Evaluating the Safety and Efficacy of GrafixPL™PRIME for the Treatment of Chronic Venous Leg Ulcers

Venous Leg Ulcer Clinical Trial

Official title:

A Multicenter, Prospective, Randomized, Open-Label Study With a Crossover Extension Option to Evaluate the Safety and Efficacy of GrafixPL™PRIME for the Treatment of Chronic Venous Leg Ulcers

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03543007
• Other study ID #: 2018-0480
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2018
• Est. completion date: January 1, 2023

Study information

• Verified date: May 2018
• Source: Georgetown University
• Contact: Paul J Kim, DPM, MS
• Phone: 202-444-0359
• Email: paul.j.kim[@]gunet.georgetown.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Approximately 200 patients (100 in each treatment group) nationally with chronic venous leg ulcers will be randomized to GrafixPL™PRIME plus standard compression therapy or standard compression therapy alone for up to 12 weeks in order to compare the clinical outcomes between the two groups. Specifically, at this Georgetown site, approximately 30 subjects will be recruited.

Description:

The present study is a multi-center, prospective, randomized, open-label trial to evaluate the efficacy of GrafixPL™PRIME plus standard compression therapy for the treatment of chronic venous leg ulcers (VLUs). GrafixPL™PRIME is a commercially available product.

At the screening visit, patients will have their blood drawn and a urine sample will have to be provided. Throughout visits, culture swabs of the wound will be taken.

Approximately 30 patients (15 in each treatment group) at this site will be randomized at a 1:1 ratio to GrafixPL™PRIME plus standard compression therapy or standard compression therapy alone for up to 12 weeks. Allowing for a randomized not treated patient population of 2%, the study is planned for 196 evaluable patients.

Subjects will be in the study for up to 38 weeks.

Subjects randomized to Cohort A: (GrafixPL™PRIME plus standard compression therapy) or Cohort B: (standard compression therapy only). Randomization means that you are put into a group by chance. It is like flipping a coin. Which group you are put in is done by a computer. Neither you nor the researchers will choose what group you will be in. You will have an equal chance of being placed in any group. Neither you nor the investigator will know what group you are in.

Treatment Regimen: All Subjects will receive standard compression therapy weekly throughout the study starting with Screening Visit 1. Multi-layer compression materials will be provided.

All subjects will be asked to complete a Cardiff Wound Impact Schedule (CWIS) survey and a Work Productivity and Activity Impairment Questionnaire every visit after their screening visits.

Cohort A: (GrafixPL™PRIME plus standard compression therapy)

Subjects randomized to GrafixPL™PRIME plus standard compression therapy will receive applications of GrafixPL™PRIME plus standard compression therapy once weekly for up to 12 weeks. Subjects randomized to standard compression therapy alone will receive standard compression therapy once weekly for up to 12 weeks. Both GrafixPL™PRIME plus standard compression therapy and standard compression therapy alone subjects will return for weekly visits until the ulcer has closed or until the End of Treatment Visit. Subjects randomized to treatment with GrafixPL™PRIME plus standard compression therapy will receive GrafixPL™PRIME plus standard compression therapy on Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70 and 77 (plus or minus 3 days) unless ulcer closure is achieved within the 12 week Treatment Phase. If ulcer closure is not achieved, subjects will continue in the study until the End of Treatment Visit. If ulcer closure is achieved, subjects will be followed for up to 168 days (plus or minus 7 days) after the End of Treatment Visit in the Follow-Up Phase.

Cohort B: (standard compression therapy only)

Subjects in the standard compression therapy alone group whose ulcers are not closed at the End of the Treatment Visit will be offered GrafixPL™PRIME plus standard compression therapy in the Crossover Extension Treatment Phase. Subjects randomized to standard compression therapy alone will receive standard compression therapy on Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 70, and 77 (plus or minus 3 days) unless ulcer closure is achieved within the 12 week Treatment Phase. Those who do not achieve ulcer closure within the 12 week Treatment Phase are eligible for the Crossover Extension Treatment Phase for up to 12 weeks of treatment with GrafixPL™PRIME plus standard compression therapy.

These subjects are eligible for up to 12 treatments (once weekly for 12 weeks) of GrafixPL™PRIME plus standard compression therapy. Subjects randomized to GrafixPL™PRIME plus standard compression therapy in the Treatment Phase whose ulcers do not close are not eligible for the Crossover Extension Treatment Phase.

The maximum duration of patient participation in this study is expected to be approximately 38 weeks from the initial Screening Visit to completion of the Follow-Up Visits.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: January 1, 2023
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

1. 18 years or older, as of the date of screening

2. An Index Ulcer that is chronic (defined as present for greater than or equal to 4 weeks, but not present for more than 52 weeks at Screening Visit 1)

3. Index Ulcer is located on the leg, below the knee and above the malleoli (ulcer may be inclusive of the malleoli)

4. The Index Ulcer is between 1 cm squared and 25 cm squared, inclusive, at the Screening and Baseline Visits. The longest dimension of the index ulcer cannot exceed 10 cm at the Baseline Visit.

5. The Index Ulcer has had compression for greater than or equal to 2 weeks at Screening Visit 1.

6. The Index Ulcer extends into the dermis or subcutaneous tissue without evidence of exposed muscle, tendon, bone, or joint capsule.

