Clinical trial NCT02566603: PRTX-100-203 Open-Label, Dose Escalation Study in Adult Patients With ITP
Official title: A Phase 1b Open-Label, Dose Escalation Study of PRTX-100 in Adult Patients With Persistent/Chronic Immune Thrombocytopenia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Immune Thrombocytopenia
Keywords: ITP
Thrombocytopenia
Lead sponsor: Protalex, Inc.
Sponsor class: INDUSTRY
First posted: 2015-10-02
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 337 Days
Secondary outcomes:
measure: Overall platelet response, change from baseline (Day 1)
timeFrame: Days 1, 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337
measure: Complete platelet response (number of patients)
timeFrame: Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337
measure: Time to platelet response (number of days)
timeFrame: Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337
measure: Durability of platelet response (number of days)
timeFrame: Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337
measure: Concomitant ITP medication use (number of subjects)
timeFrame: 337 Days
Other outcomes:
Locations:
city: Pessac
country: France
facility: Haut-Levêque Hospital
state: Bordeaux
city: Pierre-Bénite
country: France
facility: CH Lyon Sud
state: Lyon
city: Caen
country: France
facility: Côte de Nacre Hospital
city: Créteil
country: France
facility: Mondor Hospital
city: Dijon
country: France
facility: University Hospital
city: Lille
country: France
facility: Claude Huriez Hospital
city: Marseille
country: France
facility: CH La Timone
city: Nantes
country: France
facility: CHU
city: Toulouse
country: France
facility: Canceropole
city: London
country: United Kingdom
facility: Hammersmith Hospital
state: OHS
city: London
country: United Kingdom
facility: UCLH
state: UK
city: London
country: United Kingdom
facility: Guy's and St. Thomas Hospital
state: UK
city: London
country: United Kingdom
facility: St. Georges' Hospital
state: UK
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: UK
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
state: UK
city: London
country: United Kingdom
facility: Royal London Hospital
Study officials:
affiliation: Protalex, Inc.
name: William E Gannon, MD
role: STUDY_DIRECTOR
References: