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Personalized Therapies in Inflammatory Complex Disease (PIMOC)

Primary Purpose

Inflammatory Disease, Autoimmune Diseases

Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Kineret
Humira
Stelara
Cosentyx
Roactemra
Rituximab
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Inflammatory Disease focused on measuring Personalized treatment, Inflammatory diseases, auto-inflammatory diseases, auto-immune diseases, Targeted treatments, skin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients (men or women) aged 18 years old and over
  • Patients presenting inflammatory non classified disease targeting at least 2 organs involvement: skin, lymph nodes, hemopoietic system, joints, digestive tract. Skin involvement is mandatory in order to be able to compare involved and non-involved tissue
  • Signed informed consent

The disease should be considered as non-classified despite classical and adapted investigations and evaluation through expert committee meeting.

The disease alters significantly quality of life. The impairment of quality of life will be assessed based on the investigator's assessment.

The disease has been resistant to at least two prior lines of treatment

Exclusion Criteria:

  • Patients presenting disease which is not featured by lesional and healthy skin areas, easy to biopsy
  • Patients refusing biopsies
  • Pregnancy
  • Women of child-bearing potential unable to receive highly efficient contraception such as combined oral contraceptives, intra-uterine disposals, hormonal implants or the use of male condoms recommended in case of unstable or irregular partner or as a replacement method for transient unacessebility to hormonal method
  • Breastfeeding
  • Patients presenting disease needing urgent therapeutic measures
  • Patients without health insurance or social security
  • Participation in another interventional trial
  • Patients under legal protection

  • Patients unable to respect the wash out delay of previously taken medications before biopsy and before treatment initiation :

    • Hydroxychloroquine (wash out period = 30 days)
    • Chloroquine (wash out period = 7 days)
    • Colchicine (wash out period = 7 days)
    • Methotrexate (wash out period = 7 days)
    • Ciclosporine (wash out period = 14 days)
    • Azathioprine (wash out period = 14 days)
    • Mycophenolate mofetil (wash out period = 14 days)
    • Disulone (wash out period = 7 days)
    • Corticosteroids (=prednisone, prednisolone, dexamethasone, methylprednisolone) (wash out period = 7 days for doses greater than 5mg)
  • Patients with contra-indications to treatments : Severe or active infections including tuberculosis

Sites / Locations

  • Hôpital CochinRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Kineret

Humira

Stelara

Cosentyx

Roactemra

Rituximab

Arm Description

Outcomes

Primary Outcome Measures

Composite clinico-biological evaluation
Response will be assessed at month 6 with a composite endpoint defined as improvement of at least of 2 of the 3 following parameters: 50% improvement of the systemic activity assessed by the clinician following a visual analog scale (0-10), where clinician will be asked the following question: "Please indicate, according to your clinical experience and taking into account all systemic manifestations, the level of disease activity in this patient using the following scale:" and/or 50% improvement of cutaneous activity assessed by the involved skin surface area (according the rule of 9%). Standardised skin pictures will be done in order to centrally review cutaneous response. and/or 50% decrease or normalisation of biological markers of inflammation (either CRP, ESR or fibrin)

