(S)-3-(4-ACETAMIDOPHENYL)-2-METHOXYPROPANOIC ACID for Acne vulgaris

Inclusion criteria

• {"criterion_text":"- Informed consent obtained"}
• {"criterion_text":"- Male and female patients aged ≥ 9 and <50 years"}
• {"criterion_text":"- Diagnosis at screening and baseline visits: a) Patient affected by facial acne vulgaris with: Investigator’s Global Assessment (IGA) score: • equal to 3–4 if patient is > 14 and < 50 years old • ≥ 2 if the patient is ≥ 9 and ≤ 14 years old. Face Inflammatory lesions: ≥ 20 and ≤ 100 inflammatory lesions (papules and pustules) and ≤ 1 nodules on the face. Face Non-inflammatory lesions: ≥ 20 and ≤ 100 non-inflammatory lesions (open and closed comedones) on the face. b) Optional: The patient has a truncal acne on areas of the trunk (shoulders, upper back and upper anterior chest) accessible for patient’s self-application of study medication with a severity grade equals to 2 or 3 on the Physician Global Assessment (PGA) scale. The patient has a minimum of 20 inflammatory lesions (papules and pustules) and 20 non-inflammatory lesions (open and closed comedones), but no more than 100 non-inflammatory lesion and no more than 100 inflammatory lesion and ≤ 1 nodules on on areas of the trunk (shoulders, upper back and upper anterior chest) reachable to patient’s self-application of study medication at screening and baseline."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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 baseline visit b) A non-hormonal intrauterine device (IUD) must be started at least 2 months before the baseline visit."}

Exclusion criteria

• {"criterion_text":"- Acne: • Patients with a known history of acne, persistent and unresponsive to topical and/or oral treatments within 6 months before randomization • 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"}
• {"criterion_text":"- *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."}
• {"criterion_text":"- Patient with underlying uncontrolled or unstable conditions (including but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal and auto-immune), 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"}
• {"criterion_text":"- History of alcohol or other substance abuse within one year before screening"}
• {"criterion_text":"- Patient(s) and parents/guardian(s) (if applicable) unable to communicate or cooperate with the investigator due to e.g., language problems, impaired cerebral function, bad mental conditions"}
• {"criterion_text":"- Patients who may be unreliable for the study including patients who are unable to return for the scheduled visits"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Known or suspected hypersensitivity to any active or inactive ingredient in the study medications. Patients with a history of an allergic reaction or significant sensitivity to the formulations’ ingredients"}
• {"criterion_text":"- Patients who are currently using, will use during the study, or discontinued less than 4 weeks before study baseline the use of prescribed and/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"}
• {"criterion_text":"- Patients who are currently using, will 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"}
• {"criterion_text":"- Patients who are currently using, will 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"}
• {"criterion_text":"- Patients who are currently using, will 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"}
• {"criterion_text":"- Known systemic diseases that can lead to acneiform eruptions: i. Increased androgen production. 1) Adrenal origin: e.g., Cushing’s disease, 21-hydroxylase deficiency; 2) Ovarian origin: e.g., polycystic ovarian syndrome, ovarian hyperthecosis ii. Cryptococcosis disseminated iii. Dimorphic fungal infections iv. Behçet’s disease v. Systemic lupus erythematosus (SLE)"}
• {"criterion_text":"- Participation in the evaluation of any investigational product or device within 24 weeks before study baseline"}
• {"criterion_text":"- Patients with other active skin diseases (duplicate entry may appear in dataset)"}

Primary endpoints

• {"endpoint_text":"- The following family of Efficacy Endpoint E1 and E2 will be evaluated: a. Endpoint 1 (E1): the relative change from baseline in total lesion count (inflammatory plus non-inflammatory) at V5/Wk12 on the face","definition_or_measurement_approach":"Relative change from baseline in total lesion count (inflammatory + non-inflammatory) measured on the face at Visit 5 / Week 12."}
• {"endpoint_text":"- The following family of Efficacy Endpoint E1 and E2 will be evaluated: b. Efficacy Endpoint 2 (E2): proportion of patients with an IGA success at V5/Wk12. IGA success is defined according to the patient’s age as: • a score of “clear” (score = 0) or “almost clear” (score = 1) for patients aged ≥ 9 and ≤ 14 years • a score of “clear” (score = 0) or “almost clear” (score = 1) and at least a 2-score point reduction in IGA at V5/Wk12 for patients aged > 14 and < 50 years","definition_or_measurement_approach":"Proportion of patients achieving IGA success at Visit 5/Week 12. IGA success defined by age: for patients ≥9 and ≤14: IGA score 0 or 1; for patients >14 and <50: IGA score 0 or 1 plus at least 2-point reduction from baseline."}

