Phase IIb and III Safety and Efficacy Study Chlorin E6 Gel Photodynamic Therapy for Diabetic Foot Ulcers:

Summary

Protocol No. CHLORIN E6-IIB/III-01/Protocol/1.1 Title:Single-Centre, open-labeled, randomized, Phase IIb and Phase III clinical studies to evaluate the safety, tolerability, and efficacy of Chlorin E6 (Gel Formation) as a photosensitizing agent for the management of Diabetic Foot Ulcers with Photodynamic Therapy. Sponsor Synverdis GmbH, Heidelberg, Germany. Study Phase: Phase IIb(Completed) \& Phase III(Ongoing) Indication : Diabetic Foot Ulcers Study Population: This study will be conducted on diabetic participants who are 18 years of age or older, with a documented diagnosis of diabetes and foot ulceration that has been present for at least 4 weeks. Sample Size of Phase IIb: 30 participants were enrolled. Phase III: 300 participants will be enrolled. Intervention Investigational Product: Chlorin E6 gel Specification: 1.0 mg/cm2 of Chlorin E6 1% W/V in gel-form Formulation: Gel Storage and Transportation: Store and ship at 2\~8°C, avoiding freezing. Standard of Care Treatment: a. Surgical Intervention: Debridement of the wound will be performed for all the participants. b. Medical Intervention: i. Antibiotics: Targeted to aerobic Gram-positive cocci in mild to moderate infections. \- Moxifloxacin * Linezolid * Co-Amoxiclav * Piperacillin + Tazobactam * Clindamycin Dosage \& Application Patients will receive 1.0 mg/cm2 of Chlorin E6 1% W/V in gel form by local application on the ulcer. Approximately 30 minutes after the study drug administration, the ulcer will be washed thoroughly with normal saline. Then it will be illuminated with light at 660 to 670 nm from an approved laser source with a calculated light dose of 100 J/cm2. Light will be applied to the entire surface of the ulcer for 11 minutes. The wound will then be illuminated with UV light to assess the effectiveness of Photodynamic Therapy (PDT) and a further 11 minutes of therapy will be carried out if required. Study Objectives Phase IIb: Primary Objectives: 1. To determine the safety and efficacy of a local Chlorin E6-mediated Photodynamic Therapy in patients with diabetic foot ulcers. 2. To determine the effect of Chlorin E6 on the healing of diabetic foot ulcers defined by a reduction in size and depth of the ulcer. 3. To compare the efficacy and healing rates of Diabetic foot ulcers with and without local Chlorin E6-mediated Photodynamic Therapy along with standard of care (SOC) management. 4. To determine the eradication ratio of pathogenic bacteria through the synergistic effect of local Chlorin E6-mediated Photodynamic Therapy. Phase III: Primary Objectives: 1. To determine the safety and efficacy of a local Chlorin E6-mediated Photodynamic Therapy in patients with diabetic foot ulcers. 2. To determine the effect of Chlorin E6 on the healing of diabetic foot ulcers defined by reduction in size and depth of ulcer. 3. To compare the efficacy and rates of healing of Diabetic Foot Ulcer (DFU) with and without local Chlorin E6-mediated Photodynamic Therapy along with standard of care management. 4. To determine the eradication ratio of pathogenic bacteria through the synergistic effect of local Chlorin E6-mediated Photodynamic Therapy. Secondary Objectives: 1. To determine the rates of recurrence of diabetic foot ulcers during 6 months after local Chlorin E6-mediated Photodynamic Therapy. 2. To determine the reduction in rates of amputation during 6 months after local Chlorin E6-mediated Photodynamic Therapy. Study Endpoints Phase IIb: Primary endpoints: Safety: • Solicited local and systemic AEs within 30 minutes and 7 days after product administration/application; Secondary endpoints: Safety: • Unsolicited AEs within 28 days after product administration/application; • SAEs throughout 3 months after product administration/application; • Abnormal laboratory value analysis on Day 14 after product administration/application; Efficacy: • No growth on culture of wound base swab at 1 week after product administration/ application. * Rate of healing \> 15 % in 1 week or \>50% in 1 month Phase III: Primary endpoints: Safety: * Solicited local and systemic AEs within 30 minutes and 7 days after product administration/application; Secondary endpoints: Safety: * Unsolicited AEs within 28 days after product administration/application; * SAEs throughout 6 months after product administration/application; * Abnormal laboratory value analysis on Day 14 after product administration/application; Efficacy: * No growth on culture of wound base swab at 1 week after product administration/ application. * Rate of healing \> 15 % in 1 week or \>50% in 1 month. Phase IIB of this trial is completed and screening of Phase III is started on 31-Mar-2026.

