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Efficacy and Safety of DAPSone as a Second-line Option in Adult Immune Thrombocytopenia (DAPS-ITP)

Primary Purpose

Adult Immune Thrombocytopenia (ITP), Dapsone

Status

Unknown status

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

Dapsone (Disulone®)

Prednisone (Cortancyl®) alone followed by monitoring and "standard of care"

Prednisone (Cortancyl®)

About this trial

This is an interventional treatment trial for Adult Immune Thrombocytopenia (ITP) focused on measuring ITP, Dapsone

Eligibility Criteria

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

Inclusion Criteria:

Age ≥ 18 years
Diagnosis of primary ITP according to the standard definition and international guidelines.
Previous transient response to corticosteroids ± intravenous immunoglobulin defined by an increase of the platelet count above 30 x 109/L with at least a twofold increase of the pre-treatment count.
At least platelet count ≤ 30 x 109/L within the 2 weeks before inclusion with a platelet count at time of inclusion below 50 x 109/L, or platelet count < 50 x 109/L at any time point in patients requiring treatment (i.e., patients with bleeding symptoms, elderly patients with comorbidities and/or patients on aspirin for example, or other reason at the investigator discretion) (modified by amendment 8/11/2016)
Normal marrow aspirate for patients aged of 60 and above.
Negative pregnancy test and effective method of contraception for women of childbearing age over the study period.
Informed consent.
Patient affiliated to the French National Social Security System

Exclusion Criteria:

Secondary ITP. Patients with positive antinuclear antibodies and/or positive antiphospholipid antibodies not fulfilling the classification criteria for systemic lupus erythematosus and/or antiphospholipid antibody syndrome will not be excluded.
Platelet count ≥ 50 x 109/L or between 30 and 50 x 109/L and no bleeding symptoms and no need for treatment (modified by amendment 8/11/2016)
Severe bleeding manifestations defined a bleeding score ≥ 8
No previous transient response to corticosteroids ± intravenous immunoglobulin.
Previous ITP treatment other than corticosteroids and intravenous immunoglobulin (including rituximab and splenectomy).
Active severe infection or history of severe infection within 4 weeks before inclusion.
History of allergy to sulfonamides.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
History of methemoglobinemia
Hemoglobin level < 11g/dL and/or neutrophil count < 1,500/ gL.
History of autoimmune (Evans' syndrome) or hereditary haemolytic anemia.
Liver or kidney function impairment (creatinine clearance < 30 ml/min, ALT, AST >2 times upper normal limit). (modified by amendment 8/11/2017)
Hepatitis C virus (HCV) Ab, HIV Ab, HBsAg, seropositive status. (modified by amendment 8/11/2017)
Concomitant medical condition requiring anticoagulation. (modified by amendment 8/11/2017)
Pregnancy or lactation.

Sites / Locations

Henri Mondor HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Dapsone: (Disulone®)

Prednisone (Cortancyl®) alone and "standard of care"

Arm Description

Dapsone: Disulone® given orally at 100 mg per day

Prednisone (Cortancyl®) alone at 1 mg/kg for 3 weeks followed by monitoring and "standard of care" (control arm)

Outcomes

Primary Outcome Measures

Overall response-rate.

Secondary Outcome Measures

Assess the safety of dapsone especially the incidence of cutaneous adverse effects.

Compare the overall response rate .

platelet count > 30 x 109/L with at least a doubling of the pre-treatment count in the absence of any other ITP treatment in both arms

Proportion of patients with complete response in both arms, defined as follows: - Proportion of patients with a platelet count > 100 x 109/L in the absence use of any other ITP directed therapies

Proportion of non-responders patients (primary failure)

Patients will be considered as being non-responders if: Their platelet count at the end of the study is < 30 x 109/L, but also, in the setting of this study if: They need a rescue therapy (a new course of corticosteroids and/or intravenous immunoglobulin) more than 6 weeks after inclusion. or They receive any other treatment for ITP than dapsone or prednisone (including rituximab, splenectomy and Tpo-R agonists) over the study period

Number of days to treatment failure in both arms

Mechanisms of action of Dapsone: degree of phagocytosis of autologous platelets and red blood cells, cytokines profile expression (including IL-8), whole blood gene expression signature between responders and non-responders.

