A Study to Evaluate Safety and Efficacy of APO-2 at Three Different Doses in Patients With Diabetic Foot Ulcer

NCT04277598 | Completed Phase 1 DMC

• 1 other identifier: MARSYAS II
• Study Type: interventional
• Target: 159
• Locations: 4 countries
• Sites: 14

Brief Summary

The MARSYAS II study which will be conducted in patients with diabetic foot ulcer (DFU) consists of a Lead-In Phase for safety assessment of multiple doses of the biologic investigational medicinal product (IMP) APO-2 and of a Main Phase (Phase II Study) to assess the efficacy and safety of the IMP. The phase II study will be a randomized study at multiple clinical centers and it will be double-blind meaning that neither the investigator nor the treated patient know if the IMP or a placebo is applied; the study will investigate the safety and clinical efficacy of multiple dose administrations at three dose levels of APO-2 (low dose, medium dose or high dose) compared with placebo.

Conditions

Diabetic Foot Ulcer (DFU)

Outcome Measures

Primary Outcomes (1)

• Wound area reduction after 4 weeks treatment with APO-2

  Percentage reduction in wound area from visit 2 (baseline) at day 1 to visit 14 (end of treatment) at week 4

  week 4 post baseline

Secondary Outcomes (9)

• >50 % reduction in wound area

  week 4 post baseline

• Wound size

  Day 1 and week 1,2 3,4,6,8,12 post baseline

• Proportion of patients with complete wound closure

  week 4, 6, 8 and 12 post baseline

• Time to complete wound closure

  A priori specification not possible; between baseline and week 12 post baseline

• Recurrence rate of the ulcer

  week 4, 6, 8 and 12 post baseline

Study Arms (6)

Lead In Phase: APO-2: 25U/ml

EXPERIMENTAL

Topical administration of APO-2, 25 U/ml; Approximalety 0.5 ml per square cm wound;

Biological: APO-2

Lead In Phase: Placebo

PLACEBO COMPARATOR

Topical administration of placebo; Approximalety 0.5 ml per square cm wound;

Other: Placebo

Main Phase: APO-2: 12.5 U/ml

EXPERIMENTAL

Topical administration of APO-2, 12.5 U/ml; Approximalety 0.5 ml per square cm wound;

Biological: APO-2

Main Phase: APO-2: 25 U/ml

EXPERIMENTAL

Topical administration of APO-2, 25 U/ml; Approximalety 0.5 ml per square cm wound;

Biological: APO-2

Main Phase: APO-2: 50 U/ml

EXPERIMENTAL

Topical administration of APO-2, 50 U/ml; Approximalety 0.5 ml per square cm wound;

Biological: APO-2

Main Phase: Placebo

PLACEBO COMPARATOR

Topical administration of placebo; Approximalety 0.5 ml per square cm wound;

Other: Placebo

Interventions

APO-2 BIOLOGICAL

APO-2: dose adjusted gel for topical administration.

Lead In Phase: APO-2: 25U/ml; Main Phase: APO-2: 12.5 U/ml; Main Phase: APO-2: 25 U/ml; Main Phase: APO-2: 50 U/ml

Placebo OTHER

Placebo gel for topical administration.

Lead In Phase: Placebo; Main Phase: Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is between 18 and 80 years of age
• Patients with Type I or Type II diabetes with a glycosylated hemoglobin (HbA1c) of ≤ 12 %, obtained at enrollment or within 30 days prior to study enrollment
• Patients who have a wound defined as diabetic foot ulcer present for ≥ 4 weeks
• Foot ulcer Wagner grade I - II or ARMSTRONG grade I-A (superficial, non-infected, non-ischemic wound not involving tendon, capsules, or bone) or II-A (non-infected, non-ischemic wound penetrating to tendon or capsule but not to the bone or joint)
• Estimated foot ulcer surface area between ≥ 0.8 cm2 and ≤ 8 cm2 as measured at day of randomization assessed using the eKare imaging and measurement device
• Wound area has not changed by more than 30 % between screening visit and randomization visit (at least 14 days)
• Adequate arterial blood perfusion measured on the leg with treated wound (ABI \[ankle brachial index\] ≥0.5 \[the lowest ABI measured value will be used as reference\], or toe pressure \> 40 mmHg, or tcPO2 \> 40 mmHg) within the past 6 months including patients with mild to moderate peripheral arterial disease (Fontaine Stage I and II)
• Patient must adhere to off-loading of the ulcer area (in mobile patients adherence to off-loading footwear during the study is mandatory)
• Patient is able to give written informed consent prior to study start and to comply with the study requirements
• Women of childbearing potential agree using adequate birth control methods during the study

You may not qualify if:

