Efficacy of an Adapted Antibiotherapy in Hurley Stage 2 Hidradenitis Suppurativa Patients

Hidradenitis Suppurativa Clinical Trial

— ABCESS2  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05821478
• Other study ID #: 2018-018
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 15, 2024
• Est. completion date: September 15, 2026

Study information

• Verified date: January 2024
• Source: Institut Pasteur
• Contact: Maïa Delage-Toriel, MD
• Phone: +33 1 40 61 30 77
• Email: maia.delage-toriel[@]pasteur.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 92
• Est. completion date: September 15, 2026
• Est. primary completion date: December 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

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).

Related Conditions & MeSH terms

• Hidradenitis
• Hidradenitis Suppurativa

Intervention

Drug:
• ROCEPHIN, metronidazole, RIFADIN, IZILOX, placebo combination therapy
a 3-week course of ceftriaxone injection + oral metronidazole followed by a 3-week course of oral rifampicin + moxifloxacin +metronidazole followed by a 6-week course of oral rifampicin + moxifloxacin
• Lymecyclin and corresponding placebos of the experimental arm
12-week course of oral lymecycline.

Locations

Country	Name	City	State
France	Hôpital Edouard Herriot	Lyon
France	Hôpital de la Timone	Marseille
France	Centre Médical de l'Institut Pasteur	Paris
France	Hopital St Joseph	Paris
France	CHU de Rouen	Rouen

Sponsors (5)

Lead Sponsor	Collaborator
Institut Pasteur	Assistance Publique Hopitaux De Marseille, Centre Hospitalier Universitaire de Caen, Hôpital Necker-Enfants Malades, Ministry of Health, France

Country where clinical trial is conducted

France, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients reaching clinical remission at week 12, defined by an improvement of 90% of the IHS4 score from the baseline (IHS4 (1))	The clinical remission is defined as a 90% improvement of the International Hidradenitis Suppurativa Severity Score (IHS4) at week 12 compared to the baseline.; The IHS4 score is a validated composite score developped to assess dynamically HS severity (1). It is calculated by adding the number of inflammatory nodules to the number of abscesses multiplied by 2 and to the number of draining tunnels multiplied by 4. A total score of 3 or less corresponds to mild severity HS, 4-10 to moderate severity HS and 11 or higher to severe disease.	at week 12
Secondary	Change in Physician Global Assessment (PGA)	Physician assessment describe by differents severity : from Clear (no nodule) to Very severe (more than 5 abscesses or fistulas) Score evaluated at baseline / week 6 / week 12/ week 24/ week 52	from baseline to week 52
Secondary	Change in Modified Sartorius score	Score calculated by points from 0 (better) with differents parameters involved such as location / number / size / type of lesions Score evaluated at baseline / week 6 / week 12/ week 24/ week 52	from baseline to week 52
Secondary	Change in Hurley Score	Score described with 3 stages from I (less severity) to III (most severe) Score evaluated at baseline / week 6 / week 12/ week 24/ week 52	from baseline to week 52
Secondary	Change in Hidradenitis Suppurativa Severity Score (IHS4) score	Score calculated by points from <3pts (Mild) to > 11pts (Severe) by nb of nodules, nb of abscesses and nb of draining tunnels Score evaluated at baseline / week 6 / week 12/ week 24/ week 52	from baseline to week 52
Secondary	Change in Hidradenitis Suppurativa Clinical Response (HiSCR) score	Global Assessment score of clear, minimal, or mild evaluated by (i) at least a 50% reduction in AN (abscess and nodule count), (ii) no increase in the number of abscesses and (iii) no increase in the number of draining fistulas from baseline Score evaluated at baseline / week 6 / week 12/ week 24/ week 52	from baseline to week 52
Secondary	Change in Dermatology Life Quality Index (DLQI) score (Patient's HS evaluation)	Evaluated with the Dermatology Life Quality Index (DLQI) Score calculated by points from 0 to 30 following patient answers on quality of life questions Score evaluated at baseline / week 6 / week 12/ week 24/ week 52	from baseline to week 52
Secondary	Change of patient pain	Intensity of pain evaluated with the visual analog scale (VAS) from 0 (no pain) to 10 (pain as bad as it could possible be) Score evaluated at baseline / week 6 / week 12/ week 24/ week 52	from baseline to week 52
Secondary	Microbiological bacterial Change on the worst lesion microbiome at W12	By identification of microbiology bacterial metagenomics (by skin lesional swab sample)	at baseline and week 12
Secondary	Microbiological metagenomics Change on the worst lesion microbiome at W12	By identification of multidrug resistant bacteria (by rectal swab sample)	at baseline and week 12
Secondary	Number of pain killers received by patients	Number of pain killers prescribed for flares (acute worsening of one or more HS lesions)	from baseline to week 52
Secondary	Number of antibiotic treatments received by patients	Number of antibiotic treatments prescribed for flares (acute worsening of one or more HS lesions)	from baseline to week 52
Secondary	Time without flare of HS	Evaluated by number of flares reported or not using a patient journal	from baseline to week 52
Secondary	Change in BMI	Calculated by combined weight and height measures	from baseline to week 52
Secondary	Abnormal biological value of Hemoglobin	measured in g/L, compared to normal ranges	from baseline to week 12
Secondary	Abnormal biological value of white cells	measured in units of cells / mm3 , compared to normal ranges	from baseline to week 12
Secondary	Abnormal biological value of neutrophils	measured in units of cells / mm3 , compared to normal ranges	from baseline to week 12
Secondary	Abnormal biological value of platelet count	measured in units of cells / mm3 , compared to normal ranges	from baseline to week 12
Secondary	Abnormal value of AST liver enzyme	AST value > 4 x Upper limit of normal	from baseline to week 12
Secondary	Abnormal value of ALT liver enzyme	ALT value > 4 x Upper limit of normal	from baseline to week 12
Secondary	Number of adverse events of all kind	AE defined by SOC and PT according to MedDra dictonnary	from baseline to week 52
Secondary	Non complete drug administration	Evaluated by total number of capsules not taken according to patient journal	from baseline to week 12