Randomized, Placebo-crontrolled Clinical Trial Evaluating the Efficacy and Safety of Heparan Sulfate 120 mg Prolonged-Release Tablets Compared With Placebo in Patients With Chronic Venous Disease (CLR-18)

Multicenter, Randomized, Double-blind, Placebo-controlled, Phase III Study to Evaluate Efficacy and Safety of CLR-07-23 (Heparan Sulfate 120 mg Prolonged-release Tablets) in the Treatment of Primary Chronic Venous Disease

This multicenter, randomized, double-blind study is a phase III evaluates the safety and effectiveness of CLR prolonged-release tablets in patients with chronic venous insufficiency, has been shown to be effective in reducing the symptoms of itching, edema, spontaneous pain, and night cramps chronic venous disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Venous Insufficiency of Leg; Chronic Venous Disease; Vein Disease
• Intervention / Treatment: Other: CLR Placebo; Drug: CLR Tablets - Heparan Sulphate

• Study Type: Interventional
• Enrollment (Estimated): 174
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants with an age ≥ 18 and ≤ 80 years
• Diagnosed primary venous disease of the lower limbs in stage C2 - C5 according to the CEAP classification, involvement of the venous system of the lower limbs is verified by duplex ultrasonography
• Presence of objective signs and subjective symptoms of the disease (classified according to rVCSS score ≥ 4)
• Participants not using or planning to use compression therapy by their own decision
• Provision of written informed consent as approved by the Ethics Committee (EC).

Exclusion Criteria:

• Use of a venoactive drug in the last month
• Regular use of compression therapy or use of mechanical devices for reduction of edema in the last month
• Heart Failure (NYHA class III and IV), congestive heart failure with peripheral edema
• eGFR < 30 mL/min/1.73 m² at screening or chronic kidney disease documented in the medical history
• ALT or AST more than 3 times the upper limit of normal range at screening or advanced liver disease documented in the medical history
• Deep venous thrombosis lower limb thrombosis and / or documented residual venous obstruction or deep venous reflux due to post-thrombotic alterations in the deep venous system
• Superficial venous thrombosis of the lower limbs in the previous 6 months
• Congenital venous/lymphatic malformation
• Neuropathy of any aetiology
• Diabetic foot syndrome
• Refractory (uncontrollable) hypertension (inability to therapeutically achieve a systolic blood pressure ≤ 160 mmHg or a diastolic blood pressure ≤ 100 mmHg)
• Symptomatic ischemic disease of lower limbs
• Lymphoedema: primary, posttraumatic, postoperative, post-radiation, malignant
• Manual/instrumental lymphatic drainage in the last 3 months
• Invasive procedure on the lower limbs in the last 6 months
• Trauma of the lower extremity that has not fully healed
• Use of oral/parenteral anticoagulants
• Use of dual antiplatelet therapy
• Use of loop diuretics

• Use of oestrogens or progesterone and its derivates

  -. Use of oral/parental corticosteroids in the last 6 weeks

• Chronic pain treatment ≥ 14 days
• Use of psychopharmaceuticals affecting fluid retention (antipsychotics, combined antidepressants)
• Severe obesity (BMI > 40 kg/m2)
• Participants with active malignant disease or malignant disease in remission for less than 5 years
• Myeloproliferative or immune disorders
• Contraindications to the IMP/Placebo administration
• Hypersensitivity to the IMP/Placebo excipients. General Conditions
• Pregnant or breastfeeding women
• Women of child-bearing potential not using at least one effective contraceptive method for the entire trial

• Participation in other investigational drug or device clinical trials within 30 days prior to study screening

  -. Participants legally or mentally incapacitated unable to give informed consent for the participation in this trial

• Participants unable or unwilling to comply with appointments or all protocol requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants in this arm receive a placebo tablet identical in appearance to the active treatment, administered orally once daily.	Other: CLR Placebo; Oral placebo tablets administered once daily for one year.
Active Comparator: Heparan Sulphate; Participants in this arm receive active treatment with heparan sulphate tablets, administered orally once daily.	Drug: CLR Tablets - Heparan Sulphate; Oral heparan sulphate tablets, one tablet administered once daily for one year.; Other Names: treatment arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in the Revised Venous Clinical Severity Score (rVCSS) at Visit 5	Revised Venous Clinical Severity Score (rVCSS) at Visit 5 (V5) compared to Visit 1 (V1) in the two groups. The rVCSS is a clinical scale used to assess the severity of chronic venous disease. The total score ranges from a minimum of 0 (indicating no venous disease) to a maximum of 30 (indicating severe venous disease). Higher scores mean a worse clinical outcome.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant Self-Assessment of Pain Severity via Visual Analog Scale (VAS) at Visit 2 and Visit 5 Compared to Visit 1	Pain severity assessed by the participant using the Visual Analog Scale (VAS). The unabbreviated scale title is the Visual Analog Scale. The score ranges from a minimum value of 0 (representing "no pain") to a maximum value of 100 (representing "the worst possible pain"). Higher scores mean a worse outcome (greater pain severity). Unit of measure: score	one year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life Assessment via Chronic Venous Insufficiency Quality of Life (CIVIQ-20) Questionnaire at Visit 5 Compared to Visit 1	Quality of life specific to chronic venous disease assessed via the Chronic Venous Insufficiency Quality of Life (CIVIQ-20) Questionnaire. The total score ranges from a minimum of 20 (excellent quality of life/no symptoms) to a maximum of 100 (worst quality of life/severe symptoms). Higher scores mean a worse outcome. Unit of measure: score	one year
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)	Safety and tolerability evaluated through the quantitative and qualitative assessment of Adverse Events (AEs) and Serious Adverse Events (SAEs) reported throughout the study period. Unit of measure: Percentage of Participants	one year

Collaborators and Investigators

• Sponsor: Barbara Maglione

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: June 17, 2026
• First Submitted That Met QC Criteria: June 29, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Carbohydrates; Glycosaminoglycans; Polysaccharides; Heparitin Sulfate
• Other Study ID Numbers: CLR-07-23

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