Secondary endpoints

• {"endpoint_text":"- Efficacy endpoint - FACE: Absolute change from baseline in total lesion count at V5/Wk12","definition_or_measurement_approach":"Absolute change from baseline in total lesion count on the face measured at Visit 5 / Week 12."}
• {"endpoint_text":"- Efficacy endpoint - FACE: Percentage of patients who achieve an IGA success over the study duration (i.e., score of 1 [almost clear] or 0 [clear] for patients aged ≥ 9 and ≤ 14 years; score of 1 [almost clear] or 0 [clear] and at least a two-grade improvement from baseline for patients aged > 14 and < 50 years)","definition_or_measurement_approach":"Percentage of patients achieving IGA success during the study duration, defined as specified by age groups (see primary endpoint E2 definition)."}
• {"endpoint_text":"- Efficacy endpoint - FACE: Change from baseline in total lesion count over the study duration","definition_or_measurement_approach":"Change from baseline in total lesion count on the face assessed longitudinally over study visits."}
• {"endpoint_text":"- Efficacy endpoint - FACE: Change from baseline in inflammatory lesion count over the study duration","definition_or_measurement_approach":"Change from baseline in inflammatory lesion count on the face assessed over study visits."}
• {"endpoint_text":"- Efficacy endpoint - FACE: Change from baseline in non-inflammatory lesion count over the study duration.","definition_or_measurement_approach":"Change from baseline in non-inflammatory lesion count on the face assessed over study visits."}
• {"endpoint_text":"- Efficacy endpoint - TRUNK: Absolute change from baseline in total lesion count at V5/Wk12","definition_or_measurement_approach":"Absolute change from baseline in total lesion count on the trunk at Visit 5 / Week 12."}
• {"endpoint_text":"- Efficacy endpoint - TRUNK: Percentage of patients who achieve a PGA score of 1 (almost clear) or 0 (clear) and at least a two-grade improvement from baseline over the study duration","definition_or_measurement_approach":"Percentage of patients achieving PGA success on the trunk (score 0 or 1 plus ≥2-grade improvement from baseline) over study duration."}
• {"endpoint_text":"- Efficacy endpoint - TRUNK: Change from baseline in truncal total lesion total count over the study duration","definition_or_measurement_approach":"Change from baseline in total lesion count on the trunk assessed over study visits."}
• {"endpoint_text":"- Efficacy endpoint - TRUNK: Change from baseline in truncal inflammatory lesion count over the study duration","definition_or_measurement_approach":"Change from baseline in inflammatory lesion count on the trunk assessed over study visits."}
• {"endpoint_text":"- Efficacy endpoint - TRUNK: Change from baseline in truncal non-inflammatory lesion count over the study duration.","definition_or_measurement_approach":"Change from baseline in non-inflammatory lesion count on the trunk assessed over study visits."}
• {"endpoint_text":"- Efficacy endpoint - OTHER: Dermatology Life Quality Index (DLQI) / Children’s Dermatology Life Quality Index (C-DLQI (C-DLQI for patients from 9 to 16 years old), completed by the patient at the Baseline and Week 12/EoT visits (prior to any Investigator assessments to not impact the patient’s answers to the quality of life questionnaire)","definition_or_measurement_approach":"DLQI and C-DLQI completed by patients at Baseline and Week 12/EoT (prior to investigator assessments)."}
• {"endpoint_text":"- Efficacy endpoint - OTHER: Additional assessment at the Baseline and Week 12/EoT visits.","definition_or_measurement_approach":"Additional assessments performed at Baseline and Week 12/EoT as per protocol."}
• {"endpoint_text":"- Efficacy endpoint - OTHER: Additional Monitoring (not mandatory, following specific consent) at the Baseline and Week 12/EoT visits.","definition_or_measurement_approach":"Optional additional monitoring for subjects who provide specific consent, at Baseline and Week 12/EoT."}
• {"endpoint_text":"- Safety and tolerability 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","definition_or_measurement_approach":"Incidence and characterization of AEs/TEAEs/ADRs/SAEs during the study, with focus on local dermal TEAEs and systemic TEAEs."}
• {"endpoint_text":"- Safety and tolerability endpoint: Frequency of discontinuation of treatment due to TEAEs","definition_or_measurement_approach":"Frequency and reasons for treatment discontinuation due to TEAEs."}
• {"endpoint_text":"- Safety and tolerability endpoint: Changes from baseline of vital signs during the study","definition_or_measurement_approach":"Changes from baseline in vital signs recorded during study visits."}
• {"endpoint_text":"- Safety and tolerability endpoint: Physical examination during the study","definition_or_measurement_approach":"Physical examinations performed during the study to assess safety."}
• {"endpoint_text":"- Safety and tolerability endpoint: Change from baseline of local tolerability- Application site signs/symptoms during the study* *Local tolerability will be evaluated on the basis of 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.","definition_or_measurement_approach":"Local tolerability assessed by signs/symptoms (application site non-lesional erythema, exfoliation, dryness, stinging, burning, itching) scored on 0-3 scale; change from baseline evaluated."}
• {"endpoint_text":"- Safety and tolerability endpoint: Assessment of overall application site irritation at V5/Wk12.","definition_or_measurement_approach":"Overall application site irritation assessment at Visit 5 / Week 12."}

