Clinical trial NCT05821478: Efficacy of an Adapted Antibiotherapy in Hurley Stage 2 Hidradenitis Suppurativa Patients
Official title: A Multicentric Randomized Double-Blind Phase 3 Trial Evaluating the Efficacy of an Adapted Antibiotherapy in Hurley Stage 2 Active Hidradenitis Suppurativa Patients Versus Tetracycline Derivative
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Hidradenitis Suppurativa
Keywords: Hidradenitis Suppurativa
Antibioresistance
Antibiotherapy
Lead sponsor: Institut Pasteur
Sponsor class: INDUSTRY
Collaborators: name: Centre Hospitalier Universitaire de Caen
name: Hôpital Necker-Enfants Malades
name: Ministry of Health, France
name: Assistance Publique Hopitaux De Marseille
First posted: 2023-04-20
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentric randomized double-blind phase 3 trial
Primary purpose: TREATMENT

Brief summary: The study evaluates the efficacy of an adapted antibiotherapy in Hurley stage 2 active Hidradenitis Suppurativa patients versus tetracycline derivative

Detailed description: The antibiotic strategy is targeted against specific pathobionts which have been identified in HS lesions by the investigator's team.

Half of participants will receive a 3-week course of ceftriaxone + metronidazole treatment followed by 3 weeks of rifampicin + moxifloxacin + metronidazole combination, then 6 weeks of rifampin + moxifloxacin (experimental groupe), versus a 12 weeks course of lymecycline (control group) Double blind treatment phase will stop at week 12. All patients whatever their randomization arm or their remission status will begin follow-up treatment according to standard care recommendations (Société Française de Dermatologie): lymecycline, doxycycline or cotrimoxazole. Prescription will be upon decision of the investigator.

This maintenance treatment is not experimental.

Eligibility criteria: Inclusion Criteria:

* Adults \< 60 years old
* Diagnosis of HS according to European Dermatology guidelines:

  * Recurrent inflammation occurring more than 2 times in the past 6 months in the inverse regions of the body, presenting with nodules, sinus-tracts and/or scarring.
  * Signs: Involvement of axilla, genitofemoral area, perineum, gluteal area (and infra-mammary areafor women). Presence of nodules (inflamed or noninflamed), sinus tracts (inflamed or noninflamed), abscesses, scarring (atrophic, mesh-like, red, hypertrophic or linear)
* Active HS with i) ≥ 1 year of evolution and ii) ≥ 4 flares during the previous year
* Clinical severity of HS at inclusion: Hurley stage 2
* BMI \< 35
* Written informed consent from patient
* Patient able to complete DLQI
* Patients affiliated to the French health system (Assurance Maladie), except French state medical aid beneficiaries (Aide Médicale d'Etat)
* Active compatible contraception for men and women of childbearing or inability to procreate
* Available laboratory blood test performed within the last 2-months

Non inclusion Criteria:

* Person \< 18 and ≥ 60 years old
* Former stage 3 HS
* Previous use of the experimental treatment
* Unauthorized drugs for the study during the month preceding the inclusion
* Any contra-indication to study treatments or excipient (e.g. lactose, cornstarch, riboflavin notably):

pregnancy, breastfeeding, known allergy to experimental or reference drugs, wheat allergy, tendinopathy, QT prolongation, bradycardia, heart failure, heart rhythm disturbances, hydroelectrolytic disorders, hypokalemia, coagulation disorders, severe liver/kidney dysfunction, porphyria, mandatory use of nonsteroidal anti-inflammatory drugs (NSAIDs) for other medical conditions

* Unbalanced diabetes (ie HbA1c above 7%)
* Dysphagia, untreated gastro-oesophageal reflux/ulcer
* BMI ≥ 35
* Immune suppression, inflammatory disease, including gastroenterologic and rheumatologic inflammatory conditions
* Lactase deficiency, lactose and galactose intolerance
* Malabsorption syndrome
* Person living in the same household as another patient
* Person under guardianship or curatorship
* Individuals with any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives (e.g patient unable to complete DLQI, or poor predictable observance
* Participation in another interventional research on health products studies
* Patients requiring repeated (more than 3/year) use of antibiotics for a chronic disease other than HS
* Alcohol-dependant patients defined as an addiction to alcohol with a negative impact on health, social or personal life

Exclusion criteria:

Pregnancy QT prolongation Abnormal result of routine lab tests corresponding to contra-indication to study treatments Unauthorized drug for the study during all the study (from study treatments interactions listed in the SmPC, Cf. unauthorized drug listed in non-inclusion criteria).