Secondary Outcome Measures

Number of Infections
to evaluate tolerance
liver cell count toxicities
to evaluate tolerance
kidney cell count toxicities
to evaluate tolerance
blood cell count toxicities
to evaluate tolerance
Change in Physician Global Assessment (PGA)
to evaluate clinical efficiency
Change in Physician Global Assessment (PGA)
to evaluate clinical efficiency
Change in Physician Global Assessment (PGA)
to evaluate clinical efficiency
Change in continuous PGA
to evaluate clinical efficiency
Change in continuous PGA
to evaluate clinical efficiency
Change in British Isles Lupus Assessment Group (BILAG)
to evaluate clinical efficiency
Change in British Isles Lupus Assessment Group (BILAG)
to evaluate clinical efficiency
Change in British Isles Lupus Assessment Group (BILAG)
to evaluate clinical efficiency
Change in British Isles Lupus Assessment Group (BILAG)
to evaluate clinical efficiency
Change in Systemic Lupus Erythematosus Responder Index (SRI)
to evaluate clinical efficiency
Change in Systemic Lupus Erythematosus Responder Index (SRI)
to evaluate clinical efficiency
Change in Systemic Lupus Erythematosus Responder Index (SRI)
to evaluate clinical efficiency
Change in Systemic Lupus Erythematosus Responder Index (SRI)
to evaluate clinical efficiency
Change in Cutaneous Lupus Disease Area and Severity Index (CLASI)
to evaluate clinical efficiency
Change in Cutaneous Lupus Disease Area and Severity Index (CLASI)
to evaluate clinical efficiency
Change in Cutaneous Lupus Disease Area and Severity Index (CLASI)
to evaluate clinical efficiency
Change in Cutaneous Lupus Disease Area and Severity Index (CLASI)
to evaluate clinical efficiency
Change in 36-Item Short Form Health Survey (SF36)
to evaluate clinical efficiency
Change in 36-Item Short Form Health Survey (SF36)
to evaluate clinical efficiency
Change in 36-Item Short Form Health Survey (SF36)
to evaluate clinical efficiency
Change in 36-Item Short Form Health Survey (SF36)
to evaluate clinical efficiency
Change in CRP
to evaluate biological efficiency
Change in CRP
to evaluate biological efficiency
Change in CRP
to evaluate biological efficiency
Change in CRP
to evaluate biological efficiency
Change in CRP
to evaluate biological efficiency
Change in ESR (Erythrocyte sedimentation rate)
to evaluate biological efficiency
Change in ESR (Erythrocyte sedimentation rate)
to evaluate biological efficiency
Change in ESR (Erythrocyte sedimentation rate)
to evaluate biological efficiency
Change in ESR (Erythrocyte sedimentation rate)
to evaluate biological efficiency
Change in ESR (Erythrocyte sedimentation rate)
to evaluate biological efficiency
Change in Fibrin
to evaluate biological efficiency
Change in Fibrin
to evaluate biological efficiency
Change in Fibrin
to evaluate biological efficiency
Change in Fibrin
to evaluate biological efficiency
Change in Fibrin
to evaluate biological efficiency
Decreased in serum increased cytokines, in selected RNA in peripheral blood and skin specimens
to evaluate targeted biological efficiency
Decreased in serum increased cytokines, in selected RNA in peripheral blood and skin specimens
to evaluate targeted biological efficiency
Decreased in serum increased cytokines, in selected RNA in peripheral blood and skin specimens
to evaluate targeted biological efficiency
Decreased in serum increased cytokines, in selected RNA in peripheral blood and skin specimens
to evaluate targeted biological efficiency
RNA analysis of targeted cytokines and RNA sequencing

Full Information

First Posted
June 25, 2018
Last Updated
October 10, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT03651518
Brief Title
Personalized Therapies in Inflammatory Complex Disease
Acronym
PIMOC
Official Title
Personalized Targeted Therapies in Inflammatory Complex Multi Organ Disease
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 20, 2020 (Actual)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

