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Diabetic Foot Ulcer (DFU)Phase 1/2NCT04277598

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

A Phase 1/2 study testing APO-2 in people with Diabetic Foot Ulcer (DFU), run by Aposcience AG at 14 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Diabetic Foot Ulcer (DFU)
What is being tested?
APO-2
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
159 participants
Where
14 sitesin 4 countries
Study dates
9 Oct 2020to 6 Dec 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • A patient with more than one diabetic foot ulcer may be included in the study but only one ulcer will be selected for the investigational treatment based on Investigator judgment as far as the ulcer meets the inclusion criteria (the largest ulcer fitting the inclusion criteria will be selected as index ulcer)
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  • 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

Who cannot join

  • 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)
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  • Raynaud disease or any other severe peripheral microvascular disease, current diagnosis of vasculitis
  • 7a. 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
  • 8. 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)
  • 9. 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.
  • 10. Patient with history of malignancy within the wound; history of radiation therapy to the wound region
  • 11. Patients who have undergone wound treatments with growth factors, dermal substitutes, or other biological therapies within the last 30 days or during the study
  • 12. Patients who received oral or parenteral corticosteroids, immunosuppressants, or cytotoxic agents within 30 days preceding the first study drug administration, or plan to use these medications during the study period
  • 13. Patients who are pregnant or breastfeeding
  • 14. Mental condition rendering the patient (or the patient's legally acceptable representative[s]) unable to understand the nature, scope and possible consequences of the study
  • 15. Patients who are incarcerated, including prisoners or patients compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness
  • 16. Therapy with another investigational agent within thirty days of screening, or during the study
  • 17. Patients who are considered by the investigator to have a significant disease, which can impact the study; patients who are considered not suitable for the study by the investigator
  • 18. Employee at the study site, spouse/partner or relative of any study staff (e.g. investigator, sub-investigators, or study nurse) or relationship to the sponsor

Trial locations and contacts

14 sites in 4 countries.

14 sites in 4 countries

Austria6 sites

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

    Graz, 8036

  • Medizinische Universität Innsbruck; Univ.-Klinik für Gefäßchirurgie

    Innsbruck, 6020

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

    Klagenfurt, 9020

  • Kepler Universitätsklinikum Linz; Klinik für Dermatologie und Venerologie

    Linz, 4021

  • Clinic Hietzing; Wiener Gesundheitsverbund

    Vienna, 1130

  • Klinikum Wels-Grieskirchen; Abteilung für Haut- und Geschlechtskrankheiten

    Wels, 4600

Other trials in Austria

Czechia4 sites

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

    Brno, 65691

  • University hospital Vinohrady

    Prague, 100 34

  • Central military hospital - Military university hospital Prague

    Prague, 169 02

  • Masaryk hospital in Usti nad Labem

    Ústí nad Labem, 401 13

Other trials in Czechia

Poland3 sites

  • NZOZ "Mikomed"

    Lodz, 94-238

  • Podos clinic

    Warsaw, 02-541

  • Pracownia Badań Klinicznych Salus

    Wroclaw, 50570

Other trials in Poland

Germany1 site

  • Universitätsklinikum Essen, Klinik für Endokrinologie und Stoffwechselerkrankungen

    Essen, 45147

Other trials in Germany

About this study

Official title: A Randomized, Placebo-controlled, Double-blind Study to Evaluate Safety and Dose Dependent Clinical Efficacy of APO-2 at Three Different Doses in Patients With Diabetic Foot Ulcer

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.

Read the detailed description

APOSEC is a secretome released by cultured, stressed peripheral blood mononuclear cells (PBMC) in medium. Content analysis revealed that APOSEC harbors a myriad of proteins, exosomes, lipids, phospholipids, cholesterols as well as antimicrobial peptides. It was shown that the topical application of APOSEC mixed with a hydrogel, called APO-2, promotes/enhances wound healing.

The MARSYAS II main study will be a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-ranging phase II study to investigate the safety and clinical efficacy of multiple dose administrations at three dose levels of APO-2 compared with placebo in patients with diabetic foot ulcer (DFU).

The main study will be preceded by a safety lead-in period evaluating multiple dose safety (25 U/ml APO-2) in patients with DFU in a cohort of 12 patients randomized at a ratio of 3:1 between APO-2 and placebo at 2 to 4 study sites. The minimum duration of an individual patient in the safety lead-in period is 93 days (including screening), with a maximum of approximately 117 days.

