Clinical trial NCT02401061: PRTX-100-202 Open-Label, Dose Escalation Study in Adult Patients With ITP
Official title: A Phase 1/2, 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: 2015-03-27
Enrollment: 13
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.

Funding Source - FDA OOPD (1R01FD005750-01A1)


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 regime for the treatment of ITP. Splenectomy is considered one standard ITP treatment
5. A mean platelet count of \< 30,000/μL, with no individual platelet count \> 35,000/μL; or for those subjects receiving a constant dose of permitted treatments for ITP: a mean platelet count \< 50,000/μL, with no count greater than 55,000/μL. (Note: 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 receiving eltrombopag or romiplostim, the dose must have been stable for ≥ 21 days prior to the first dose of PRTX-100
8. 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.
9. Any prior treatment with rituximab or any other anti-CD20 agent must have been \> 6 months prior to the first dose of PRTX-100
10. If female, must not be pregnant (pregnancy testing will be performed locally in all female patients of childbearing potential), 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. 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
3. Evidence of active infection requiring antibiotic therapy ≤ 14 days prior to the first dose of PRTX- 100
4. 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.
5. Medical history of vasculitis or lupus erythematosus
6. Propensity to allergic reactions defined as a history of allergic reaction to more than one medication
7. 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
8. Seropositive for human immunodeficiency virus (HIV)
9. 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) and evidence of current or active infection (e.g. HCV RNA test)
10. History suggestive of substance abuse
11. History or evidence on physical examination or screening laboratory tests of any systemic disease or any acute or chronic illness that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the study drug
12. Treatment with IVIG ≤ 14 days prior to the first dose of PRTX-100
13. Treatment with an anti-Rh D antigen agent (e.g. WinPho) ≤ 14 days prior to the first dose of PRTX-100
14. Use of any investigational drug, other than eltrombopag or romiplostim, ≤ 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to the first dose of RTX-100
15. Not willing to stay at the study site for 4 hours after each PRTX-100 infusion

Primary outcomes:
measure: Platelet Response, Change from Baseline
timeFrame: Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337
Secondary outcomes:
measure: Complete platelet response, Change from Baseline
timeFrame: Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337
measure: Time to platelet response defined as the mean number of days from first PRTX-100 dose until platelet response
timeFrame: Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337
measure: Durability of platelet response
timeFrame: Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337
measure: Concomitant ITP medication use (frequency and amount)
timeFrame: Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337
measure: Adverse Events
timeFrame: Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Farmington Hills
country: United States
facility: Michigan Center of Medical Research
state: Michigan
city: New York
country: United States
facility: Weil-Cornell Medical College
state: New York
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: AB
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: Leichester
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich Hospital
Study officials:
affiliation: Protalex, Inc.
name: William E Gannon Jr., MD
role: STUDY_DIRECTOR
References: