A long-term study to assess the safety and efficacy of a gel treatment in subjects with Acne Vulgaris
| ISRCTN | ISRCTN49040930 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN49040930 |
| EudraCT/CTIS number | 2023-510342-24 |
| IRAS number | 1010207 |
| Secondary identifying numbers | NAC-GED-0507-ACN-01-23-LT, CPMS 60291 |
- Submission date
- 02/07/2024
- Registration date
- 04/11/2024
- Last edited
- 25/04/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Skin and Connective Tissue Diseases
Plain English Summary
Background and study aims
This study is to assess the efficacy and safety of a gel in the long-term treatment (up to 52 weeks) in patients with acne vulgaris. The study is an open-label, non- comparative study, which means that all participants will receive the treatment gel for the duration of the study.
Who can participate?
Males or females aged between >9 and <50 years of age suffering from acne vulgaris may be able to take part.
What does the study involve?
Study participants will be required to apply the gel treatment themselves, once daily for a minimum of 12 weeks. From week 12 up to 52 weeks, patients’ treatment will be determined by an assessment of acne symptoms.
The study will include up to 8 on-site study visits for a duration of up to 52 weeks. These visits would last for approximately 1-2 hours, some of which will include physical assessments and investigations, including an assessment of acne symptoms and collection of height, weight, and vital signs. Blood samples will also be collected for safety analysis, and a urine pregnancy test will be performed for females of childbearing potential. Participants will also complete a questionnaire, which will assess how their condition affects their daily life.
In previous studies, the treatment gel has been shown to be safe and well tolerated and a reduction of acne symptoms was found. This study will help gather further information on the effects of this gel and may offer an alternative treatment for patients suffering from acne vulgaris.
The study is taking place in multiple sites across 5 EU Countries, and 400 participants will be recruited. In the UK, 16 sites will be taking part, including both primary and secondary care NHS sites and some private research sites.
What are the possible benefits and risks of participating?
Benefits:
Not provided at time of registration
Risks:
Based on the results from two previous large Phase II studies, the active IMP (N-Acetyl-GED-0507-34-LEVO gel 5% (5 mg/100 mg)), is considered to be safe and well tolerated, and there were no significant differences between the proposed pediatric and adult populations. In a large randomised double blind controlled clinical trial (NAC-GED-0507-ACN-01-18), the percentage of patients who had one or more AEs was 19%, 16% and 19% in the NAC-GED 5%, NAC-GED 2% and vehicle groups, respectively.
In general, the administration of the IMP may result in some minor side effects such as an allergic or irritant reaction, which may manifest as itching or redness of the skin with papules and blisters. In rare cases, there may be more generalised dermal sensitisation responses, which improve once the treatment stops. Moreover, as the amount to be applied to the skin is relatively small, no systemic side effects are expected.
For those participants who will be assigned to receive no treatment for a duration of the study (from week 12- 52), as their condition will not be treated with an active medication for that time, their acne symptoms may become worse, stay the same or improve.
In terms of study procedures, blood draws may result in bruising or pain where the sample is taken and in some cases, there is a risk of infection, lightheadedness and/ or fainting.
With regards to risks associated with pregnancy and breastfeeding, the safety of the study drug for embryos/fetuses is not fully known. Females who are pregnant or breastfeeding, or those who plan to become pregnant during the study period will be excluded from enrollment. Additionally, all females of childbearing potential will be required to undertake a pregnancy test and shall also be required to use an acceptable effective contraceptive method throughout the entire study.
Although acne is not a life-threatening condition, it can be a significant source of distress for patients and can be associated with depression, anxiety and poor self-esteem. Patients will be required to complete either a Dermatology Life Quality Index (DLQI) (age 17 and older) or a Children’s Dermatology Life Quality Index (C-DLQI) (for 16 years and younger). By completing these questionnaires, there is a risk that some participants may experience some psychological or emotional stress. Similarly, as there is a chance that participants' acne symptoms may become worse or remain the same during the study, this may also contribute to participants experiencing psychological or emotional stress.
However, the participants' health and wellbeing will be closely monitored during the study and will include collection of all Adverse Events (AEs), Treatment-Emergent Adverse Events (TEAES), Adverse Drug Reactions (ADRs) and Serious Adverse Events (SAEs). Changes from baseline of vital signs, laboratory tests and local tolerability plus physical examinations and an assessment of overall application of site irritation, will also be conducted to ensure prompt follow-up with participants if required. Moreover, additional phone calls will be included for all patients aged 9 to <12 years to ensure that any local tolerability or safety issues are promptly identified. The Investigator will be asked to promptly fill in the eCRF page relating to the phone contact. In case of safety issues, an immediate automatic notification will be sent to the Data Safety Monitoring Board (DSMB). A DSMB will also be established to undertake periodic risk-benefit assessments during the clinical trial.
The study will include up to 8 on-site visits over a duration of 52 weeks. The visits will last for 1-2 hours and will include some physical assessments and investigations. Participants will be appropriately reimbursed for any travel expenses incurred and will be made fully aware of the commitment required before consenting. At four selected sites in the UK, participants will also have the option to consent to the collection of photographic scar monitoring of which images of the participants face will be shared: internally (to the attention of PPM Services’ collaborators) and/or externally (to the attention of the public and/or health care professionals during any event and/or manifestation whatsoever). This type of assessment has the potential to cause some emotional stress however, information will be provided to participants via a participant information sheet in a way that enables them to clearly understand what is involved in the study, should they consent to take part.
Taking into account these risks and benefits, the performance of the trial can be considered low risk for all ages considered, since the expected benefits appear greater at present than the risks for the volunteers.
Where is the study run from?
The research will be conducted in the UK by LINK Medical Research, a Clinical Research Organisation.
When is the study starting and how long is it expected to run for?
June 2024 to December 2026
Who is funding the study?
PPM Services S.A. (Switzerland)
Who is the main contact?
Elisha Peers
Dr Simon Royal, Simon.Royal@nottingham.ac.uk
Contact information
Scientific
10 John Street
London
WC1N 2EB
United Kingdom
Principal Investigator
Cripps Health Centre, University Park
Nottingham
NG7 2QW
United Kingdom
| Phone | +44 115 8468888 |
|---|---|
| Simon.Royal@nottingham.ac.uk |
Study information
| Study design | Interventional non randomized |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Home |
| Study type | Safety, Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A long-term safety and efficacy study of N-Acetyl-GED-0507-34-LEVO gel 5%, in subjects with acne vulgaris (GEDACNE-LT) |
| Study acronym | GEDACNE LT |
| Study hypothesis | The primary objective of the study is to determine the long-term safety of 5% N-Acetyl-GED-0507-34-Levo gel, applied once daily (OD) for a total treatment period up to 52 weeks in patients with acne vulgaris. Efficacy will be evaluated as a secondary objective. Efficacy will be assessed by the investigator using acne lesion count and IGA at V2/Day1 (Baseline) and weeks 4, 12, 26, 38 and 52. Acne lesion count and IGA will also be performed for inclusion at V1 (screening) and in case of Early Termination Visit (ETV). |
| Ethics approval(s) |
Approved 29/10/2024, London Hampstead Research Ethics Committee (Previously Royal Free Hospital and Medical School Research Ethics Committee then North West London REC 2, London, -, United Kingdom; +44 (0)2071048171; hampstead.rec@hra.nhs.uk), ref: 24/LO/0552 |
| Condition | Acne vulgaris |
| Intervention | IMP: N-Acetyl-GED-0507-34-Levo 5% gel (5 mg/100 mg) Each patient will apply a bean-sized amount of gel as a thin film, once daily (OD), to the entire facial skin area and the affected skin areas of the trunk accessible for self-application (i.e., shoulders, upper back, and upper anterior chest). The application is to dry and, cleansed skin, avoiding the eyes, lip region, and mucous membranes. The treatment period will be 52 weeks (364 applications). For patients from the Phase 3 pivotal studies (NAC-GED-0507-ACN-01-23-A and NAC-GED-0507-ACN-01-23-B) this treatment duration includes the 12-week treatment period. These patients will apply the active medication once a day (OD) for an additional 9 months of treatment (for a total of up to 12 months; 0 or 3 months in the Phase 3 pivotal study [blinded assignment to IMP or placebo] and an additional 9 months in this open-label long-term extension study). |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Therapy |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | N-Acetyl-GED-0507-34-Levo 5% g [(S)-3-(4-ACETAMIDOPHENYL)-2-METHOXYPROPANOIC ACID] |