Full Information

NCT ID

NCT02627417

First Posted

November 3, 2015

Last Updated

July 24, 2017

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT02627417

Brief Title

Efficacy and Safety of DAPSone as a Second-line Option in Adult Immune Thrombocytopenia

Acronym

DAPS-ITP

Official Title

Prospective Multicenter Randomized Open-label Controlled Trial Assessing Efficacy and Safety of DAPSone as a Second-line Option in Adult Immune Thrombocytopenia

Study Type

Interventional

2. Study Status

Record Verification Date

July 2017

Overall Recruitment Status

Unknown status

Study Start Date

December 2015 (undefined)

Primary Completion Date

May 2019 (Anticipated)

Study Completion Date

May 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Due to its expected efficacy based on the retrospective data available in ITP, its relatively good safety profile and its very low cost , dapsone could be a good steroid-sparing second-line option for adults with ITP. This study is a phase III prospective multicenter randomized open trial comparing two treatment strategies: Arm A (experimental arm): prednisone at 1 mg/kg for 3 weeks + dapsone at 100 mg per day up to week 52 if an initial response is achieved. Arm B (control arm): prednisone alone at 1 mg/kg for 3 weeks followed by monitoring and "standard of care" The aim of the study is to demonstrate the efficacy of dapsone based on the overall response rate (including response and complete response) as a second-line treatment for adults with newly-diagnosed persistent or chronic (modified by amendment 08/11/2016) ITP not achieving a durable response with corticosteroids. The primary endpoint will be the overall response-rate (response or complete response according to standard definitions) in both arms at week 52 (1 year). The secondary endpoints are the following : To assess the safety of dapsone over the study period and especially the incidence of cutaneous reactions. To analyze the overall response rate (platelet count > 30 x 109/L with at least a doubling of the pre-treatment count in the absence of any other ITP treatment) in both treatment arms at week 24. To compare the rate of complete response and failure in both arms at 24 and 52 weeks. To compare time to treatment failure (TTF) in both arms To investigate the mechanisms of action of dapsone in ITP in a subgroup of patients (ancillary study)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Adult Immune Thrombocytopenia (ITP), Dapsone

Keywords

ITP, Dapsone

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

216 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dapsone: (Disulone®)

Arm Type

Experimental

Arm Description

Dapsone: Disulone® given orally at 100 mg per day

Arm Title

Prednisone (Cortancyl®) alone and "standard of care"

Arm Type

Active Comparator

Arm Description

Prednisone (Cortancyl®) alone at 1 mg/kg for 3 weeks followed by monitoring and "standard of care" (control arm)

Intervention Type

Drug

Intervention Name(s)

Dapsone (Disulone®)

Other Intervention Name(s)

experimental arm

Intervention Description

Experimental group will receive dapsone at a fixed dose of 100 mg per day for a total of 12 months unless they fail to respond to the treatment.

Intervention Type

Drug

Intervention Name(s)

Prednisone (Cortancyl®) alone followed by monitoring and "standard of care"

Other Intervention Name(s)

control arm

Intervention Description

Patients randomized in the control arm will be treated only prednisone at a daily dose of 1 mg per kg for 2 weeks and then tapered and stopped over a week for a total of 3 consecutive weeks. After this 3 weeks period, patients from arm B will be left without treatment and monitored.

Intervention Type

Drug

Intervention Name(s)

Prednisone (Cortancyl®)

Other Intervention Name(s)

experimental arm

Intervention Description

Experimental group will receive prednisone at a daily dose of 1 mg per kg for 2 weeks and then tapered and stopped over a week for a total of 3 consecutive weeks.

Primary Outcome Measure Information:

Title

Overall response-rate.

Time Frame

at week 52

Secondary Outcome Measure Information:

Title

Assess the safety of dapsone especially the incidence of cutaneous adverse effects.

Time Frame

over the study period (up to 52 weeks)

Title

Compare the overall response rate .

Description

platelet count > 30 x 109/L with at least a doubling of the pre-treatment count in the absence of any other ITP treatment in both arms

Time Frame

at week 24

Title

Proportion of patients with complete response in both arms, defined as follows: - Proportion of patients with a platelet count > 100 x 109/L in the absence use of any other ITP directed therapies

Time Frame

at 24 and at 52 weeks

Title

Proportion of non-responders patients (primary failure)

Description

Time Frame

at 24 and at 52 weeks

Title

Number of days to treatment failure in both arms

Time Frame

over the study period (up to 52 weeks)

