| CTRI Number |
CTRI/2010/091/003049 [Registered on: 03/02/2011] |
| Last Modified On: |
18/03/2013 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
Type of Study
Modification(s)
|
Biological |
| Study Design |
Other |
Public Title of Study
Modification(s)
|
A multi-centre, single intravenous dose, exploratory dose-finding, open label trial on the safety and efficacy of Sym001 in the treatment of Immune Thrombocytopenic Purpura (ITP) in RhD positive, non-splenectomized adult subjects. |
Scientific Title of Study
Modification(s)
|
A multi-centre, single intravenous dose, exploratory dose-finding, open label trial on the safety and efficacy of Sym001 in the treatment of Immune Thrombocytopenic Purpura (ITP) in RhD positive, non-splenectomized adult subjects. |
| Trial Acronym |
SYM-001 |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| NCT00718692 |
ClinicalTrials.gov |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
DrSanjay Gupta |
| Designation |
Chief Operating officer |
| Affiliation |
Asiatic Clinical Research Pvt. Ltd. |
| Address |
169/53, 14th main road, 1st Block east,
Jayanagar
Bangalore
KARNATAKA
560 011
India |
| Phone |
91-41681122 |
| Fax |
91-41213841 |
| Email |
sanjay@asiaticlinical.com |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Mr Subramanian |
| Designation |
Project Manager |
| Affiliation |
Project Manager |
| Address |
169/53, 14th Main Road, 1st Block East
Jayanagar
Bangalore
KARNATAKA
560011
India |
| Phone |
91-41681122 |
| Fax |
91-41213841 |
| Email |
subramanian@asiaticlinical.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Mr Subramanian |
| Designation |
Project Manager |
| Affiliation |
Asiatic Clinical Research Pvt. Ltd. |
| Address |
169/53, 14th Main Road, 1st Block East
Jayanagar
Bangalore
KARNATAKA
560011
India |
| Phone |
91-41681122 |
| Fax |
91-41213841 |
| Email |
subramanian@asiaticlinical.com |
|
Source of Monetary or Material Support
Modification(s)
|
|
Primary Sponsor
Modification(s)
|
| Name |
Symphogen AS |
| Address |
A/S Elektrovej bld. 375, DK-2800 Lyngby, Denmark Telephone Number: +45 4526 5050 Fax Number: +45 4526 5060 |
| Type of Sponsor |
Other [Biotechnological] |
|
|
Details of Secondary Sponsor
|
|
Countries of Recruitment
Modification(s)
|
India
Austria
Belgium
Germany
Greece
Israel
Poland
Serbia
Turkey
Ukraine
United Kingdom
United States of America |
Sites of Study
Modification(s)
|
| No of Sites = 7 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr SVSSPrasad |
Apollo Hospital, Hyderabad |
Apollo Health City,Jubilee Hills,
Hyderabad
ANDHRA PRADESH |
040-23431725
cvpr01@aherf-smo.org |
| Dr. Satish Kumar |
Columbia Asia Hospital |
eshwanthpur, #26/1 Feet, ,Dr. Rajkumar Road Malleshwaram West-560 055
Bangalore
KARNATAKA |
80 39898969
satishkumar.a@columbiaasia.in |
| Dr Mukyaprana Prabhu |
Kasturba Medical College Hospital |
Kasturba Medical College (KMC),
|
09449592986
mmukhyaprana@yahoo.com |
| Dr Arun Narayan |
M S Ramaiah Hospital, Bangalore |
M. S. Ramaiah Mecial College & Hospital,MSR Nagar, MSRIT Post,-560 054
Bangalore
KARNATAKA |
91-9341255517
drarunnarayan@gmail.com |
| Dr Rahul Bhargava |
Medanta Cancer Hospital, Gurgoan |
Medanta Cancer Institute,Sector 38-122 001
Gurgaon
HARYANA |
91-9968000220
bhargava777@gmail.com |
| Dr Sharat Damodar |
Narayana Hrudayalaya Hospital, |
Narayana Hrudayalaya, No. 258/A, Bommasandra Industrial Area, ,Anekal Taluk-560 099
Bangalore
KARNATAKA |
080-27835000
drsharat.damodar@gmail.com |
| DrCecil Ross |
St. Johns Medical College Hospital, Bangalore |
St. Johns Medical College Hospital,Sarjapur Road-
Bangalore
KARNATAKA |
91-9448493705
cecilross@bsnl.in |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 6 |
| Name of Committee |
Approval Status |
| Ethics Committee Apollo Hospital Hyderabad |
Approved |
| Institutional Ethics Committee of Columbia Asia Hospital |
Approved |
| M S Ramaiah Hospital Ethical Review Board |
Approved |
| Manipal University Ethics Committee |
Approved |
| Narayana Heudayalaya Medical Ethics Committee |
Approved |
| St. Johns Medical College Hospital Institutional Ethical Review Board |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
Immune Thrombocytopenic Purpura (ITP) in RhD positive, non-splenectomized adult subjects , |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Intervention |
Sym001 drug product |
The Sym001 drug product contains 0.6 mg/mL of Sym001 recombinant human anti-RhD IgG in 50 mM citrate-phosphate buffer, 150 mM sodium chloride and 0.05% polysorbate 20, pH 6.0. |
| Comparator Agent |
NIL |
NIL |
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Informed consent obtained before any trial-related procedures.