In the main study 120 eligible patients will be randomized at a ratio of 1:1:1:1 between APO-2 (three doses) and placebo. Patients will be stratified by wound size (at least 20% of patients will need to have wound size > 4 square cm), and randomly assigned to 1 of 4 treatment groups (low dose [12.5 U/ml], medium dose [25 U/ml], high dose [50 U/ml] or placebo). After randomization, patients will receive IMP three times per week during the 4-week active treatment period. 0.5 ml IMP will be applied per square cm wound surface area for each dose group.

Being tested
APO-2, Placebo
Medical subject headings
Diabetic Foot

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APO-2Biological

    APO-2: dose adjusted gel for topical administration.

  • PlaceboOther

    Placebo gel for topical administration.

Study groups in NCT04277598
Study groupRoleWhat they receive
Lead In Phase: APO-2: 25U/mlExperimentalTopical administration of APO-2, 25 U/ml; Approximalety 0.5 ml per square cm wound;
Receives: Biological: APO-2
Lead In Phase: PlaceboPlacebo comparatorTopical administration of placebo; Approximalety 0.5 ml per square cm wound;
Receives: Other: Placebo
Main Phase: APO-2: 12.5 U/mlExperimentalTopical administration of APO-2, 12.5 U/ml; Approximalety 0.5 ml per square cm wound;
Receives: Biological: APO-2
Main Phase: APO-2: 25 U/mlExperimentalTopical administration of APO-2, 25 U/ml; Approximalety 0.5 ml per square cm wound;
Receives: Biological: APO-2
Main Phase: APO-2: 50 U/mlExperimentalTopical administration of APO-2, 50 U/ml; Approximalety 0.5 ml per square cm wound;
Receives: Biological: APO-2
Main Phase: PlaceboPlacebo comparatorTopical administration of placebo; Approximalety 0.5 ml per square cm wound;
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: week 4 post baseline

Secondary outcomes (9)

  1. >50 % reduction in wound area

    Proportion of patients with >50 % reduction in wound area from day 1 (baseline) to week 4 (end of treatment)

    Measured: week 4 post baseline

  2. Wound size

    Wound size at day 1 and 1, 2, 3, 4, 6, 8 and 12 weeks after day 1

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

  3. Proportion of patients with complete wound closure

    Proportion of patients with complete wound closure during 12-week follow-up period

    Measured: week 4, 6, 8 and 12 post baseline

  4. Time to complete wound closure

    Time point at which complete wound closure is achieved

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

  5. Recurrence rate of the ulcer

    Recurrence rate of the ulcer during 12-week follow-up period

    Measured: week 4, 6, 8 and 12 post baseline

  6. Clinical assessment of peripheral neuropathy

    Assessment of severity level of peripheral neuropathy using a 10 g monofilament (Semmes-Weinstein) and a standard 128 Hz tuning fork with scaling (0 = no sense, 8 = good sense)

    Measured: day 1 and week 4 and 12 post baseline

  7. Assessment of local IMP tolerability

    Number of patients with local adverse events with causal relationship to study medication or serious adverse events with causal relationship to study medication

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

  8. Evaluation of wound pain: visual analogue scale

    Evaluation of wound pain by visual analogue scale (score of 0 cm = no pain, score of 10 cm = worst pain)

    Measured: day 1 and week 4,6, 8 and 12 post baseline

  9. Evaluation of Quality of Life: questionnaire

    Evaluation of Quality of Life (QoL) using Wound QoL questionnaire. Answers to each item are coded with numbers (0='not at all' to 5='very much').

    Measured: day 1 and week 4 and 12 post baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Feb 2020
  2. Study start9 Oct 2020
  3. Primary completion6 Dec 2023
  4. Study completion6 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
159 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04277598
Sponsor's protocol ID
MARSYAS II
Status last verified
Jan 2024
First submitted
18 Feb 2020
Last updated
31 Jan 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33407796

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing APO-2 in people with Diabetic Foot Ulcer (DFU), run by Aposcience AG at 14 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Austria, Czechia, Poland, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Wound area reduction after 4 weeks treatment with APO-2 (time frame: week 4 post baseline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04277598, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2024.

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