Other endpoints

• {"endpoint_text":"- Efficacy endpoint - OTHER: Dermatology Life Quality Index (DLQI) / Children’s Dermatology Life Quality Index (C-DLQI (C-DLQI for patients from 9 to 16 years old), completed by the patient at the Baseline and Week 12/EoT visits (prior to any Investigator assessments to not impact the patient’s answers to the quality of life questionnaire)","definition_or_measurement_approach":"DLQI / C-DLQI completed by patient at Baseline and Week 12/EoT."}
• {"endpoint_text":"- Efficacy endpoint - OTHER: Additional assessment at the Baseline and Week 12/EoT visits.","definition_or_measurement_approach":"Additional specified assessments at Baseline and Week 12/EoT."}
• {"endpoint_text":"- Efficacy endpoint - OTHER: Additional Monitoring (not mandatory, following specific consent) at the Baseline and Week 12/EoT visits.","definition_or_measurement_approach":"Optional additional monitoring for consenting patients at Baseline and Week 12/EoT."}

Italy

Earliest CTIS Part Ii Submission Date

29-08-2024

Latest Decision Or Authorization Date

16-04-2025

Processing Time Days

230

Number Of Sites

10

Number Of Participants

100

Spain

Earliest CTIS Part Ii Submission Date

19-09-2024

Latest Decision Or Authorization Date

21-04-2025

Processing Time Days

214

Number Of Sites

6

Number Of Participants

60

Poland

Earliest CTIS Part Ii Submission Date

06-09-2024

Latest Decision Or Authorization Date

10-11-2025

Processing Time Days

430

Number Of Sites

15

Number Of Participants

150

Primary sponsor

Full Name

PPM Services S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

PCI Pharma Services Germany GmbH

Responsibilities

IMP storage, distribution and destruction in Europe; packaging activities (as listed in sponsor duties)

Name

Clinigen Clinical Supplies Management GmbH

Responsibilities

IMP storage, distribution and destruction

Name

Hippocrates Research S.r.l.

Responsibilities

Site management and study conduct duties (codes listed: 1,12,2,5,6,9)

Name

RCTS Randomized Clinical Trials

Responsibilities

Study management (codes 1,12,2,5)

Name

LINK Medical Research AB

Responsibilities

Study management (codes 1,12,2,5)

Name

Biotec Services International Limited

Responsibilities

IMP secondary packaging & labelling; IMP storage, distribution and destruction in UK; Final QP release in UK

Name

Astrum Cro Spain S.L.

Responsibilities

Site management and study conduct (codes 1,12,2,5)

Name

Associated Medical Clinical Science Services Sp. z o.o.

Responsibilities

Site management and study conduct (codes 1,12,2,5)

Name

Valos S.r.l.

Responsibilities

Code 10 (as listed in sponsor duties)

Name

Ethical GmbH

Responsibilities

e-TMF system management; other listed duties (codes 3,7)

Third parties

• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"code 14; IMP Storage, distribution and destruction in Europe","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Clinigen Clinical Supplies Management GmbH","duties_or_roles":"code 14; IMP Storage, distribution and destruction.","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Hippocrates Research S.r.l.","duties_or_roles":"code 1; code 12; code 2; code 5; code 6; code 9","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Millmount Healthcare Limited","duties_or_roles":"code 14; Final QP release EU","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Ethical GmbH","duties_or_roles":"e-TMF system; code 3; code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"RCTS Randomized Clinical Trials","duties_or_roles":"code 1; code 12; code 2; code 5","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"LINK Medical Research AB","duties_or_roles":"code 1; code 12; code 2; code 5","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Biotec Services International Limited","duties_or_roles":"code 14; IMP Secondary Packaging & Labelling. IMP storage, distribution and destruction in UK. Final QP release in UK","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Astrum Cro Spain S.L.","duties_or_roles":"code 1; code 12; code 2; code 5","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Poland","full_name":"Associated Medical Clinical Science Services Sp. z o.o.","duties_or_roles":"code 1; code 12; code 2; code 5","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Valos S.r.l. In Forma Abbreviata Va Los S.r.l.","duties_or_roles":"code 10","organisation_type":"Pharmaceutical company"}