search
Back to results

Efficacy of an Adapted Antibiotherapy in Hurley Stage 2 Hidradenitis Suppurativa Patients (ABCESS2)

Primary Purpose

Hidradenitis Suppurativa

Status
Not yet recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
ROCEPHIN, metronidazole, RIFADIN, IZILOX, placebo combination therapy
Lymecyclin and corresponding placebos of the experimental arm
Sponsored by
Institut Pasteur
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hidradenitis Suppurativa focused on measuring Hidradenitis Suppurativa, Antibioresistance, Antibiotherapy

Eligibility Criteria

18 Years - 59 Years (Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Hôpital Edouard Herriot
  • Hôpital de la Timone
  • Centre Médical de l'Institut Pasteur
  • Hopital St Joseph
  • CHU de Rouen

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Experimental treatment

Control

Arm Description

a 3-week course of ceftriaxone (Rocephin) IV injection (daily dose 2g/day) + oral metronidazole (daily dose 1500mg) followed by a 3-week course of oral rifampicin (Rifadin with 10mg/kg/day) + moxifloxacin (Izilox daily dose 400mg) + metronidazole (daily dose 1500mg) followed by a 6-week course of oral rifampicin (Rifadin with 10mg/kg/day) + moxifloxacin (Izilox daily dose 400mg). A placebo for lymecycline will also be administered during this intensive treatment phase

12-week course of oral lymecycline (Tetralysal daily dose 452mg) Placebos for all experimental drugs will also be administered during this intensive treatment phase

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
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
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
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
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
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
Microbiological bacterial Change on the worst lesion microbiome at W12
By identification of microbiology bacterial metagenomics (by skin lesional swab sample)
Microbiological metagenomics Change on the worst lesion microbiome at W12
By identification of multidrug resistant bacteria (by rectal swab sample)
Number of pain killers received by patients
Number of pain killers prescribed for flares (acute worsening of one or more HS lesions)
Number of antibiotic treatments received by patients
Number of antibiotic treatments prescribed for flares (acute worsening of one or more HS lesions)
Time without flare of HS
Evaluated by number of flares reported or not using a patient journal
Change in BMI
Calculated by combined weight and height measures
Abnormal biological value of Hemoglobin
measured in g/L, compared to normal ranges
Abnormal biological value of white cells
measured in units of cells / mm3 , compared to normal ranges
Abnormal biological value of neutrophils
measured in units of cells / mm3 , compared to normal ranges
Abnormal biological value of platelet count
measured in units of cells / mm3 , compared to normal ranges
Abnormal value of AST liver enzyme
AST value > 4 x Upper limit of normal
Abnormal value of ALT liver enzyme
ALT value > 4 x Upper limit of normal
Number of adverse events of all kind
AE defined by SOC and PT according to MedDra dictonnary
Non complete drug administration
Evaluated by total number of capsules not taken according to patient journal

Full Information

First Posted
April 16, 2019
Last Updated
September 29, 2023
Sponsor
Institut Pasteur
Collaborators
Centre Hospitalier Universitaire de Caen, Hôpital Necker-Enfants Malades, Ministry of Health, France, Assistance Publique Hopitaux De Marseille
search

1. Study Identification

Unique Protocol Identification Number
NCT05821478
Brief Title
Efficacy of an Adapted Antibiotherapy in Hurley Stage 2 Hidradenitis Suppurativa Patients
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 15, 2023 (Anticipated)
Primary Completion Date
February 15, 2025 (Anticipated)
Study Completion Date
February 15, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Pasteur
Collaborators
Centre Hospitalier Universitaire de Caen, Hôpital Necker-Enfants Malades, Ministry of Health, France, Assistance Publique Hopitaux De Marseille

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hidradenitis Suppurativa
Keywords
Hidradenitis Suppurativa, Antibioresistance, Antibiotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Multicentric randomized double-blind phase 3 trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
92 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental treatment
Arm Type
Experimental
Arm Description
a 3-week course of ceftriaxone (Rocephin) IV injection (daily dose 2g/day) + oral metronidazole (daily dose 1500mg) followed by a 3-week course of oral rifampicin (Rifadin with 10mg/kg/day) + moxifloxacin (Izilox daily dose 400mg) + metronidazole (daily dose 1500mg) followed by a 6-week course of oral rifampicin (Rifadin with 10mg/kg/day) + moxifloxacin (Izilox daily dose 400mg). A placebo for lymecycline will also be administered during this intensive treatment phase
Arm Title
Control
Arm Type
Active Comparator
Arm Description
12-week course of oral lymecycline (Tetralysal daily dose 452mg) Placebos for all experimental drugs will also be administered during this intensive treatment phase
Intervention Type
Drug
Intervention Name(s)
ROCEPHIN, metronidazole, RIFADIN, IZILOX, placebo combination therapy
Other Intervention Name(s)
Experimental treatment
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Lymecyclin and corresponding placebos of the experimental arm
Other Intervention Name(s)
Control treatment
Intervention Description
12-week course of oral lymecycline.
Primary Outcome Measure Information:
Title
Percentage of patients reaching clinical remission at week 12, defined by an improvement of 90% of the IHS4 score from the baseline (IHS4 (1))
Description
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.
Time Frame
at week 12
Secondary Outcome Measure Information:
Title
Change in Physician Global Assessment (PGA)
Description
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
Time Frame
from baseline to week 52
Title
Change in Modified Sartorius score
Description
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
Time Frame
from baseline to week 52
Title
Change in Hurley Score
Description
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
Time Frame
from baseline to week 52
Title
Change in Hidradenitis Suppurativa Severity Score (IHS4) score
Description
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
Time Frame
from baseline to week 52
Title
Change in Hidradenitis Suppurativa Clinical Response (HiSCR) score
Description
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
Time Frame
from baseline to week 52
Title
Change in Dermatology Life Quality Index (DLQI) score (Patient's HS evaluation)
Description
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
Time Frame
from baseline to week 52
Title
Change of patient pain
Description
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
Time Frame
from baseline to week 52
Title
Microbiological bacterial Change on the worst lesion microbiome at W12
Description
By identification of microbiology bacterial metagenomics (by skin lesional swab sample)
Time Frame
at baseline and week 12
Title
Microbiological metagenomics Change on the worst lesion microbiome at W12
Description
By identification of multidrug resistant bacteria (by rectal swab sample)
Time Frame
at baseline and week 12
Title
Number of pain killers received by patients
Description
Number of pain killers prescribed for flares (acute worsening of one or more HS lesions)
Time Frame
from baseline to week 52
Title
Number of antibiotic treatments received by patients
Description
Number of antibiotic treatments prescribed for flares (acute worsening of one or more HS lesions)
Time Frame
from baseline to week 52
Title
Time without flare of HS
Description
Evaluated by number of flares reported or not using a patient journal
Time Frame
from baseline to week 52
Title
Change in BMI
Description
Calculated by combined weight and height measures
Time Frame
from baseline to week 52
Title
Abnormal biological value of Hemoglobin
Description
measured in g/L, compared to normal ranges
Time Frame
from baseline to week 12
Title
Abnormal biological value of white cells
Description
measured in units of cells / mm3 , compared to normal ranges
Time Frame
from baseline to week 12
Title
Abnormal biological value of neutrophils
Description
measured in units of cells / mm3 , compared to normal ranges
Time Frame
from baseline to week 12
Title
Abnormal biological value of platelet count
Description
measured in units of cells / mm3 , compared to normal ranges
Time Frame
from baseline to week 12
Title
Abnormal value of AST liver enzyme
Description
AST value > 4 x Upper limit of normal
Time Frame
from baseline to week 12
Title
Abnormal value of ALT liver enzyme
Description
ALT value > 4 x Upper limit of normal
Time Frame
from baseline to week 12
Title
Number of adverse events of all kind
Description
AE defined by SOC and PT according to MedDra dictonnary
Time Frame
from baseline to week 52
Title
Non complete drug administration
Description
Evaluated by total number of capsules not taken according to patient journal
Time Frame
from baseline to week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maïa Delage-Toriel, MD
Phone
+33 1 40 61 30 77
Email
maia.delage-toriel@pasteur.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Aude Nassif, MD
Phone
01 40 61 30 77
Email
aude.nassif@pasteur.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maïa Delage-Toriel, MD
Organizational Affiliation
Institut Pasteur
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Edouard Herriot
City
Lyon
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Denis Jullien, MD, PhD
Email
denis.jullien@chu-lyon.fr
Facility Name
Hôpital de la Timone
City
Marseille
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie-Aleth Richard, MD, PhD
Email
MarieAleth.RICHARD@ap-hm.fr
Facility Name
Centre Médical de l'Institut Pasteur
City
Paris
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maïa Delage-Toriel, MD
Email
maia.delage-toriel@pasteur.fr
First Name & Middle Initial & Last Name & Degree
Aude Nassif
Facility Name
Hopital St Joseph
City
Paris
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charlotte FITE, Dr
Email
cfite@ghpsj.fr
Facility Name
CHU de Rouen
City
Rouen
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne-Bénédicte Duval-Modeste, Dr
Email
AB.Duval-Modeste@chu-rouen.fr

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All IPD that underlie results in a publication
IPD Sharing Time Frame
After publication, for 25 years
IPD Sharing Access Criteria
By publication in scientific journals and / or presented in scientific or medical meetings
Citations:
PubMed Identifier
28379372
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.
Results Reference
background
PubMed Identifier
25418454
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.
Results Reference
background
PubMed Identifier
21109728
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.
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs