An open-label, multicentre efficacy and safety study of a human immunoglobulin (project code I10E) in patients with primary Immune ThrombocytoPenia (ITP)

• Register: EUCTR
• Last refreshed on: 26 August 2013
• Main ID: EUCTR2011-001354-29-DE
• Date of registration: 06/10/2011
• Prospective Registration: Yes
• Primary sponsor: LFB BIOTECHNOLOGIES
• Public title: An open-label, multicentre efficacy and safety study of a human immunoglobulin (project code I10E) in patients with primary Immune ThrombocytoPenia (ITP)
• Scientific title: An open-label, multicentre efficacy and safety study of I10E in patients with primary Immune ThrombocytoPenia (ITP)
• Date of first enrolment: 12/10/2011
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-001354-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

France, Germany, Hungary, Italy, Poland, Russian Federation, Spain, Ukraine

Contacts

• Name: Clinical trial information desk
• Affiliation: LFB BIOTECHNOLOGIES

• Name: Clinical trial information desk
• Affiliation: LFB BIOTECHNOLOGIES

Key inclusion & exclusion criteria

Inclusion criteria:
1. Both genders

2. Age between 18 to < 80 year old

3. Chronic Primary ITP
- ITP diagnosis being defined by ASH-2011 and BCSH 2010 criteria adopting the new consensus terminology proposed by an international working group (Rodeghiero et al, 2009):
? Isolated thrombocytopenia diagnosed with platelet count
<100 x 10exp9/l and no abnormality of cells of other haematological
lineage and,
? Normal bone marrow (if available), or history of response to an
ITP treatment (corticosteroids, IVIg, anti-D) and,
? Failure to find any other causes of thrombocytopenia.

- Chronic ITP with bleeding(s) or an increased risk of bleeding:
? More than 12 months from diagnosis of ITP and,
? Platelet counts < 30 x 10exp9/l at the time of inclusion.
Note: Refractory ITP may be included and is defined by the failure to achieve a response or by the loss of response after splenectomy and the need of treatment (s) to minimize the risk of bleeding considered as clinically
significant by the investigator.

4. Written informed consent.
5. Patient is covered by health care insurance system.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Known hypersensitivity to the active substance or to any of the excipients.

2. Patient with IgA deficiency except if the absence of anti IgA antibodies is documented.

3. History of cardiac insufficiency (NYHA III/IV), cardiomyopathy, congestive heart failure, or severe hypertension (systolic blood pressure > or = to160 mmHg and diastolic blood pressure > or = to 100 mmHg).

4. History of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within the last 12 months in patients aged < 65 years and at any time in patients aged from 65 to 79 years.

5. Patient known to be infected with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus.

6. Treatment that could induce thrombocytopenia within 15 days prior to inclusion.

7. Recent previous treatment, the action of which may interfere with the assessment of the investigational medicinal product:
- Initiation of corticosteroids or regular increase in the steroid dose within the last 4 weeks (EMA/CHMP/BPWP/94033/2007 rev.2),
- IVIg within the last 4 weeks,
- Anti-D within the last 4 weeks,
- Cyclosporin A within 4 weeks,
- Immunomodulator (as vincristin, vinblastin) within the last month,
- Immunosuppressor (azathioprine, cyclophosphamide) within the last 4 weeks,
- Anti-CD20 (rituximab) within the last 4 months,
- Antigonadotropin Hormone (danazol) within the last 6 months,
- Thrombopoietin receptors agonist (eltrombopag, romiplostim) within the last 4 weeks,

8. Splenectomy required during the study period or within the two previous months.

9. Severe haemorrhagic syndrome whether life-threatening or not, such as intracranial haemorrhage, gastrointestinal haemorrhage, gynaecological
haemorrhage with deglobulisation of more than 2g/dL or major cutaneous-mucosal haemorrhagic syndrome.

10. Severe bleeding or planned surgery requiring platelets transfusion at time of inclusion, or whole blood transfusion.

11. Plasma exchange 4 weeks before inclusion.

12. Concomitant disease that may induce a secondary immune thrombocytopenia, as:
- Clinical active systemic lupus erythematous with more than 4 American College of Rheumatology criteria,
- Lymphoproliferative disease or active malignant condition requiring antineoplastic or cytotoxic treatment.

13. Known hepatic disorder including total bilirubin > 2 x upper limit of normal range, alanine aminotransferase (ALT) or aspartate amino transferase (AST) > 3 x upper limit of normal range.

14. Prior episode of renal insufficiency or creatinine clearance values < 80 ml/min/1.73 m2 before inclusion (Modified Diet in Renal Disease calculation).

15. Medical history of haemolysis or haemolytic anaemia during prior IVIg therapy or any other concomitant disease of clotting system (i.e. haemophilia).

16. Administration of another investigational medicinal product within the last month.

17. Any serious medical condition that would interfere with the clinical assessment of I10E or prevent the patient to comply with the protocol requirements.

18. Pregnant with positive results pregnancy urinary test or breastfeeding woman, or woman of childbearing potential without effective contraception (effective contraception are: injectable, patch or combined
oral estro-progestative or progestative contraceptives, intra-uterine devices of type 'copper T' and levonorgest releasing IU systems, depot intramuscular medroxyprogesteron, s

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

ITP diagnosis being defined by ASH-2011 and BCSH 2010 criteria adopting the new consensus terminology proposed by an international working group (Rodeghiero et al, 2009)
MedDRA version: 15.1 Level: LLT Classification code 10023095 Term: ITP System Organ Class: 100000004851

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Product Name: HUMAN NORMAL IMMUNOGLOBULIN FOR INTRVENOUS USE
Product Code: I10E
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: HUMAN NORMAL IMMUNOGLOBULIN FOR INTRAVENOUS USE
Current Sponsor code: I10E
Other descriptive name: human Immunoglobulin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): The primary endpoint is the number and percentage of patients with responses (including complete responses) during the investigational period.

Patients with response (R):
- Platelet counts > or = to 30 x 10 exp9/l and at least 2-fold increase of baseline platelet count confirmed on at least 2 separate visits at least 7 days apart.
- And absence of new bleeding.

· Patients with complete response (CR):
- Platelet count > or = to 100 x 10 exp9/l, confirmed on at least 2 separate visits at least 7 days apart.
- And absence of new bleeding.

Secondary Objective: To assess the biological and clinical safety profile of I10E.

Main Objective: To assess the efficacy of I10E in increasing platelet count and controlling bleedings in patients suffering from primary Immune ThrombocytoPenia (ITP).

Timepoint(s) of evaluation of this end point: confirmed on at least 2 separate visits at least 7 days apart during the study period.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: see details provided in section E 5.2.

Secondary end point(s): Efficacy criteria:
- Number and % of patients with complete response (CR) during the investigational period.
- Time to response i.e. time from starting treatment to time of platelet response achievement (platelet count > or = to 30 x 10 exp9/l) in the responder
population.
- Maximum platelet counts and time to reach the maximum platelet count.
- Number and % of non-responders patients (NR) during the investigational period.
- Number and % of patients with a loss of R and CR during the investigational period.
- Duration of response defined as the number of days from the first day of the response (CR or R) to the first day of the loss of response (CR or R).
- Number and % of patients with platelet count > or = to 50 x 10 exp9/l at Day 5, Day 6 and Day 7.
- Evaluation of pre-existing bleedings (Khellaf score and WHO score assessed at baseline, Day 2, Day 14 and Day 30)

Secondary ID(s)

I10E-0719

Source(s) of Monetary Support

LFB BIOTECHNOLOGIES