Immune Thrombocytopenia
Conditions
Keywords
ITP, Thrombocytopenia
Brief summary
Pre-clinical and clinical evaluations show that PRTX- 100 has biological activity that may lead to improved platelet levels where these are decreased due to immunological pathologies and that PRTX-100 has an acceptable safety profile. In vivo treatment with PRTX-100 has been shown to raise platelet counts in a mouse model of immune thrombocytopenia (ITP). The primary objective of the study is to assess the efficacy of PRTX-100 in terms of platelet response in patients with chronic/persistent ITP.
Interventions
DRUGPRTX-100
Four weekly infusions of PRTX-100 at a level of 3 micrograms of PRTX-100 per kilogram of patient weight, infused over 30 minutes, followed by four hours of observation after start of infusion.
Sponsors
Protalex, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide written informed consent prior to initiation of any study-related procedures 2. Male or female ≥ 18 years of age 3. ITP that has persisted for ≥ 3 months. ITP must be diagnosed in accordance The American Society of Hematology 2011 Evidence-based Practice Guideline for Immune Thrombocytopenia (Neunert et al. 2011) or the International Consensus Report on The Investigation and Management of Primary Immune Thrombocytopenia (Provan et al. 2010), as locally applicable. 4. Received ≥ 1 typical regimen for the treatment of ITP. Splenectomy is considered one regimen. 5. A mean platelet count of \< 30,000/μL with no individual platelet count \> 55,000/μL. The mean platelet count must be determined based on 2 platelet counts including one obtained within ≤ 7 days of first PRTX-100 dose and the other within ≤ 30 days of the first dose of PRTX-100. 6. If on corticosteroids, a dose of \< 1 mg/kg prednisone per day or equivalent that has been stable for ≥ 21 days prior to the first dose of PRTX-100. High-dose pulse steroid therapy is NOT allowed within 14 days prior to the first dose of PRTX-100. 7. If on steroid-sparing adjunctive immunosuppression with cyclosporine, azathioprine, mycophenolate, or 6-mercaptopurine, the dose must have been stable for ≥ 30 days prior to the first dose of PRTX-100 and must be expected to remain stable through study Day 29, unless dose reduction is required due to toxicities. Treatment with other cytotoxic agents (e.g. cyclophosphamide, vincristine) are not allowed within three months prior to the first dose of PRTX- 100. 8. Any prior treatment with rituximab or any other anti-CD20 agent must have been \> 6 months prior to the first dose of PRTX-100 9. If female, must not be pregnant (as indicated by screening negative pregnancy test), must not be nursing and must be one of the following: * Surgically sterile (bilateral tubal ligation, hysterectomy) * Postmenopausal with last natural menses \> 24 months prior * Premenopausal and using an acceptable form of birth control. Acceptable forms of birth control include: hormonal contraceptives (implantable, oral, patch) used for ≥ 2 months prior to screening or double barrier methods (any combination of two of the following: intrauterine device \[IUD\], male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). All premenopausal females must have a negative urine or serum pregnancy test at screening and on Day 1 prior to first PRTX-100 treatment.
Exclusion criteria
1. Splenectomy ≤ 90 days prior to the first dose of PRTX-100 2. Exposure to TPO-RA within 2 weeks before inclusion 3. Previous treatment with rituximab within \<6 months prior to the first dose of PRTX-100 4. Bleeding score ≥ 8 (Khellaf M et al. Haematologica 2005) 5. Unstable coronary artery disease or other medical condition (such as type 1 diabetes) that, in the investigator's opinion, might increase the risk to the patient 6. Evidence of active infection requiring antibiotic therapy ≤ 14 days prior to the first dose of PRTX-100 7. Myelodysplastic syndrome. If clinically significant anemia or pancytopenia exists, documentation of a bone marrow aspirate within 24 months prior to the first dose of PRTX- 100 showing no evidence of myelodysplasia is required. 8. Medical history systemic lupus erythematosus or any cause of secondary ITP 9. History of any treatment for cancer within the past two years other than basal cell or squamous cell carcinoma of the skin that has been treated with curative intent 10. Seropositive for human immunodeficiency virus (HIV) 11. History of acute/chronic hepatitis B or C and/or carriers of hepatitis B or C (positive for hepatitis B surface antigen or positive anti-hepatitis C antibody test) 12. History suggestive of substance abuse 13. Clinically significant abnormalities in screening laboratory tests, including: * Absolute neutrophil count \< 1.0 x109/L * Hemoglobin \< 10 g/dL * Absolute lymphocyte count \< 0.8 x109/L * Alanine transaminase (ALT) or aspartate transaminase (AST) \> 2 x upper limit of normal (ULN) * Lactate dehydrogenase \> 3 x ULN * Total bilirubin level \>1.5 x ULN * Serum creatinine level \> 0.14 mmol/L (1.6 mg/dL) in males or 0.12 mmol/L (1.4 mg/dL) in females 14. Treatment with IVIG ≤ 14 days prior to the first dose of PRTX-100 15. Treatment with an anti-Rh D antigen agent (e.g. WinRho®) ≤ 14 days prior to the first dose of PRTX-100 16. Use of any investigational drug ≤ 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to the first dose of PRTX-100
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by Toxicity Grading Criteria based on RCTC v 2.0 and CTCAE v 4.03 | 337 Days | Adverse events from AEs, SAEs, infusion reactions, clinical laboratory tests (hematology, blood chemistry and urinalysis), vital signs, physical findings and ECGs over the course of the study. AE severity will be graded according to Toxicity Grading Criteria derived from published standards. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete platelet response (number of patients) | Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337 | The number of patients demonstrating a complete platelet response, defined as a platelet count ≥ 100,000/μL. |
| Overall platelet response, change from baseline (Day 1) | Days 1, 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337 | Defined as a platelet count ≥ 30,000/μL and at least a doubling of baseline platelet count in patients with a baseline platelet count \<30,000/μL in the absence of any concomitant rescue therapy. |
| Time to platelet response (number of days) | Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337 | The mean number of days from first PRTX-100 dose (Day 1) until platelet response. |
| Durability of platelet response (number of days) | Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337 | The number of days from first documented platelet response to first platelet count below platelet response criteria. |
| Concomitant ITP medication use (number of subjects) | 337 Days | The number of subjects considered non-responders based on concomitant ITP medication use by cohort and overall. ITP medications include thrombopoietin receptor agonists (TPO-RAs), steroid-sparing adjunctive immunosuppressive treatment (e.g. cyclosporine, azathioprine, mycophenolate), and any ITP rescue medications (e.g. IVIG) received during the study Screening and Treatment Periods. |
Countries
France, United Kingdom
Outcome results
None listed