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

Inclusion criteria

• {"criterion_text":"- Informed consent obtained\n- Male and female patients aged ≥ 9 and < 50 years. Patients who turned 50 during the pivotal study can rollover to the LT study.\n- 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.\n- 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.\n- 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

• {"criterion_text":"- 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."}
• {"criterion_text":"- Participation in the evaluation of any other investigational product or device within 24 weeks before study baseline."}
• {"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), 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/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."}
• {"criterion_text":"- Patients who may be unreliable for the study including patients who are unable to return for the scheduled visits."}
• {"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":"- 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 medication. Patients with a history of an allergic reaction or significant sensitivity to the formulations’ ingredients."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Incidence and reporting of AEs/TEAEs/ADRs/SAEs collected throughout study; special attention to local TEAEs in treated facial area and systemic TEAEs (standard AE/SAE reporting)."}
• {"endpoint_text":"- Safety endpoint: Frequency of discontinuation of treatment due to TEAEs","definition_or_measurement_approach":"Frequency (proportion) of patients who discontinue treatment because of treatment-emergent adverse events."}
• {"endpoint_text":"- Safety endpoint: Changes from baseline of vital signs during the study","definition_or_measurement_approach":"Change from baseline in vital sign measurements taken at scheduled visits over study duration."}
• {"endpoint_text":"- Safety endpoint: Physical examination during the study","definition_or_measurement_approach":"Findings from physical examinations performed during study visits compared to baseline."}
• {"endpoint_text":"- Safety endpoint: Changes from baseline of laboratory test over the study duration.","definition_or_measurement_approach":"Laboratory test values collected at scheduled visits; changes from baseline summarized."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Local tolerability assessed by listed signs/symptoms; each assigned severity score on 0–3 scale (0=absent to 3=severe); change from baseline will be evaluated."}
• {"endpoint_text":"- Safety endpoint: Assessment of overall application site irritation over the study duration.","definition_or_measurement_approach":"Overall assessment of application site irritation collected across visits (clinical assessment of irritation over study duration)."}

Secondary endpoints

• {"endpoint_text":"- Efficacy endpoint - FACE: Percentage of patients who have improvement of IGA score at each time point (1,2 points), vs baseline score","definition_or_measurement_approach":"Proportion of patients achieving an improvement of 1- or 2-point change in Investigator’s Global Assessment (IGA) from baseline at each scheduled timepoint."}
• {"endpoint_text":"- Efficacy endpoint - FACE: The percentage change from baseline in total lesion count (inflammatory plus non-inflammatory) at each time point","definition_or_measurement_approach":"Percent change from baseline in total lesion count (inflammatory + non-inflammatory) at each scheduled timepoint."}
• {"endpoint_text":"- Efficacy endpoint - FACE: Absolute change from baseline in total lesion count at each time point","definition_or_measurement_approach":"Absolute difference from baseline in total lesion count at each scheduled timepoint."}
• {"endpoint_text":"- Efficacy endpoint - FACE: Change from baseline in inflammatory lesion count (percentage and absolute), at each time point","definition_or_measurement_approach":"Change from baseline in inflammatory lesion count reported as both percent and absolute change at each scheduled timepoint."}
• {"endpoint_text":"- Efficacy endpoint - FACE: Change from baseline in non-inflammatory lesion count (percentage and absolute), at each time point","definition_or_measurement_approach":"Change from baseline in non-inflammatory lesion count reported as both percent and absolute change at each scheduled timepoint."}
• {"endpoint_text":"- Efficacy endpoint - TRUNK: Percentage of patients who have improvement of PGA score at each time point (1,2 points), vs baseline score","definition_or_measurement_approach":"Proportion of patients achieving a 1- or 2-point improvement in Physician Global Assessment (PGA) for truncal acne vs baseline at each timepoint."}
• {"endpoint_text":"- Efficacy endpoint - TRUNK: The percentage change from baseline in total lesion count (inflammatory plus non-inflammatory) at each time point","definition_or_measurement_approach":"Percent change from baseline in total truncal lesion count (inflammatory + non-inflammatory) at each scheduled timepoint."}
• {"endpoint_text":"- Efficacy endpoint - TRUNK: Absolute change from baseline in total lesion count at each time point","definition_or_measurement_approach":"Absolute change from baseline in total truncal lesion count at each scheduled timepoint."}
• {"endpoint_text":"- Efficacy endpoint - TRUNK: Change from baseline in inflammatory lesion count (percentage and absolute), at each time point","definition_or_measurement_approach":"Change from baseline in truncal inflammatory lesion count (percent and absolute) at each scheduled visit."}
• {"endpoint_text":"- Efficacy endpoint - TRUNK: Change from baseline in non-inflammatory lesion count (percentage and absolute), at each time point.","definition_or_measurement_approach":"Change from baseline in truncal non-inflammatory lesion count (percent and absolute) at each scheduled visit."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Patient-completed DLQI or C-DLQI (for ages 9–16) at Baseline, Week 12 and Week 52, collected before investigator assessments."}
• {"endpoint_text":"- Efficacy endpoint - OTHER: Additional Assessment by Scale for Acne Severity of additional evaluation at Baseline, Wk12, Wk26, Wk38 and Wk52 visits.","definition_or_measurement_approach":"Additional acne severity scale assessments at Baseline, Week12, Week26, Week38 and Week52."}
• {"endpoint_text":"- Efficacy endpoint - OTHER: At Baseline, Wk12 and Wk52 additional documentation will be optional. The area defined for additional assessments is only the face.","definition_or_measurement_approach":"Optional additional documentation (face only) at Baseline, Week12 and Week52."}

Italy

Earliest CTIS Part Ii Submission Date

30-08-2024

Latest Decision Or Authorization Date

03-10-2024

Processing Time Days

34

Number Of Sites

18

Number Of Participants

100

Spain

Earliest CTIS Part Ii Submission Date

26-08-2024

Latest Decision Or Authorization Date

03-10-2024

Processing Time Days

38

Number Of Sites

13

Number Of Participants

60

Poland

Earliest CTIS Part Ii Submission Date

09-09-2024

Latest Decision Or Authorization Date

07-10-2024

Processing Time Days

28

Number Of Sites

26

Number Of Participants

160

Primary sponsor

Full Name

PPM Services S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Third parties

• {"country":"France","full_name":"RCTS Randomized Clinical Trials","duties_or_roles":"codes: 1,12,2,5","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Clinigen Clinical Supplies Management GmbH","duties_or_roles":"codes: 14,15; details: IMP Storage, distribution and destruction.","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Biotec Services International Limited","duties_or_roles":"codes: 14,15; details: IMP Secondary Packaging & Labelling. IMP storage, distribution and destruction in UK. Final QP release in UK.","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Associated Medical Clinical Science Services Sp. z o.o.","duties_or_roles":"codes: 1,12,2,5","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"}
• {"country":"Switzerland","full_name":"Ethical GmbH","duties_or_roles":"codes: 15,3,7; details include e-TMF system","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"GBA Central Lab Services GmbH","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Italy","full_name":"Hippocrates Research S.r.l.","duties_or_roles":"codes: 1,12,2,5,6,9","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Astrum Cro Spain S.L.","duties_or_roles":"codes: 1,12,2,5","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"codes: 14,15; details: IMP Storage, distribution and destruction in Europe","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Millmount Healthcare Limited","duties_or_roles":"codes: 14,15; details: Final QP release EU","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"LINK Medical Research AB","duties_or_roles":"codes: 1,12,2,5","organisation_type":"Pharmaceutical company"}