• History of anaphylaxis, known hypersensitivity to sodium alginate, propylene glycol, methylene-blue or chicken-egg
• Target ulcer is over a deformity (such as Charcot deformity) that interferes with off-loading based on investigator's opinion
• Index wound duration of \> 3 years without intermittent healing
• Clinical evidence of ulcer bed infection or patients requiring intravenous (IV) antibiotics to treat the index wound infection at time of randomization
• Current evidence of osteomyelitis, cellulitis, or other evidence of infection including pus drainage from the wound site, or documented history of osteomyelitis at the target wound location during the 8 weeks preceding the screening visit
• Major uncontrolled medical disorder(s) such as severe uncontrolled leg edema, concurrent medication, or other issue that renders the patient unsuitable for participation in the study, including but not limited to: comorbid condition with an estimated life expectancy of ≤ 12 months, hemoglobin A1c (Hba1c) \> 12 % at screening, patients on dialysis, patients with severe pulmonary (requiring home oxygen, uncontrolled COPD Gold III/ IV) or cardiovascular conditions (heart failure NYHA IV, uncontrolled hypertension systolic BP by repeated measurement \> 180 mmHg)
• Raynaud disease or any other severe peripheral microvascular disease, current diagnosis of vasculitis
• a. Patients with PAD who
• have not been assessed by vascular imaging as per standard of care or
• have acute peripheral artery occlusion of the index extremity or
• have PAD Fontaine Stage III and IV or
• have PAD with planned revascularization during the upcoming 6 months or
• had Angioplasty for re-perfusion in the lower extremity with target ulcer during 3 months preceding the screening visit
• \. Dermatologic comorbid disease (e.g. pyoderma gangrenosum, vasculopathy or vasculitic ulcers), history of Systemic Lupus Erythematosus with elevated anti-DNA antibody titers, Buerger's disease (thromboangiitis obliterans)
• \. Patient currently treated for an active malignant disease or prior diagnosis of an active malignant disease who is disease free for less than 1 year. Treatment with anticancer therapy (chemotherapy, immunotherapy, radiotherapy, targeted therapy or gene therapy) within 3 months before the first administration of investigational product or at any time during the study.

Sponsors & Collaborators

• Aposcience AG: lead
• FGK Clinical Research GmbH: collaborator

Study Sites (14)

LKH-Universitätsklinikum Graz; Klinische Abteilung für Plastische, Ästhetische und Rekonstruktive Chirurgie

Graz, 8036, Austria

Location

Medizinische Universität Innsbruck; Univ.-Klinik für Gefäßchirurgie

Innsbruck, 6020, Austria

Location

A.ö. Krankenhaus der Elisabethinen Klagenfurt GmbH; Abteilung für Chirurgie

Klagenfurt, 9020, Austria

Location

Kepler Universitätsklinikum Linz; Klinik für Dermatologie und Venerologie

Linz, 4021, Austria

Location

Clinic Hietzing; Wiener Gesundheitsverbund

Vienna, 1130, Austria

Location

Klinikum Wels-Grieskirchen; Abteilung für Haut- und Geschlechtskrankheiten

Wels, 4600, Austria

Location

University hospital at St. Anny; Fakultní nemocnice u sv. Anny

Brno, 65691, Czechia

Location

University hospital Vinohrady

Prague, 100 34, Czechia

Location

Central military hospital - Military university hospital Prague

Prague, 169 02, Czechia

Location

Masaryk hospital in Usti nad Labem

Ústí nad Labem, 401 13, Czechia

Location

Universitätsklinikum Essen, Klinik für Endokrinologie und Stoffwechselerkrankungen

Essen, 45147, Germany

Location

NZOZ "Mikomed"

Lodz, 94-238, Poland

Location

Podos clinic

Warsaw, 02-541, Poland

Location

Pracownia Badań Klinicznych Salus

Wroclaw, 50570, Poland

Location

Related Publications (1)

• Gugerell A, Gouya-Lechner G, Hofbauer H, Laggner M, Trautinger F, Almer G, Peterbauer-Scherb A, Seibold M, Hoetzenecker W, Dreschl C, Mildner M, Ankersmit HJ. Safety and clinical efficacy of the secretome of stressed peripheral blood mononuclear cells in patients with diabetic foot ulcer-study protocol of the randomized, placebo-controlled, double-blind, multicenter, international phase II clinical trial MARSYAS II. Trials. 2021 Jan 6;22(1):10. doi: 10.1186/s13063-020-04948-1.

  PMID: 33407796 DERIVED

MeSH Terms

Conditions

Diabetic Foot

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Study Officials

• Hendrik J Ankersmit, Univ.Prof.Dr.

  Aposcience AG

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: During Safety Lead In Phase 12 patients will be randomized to one of two study arms at a ratio of 3:1 between APO-2 and placebo. During the Main Phase 108 patients will be randomized to one of the four study arms at a ratio of 1:1:1:1 between APO-2 (three doses) and placebo.

Study Record Dates

• First Submitted: February 18, 2020
• First Posted: February 20, 2020
• Study Start: October 9, 2020
• Primary Completion: December 6, 2023
• Study Completion: December 6, 2023
• Last Updated: January 31, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (6); CZ (4); PL (3); DE (1)