Title

Time Frame

over the study period (52 weeks)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥ 18 years Diagnosis of primary ITP according to the standard definition and international guidelines. Previous transient response to corticosteroids ± intravenous immunoglobulin defined by an increase of the platelet count above 30 x 109/L with at least a twofold increase of the pre-treatment count. At least platelet count ≤ 30 x 109/L within the 2 weeks before inclusion with a platelet count at time of inclusion below 50 x 109/L, or platelet count < 50 x 109/L at any time point in patients requiring treatment (i.e., patients with bleeding symptoms, elderly patients with comorbidities and/or patients on aspirin for example, or other reason at the investigator discretion) (modified by amendment 8/11/2016) Normal marrow aspirate for patients aged of 60 and above. Negative pregnancy test and effective method of contraception for women of childbearing age over the study period. Informed consent. Patient affiliated to the French National Social Security System Exclusion Criteria: Secondary ITP. Patients with positive antinuclear antibodies and/or positive antiphospholipid antibodies not fulfilling the classification criteria for systemic lupus erythematosus and/or antiphospholipid antibody syndrome will not be excluded. Platelet count ≥ 50 x 109/L or between 30 and 50 x 109/L and no bleeding symptoms and no need for treatment (modified by amendment 8/11/2016) Severe bleeding manifestations defined a bleeding score ≥ 8 No previous transient response to corticosteroids ± intravenous immunoglobulin. Previous ITP treatment other than corticosteroids and intravenous immunoglobulin (including rituximab and splenectomy). Active severe infection or history of severe infection within 4 weeks before inclusion. History of allergy to sulfonamides. Glucose-6-phosphate dehydrogenase (G6PD) deficiency. History of methemoglobinemia Hemoglobin level < 11g/dL and/or neutrophil count < 1,500/ gL. History of autoimmune (Evans' syndrome) or hereditary haemolytic anemia. Liver or kidney function impairment (creatinine clearance < 30 ml/min, ALT, AST >2 times upper normal limit). (modified by amendment 8/11/2017) Hepatitis C virus (HCV) Ab, HIV Ab, HBsAg, seropositive status. (modified by amendment 8/11/2017) Concomitant medical condition requiring anticoagulation. (modified by amendment 8/11/2017) Pregnancy or lactation.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

MARC MICHEL, Prof. M.D

Phone

(0)1 49 81 20 76

Ext

+33

marc.michel2@aphp.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

MARC MICHEL, Prof. M.D

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Principal Investigator

Facility Information:

Facility Name

Henri Mondor Hospital

City

Creteil

ZIP/Postal Code

94010

Country

France

Individual Site Status

Recruiting

12. IPD Sharing Statement

Citations:

PubMed Identifier

1873232

Citation

Durand JM, Lefevre P, Hovette P, Mongin M, Soubeyrand J. Dapsone for idiopathic autoimmune thrombocytopenic purpura in elderly patients. Br J Haematol. 1991 Jul;78(3):459-60. doi: 10.1111/j.1365-2141.1991.tb04467.x. No abstract available.

Results Reference

background

PubMed Identifier

8342569

Citation

Godeau B, Oksenhendler E, Bierling P. Dapsone for autoimmune thrombocytopenic purpura. Am J Hematol. 1993 Sep;44(1):70-2. doi: 10.1002/ajh.2830440117.

Results Reference

background

PubMed Identifier

7794776

Citation

Hernandez F, Linares M, Colomina P, Pastor E, Cervero A, Perez A, Perella M. Dapsone for refractory chronic idiopathic thrombocytopenic purpura. Br J Haematol. 1995 Jun;90(2):473-5. doi: 10.1111/j.1365-2141.1995.tb05179.x.

Results Reference

background

PubMed Identifier

9163598

Citation

Godeau B, Durand JM, Roudot-Thoraval F, Tenneze A, Oksenhendler E, Kaplanski G, Schaeffer A, Bierling P. Dapsone for chronic autoimmune thrombocytopenic purpura: a report of 66 cases. Br J Haematol. 1997 May;97(2):336-9. doi: 10.1046/j.1365-2141.1997.412687.x.

Results Reference

background

PubMed Identifier

16146539

Citation

Damodar S, Viswabandya A, George B, Mathews V, Chandy M, Srivastava A. Dapsone for chronic idiopathic thrombocytopenic purpura in children and adults--a report on 90 patients. Eur J Haematol. 2005 Oct;75(4):328-31. doi: 10.1111/j.1600-0609.2005.00545.x.

Results Reference

background

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Efficacy and Safety of DAPSone as a Second-line Option in Adult Immune Thrombocytopenia

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