Study to find out if the investigational product HP802-247 can help people to treat certain type of leg ulcer

Phase 1

• Conditions: Chronic venous leg ulcer; MedDRA version: 16.0Level: LLTClassification code 10066677Term: Chronic leg ulcerSystem Organ Class: 100000004858; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2012-003286-18-BE
• Lead Sponsor: Smith & Nephew Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-09-17
• Last Update Posted: 8 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 440

Inclusion Criteria

1. Provide informed consent.
2. Age of 18 years and above and of either sex.
3. Willing to comply with protocol instructions, including allowing all trial assessments.
4. Men, women not of child-bearing potential, and women of child-bearing potential (those who are not premenarchal, not surgically sterilized [hysterectomy or bilateral oophorectomy], or not post-menopausal), may participate in the trial if they meet all of the following conditions:
• Not breast feeding
• A negative serum pregnancy test at screening
• Agree to undertake a serum pregnancy test upon exiting the trial
• Do not intend to become pregnant during the trial
• Using adequate birth control methods and agree to continue using those methods for the duration of the trial.

Adequate birth control methods are defined as: hormonal—oral, implantable or injectable contraceptives; mechanical—spermicide in conjunction with a barrier such as a condom or diaphragm; IUD; or surgical sterilization of partner.

NOTE: Women who have had a bilateral tubal ligation are not considered to have been surgically sterilized and must agree to the conditions as specified above.
5. Have a venous leg ulcer (VLU) between the knee and ankle (at or above the malleolus), with a surface area = 2.0 cm2 and = 12.0 cm2 confirmed using the ARANZ Silhouette wound imaging and measurement device.
• If the subject presents with > 1, but = 3 venous leg ulcers on the same leg, the largest qualifying ulcer will be selected as the target ulcer.
• A true single target ulcer MUST be at least 1.0 cm from any other VLU and will be used for treatment and evaluation throughout the trial.
• If the target ulcer is less than 1.0 cm from another VLU, the ulcers may be combined and traced as a single target ulcer provided at least one of the ulcers is greater than or equal to 2.0 cm2 in area. The total surface area must be = 12.0 cm2.
6. Venous insufficiency confirmed by duplex Doppler ultrasound examination for valvular or venous incompetence.
• Availability of a complete report of a previous examination performed within 12 months of screening will be acceptable.
• Plethysmography may be used as an alternative method for confirmation of venous insufficiency in absence of availability of a duplex Doppler ultrasound exam.
7. Arterial supply adequacy confirmed by any one of the following:
• Great toe pressure = 50 mm/Hg
• Systolic blood pressure Ankle Brachial Index (ABI) in the range = 0.8 to = 1.1
• TcPO2 = 40 mmHg from the foot
8. Target ulcer involves a full thickness skin loss, but WITHOUT exposure of tendon, muscle, or bone.
9. Target ulcer duration = 6 weeks but = 104 weeks (24 months).
10. Acceptable state of health and nutrition with pre-albumin levels of = 10 mg/dL (0.10 g/L), serum albumin = 2.0 g/dL (20 g/L), per the Screening central lab report, and no abnormal laboratory values that, in the opinion of the Principal Investigator, place the subject at risk for the trial. Refer to Appendix 18.4 for further details.
11. Per Screening central lab, an HbA1C < 12.0% (108 mmol/mol)
12. Karnofsky score = 60%
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 264
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 176

Exclusion Criteria

1. History of anaphylaxis, serum sickness, or erythema multiforme reaction to aprotinin, bovine serum albumin or bovine serum proteins, penicillin, streptomycin, amphotericin B, , polysorbate 80 or any substance used in the manufacturing of HP802-247 or its vehicle.
2. Prior diagnosis of Systemic Lupus Erythematosus with elevated anti-DNA antibody titers, Buerger’s disease (thromboangiitis obliterans), current diagnosis of vasculitis, or current diagnosis of claudication.
3. Therapy with another investigational agent within thirty (30) days of Screening, or during the trial.
4. A target ulcer of non-venous etiology (e.g., sickle cell anemia, necrobiosis lipoidica diabeticorum, pyoderma gangrenosum, vasculopathic or vasculitic).
5. Deep Vein Thrombosis (DVT) that is acute, defined as the first 10 days from onset of symptoms, or any DVT for which compression bandaging is considered by the Investigator to be contraindicated.
6. Clinical evidence of ulcer bed infection as described in the Study Guide.
7. Documented history of osteomyelitis at the target wound location within 6 months preceding the Screening Visit.
8. Refusal of or inability to tolerate compression therapy.
9. Therapy of the target ulcer with autologous skin graft, Apligraf™, or Dermagraft™ within 30 days preceding the Screening Visit.
10. Therapy of the target ulcer with topical growth factors within 1 week preceding the Screening Visit.
11. Per Screening central lab hematology† report, WBC < 2.0 x 10 (to the power 9)/L, neutrophils < 1.0 x 10 (to the power 9)/L, platelets < 100 x10 (to the power 9)/L, and Hgb < 8.0 g/dL.
12. Per Screening central lab chemistry† report, serum total bilirubin or serum creatinine = 2 times the upper limit of the normal value (ULN); or, aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase = 3 times ULN.
13. Current therapy with systemic antibiotics.
14. Current systemic therapy with cytotoxic drugs.
15. Current therapy with chronic (> 10 days) oral corticosteroids.
16. Current therapy with TNFa inhibitors other than Trental® (pentoxifylline).
17. History of cancer in the preceding 5 years (other than carcinoma in situ of the cervix or adequately treated non-melanoma skin cancers).
18. Any prior exposure to HP802-247 or its vehicle.
Additional Exclusion Criteria Prior to Randomization
19. A rate of healing of the target ulcer by > 0.349 cm during the Run-in period (defined as Run-in Visit 1 to Run-in Visit) 20. Use of excluded concomitant medications or procedures during the Run-in period.
21. A clinically diagnosed infection of the target ulcer requiring treatment.
22. Muscle, tendon, or bone exposure in the target ulcer.
23. Severe uncontrolled edema of the target ulcer leg.
24. In the judgment of the Investigator, the subject is not able to tolerate compression therapy as required by protocol or is not an appropriate trial subject.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified