A multicenter, randomized, double-blind, active-control phase III clinical trial of WOXheal® [Diperoxochloric acid] topical solution in the treatment of pressure ulcers – in comparison with the active-control 0.9% sodium chloride topical solution in addition to standard of care

Study title: A multicenter, randomized, double-blind, active-control phase III clinical trial of WOXheal® [Diperoxochloric acid] topical solution in the treatment of pressure ulcers – in comparison with the active-control 0.9% sodium chloride topical solution in addition to standard of care.

Investigational medicinal product:

Test product: Diperoxochloric Acid Topical Solution

Pack contains two bottles:

Bottle A: Diperoxochloric acid concentrate (each ml of solution contains: Diperoxochloric Acid Concentrate- 1.16 mg)

Bottle B: Sterile Sodium Chloride Solution BP 0.9% w/v (Cutaneous Solution)

Composition:

Sodium Chloride IP- 0.9% w/v in sterile neutralized aqueous vehicle - q.s.

Reconstituted Solution (Bottle A + Bottle B) in bottle B:

Each ml of solution contains: Diperoxochloric acid - 0.29 mg

Active-control product:

Pack contains two bottles:

Bottle A: Sterile Sodium Chloride Solution BP 0.9% w/v (Cutaneous Solution)

Bottle B: Sterile Sodium Chloride Solution BP 0.9% w/v (Cutaneous Solution)

Composition:

Sodium Chloride IP- 0.9% w/v in sterile neutralized aqueous vehicle - q.s.

Reconstituted Solution (Bottle A + Bottle B) in bottle B:

Each ml of solution contains: Sodium Chloride IP- 0.9% w/v

Patients will be asked to use the reconstituted solution within 14 days once it is prepared. Reconstituted solution should not be used after 14 days of mixing/ reconstitution.

Study Methods & procedure:

On day 0, patient/ patient’s legally acceptable representative [LAR] will be informed by the delegated staff of clinical trial site under supervision of investigator about the objectives and procedure and duration of this trial along with entire information about the study drugs along with possible adverse events as well as responsibilities of the patient throughout the trial. Sufficient time would be given to the patient for understanding the procedures of the trial and following his/ her voluntary informed consent, the Patient would be screened for participation in the trial.

A detailed medical history will be obtained from all enrolled Patients, which will be followed by thorough clinical examination.

Following the screening procedure as part of this trial, the eligibility of the patient to participate in the trial would be decided by the investigator based on the inclusion-exclusion criteria described in the protocol.

Depending on the size of the dressing [5×5 or 5×10 or 10×10 or as per investigator’s discretion depending on wound surface area], one or two or more units of investigational product will be provided to the Patient at each visit by the investigator at no cost. Since the trial has double-blind study design, the patient or the investigator would not know the identity of investigational product [Test or active-control].

Total duration of the clinical trial for any patient who is randomized and enrolled will be maximum of 8 weeks. The trial could end prior to week 8 for an individual patient, if complete wound closure is achieved earlier. On the other hand, the investigator could switch the patient on alternative treatment modality, if there is no satisfactory response observed from the treatment. However, from the enrolment in the study on day 0, it is advised that the patient should complete at least 4 weeks, to qualify him/ her for the decision of switching to alternative treatment modality due to unsatisfactory treatment response. This will not be considered as adverse event.

Patients will be instructed to prepare the reconstituted solution (ready to use solution) as per the instructions given below.

Open ‘Bottle A’ and ‘Bottle B’.

Pour the contents of Bottle A in to Bottle B.

Close the bottle B with bottle cap.

Discard the bottle A.

Mix the content by gently moving the bottle upside down for 5 times.

Patients will be asked to use the reconstituted solution within 14 days once it is prepared. Reconstituted solution should not be used after 14 days of mixing/ reconstitution.

Patient will be instructed to use the reconstituted solution as per the instructions given below:

Wash hands thoroughly before applying DPOCL topical solution.

Take out the dropper from the plastic bag (provided in the pack) and fill it on the bottle B.

Apply 3.5 mL of this solution with help of the dropper on the 5 × 5 cm dressing (inner gauze) to bring the dressing to earth moist conditions. As per size of the dressing, the dose would vary, i.e. for 5 × 10 cm dressing (inner gauze), 7 mL solution would be needed, whereas for 10 × 10 cm dressing (inner gauze), 14 mL solution would be needed. Similarly, for 4 × 4 cm dressing (inner gauze), 2.5 mL solution would be needed. [Since the maximum wound surface area in this trial is ≤ 50 cm2, 10 × 10 cm dressing (inner gauze) may not be required].

Do not touch dropper to the dressing or gauze.

Then apply this inner gauze on the wound.

Cover this inner gauze with outer gauze which will prevent the wound area from running dry.

Fix the gauze in position by rolling the bandage over the gauze and secure the ends by the microtape.

Daily remove the outer bandage and apply investigational product on inner bandage without removing the inner bandage form the wound.

Change the outer gauze daily and inner gauze on every alternate day.

Patients will be instructed to keep a note of daily symptoms and inform the investigator.

In case of adverse event/ serious adverse event irrespective of whether it is due to study procedure or study drug and anytime within 8 weeks from the enrolment, the investigator could withdraw the patient and switch to appropriate    medical or surgical management of the said AE/ SAE.

All the patients will be asked to revisit the clinical trial center for efficacy and safety assessment on day 7, day 14, day 21, day 28, day 42 and day 56. For each visit, a grace period of ± 3 days will be given to patients and will not be considered as protocol deviation.

If the CWC is achieved prior to scheduled visit, it is acceptable to ask the patient to visit the clinical trial site for evaluation of CWC. Alternatively, if the patient experiences any AE or SAE, he/ she could visit the clinical trial site before the scheduled visit.

In case the CWC is achieved prior to scheduled day of visit, the patient could come to the hospital and procedures related to end-of-treatment [EOT] and post-study safety assessment would be done. This, again would not be considered as protocol deviation.

If the wound is not completely healed at the end of the trial (Day 56) then it will be decided by the investigator whether the treatment is needed and should be continued until CWC. In this case the patient would be provided with investigational product after opening the blind.