Eligibility

Inclusion Criteria:

1. Patients with diagnosis of Diabetes mellitus, with diabetic foot ulcer.
2. Males and females subject of age 18 years and above.
3. HbA1c of less than 12% and random blood sugars of less than 350 mg/dl.
4. Vitally stable patient with no clinical signs of sepsis, a qSOFA (quick Sepsis-Related Organ Failure Assessment) score of \<2.
5. ABI (Ankle Brachial Index) 0.7 to 1.2.
6. Lower extremity ulcer of more than 30 days duration and less than 2 years duration.
7. Total wound surface area between 0.5 to 20 cm.
8. Deep wounds extending up to muscles (University of Texas Grade \& Stage 1A, 1B, 2A \& 2B) will be included.
9. Patients giving written informed consent to participate in the study after a full understanding of the implications and constraints of the study protocol.
10. Understand the content of the ICF, and voluntarily sign the ICF (If the participant is unable to sign the ICF on his/her own due to illiteracy, an impartial witness is needed).
11. The subject can understand the research process and is willing and able to comply with all research proposals and other requirements of the study.
12. Able to cooperate to complete the scheduled follow-ups till the end of the study

Exclusion Criteria:

1. The vital signs or physical examination are clinically significantly abnormal as determined by the investigators in screening.
2. A history of severe allergy (including drugs, vaccines, and foods) or allergy to any component of the experimental product.
3. Subjects diagnosed with a serious disease, congenital malformation or chronic disease (including but not limited to serious: respiratory disease, cardiovascular disease, serious cerebrovascular disease, kidney disease, serious or uncontrollable diabetes, autoimmune disease, thrombocytopenic purpura, thalassemia, malignant tumor, hereditary allergic constitution, etc.) that may interfere with the conduct or completion of the study;
4. Participating in or planning to participate in other clinical trials (drugs or vaccines) within 3 months prior to participating in this study;
5. Other circumstances considered by the investigator as inappropriate to participate in the study.
6. Vitally unstable patients with clinical signs and symptoms of sepsis, qSOFA score ≥2.
7. More than 2 ulcers in the foot and leg.
8. Deep wounds extending into bone (UoT Criteria any Grade stage C \& D, Grade 3).
9. Subjects with moderate to severe obstruction on ABI (\<0.7 or \>1.3).
10. Patients with HbA1c more than 12% and random blood sugar of more than 350 mg /dl.
11. Subjects with evidence of cardiac disease or heart failure on ECG or echocardiography
12. Patients with eGFR (Estimated Glomerular Filtration Rate) of less than 60 ml/min/1.73 m2.
13. Pregnant or breast-feeding females or women of childbearing potential not using contraception.
14. Hypersensitivity to investigational product/Chlorophyll-driven compounds.
15. Diagnosed case of porphyria.
16. Ophthalmological disease requiring slit-lamp examination or Yag-laser within the next 30 days or anti-VEGF therapy/injection.
17. Patients who do not give written informed consent
18. Subjects unable or unwilling to meet protocol requirements.
19. Ulcer of non-diabetic etiology, such as venous, arterial, and burn wounds
20. Ulcer is less than 3 cm in distance from any other ulcer on the same extremity.
21. Ulcer presents with any of the following: osteomyelitis, exposed bone or gangrene.
22. Ulcer surface area has decreased \> 40% between screening and at randomization (visit 1) as assessed by the imaging system
23. Has medically documented history of HIV
24. Has severe protein malnutrition as defined by Serum Albumin \< 2.5 g/dL.
25. Has serum aspartate aminotransferase (AST, SGOT, GOT) or serum alanine aminotransferase (ALT, SGPT, GPT) levels greater than twice the upper limit of normal
26. Has a medically documented or self-reported history, within the previous 12 months from date of screening visit, of alcohol or substance abuse.
27. Has received previous treatment with the following during the 60 days prior to screening: immunosuppressive agents, radiation, chemotherapy, growth factors at the site of the Ulcer, split- or full-thickness skin graft at the site of the Ulcer, biologically active (or engineered) cellular or acellular product(s) at the site of the study ulcer, investigational drug or device
28. Has ESR \> 70 mm/h and CRP \> 100 mg/L at time of screening

Conditions2

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