2. Age > 18.
3. Confirmed presence of thrombocytopenia with platelet count < 30,000/mm3 at the pre-dose visit. In each cohort < 200 μg/kg a maximum of 3 subjects will be included with platelet counts < 10,000/mm3, and in cohorts > 200 μg/kg a maximum of 1 subject with platelet counts < 10,000/mm3 will be included in order to limit variability. Two individual pre-dose platelet counts taken on the dosing day and within > 1 hour interval between each other and both being < 30,000/mm3 will be used to confirm thrombocytopenia.
4. History of isolated ITP (thrombocytopenia with no known aetiology, blood smear showing normal appearing platelets or if performed, a bone marrow showing adequate thrombopoïesis and normal erythroid and myeloid morphology).
5. RhD- positive serology.
6. Previous treatment and response to first line therapy for ITP (corticosteroids, anti-D or IVIg), with response being defined as an increase in platelet count to ≥30,000/mm3.
7. If female and of child-bearing potential, subject has a negative pregnancy test at screening.
8. If subject is a female of child-bearing potential, subject agrees to use a medically accepted form of contraception from the time of enrolment (at screening) to completion of all follow-up trial visits.
|
|
| ExclusionCriteria |
| Details |
1. Known clinical picture suggestive of other causes of thrombocytopenia, especially systemic lupus erythematosus, antiphospholipid syndrome, Evans syndrome, immunodeficiency states, lymphoproliferative disorders, liver disease, ingestion of drugs such as quinidine/quinine, heparin and sulfonamides and hereditary thrombocytopenia confirmed by relevant laboratory findings.
2. Suspected infection with HIV, hepatitis C, H. pylori unless corresponding laboratory tests are negative
3. Clinical splenomegaly (the spleen should not be palpable at more than 1 finger breadth below the costal margin).
4. History of abnormal bone marrow examination (except ITP-typical megacaryocytosis).
5. At pre-dose visit: an ongoing haemorrhage corresponding to a grade 3 or 4 on the WHO bleeding scale.
6. History of anaphylaxis or hypersensitivity reactions following anti-D treatment.
7. Current immune haemolytic anaemia.
8. Underlying haemolytic condition (e.g. reticulocyte count > 3%).
9. Planned surgery during the 15 days post dosing.
10. Haemoglobin pre-dose value lower than 2.0 g/dL below the lower limit of the laboratory normal range for gender and age.
11. History of splenectomy.
12. Known current malignancy (except basal cell carcinoma).
13. Received other investigational agent within 3 months prior to enrolment.
14. Positive DAT (direct Coombs-test) at screening unless subject has received treatment with IVIg or anti-D products within 3 months prior to screening with prior negative DAT.
15. Known non-responders to most recent anti-D treatment (despite any initial response to treatment).
16. Any other current treatment for ITP except corticosteroids (Prednisone or Dexamethasone) at doses equivalent to ≤30 mg prednisone/day if the daily dose has been constant for 2 weeks or more before trial drug administration.
17. Therapy with IVIg within 2 weeks prior to enrolment or with anti-D or any other treatment of ITP within 4 weeks prior to enrolment.
18. Therapy with tranexamic acid, alkylating agents or any anti-CD20 antibodies within 8 weeks prior to enrolment.
19. Any antithrombotic treatment (except acetyl salicylic acid at doses up to 150 mg daily) within 7 days prior to pre-dosing visit or planned during the trial.
20. PT/INR and aPTT out of normal range at the pre-dose visit.
21. History of venous or arterial thrombosis or known thrombophilia.
22. Diseases other than ITP that may influence the result of the trial as judged by the Investigator.
23. Creatinine 25% or more above normal range value, alanine aminotransferase (ALT) and alkaline phosphatase (ALP) 100% above normal range value, and albumin 25% or more below normal range value.
24. Current or planned treatment with erythropoietin.
25. Subject is pregnant, breast feeding or intends to become pregnant
|
|
Method of Generating Random Sequence
Modification(s)
|
Other |
Method of Concealment
Modification(s)
|
Not Applicable |
Blinding/Masking
Modification(s)
|
Not Applicable |
Primary Outcome
Modification(s)
|
| Outcome |
TimePoints |
| Incidence and severity of AEs, including SAEs and Adverse Events of Special Interest (AESIs) |
during the 6-week trial period |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Safety Endpoints:
1. Maximum fall in Haemoglobin from baseline and until day 7 after administration of Sym001.
2. Acute infusion related reactions (41).
3. Presence of anti-Sym001 antibodies at pre-dose, 15 and 28 days and at 6 weeks.
4. Change from baseline in: interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), IL-6 and tumour necrosis factor α (TNF α) at 30 minutes, 2, 8, 24, 48 and 72 hours and at day 7.
5. Clinically relevant changes in laboratory parameters, ECGs and vital signs.
6. Complement activation at 5-8 hours and 7 days post dosing.
Efficacy Endpoints:
1. Percentage of subjects with platelet count > 30,000/mm3 and increase in platelet count by > 20,000/mm3 from baseline at 72 hours (major efficacy endpoint), 7 and 15 days.
2. Percentage of subjects, at 24, 48 and 72 hours, at 7, 15, and 28 days and at 6-weeks, with platelet count:
a. ≥ 50,000/mm3
b. ≥ 30,000/mm3
c. Increase of > 20,000/mm3 from baseline.
3. Change of platelet count at 24, 48, 72 hours, 7, 15, 28 days and 6 weeks from baseline.
4. Time to platelet count:
a. ≥ 50,000/mm3
b. ≥ 30,000/mm3
c. Increase of > 20,000/mm3 from baseline
5. Number of days with platelet count:
a. ≥ 30,000/mm3 and increase of > 20,000/mm3 from baseline
b. ≥ 50,000/mm3
c. ≥ 30,000/mm3
d. Increase of > 20,000/mm3 from baseline.
6. AUC for platelet count from baseline to 6-weeks.
7. Change in WHO bleeding scale from baseline (42).
8. Percentage of subjects requiring Rescue Medication.
9. PK parameters (AUC, Cmax, Cmin, T½) for Sym001.
Binding of Sym001 to RBCs:
DAT at screening, 24 hours, 28 days and 6-weeks post dosing.
|
Varying timepoints for different endpoints. |
|
Target Sample Size
Modification(s)
|
Total Sample Size="66"
Sample Size from India="10"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
Phase of Trial
Modification(s)
|
Phase 2 |
Date of First Enrollment (India)
Modification(s)
|
03/05/2011 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
07/07/2008 |
| Date of Study Completion (Global) |
Date Missing |
Estimated Duration of Trial
Modification(s)
|
Years="0"
Months="8"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Completed |
| Recruitment Status of Trial (India) |
Completed |
Publication Details
Modification(s)
|
Nil |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
Modification(s)
|
Immune Thrombocytopenic Purpura (ITP): ITP is an autoimmune disease mediated by anti-platelet autoantibodies that cause opsonisation and platelet elimination through binding to FcγR-bearing phagocytic cells in the Reticuloendothelial System (RES) and especially in the spleen, leading to a reduced platelet count (thrombocytopenia). ITP is a primary form of immune thrombocytopenia where typically no aetiology can be found. Thrombocytopenia is defined by platelet counts < 150,000/mm3 and is characterized clinically by increased bruising tendency. However, ITP often presents as spontaneous bleeding in individuals with platelet counts of less than 20,000/mm3. Subjects with platelet counts < 10,000/mm3 may present with severe cutaneous bleedings, gingival bleeding, epistaxis, haematuria or menorrhagia. Spontaneous intracranial bleeding and other spontaneous internal bleeding can be seen in severe thrombocytopenia with platelet counts below 5,000/mm3 (2). ITP in individuals with platelet counts above 30,000/mm3 is most often diagnosed incidentally after a routine complete blood cell count. Some bleeding risk is present in subjects with platelet counts between 30,000/mm3 and 50,000/mm3 depending on the coexisting factors for bleeding (3). ITP is also characterized by an increased proportion of immature peripheral platelets, and to some extent by an increased proportion of megakaryocytes in the bone marrow. This is a ?multi-centre, single intravenous dose, exploratory dose-finding, open label trial on the safety and efficacy of Sym001 in the treatment of Immune Thrombocytopenic Purpura (ITP) in RhD positive, non-splenectomized adult subjects.? Sym001 is a clear colourless sterile liquid for injection filled into 10 mL glass injection vials with a bromobutyl rubber stopper. The vials are sealed with aluminium caps. The Sym001 drug product contains 0.6 mg/mL of Sym001 recombinant human anti-RhD IgG in citrate-phosphate buffer, sodium chloride and polysorbate 20, pH 6.0. The active ingredient in Sym001 is a mixture of 25 anti-RhD antibodies produced by expression in recombinant Chinese Hamster Ovary (CHO) cells. This is a global clinical trial and the participating countries are:- Germany, Belgium, U.K, Serbia, Poland, Spain, Romania, Russia, Ukraine, Israel, India, US, Australia. A maximum of 66 RhD positive, non-splenectomized ITP patients would be enrolled globally and it will be a Competitive Recruitment. A total of 20 subjects would be recruited from India. Patient recruitment in India is expected to start from 15-Feb-2011. |