Week 24
Secondary	To estimate the treatment effect, as measured by partial response, between CBL-514 and placebo, at Weeks 4, 8, 12, 16, 20, and 24.	Percentage of lipomas with partial response lasting for at least 4 weeks as measured by ultrasound (read by central reviewer) after treatment with CBL-514 compared to placebo.	Up to Week 24
Secondary	To estimate the treatment effect, as measured by partial response, between CBL-514 and placebo, at Weeks 4, 8, 12, 16, 20, and 24.	Percentage of lipomas with partial response lasting for at least 8 weeks as measured by ultrasound (read by central reviewer) after treatment with CBL-514 compared to placebo.	Up to Week 24
Secondary	To estimate the treatment effect, as measured by partial response, between CBL-514 and placebo, at Weeks 4, 8, 12, 16, 20, and 24.	Time to first occurrence of partial response on each lipoma in CBL-514 group compared to placebo.	Up to Week 24
Secondary	To evaluate the treatment effect, as measured by change in volume, between CBL-514 and placebo, at Weeks 4, 8, 12, 16, 20, and 24.	Percentage change from baseline in lipoma volume as measured by ultrasound (read by central reviewer) at Weeks 4, 8, 12, 16, 20 and 24.	Up to Week 24
Secondary	To evaluate the treatment effect, as measured by pain, between CBL-514 and placebo, at Weeks 4, 8, 12, 16, 20, and 24.	Percentage of lipomas which achieve at least 3-score improvement as assessed by the Comparative Pain Scale after treatment with CBL-514 at Weeks 4, 8, 16, 20, and 24 compared to placebo.	Up to Week 24
Secondary	To evaluate the treatment effect, as measured by pain, between CBL-514 and placebo, at Weeks 4, 8, 12, 16, 20, and 24.	Change from baseline in pain scores on the lipomas, as assessed by the Comparative Pain Scale after treatment with CBL-514 at Weeks 4, 8, 12, 16, 20, and 24 compared to placebo.	Up to Week 24
Secondary	To evaluate the incidence of adverse events of special interests (AESI) as defined in the protocol.	Adverse events (AEs) will be assessed by recording of clinical responses (e.g. treatment-emergent adverse events (TEAEs), and injection site reactions (ISRs)).	From baseline to 8 weeks post final treatment
Secondary	To evaluate the incidence of clinically significant abnormal findings as defined in the protocol as defined in the protocol.	Assessed by significant clinical changes in safety parameter (e.g. laboratory assessments, vital signs, ECGs, physical examinations).	From baseline to 8 weeks post final treatment