| Primary outcome measure | Safety will be evaluated as the primary objective of the study up to 52 weeks: 1. Incidence of all Adverse Events (AEs), Treatment-Emergent Adverse Events (TEAES), Adverse Drug Reactions (ADRs), Serious Adverse Events (SAEs) throughout the study; with special attention to local TEAEs concerning the treated facial area (local dermal safety), and systemic TEAEs 2. Frequency of discontinuation of treatment due to TEAEs 3. Changes from baseline of vital signs during the study 4. Physical examination during the study 5. Changes from baseline of laboratory test at V5/Wk12 and V8/Wk52 6. Change from baseline of local tolerability- Application site signs/symptoms during the study* 7. Assessment of overall application site irritation at V5/Wk12, V6/Wk26, V7/Wk38 and V8/Wk52. *Local tolerability will be evaluated based on the following signs and symptoms: application site non-lesional erythema, application site exfoliation, and application site dryness, stinging, burning, itching. For each sign/symptom, a severity score will be assigned using a 4-point scale from 0 = absent to 3 = severe. |
| Secondary outcome measures | Efficacy will be evaluated as a secondary objective. IGA and PGA and lesion count assessments are to be performed by a qualified investigator. Training is required for all evaluators who perform IGA/PGA/ lesion count. Efficacy will be assessed by the investigator using acne lesion count and IGA at V2/Day1 (Baseline), Wk4, Wk12, Wk26, Wk38, Wk52. Acne lesion count and IGA will also be performed for inclusion at V1 (screening) and in case of Early Termination Visit [ETV]). Acne lesion count: Inflammatory (papules, pustules and nodules) and non-inflammatory lesions (open [blackheads] and closed [whiteheads ] comedones) on the face (including the nose) and on the trunk will be accurately counted and recorded at each visit as detailed in the study schedule. Total lesions will be calculated as the sum of inflammatory plus non-inflammatory lesions. IGA (Face): Overall severity of acne will be assessed using a 5-point scale from 0 = clear to 4 = severe at each visit as detailed in the study schedule. PGA (Trunk): Overall severity will be assessed using a 5-point scale from 0 = clear to 4 = severe at each visit as detailed in the study schedule. Secondary Efficacy endpoints: To evaluate the efficacy of 5% N-Acetyl-GED-0507-34-Levo gel after a treatment period up to 52 Wks on the following parameters: FACE 1. Percentage of patients who have improvement of IGA score at each time point (Wk4, Wk8, Wk12, Wk26, Wk38, Wk52), vs baseline score 2. The percentage change from baseline in total lesion count (inflammatory plus non-inflammatory) at each time point (Wk4, Wk8, Wk12, Wk26, Wk38, Wk52) 3. Absolute change from baseline in total lesion count at each time point (Wk4, Wk8, Wk12, Wk26, Wk38, Wk52) 4. Change from baseline in inflammatory lesion count (percentage and absolute), at each time point (Wk4, Wk8, Wk12, Wk26, Wk38, Wk52) 5. Change from baseline in non-inflammatory lesion count (percentage and absolute), at each time point (Wk4, Wk8, Wk12, Wk26, Wk38, Wk52) TRUNK 1. Percentage of patients who have improvement of PGA score at each time point (1,2 points), vs baseline score 2. The percentage change from baseline in total lesion count (inflammatory plus non-inflammatory) at each time point 3. Absolute change from baseline in total lesion count at each time point 4. Change from baseline in inflammatory lesion count (percentage and absolute), at each time point 5. Change from baseline in non-inflammatory lesion count (percentage and absolute), at each time point. OTHER ASSESSMENTS 1. Dermatology Life Quality Index (DLQI) / Children’s Dermatology Life Quality Index (C-DLQI for patients from 9 to 16 years old), completed by the patient at Baseline, Wk12, and Wk52 visits (prior to any Investigator assessments to not impact the patient’s answers to the quality-of-life questionnaires) 2. Scar Assessment by Scale for Acne Scar Severity (SCAR-S) at Baseline, Wk12, Wk26, Wk38 and Wk52 visits. 3. At selected sites, at Baseline, Wk12 and Wk52 scar 3D photographic documentation will be optional. The area defined for scar assessments is only the face. Baseline will be the last evaluation before N-Acetyl-GED-0507-34-Levo gel 5% intake. |
| Overall study start date | 28/06/2024 |
| Overall study end date | 31/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 9 Years |
| Upper age limit | 50 Years |
| Sex | Both |
| Target number of participants | 400 |
| Total final enrolment | 406 |
| Participant inclusion criteria | 1. Informed consent obtained. Written informed consent, before any study-related procedure, personally signed and dated by the patient if the patient is ≥18 years old or signed and dated by the parents or the legal guardian(s) if the patient is ≥9 to< 18 years old. An additional informed assent form must be signed by the patient if ≥9 to <18 years old to confirm his willingness to participate in the study. If the patient becomes 18 years of age during the study, the patient must provide written informed consent at that time to continue study participation. 2. Sex and age: Male and female patients aged ≥9 and <50 years. Patients who turn 50 during the pivotal study can roll over to the LT study. 3. Diagnosis at screening and baseline visits: 3.1. Patients affected by facial acne vulgaris with an Investigator’s Global Assessment (IGA) score: =1 or 2 for pivotal-naïve* patients not included in pivotal 12 Week treatment studies ≥0 for patients completing the treatment period of pivotal Phase 3 trials (NAC-GED-0507-ACN-01-23-A and NAC-GED-0507-ACN-01-23-B) 3.2. Patients affected by truncal acne (optional criteria) on areas of the trunk (shoulders, upper back and upper anterior chest) accessible for patient’s self-application of study medication with a Physician Global Assessment (PGA) severity grade: =1 or 2 for pivotal-naïve* patients not included in the pivotal 12Week treatment studies ≥0 and <4 for patients completing the treatment period of pivotal Phase 3 trials (NAC-GED-0507-ACN-01-23-A and NAC-GED-0507-ACN-01-23-B)*Pivotal-naïve: Patients not rolling over from NAC-GED-0507-ACN-01-23-A and NAC-GED-0507-ACN-01-23-B. If the pivotal-naïve patient is ≥ 9 and ≤ 14 years old and declined participation to the pivotal Phase 3 study, a 12-week period should run before inclusion in the present study. 4. Full comprehension Patients and their parents/legal guardian(s) (for <18 years old patients) can comprehend the whole nature and purpose of the study, including possible risks and side effects, and are able to cooperate with the Investigator and to comply with the requirements of the entire study. 5. Contraception and fertility: Women of childbearing potential must be using an effective contraception method during the entire duration of the study. Effective contraception methods are those considered at least“acceptable” according to CTFG Recommendations. A prior stable treatment period is required for the following reliable methods of contraception: 5.1. Hormonal oral, implantable, transdermal, or injectable contraceptives must be stable for at least 6 months before the screening visit 5.2. A non-hormonal intrauterine device (IUD) must be started at least 2 months before the screening visit. |
| Participant exclusion criteria | 1. Acne: 1.1. Patients with generalized or localized acne forms other than acne vulgaris, e.g., acne conglobata, acne fulminans, acne rosacea, secondary acne (chloracne, drug-induced acne, etc), nodule-cystic acne 1.2. Patients with acne requiring systemic treatment 2. Beard and facial/body hair, tattoos: 2.1. Patients with a beard or who intend to grow a beard and/or to perform a facial tattoo during the study 2.2. Patients with facial hair or facial tattoos that could interfere with study assessments in the investigator’s opinion 2.3. For patients with truncal acne: body hair, tattoos (or who intend to perform them) on the shoulders, upper back/upper anterior chest accessible to self-application of study medication by the patient (evaluable area) that may interfere with study assessments in investigator’s opinion. 3. Skin diseases: Patients with other active skin diseases (e.g., urticaria, atopic dermatitis, sunburn, seborrheic dermatitis, perioral dermatitis, rosacea, skin malignancies) or active skin infections in the facial or truncal region (bacterial, fungal, or viral) or any other facial or truncal disease or condition that might interfere with evaluation of acne or place the patient at unacceptable risk 4. Allergy: Known or suspected hypersensitivity to any active or inactive ingredient in the study medication. Patients with a history of an allergic reaction or significant sensitivity to the formulations’ ingredients. 5. Topical therapies: Patients who are currently using, plan to use during the study, or discontinued less than 4 weeks before study baseline the use of prescribed or over-the-counter topical therapies for the treatm. of acne, including but not limited to: corticosteroids, antibiotics, azelaic acid, benzoyl peroxide, salicylates, α-hydroxy/glycolic acid, any other topical cosmetic therapy for acne and retinoids on the face/trunk. 6. Topical skin care products and procedures: Patients who are currently using, plan to use during the study, or discontinued less than 4 weeks before study baseline the use of products for facial/truncal application containing glycolic or other acids, masks, washes or soaps containing benzoyl peroxide or salicylic acid, non-mild cleansers or moisturizers containing retinol, salicylic or alpha- or beta-hydroxy acids, facial/truncal procedures such as chemical peel, laser treatment, photodynamic therapy, acne surgery, cryodestruction or chemodestruction, x-ray therapy, intralesional steroids, dermabrasion; 7. Phototherapy: Patients who are currently using, plan to use during the study, or discontinued less than 4 weeks before study baseline phototherapy for the treatment of acne, including but not limited to: UV-A, UV-B, heliotherapy. Patients who have the need or plan to be exposed to artificial tanning devices or excessive sunlight during the study. 8. Systemic therapies: Patients who are currently using, plan to use during the study, or discontinued less than 12 weeks before study baseline the use of systemic therapies for the treatment of acne, including but not limited to: antibiotics, isotretinoin. Other systemic therapy that could affect the patient’s acne (i.e., anabolics, lithium, EGRF inhibitors, iodides, systemic corticosteroids - except inhaled corticosteroids or intrathecal corticosteroids - or other immunosuppressants), in the opinion of the investigator. 9. Known systemic diseases that can lead to acneiform eruptions: 9.1. Increased androgen production. 1) Adrenal origin: e.g., Cushing’s disease, 21-hydroxylase deficiency; 2) Ovarian origin: e.g., polycystic ovarian syndrome, ovarian hyperthecosis 9.2. Cryptococcosis disseminated 9.3. Dimorphic fungal infections 9.4. Behçet’s disease 9.5. Systemic lupus erythematosus (SLE) 10. Investigative studies: Participation in the evaluation of any other investigational product or device within 24 weeks before study baseline 11. Diseases: Patients with underlying uncontrolled or unstable conditions (including but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the Investigator's opinion could significantly compromise the patient’s safety and/or place the patient at an unacceptable risk. Any condition that in the investigator’s opinion would make it unsafe for the patient to participate in the study 12. Alcohol and other substance abuse: History of alcohol or other substance abuse within one year before screening. 13. Communication: Patient(s) and parents/legal guardian(s) (if applicable) unable to communicate or cooperate with the investigator due to e.g., language problems, impaired cerebral function, impaired mental conditions. 14. Reliability: Patients who may be unreliable for the study including patients who are unable to return for the scheduled visits. 15. Pregnancy*: Pregnant or breastfeeding women or women of childbearing potential who are planning to become pregnant during the study. *For all female patients |
| Recruitment start date | 01/09/2024 |
| Recruitment end date | 22/04/2025 |
Locations
Countries of recruitment
- England
- France
- Italy
- Poland
- Scotland
- Spain
- United Kingdom
- Wales
Study participating centres
Wellingborough
NN8 4RW
United Kingdom
Ranson Road
Chilwell
Nottingham
NG9 6DX
United Kingdom
Nottingham
NG7 2QW
United Kingdom
Birmingham
B21 9RY
United Kingdom
Stockton-on-Tees
TS19 8PE
United Kingdom
Birkenhead
Wirral
CH62 6EE
United Kingdom
Lancaster Park Road
Harrogate
HG2 7SX
United Kingdom
Leicester
LE9 7RT
United Kingdom
Orrysdale Road
West Kirby
Wirral
CH48 5AA
United Kingdom
Marton Road
Middlesbrough
TS4 3BW
United Kingdom
Soham
Ely
CB7 5JD
United Kingdom
Hamworthy
Poole
BH15 4JQ
United Kingdom
Faringdon
SN7 7YU
United Kingdom
West Kinmel Street
Rhyl
LL18 1DA
United Kingdom
Barry
CF63 1BA
United Kingdom
Glasgow
G20 7BE
United Kingdom
Sponsor information
Industry
Viale Serfontana 10
Morbio Inferiore
6834
Switzerland
| Phone | (+41) 91 6961 712 |
|---|---|
| sbellinvia@ppmservices.ch |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 31/12/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | Peer-reviewed scientific journals Internal report Submission to regulatory authorities All information supplied by the Sponsor in connection with this study shall remain the sole property of the Sponsor and is to be considered confidential information. The information obtained during this study may be made available to other physicians who are conducting other clinical studies with the investigational product, if deemed necessary by the Sponsor. |
| IPD sharing plan | All data generated or analysed during this study will be included in the subsequent results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 2.0 | 01/01/2025 | 02/04/2025 | No | No |
Additional files
Editorial Notes
25/04/2025: The recruitment end date was changed from 02/07/2026 to 22/04/2025. Total final enrolment added.
02/04/2025: Protocol, ethics approval and contact details updated.
20/03/2025: New protocol file uploaded.
16/01/2025: Internal review.
02/07/2024: Trial's existence confirmed by NHS HRA.