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

5. Study Description

Brief Summary
Inflammatory diseases may display atypical features making such patients impossible to classify. Management of these cases in daily practice cannot rely on the results of clinical trials nor on guidelines. DNA and RNA mapping have become major tools to understand and sometimes direct the treatment strategy in oncology. This study aims to test whether a precise analysis of molecular pathways in inflammatory, non classified diseases, can constitute a predictive tool of therapeutic efficiency
Detailed Description
This is a phase IIb study. The main objective of this study is to evaluate the efficacy of targeted treatments in patients displaying a non-classified, severe and resistant inflammatory disease. Targeted treatments for each patient will have been selected through an algorithm based on molecular analysis of specific altered inflammatory signaling pathway. Treatments consist in targeted therapies approved in other indications (Kineret®, Humira®, Stelara®, Cosentyx®, Roactemra® and Rituximab®) that will be given once selected using molecular analysis and decision making procedure by the Scientific committee. For each patient, one targeted treatment will be administered according to the SmPC procedure for a treatment period of 6 months. Primary efficacy endpoint: Response will be assessed at month 6 with a composite endpoint defined as improvement of at least 2 of the 3 following parameters: 50% improvement of the systemic activity assessed by the clinician following a visual analog scale (0-10 mm), and/or 50% improvement of cutaneous activity assessed by the involved skin surface area, and/or 50% decrease or normalisation of biological markers of inflammation (either CRP, ESR or fibrin). An independent adjudication committee blinded to the treatment received, will review primary endpoint for all patients based on clinical files and standardized photographs, to validate the response. Other secondary criteria will be assessed. Overall, this study will require a molecular analysis done on patient's tissue, the final aim being to evaluate efficiency and tolerance of targeted treatments chosen in a personalized analysis when classification is impossible.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammatory Disease, Autoimmune Diseases
Keywords
Personalized treatment, Inflammatory diseases, auto-inflammatory diseases, auto-immune diseases, Targeted treatments, skin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Kineret
Arm Type
Experimental
Arm Title
Humira
Arm Type
Experimental
Arm Title
Stelara
Arm Type
Experimental
Arm Title
Cosentyx
Arm Type
Experimental
Arm Title
Roactemra
Arm Type
Experimental
Arm Title
Rituximab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Kineret
Intervention Description
100 mg, once/day sc 6 months
Intervention Type
Drug
Intervention Name(s)
Humira
Intervention Description
40 mg/15 days sc 6 months
Intervention Type
Drug
Intervention Name(s)
Stelara
Intervention Description
45 mg/12 weeks sc, 6 months
Intervention Type
Drug
Intervention Name(s)
Cosentyx
Intervention Description
300mg sc every week for 1 month, then 300 mg/month sc for 5 months
Intervention Type
Drug
Intervention Name(s)
Roactemra
Intervention Description
480 mg/perf/4 weeks 6 months
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
2 sessions of 1000 mg at inclusion and 15 days after inclusion
Primary Outcome Measure Information:
Title
Composite clinico-biological evaluation
Description
Response will be assessed at month 6 with a composite endpoint defined as improvement of at least of 2 of the 3 following parameters: 50% improvement of the systemic activity assessed by the clinician following a visual analog scale (0-10), where clinician will be asked the following question: "Please indicate, according to your clinical experience and taking into account all systemic manifestations, the level of disease activity in this patient using the following scale:" and/or 50% improvement of cutaneous activity assessed by the involved skin surface area (according the rule of 9%). Standardised skin pictures will be done in order to centrally review cutaneous response. and/or 50% decrease or normalisation of biological markers of inflammation (either CRP, ESR or fibrin)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Number of Infections
Description
to evaluate tolerance
Time Frame
12 months
Title
liver cell count toxicities
Description
to evaluate tolerance
Time Frame
12 months
Title
kidney cell count toxicities
Description
to evaluate tolerance
Time Frame
12 months
Title
blood cell count toxicities
Description
to evaluate tolerance
Time Frame
12 months
Title
Change in Physician Global Assessment (PGA)
Description
to evaluate clinical efficiency
Time Frame
1 month,
Title
Change in Physician Global Assessment (PGA)
Description
to evaluate clinical efficiency
Time Frame
3 months,
Title
Change in Physician Global Assessment (PGA)
Description
to evaluate clinical efficiency
Time Frame
6 months,
Title
Change in continuous PGA
Description
to evaluate clinical efficiency
Time Frame
9 months
Title
Change in continuous PGA
Description
to evaluate clinical efficiency
Time Frame
12 months
Title
Change in British Isles Lupus Assessment Group (BILAG)
Description
to evaluate clinical efficiency
Time Frame
3 months
Title
Change in British Isles Lupus Assessment Group (BILAG)
Description
to evaluate clinical efficiency
Time Frame
6 months
Title
Change in British Isles Lupus Assessment Group (BILAG)
Description
to evaluate clinical efficiency
Time Frame
9 months
Title
Change in British Isles Lupus Assessment Group (BILAG)
Description
to evaluate clinical efficiency
Time Frame
12 months
Title
Change in Systemic Lupus Erythematosus Responder Index (SRI)
Description
to evaluate clinical efficiency
Time Frame
3 months
Title
Change in Systemic Lupus Erythematosus Responder Index (SRI)
Description
to evaluate clinical efficiency
Time Frame
6 months
Title
Change in Systemic Lupus Erythematosus Responder Index (SRI)
Description
to evaluate clinical efficiency
Time Frame
9 months
Title
Change in Systemic Lupus Erythematosus Responder Index (SRI)
Description
to evaluate clinical efficiency
Time Frame
12 months
Title
Change in Cutaneous Lupus Disease Area and Severity Index (CLASI)
Description
to evaluate clinical efficiency
Time Frame
3 months
Title
Change in Cutaneous Lupus Disease Area and Severity Index (CLASI)
Description
to evaluate clinical efficiency
Time Frame
6 months
Title
Change in Cutaneous Lupus Disease Area and Severity Index (CLASI)
Description
to evaluate clinical efficiency
Time Frame
9 months
Title
Change in Cutaneous Lupus Disease Area and Severity Index (CLASI)
Description
to evaluate clinical efficiency
Time Frame
12 months
Title
Change in 36-Item Short Form Health Survey (SF36)
Description
to evaluate clinical efficiency
Time Frame
3 months
Title
Change in 36-Item Short Form Health Survey (SF36)
Description
to evaluate clinical efficiency
Time Frame
6 months
Title
Change in 36-Item Short Form Health Survey (SF36)
Description
to evaluate clinical efficiency
Time Frame
9 months
Title
Change in 36-Item Short Form Health Survey (SF36)
Description
to evaluate clinical efficiency
Time Frame
12 months
Title
Change in CRP
Description
to evaluate biological efficiency
Time Frame
1 month
Title
Change in CRP
Description
to evaluate biological efficiency
Time Frame
3 months
Title
Change in CRP
Description
to evaluate biological efficiency
Time Frame
6 months
Title
Change in CRP
Description
to evaluate biological efficiency
Time Frame
9 months
Title
Change in CRP
Description
to evaluate biological efficiency
Time Frame
12 months
Title
Change in ESR (Erythrocyte sedimentation rate)
Description
to evaluate biological efficiency
Time Frame
1 month
Title
Change in ESR (Erythrocyte sedimentation rate)
Description
to evaluate biological efficiency
Time Frame
3 months
Title
Change in ESR (Erythrocyte sedimentation rate)
Description
to evaluate biological efficiency
Time Frame
6 months
Title
Change in ESR (Erythrocyte sedimentation rate)
Description
to evaluate biological efficiency
Time Frame
9 months
Title
Change in ESR (Erythrocyte sedimentation rate)
Description
to evaluate biological efficiency
Time Frame
12 months
Title
Change in Fibrin
Description
to evaluate biological efficiency
Time Frame
1 month,
Title
Change in Fibrin
Description
to evaluate biological efficiency
Time Frame
3 months
Title
Change in Fibrin
Description
to evaluate biological efficiency
Time Frame
6 months
Title
Change in Fibrin
Description
to evaluate biological efficiency
Time Frame
9 months
Title
Change in Fibrin
Description
to evaluate biological efficiency
Time Frame
12 months
Title
Decreased in serum increased cytokines, in selected RNA in peripheral blood and skin specimens
Description
to evaluate targeted biological efficiency
Time Frame
1 month
Title
Decreased in serum increased cytokines, in selected RNA in peripheral blood and skin specimens
Description
to evaluate targeted biological efficiency
Time Frame
3 months
Title
Decreased in serum increased cytokines, in selected RNA in peripheral blood and skin specimens
Description
to evaluate targeted biological efficiency
Time Frame
6 months
Title
Decreased in serum increased cytokines, in selected RNA in peripheral blood and skin specimens
Description
to evaluate targeted biological efficiency
Time Frame
12 months
Title
RNA analysis of targeted cytokines and RNA sequencing
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients (men or women) aged 18 years old and over Patients presenting inflammatory non classified disease targeting at least 2 organs involvement: skin, lymph nodes, hemopoietic system, joints, digestive tract. Skin involvement is mandatory in order to be able to compare involved and non-involved tissue Signed informed consent The disease should be considered as non-classified despite classical and adapted investigations and evaluation through expert committee meeting. The disease alters significantly quality of life. The impairment of quality of life will be assessed based on the investigator's assessment. The disease has been resistant to at least two prior lines of treatment Exclusion Criteria: Patients presenting disease which is not featured by lesional and healthy skin areas, easy to biopsy Patients refusing biopsies Pregnancy Women of child-bearing potential unable to receive highly efficient contraception such as combined oral contraceptives, intra-uterine disposals, hormonal implants or the use of male condoms recommended in case of unstable or irregular partner or as a replacement method for transient unacessebility to hormonal method Breastfeeding Patients presenting disease needing urgent therapeutic measures Patients without health insurance or social security Participation in another interventional trial Patients under legal protection Patients unable to respect the wash out delay of previously taken medications before biopsy and before treatment initiation : Hydroxychloroquine (wash out period = 30 days) Chloroquine (wash out period = 7 days) Colchicine (wash out period = 7 days) Methotrexate (wash out period = 7 days) Ciclosporine (wash out period = 14 days) Azathioprine (wash out period = 14 days) Mycophenolate mofetil (wash out period = 14 days) Disulone (wash out period = 7 days) Corticosteroids (=prednisone, prednisolone, dexamethasone, methylprednisolone) (wash out period = 7 days for doses greater than 5mg) Patients with contra-indications to treatments : Severe or active infections including tuberculosis
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Selim ARACTINGI, PhD
Phone
+ 33 1 58 41 19 88
Email
selim.aractingi@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Christelle AUGER
Phone
+ 33 1 58 41 11 86
Email
christelle.auger@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Selim ARACTINGI, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Cochin
City
Paris
ZIP/Postal Code
75014
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
selim ARACTINGI, PhD
Phone
+ 33 1 58 41 19 88
Email
selim.aractingi@gmail.com

12. IPD Sharing Statement

Learn more about this trial

Personalized Therapies in Inflammatory Complex Disease

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