PRTX-100-203 Open-Label, Dose Escalation Study in Adult Patients With ITP

A Phase 1b Open-Label, Dose Escalation Study of PRTX-100 in Adult Patients With Persistent/Chronic Immune Thrombocytopenia

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.

Study Overview

• Status: Terminated
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: PRTX-100; Drug: PRTX-100; Drug: PRTX-100; Drug: PRTX-100; Drug: PRTX-100

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Caen, France, 14033
    • Côte de Nacre Hospital
  • Créteil, France, 94010
    • MONDOR Hospital
  • Dijon, France, 21000
    • University Hospital
  • Lille, France, 59037
    • Claude Huriez hospital
  • Marseille, France, 13385
    • CH La Timone
  • Nantes, France, 44093
    • CHU
  • Toulouse, France, 31059
    • Canceropole
  • Bordeaux
    • Pessac, Bordeaux, France, 33600
      • Haut-levêque Hospital
  • Lyon
    • Pierre-Bénite, Lyon, France, 69495
      • CH Lyon Sud
• United Kingdom
  • London, United Kingdom
    • Royal London Hospital
  • OHS
    • London, OHS, United Kingdom, W12
      • Hammersmith Hospital
  • UK
    • London, UK, United Kingdom, NW1 2BU
      • UCLH
    • London, UK, United Kingdom, SE 19RT
      • Guy's and St. Thomas Hospital
    • London, UK, United Kingdom, SW17 0QT
      • St. Georges' Hospital
    • Plymouth, UK, United Kingdom, PL6 8DH
      • Derriford Hospital
    • Southampton, UK, United Kingdom, SO16 6YD
      • University Hospital Southampton

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PRTX-100; Patients will be assigned to consecutive PRTX-100 interventions as they are enrolled into the study. Between three and six patients will be enrolled per intervention level. Intervention levels range from 3 to 24 micrograms of PRTX-100 per kilogram of patient weight. Patients may receive up to four weekly infusions of PRTX-100 over the study treatment period. PRTX-100 doses ≤ 500 μg will be infused intravenously over 30 minutes. PRTX-100 doses > 500 μg will be infused over 60 minutes. Patients will remain under observation for 4 hours after initiation of PRTX-100 dosing for safety management.

Drug: PRTX-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.; Other Names: SpA; Staphylococcal Protein A; Drug: PRTX-100; Four weekly infusions of PRTX-100 at a level of 6 micrograms of PRTX-100 per kilogram of patient weight, infused over 30 to 60 minutes, followed by four hours of observation after start of infusion.; Other Names: SpA; Staphylococcal Protein A; Drug: PRTX-100; Four weekly infusions of PRTX-100 at a level of 12 micrograms of PRTX-100 per kilogram of patient weight, infused over 60 minutes, followed by four hours of observation after start of infusion.; Other Names: SpA; Staphylococcal Protein A; Drug: PRTX-100; Four weekly infusions of PRTX-100 at a level of 18 micrograms of PRTX-100 per kilogram of patient weight, infused over 60 minutes, followed by four hours of observation after start of infusion.; Other Names: SpA; Staphylococcal Protein A; Drug: PRTX-100; Four weekly infusions of PRTX-100 at a level of 24 micrograms of PRTX-100 per kilogram of patient weight, infused over 60 minutes, followed by four hours of observation after start of infusion.; Other Names: SpA; Staphylococcal Protein A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	337 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall platelet response, change from baseline (Day 1)	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.	Days 1, 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337
Complete platelet response (number of patients)	The number of patients demonstrating a complete platelet response, defined as a platelet count ≥ 100,000/μL.	Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337
Time to platelet response (number of days)	The mean number of days from first PRTX-100 dose (Day 1) until platelet response.	Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337
Durability of platelet response (number of days)	The number of days from first documented platelet response to first platelet count below platelet response criteria.	Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337
Concomitant ITP medication use (number of subjects)	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.	337 Days

Collaborators and Investigators

• Sponsor: Protalex, Inc.
• Investigators: Study Director: William E Gannon, MD, Protalex, Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): May 17, 2018
• Study Completion (Actual): May 17, 2018

Study Registration Dates

• First Submitted: September 30, 2015
• First Submitted That Met QC Criteria: October 1, 2015
• First Posted (Estimate): October 2, 2015

Study Record Updates

• Last Update Posted (Actual): March 25, 2019
• Last Update Submitted That Met QC Criteria: March 21, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: ITP; Thrombocytopenia
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
• Other Study ID Numbers: PRTX-100-203; 2014-005626-35 (EudraCT Number)