Development of hypersensitivity to any of the study products and/or excipients (e.g. lactose, corn starch, riboflavin).

Primary outcomes:
measure: Percentage of patients reaching clinical remission at week 12, defined by an improvement of 90% of the IHS4 score from the baseline (IHS4 (1))
timeFrame: at week 12
Secondary outcomes:
measure: Change in Physician Global Assessment (PGA)
timeFrame: from baseline to week 52
measure: Change in Modified Sartorius score
timeFrame: from baseline to week 52
measure: Change in Hurley Score
timeFrame: from baseline to week 52
measure: Change in Hidradenitis Suppurativa Severity Score (IHS4) score
timeFrame: from baseline to week 52
measure: Change in Hidradenitis Suppurativa Clinical Response (HiSCR) score
timeFrame: from baseline to week 52
measure: Change in Dermatology Life Quality Index (DLQI) score (Patient's HS evaluation)
timeFrame: from baseline to week 52
measure: Change of patient pain
timeFrame: from baseline to week 52
measure: Microbiological bacterial Change on the worst lesion microbiome at W12
timeFrame: at baseline and week 12
measure: Microbiological metagenomics Change on the worst lesion microbiome at W12
timeFrame: at baseline and week 12
measure: Number of pain killers received by patients
timeFrame: from baseline to week 52
measure: Number of antibiotic treatments received by patients
timeFrame: from baseline to week 52
measure: Time without flare of HS
timeFrame: from baseline to week 52
measure: Change in BMI
timeFrame: from baseline to week 52
measure: Abnormal biological value of Hemoglobin
timeFrame: from baseline to week 12
measure: Abnormal biological value of white cells
timeFrame: from baseline to week 12
measure: Abnormal biological value of neutrophils
timeFrame: from baseline to week 12
measure: Abnormal biological value of platelet count
timeFrame: from baseline to week 12
measure: Abnormal value of AST liver enzyme
timeFrame: from baseline to week 12
measure: Abnormal value of ALT liver enzyme
timeFrame: from baseline to week 12
measure: Number of adverse events of all kind
timeFrame: from baseline to week 52
measure: Non complete drug administration
timeFrame: from baseline to week 12
Other outcomes:
Locations:
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Marseille
country: France
facility: Hôpital de la Timone
city: Paris
country: France
facility: Centre Médical de l'Institut Pasteur
city: Paris
country: France
facility: Hopital St Joseph
city: Rouen
country: France
facility: CHU de Rouen
Study officials:
affiliation: Institut Pasteur
name: Maïa Delage-Toriel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Guet-Revillet H, Jais JP, Ungeheuer MN, Coignard-Biehler H, Duchatelet S, Delage M, Lam T, Hovnanian A, Lortholary O, Nassif X, Nassif A, Join-Lambert O. The Microbiological Landscape of Anaerobic Infections in Hidradenitis Suppurativa: A Prospective Metagenomic Study. Clin Infect Dis. 2017 Jul 15;65(2):282-291. doi: 10.1093/cid/cix285.
citation: Guet-Revillet H, Coignard-Biehler H, Jais JP, Quesne G, Frapy E, Poiree S, Le Guern AS, Le Fleche-Mateos A, Hovnanian A, Consigny PH, Lortholary O, Nassif X, Nassif A, Join-Lambert O. Bacterial pathogens associated with hidradenitis suppurativa, France. Emerg Infect Dis. 2014 Dec;20(12):1990-8. doi: 10.3201/eid2012.140064.
citation: Join-Lambert O, Coignard H, Jais JP, Guet-Revillet H, Poiree S, Fraitag S, Jullien V, Ribadeau-Dumas F, Theze J, Le Guern AS, Behillil S, Lefleche A, Berche P, Consigny PH, Lortholary O, Nassif X, Nassif A. Efficacy of rifampin-moxifloxacin-metronidazole combination therapy in hidradenitis suppurativa. Dermatology. 2011 Feb;222(1):49-58. doi: 10.1159/000321716. Epub 2010 Nov 25.