7. Patient has adequate circulation to the foot, as documented up to 14 days prior to Screening Visit 1 by either:

• Ankle Brachial Index (ABI) > 0.80 and <1.30, or

• In patients with non-compressible ankle vessels defined as an ABI greater than or equal to 1.30, a Toe Brachial Index (TBI) greater than or equal to 0.50, or

• In patients with non-compressible ankle vessels defined as an ABI greater than or equal to 1.30 and TBI cannot be performed (e.g., toe is absent, ulcers are present, or site cannot perform a TBI), a Doppler waveform in the posterior tibial or dorsalis pedis arteries at the ankle consistent with adequate flow in the foot (biphasic or triphasic) and other diagnostic confirmation of adequate flow (e.g., duplex imaging, normal pulse volume recording [PVR] testing).

8. Confirmed diagnosis of venous insufficiency, as documented up to 30 days prior to enrollment (Baseline Day 0), by either:

• Duplex ultrasonography, or

• Principal Investigator [PI] clinical assessment to include clinical signs and symptoms of venous ulcerations (e.g., hyperpigmentation of surrounding skin, varicosities, and/or lipodermatosclerosis).

In the inclusion criteria above, the word or is meant to include the case where both or multiple criteria are met as well as the case where just a single criterion is met.

Exclusion Criteria:

1. Index Ulcer is of non-venous pathophysiology

2. Gangrene is present on any part of the affected limb

3. Patient is unable to tolerate standard compression therapy

4. Glycated hemoglobin A1c (HbA1c) level of >14% in any patient with type 1 or type 2 diabetes mellitus, as documented up to 14 days prior to Screening Visit 1

5. Patient is receiving intravenous (IV) corticosteroids, immunosuppressive or cytotoxic agents at any time during the screening period

6. Patient has an ulcer within 5 cm of the Index Ulcer identified for study consideration.

7. Patient is Human Immunodeficiency Virus (HIV) positive or has Acquired Immune Deficiency Syndrome (AIDS)

8. Current evidence of infection at the Index Ulcer, including cellulitis and/or pus drainage from the ulcer site at the time of Screening and Baseline Visits.

9. Evidence of osteomyelitis at the time of Screening and Baseline Visits.

10. Patient has active malignancy other than non-melanoma skin cancer

11. Patient's Index Ulcer has decreased by greater than or equal to 30% between Screening Visit 1 and the Baseline Visit during the screening period

12. Patient has untreated alcohol or substance abuse at the time of Screening Visit 1

13. Pregnant women and women who who are breastfeeding

14. Patient is currently enrolled in or has participated in another investigational device, drug, or biological trial within 30 days prior to Screening Visit 1

15. Patient has had within 14 days of Screening Visit 1, or is currently undergoing, or is planning for ulcer treatments with growth factors, living skin, dermal substitutes or other advanced biological therapies

16. Patient is an employee, or an immediate family member of an employee, of the sponsor company or site research staff conducting the study

17. Patients who have already been randomized in Protocol 360 at any center or may not be considered for screening or for re-entry into the trial at any center, even after the End of Treatment Study Visit

18. Patients with a history of poor compliance, or an unwillingness or inability to adhere to the requirements of the protocol

In the exclusion criteria above, the word or is meant to include the case where both or multiple criteria are met as well as the case where just a single criterion is met.

Related Conditions & MeSH terms

• Chronic Leg Ulcer
• Leg Ulcer
• Postphlebitic Syndrome
• Postthrombotic Syndrome
• Ulcer
• Varicose Ulcer
• Venous Insufficiency
• Venous Leg Ulcer
• Venous Stasis

Intervention

Other:
• GrafixPL™ PRIME plus standard compression therapy
Patients randomized to treatment with GrafixPL™ PRIME plus standard compression therapy will receive GrafixPL™ PRIME plus standard compression therapy on Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70 and 77 (plus or minus 3 days) unless ulcer closure is achieved within the 12 week Treatment Phase. If ulcer closure is not achieved, patients will continue in the study until the End of Treatment Visit (84 days plus or minus 3 days after the Baseline Visit). If ulcer closure is achieved, patients will be followed for up to 168 days (plus or minus 7 days) after the End of Treatment Visit in the Follow-Up Phase.
• standard compression therapy alone
Patients randomized to standard compression therapy alone will receive standard compression therapy on Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 70, and 77 (plus or minus 3 days) unless ulcer closure is achieved within the 12 week Treatment Phase. Those who do not achieve ulcer closure within the 12 week Treatment Phase are eligible for the Crossover Extension Treatment Phase for up to 12 weeks of treatment with GrafixPL™ PRIME plus standard compression therapy.

Locations

Country	Name	City	State
United States	Medstar Georgetown University Hospital	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Georgetown University	Osiris Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and efficacy of weekly administration of GrafixPL™ PRIME plus standard compression therapy versus standard compression therapy alone	Safety adverse events will be documented to follow each subject's experience with the tissue product and the compression therapy.	12 weeks
Secondary	Time to initial ulcer closure as determined by the Investigator	Time it takes for the ulcer to heal	12 weeks
Secondary	Percent area reduction in ulcers that do not achieve closure as determined by the Wound Core Lab	Wound measurements will be recorded at each visit to track this outcome.	12 weeks
Secondary	Ulcer reoccurrence, as determined by the Investigator, for up to 6 months after initial ulcer closure in patients receiving GrafixPL™ PRIME plus standard compression therapy versus standard compression therapy alone	Once the subject's wound heals, they will be followed for up to 6 months to ensure that the wound stays healed.	6 months
Secondary	Proportion of patients in the Crossover Extension Treatment Phase who achieve complete ulcer closure defined as 100% re-epithelialization as determined by the Investigator	The number of subjects will be documents that achieve wound healing.	12 weeks
Secondary	Time to initial ulcer closure among patients in the Crossover Extension Treatment Phase as determined by the Investigator	The number of subjects that heal in the crossover extension will be documented.	94 days