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

NCT02566603 | Terminated Phase 1 DMC

• 2 other identifiers: PRTX-100-2032014-005626-35
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 16

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.

Conditions

Immune Thrombocytopenia

Keywords

ITP; Thrombocytopenia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Overall platelet response, change from baseline (Day 1)

  Days 1, 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337

• Complete platelet response (number of patients)

  Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337

• Time to platelet response (number of days)

  Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337

• Durability of platelet response (number of days)

  Days 3, 8, 15, 22, 29, 36, 43, 50, 78, 106, 169, and 337

• Concomitant ITP medication use (number of subjects)

  337 Days

Study Arms (1)

PRTX-100

EXPERIMENTAL

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

Interventions

PRTX-100 DRUG

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.

Also known as: SpA, Staphylococcal Protein A

PRTX-100

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent prior to initiation of any study-related procedures
• Male or female ≥ 18 years of age
• 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.
• Received ≥ 1 typical regimen for the treatment of ITP. Splenectomy is considered one regimen.
• 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.
• 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.
• 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.
• Any prior treatment with rituximab or any other anti-CD20 agent must have been \> 6 months prior to the first dose of PRTX-100
• 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.

You may not qualify if:

• Splenectomy ≤ 90 days prior to the first dose of PRTX-100
• Previous treatment with rituximab within \<6 months prior to the first dose of PRTX-100
• Bleeding score ≥ 8 (Khellaf M et al. Haematologica 2005)
• 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
• Evidence of active infection requiring antibiotic therapy ≤ 14 days prior to the first dose of PRTX-100
• 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.
• Medical history systemic lupus erythematosus or any cause of secondary ITP
• 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
• Seropositive for human immunodeficiency virus (HIV)
• 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)
• History suggestive of substance abuse
• 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

Sponsors & Collaborators

• Protalex, Inc.: lead

Study Sites (16)

Haut-Levêque Hospital

Pessac, Bordeaux, 33600, France

Location

CH Lyon Sud

Pierre-Bénite, Lyon, 69495, France

Location

Côte de Nacre Hospital

Caen, 14033, France

Location

Mondor Hospital

Créteil, 94010, France

Location

University Hospital

Dijon, 21000, France

Location

Claude Huriez Hospital

Lille, 59037, France

Location

CH La Timone

Marseille, 13385, France

Location

CHU

Nantes, 44093, France

Location

Canceropole

Toulouse, 31059, France

Location

Hammersmith Hospital

London, OHS, W12, United Kingdom

Location

UCLH

London, UK, NW1 2BU, United Kingdom

Location

Guy's and St. Thomas Hospital

London, UK, SE 19RT, United Kingdom

Location

St. Georges' Hospital

London, UK, SW17 0QT, United Kingdom

Location

Derriford Hospital

Plymouth, UK, PL6 8DH, United Kingdom

Location

University Hospital Southampton

Southampton, UK, SO16 6YD, United Kingdom

Location

Royal London Hospital

London, United Kingdom

Location

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia

Interventions

Staphylococcal Protein A

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antigens, Bacterial; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antigens; Biological Factors

Study Officials

• William E Gannon, MD

  Protalex, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2015
• First Posted: October 2, 2015
• Study Start: November 1, 2015
• Primary Completion: May 17, 2018
• Study Completion: May 17, 2018
• Last Updated: March 25, 2019

Record last verified: 2019-03

Locations

FR (9); GB (7)