GuARD: GR1014 cutaneous gel Against Radiation Dermatitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Graegis Pharmaceuticals Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

26 Jul 2024 → 2 Dec 2025

Decision date (initial)

2024-05-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

To investigate the safety, tolerability, and efficacy of GR1014-CG (4.7%; 2.4%) as a treatment to prevent radiodermatitis occurring with adjuvant ultra hypofractionated RT for localised, non-metastatic breast cancer after lumpectomy, versus vehicle gel.

Secondary objectives 4

1. To assess the efficacy of GR1014-CG (4.7%; 2.4%) - in reducing radiodermatitis severity versus vehicle gel. - in reducing peak radiodermatitis severity versus vehicle gel. - in reducing radiodermatitis emergence versus vehicle gel. - in delaying the onset of radiodermatitis versus vehicle gel. - in reducing the duration of radiodermatitis versus vehicle gel. - in reducing severe radiodermatitis versus vehicle gel. - in reducing the side effects of RT other than dermatitis versus vehicle gel. - in reducing patient-reported pain intensity in the irradiated skin region induced by RT versus vehicle gel. - in reducing patient-reported pruritus intensity in the irradiated skin region induced by RT versus vehicle gel. - on participants’ assessment of their quality of life during and after RT versus vehicle gel.
2. To characterise the plasma Cmax of amifostine thiol after application of GR1014-CG.
3. To assess the efficacy of GR1014-CG in reducing the skin hyperaemia during and after RT versus vehicle gel.
4. To assess the ability of GR1014-CG in preventing the loss of integrity of the skin barrier function during and after RT versus vehicle gel.

Conditions and MedDRA coding

Radiation-induced dermatitis (radiodermatitis)

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Dated, signed informed consent obtained from individuals who agree to participate in the study.
2. Female patients with age ≥18 years. Those of childbearing potential must be using highly effective contraception methods during the study and for 6 months after the last administration of the study treatment and have a negative pregnancy test at screening and no more than 10 days prior to the administration of the first dose of study treatment.
3. 3.a. Patients with primary, localised breast cancer without metastases pTis, T1-3, pN0-N1mi, M0, who have undergone breast-conserving surgical excision and require adjuvant RT. The patients should be randomised after having recovered from the last surgery and, if delivered, the adjuvant chemotherapy. The patients can be included no matter the status of oestrogen and progesterone receptors, malignancy grade, or HER2 status.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
5. Patients to be treated with ultra hypofractionated RT, 26 Gy in 5 fractions (5.2 Gy) on whole breast (EQD2 > 42.6 Gy for α/β of 3).
6. Patients with no signs of dermatitis in the breast area to be irradiated, i.e., assessed Grade 0 as per CTCAE LV radiation dermatitis grading.
7. Patients whom the investigator has deemed able to comply with the RT and investigational treatment done under the supervision of the medical personnel throughout the study period.
8. Patients affiliated with the Social Security System (France).
9. Patients who have completed the appropriate washout period for any prior interventions or treatments.

Exclusion criteria 8

1. Pregnant and breastfeeding women.
2. Patients under any treatment concomitant to RT tested in another clinical study.
3. Allergies to any of the ingredients in GR1014-CG
4. Patients protected by law (legal guardianship or protection).
5. Patients unable to adhere to the requirements of the study.
6. History of thoracic RT.
7. Participants with the presence of skin rash, ulceration, unhealed surgical wounds, biopsy sites, or open wound in the breast or chest area at visit 2.
8. Patients suffering from scleroderma, auto-immune disease, micro-vascular diseases, collagen tissue diseases, lupus, pre-existing loss of skin integrity, active eczema in the region to be treated or with a history of any of the following: drug-induced severe cutaneous adverse reaction (SCAR; including, but not limited to Stevens-Johnson syndrome/toxic epidermal necrolysis [SJS/TEN], or drug reaction with eosinophilia and systemic symptoms).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of participants with no radiation dermatitis (Common Terminology Criteria for Adverse Events latest version [CTCAE LV] grade of 0) between the first RT session and 4 weeks after the last one.

Secondary endpoints 20

1. Percentage of participants with a radiodermatitis grade ≥2 (CTCAE LV) occurring at any time between the first RT session and 4 weeks after the last one – key secondary.
2. Percentage of participants with no radiation dermatitis (CTCAE LV, grade of 0), 4 weeks after the last RT session (at Visit 10).
3. Maximum grade of radiodermatitis (CTCAE LV) reached in each participant between the first RT session and 4 weeks after the last one.
4. Assessments of radiodermatitis grade (CTCAE LV) between the first RT session and the last visit.
5. Time to onset of radiodermatitis grade ≥2 (CTCAE LV).
6. Duration of radiodermatitis grade ≥2 (CTCAE LV).
7. Percentage of participants with severe radiodermatitis (grade ≥3; CTCAE LV) occurring at any time between the first RT session and 4 weeks after the last one.
8. Number of cases of side effects of RT other than radiodermatitis occurring at any time between the first RT session and the last visit (oedema; hyperpigmentation; skin infection; need for topical and systemic antibiotics; need for topical steroids; need for analgesics; need for silicone-based dressings).
9. Absolute change from baseline in weekly averaged worst skin pain score in the irradiated area. Worst pain intensity (during the last 24 hours) will be scored daily on a 0-10 Numeric Rating Scale (NRS),) from first to last visit.
10. Absolute change from baseline in weekly averaged peak pruritus score in the irradiated area. Peak pruritus intensity (during the last 24 hours) will be scored daily on a 0-10 NRS, from first to last visit.
11. Total score and sub-scores of Dermatology Life Quality Index (DLQI) weekly addressed, from the first RT session to the last visit.
12. Breast skin surface inflammation evolution will be assessed through a repeated measures analysis of the skin colour a-star (a*) values calculated using a tristimulus colorimetric instrument in accordance with the CIELAB colour systems from the first RT session to the last visit.
13. Transepidermal water loss (TEWL) measured from the first RT session to the last visit for 4 test areas within the radiation field of the breast (1 site per quadrant) and on a control area of the volar aspect of the forearm on the non-irradiated side.
14. Serious Adverse Reactions (SARs).
15. Adverse Events of Special Interest (AESIs).
16. Percentage of study withdrawal.
17. Stop/delay in RT sessions due to safety events.
18. Cmax
19. Time to Cmax (Tmax)
20. Area under the plasma concentration-time curve from time 0 to the last measurable time point tlast (AUClast)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Graegis Pharmaceuticals Limited

Sponsor organisation

Graegis Pharmaceuticals Limited

Address

The Dorothy Hodgkin Building, Babraham Research Campus, Babraham Babraham Research Campus Babraham

City

Cambridge

Postcode

CB22 3FH

Country

United Kingdom

Scientific contact point

Organisation

Graegis Pharmaceuticals Limited

Contact name

Clinical trial Information

Public contact point

Organisation

Graegis Pharmaceuticals Limited

Contact name

Clinical trial Information

Third parties 4

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications