A Clinical Study in which patients with acne vulgaris will receive a new topical drug for long term. The safety and efficacy of the drug will be tested.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

PPM Services S.A.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

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

Trial duration

11 Nov 2024 → ongoing

Decision date (initial)

2024-10-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

PPM Services S.A. Viale Serfontana 10 6834 Morbio Inf – Switzerland

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective of the study is to determine the long-term safety of 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.

Secondary objectives 1

1. The secondary objective of the study is to determine the long-term efficacy 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.

Conditions and MedDRA coding

Acne vulgaris

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency, Italian Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002674-PIP01-19

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Informed consent obtained
2. Male and female patients aged ≥ 9 and < 50 years. Patients who turned 50 during the pivotal study can rollover to the LT study.
3. Diagnosis at screening and baseline visits: a. 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 12-Week treatment period according to protocol in the pivotal Phase 3 trials (NAC-GED-0507-ACN-01-23-A and NAC-GED-0507-ACN-01-23-B) b. 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 12-Week treatment period according to protocol in the 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 pivotal Phase 3 study, a 12-week period should run before inclusion in the present study. During the 12-week period the patients will be allowed to follow their doctor’s instructions regarding treatment of acne.
4. 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. 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: a) Hormonal oral, implantable, transdermal, or injectable contraceptives must be stable for at least 6 months before the screening visit b) A non-hormonal intrauterine device (IUD) must be started at least 2 months before the screening visit.

Exclusion criteria 15

1. Acne: • 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 • Patients with acne requiring systemic treatment.
2. Beard and facial/body hair, tattoos: • Patients with a beard or who intend to grow a beard and/or to perform a facial tattoo during the study • Patients with facial hair or facial tattoos that could interfere with study assessments in the investigator’s opinion • For patients with truncal acne: body hair, tattoos (or who intend to perform them) on the shoulders, upper back or upper anterior chest accessible to self-application of study medication by the patient (evaluable area) that may interfere with the study assessments in the investigator’s opinion.
3. 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 the evaluation of acne or place the patient at unacceptable risk.
4. 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. 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 treatment 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. 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. 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. 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: a. Increased androgen production. 1) Adrenal origin: e.g., Cushing’s disease, 21-hydroxylase deficiency; 2) Ovarian origin: e.g., polycystic ovarian syndrome, ovarian hyperthecosis b. Cryptococcosis disseminated c. Dimorphic fungal infections d. Behçet’s disease e. Systemic lupus erythematosus (SLE).
10. Participation in the evaluation of any other investigational product or device within 24 weeks before study baseline.
11. Patient 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. History of alcohol or other substance abuse within one year before screening.
13. 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. Patients who may be unreliable for the study including patients who are unable to return for the scheduled visits.
15. *Pregnant or breastfeeding women or women of childbearing potential who are planning to become pregnant during the study. *For all female patients of childbearing potential, pregnancy test result must be negative at screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Safety endpoint: 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. Safety endpoint: Frequency of discontinuation of treatment due to TEAEs
3. Safety endpoint: Changes from baseline of vital signs during the study
4. Safety endpoint: Physical examination during the study
5. Safety endpoint: Changes from baseline of laboratory test over the study duration.
6. Safety endpoint: Change from baseline of local tolerability- Application site signs/symptoms during the study* *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.
7. Safety endpoint: Assessment of overall application site irritation over the study duration.

Secondary endpoints 13

1. Efficacy endpoint - FACE: Percentage of patients who have improvement of IGA score at each time point (1,2 points), vs baseline score
2. Efficacy endpoint - FACE: The percentage change from baseline in total lesion count (inflammatory plus non-inflammatory) at each time point
3. Efficacy endpoint - FACE: Absolute change from baseline in total lesion count at each time point
4. Efficacy endpoint - FACE: Change from baseline in inflammatory lesion count (percentage and absolute), at each time point
5. Efficacy endpoint - FACE: Change from baseline in non-inflammatory lesion count (percentage and absolute), at each time point
6. Efficacy endpoint - TRUNK: Percentage of patients who have improvement of PGA score at each time point (1,2 points), vs baseline score
7. Efficacy endpoint - TRUNK: The percentage change from baseline in total lesion count (inflammatory plus non-inflammatory) at each time point
8. Efficacy endpoint - TRUNK: Absolute change from baseline in total lesion count at each time point
9. Efficacy endpoint - TRUNK: Change from baseline in inflammatory lesion count (percentage and absolute), at each time point
10. Efficacy endpoint - TRUNK: Change from baseline in non-inflammatory lesion count (percentage and absolute), at each time point.
11. Efficacy endpoint - OTHER: 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)
12. Efficacy endpoint - OTHER: Additional Assessment by Scale for Acne Severity of additional evaluation at Baseline, Wk12, Wk26, Wk38 and Wk52 visits.
13. Efficacy endpoint - OTHER: At Baseline, Wk12 and Wk52 additional documentation will be optional. The area defined for additional assessments is only the face.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

PPM Services S.A.

Sponsor organisation

PPM Services S.A.

Address

Viale Serfontana 10

City

Morbio Inferiore

Postcode

6834

Country

Switzerland

Scientific contact point

Organisation

PPM Services S.A.

Contact name

Salvatore Bellinvia

Public contact point

Organisation

PPM Services S.A.

Contact name

Salvatore Bellinvia

Third parties 12

Locations

3 EU/EEA countries · 60 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 82 files

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

Application history

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