A Phase 1b Open-Label, Dose Escalation Study of PRTX-100 in Adult Patients With Persistent/Chronic Immune Thrombocytopenia
PRTX-100-203 Open-Label, Dose Escalation Study in Adult Patients With ITP
Sponsors
Source
Protalex, Inc.
Oversight Info
Has Dmc
Yes
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.
Overall Status
Terminated
Start Date
2015-11-01
Completion Date
2018-05-17
Primary Completion Date
2018-05-17
Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Measure |
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 |
337 Days |
Secondary Outcome
Measure |
Time Frame |
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 |
Enrollment
15
Condition
Intervention
Intervention Type
Drug
Intervention Name
Description
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.
Arm Group Label
PRTX-100
Other Name
SpA
Staphylococcal Protein A
Intervention Type
Drug
Intervention Name
Description
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.
Arm Group Label
PRTX-100
Other Name
SpA
Staphylococcal Protein A
Intervention Type
Drug
Intervention Name
Description
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.
Arm Group Label
PRTX-100
Other Name
SpA
Staphylococcal Protein A
Intervention Type
Drug
Intervention Name
Description
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.
Arm Group Label
PRTX-100
Other Name
SpA
Staphylococcal Protein A
Intervention Type
Drug
Intervention Name
Description
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.
Arm Group Label
PRTX-100
Other Name
SpA
Staphylococcal Protein A
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
Gender
All
Minimum Age
18 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
William E Gannon, MD |
Study Director |
Protalex, Inc. |
Location
Facility |
Haut-Levêque Hospital Pessac Bordeaux 33600 France |
CH Lyon Sud Pierre-Bénite Lyon 69495 France |
Côte de Nacre Hospital Caen 14033 France |
Mondor Hospital Créteil 94010 France |
University Hospital Dijon 21000 France |
Claude Huriez Hospital Lille 59037 France |
CH La Timone Marseille 13385 France |
CHU Nantes 44093 France |
Canceropole Toulouse 31059 France |
Hammersmith Hospital London OHS W12 United Kingdom |
UCLH London UK NW1 2BU United Kingdom |
Guy's and St. Thomas Hospital London UK SE 19RT United Kingdom |
St. Georges' Hospital London UK SW17 0QT United Kingdom |
Derriford Hospital Plymouth UK PL6 8DH United Kingdom |
University Hospital Southampton Southampton UK SO16 6YD United Kingdom |
Royal London Hospital London United Kingdom |
Location Countries
Country
France
United Kingdom
Verification Date
2019-03-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Has Expanded Access
No
Condition Browse
Secondary Id
2014-005626-35
Number Of Arms
1
Arm Group
Arm Group Label
PRTX-100
Arm Group Type
Experimental
Description
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.
Firstreceived Results Date
N/A
Why Stopped
Enough data has been collected to allow analysis of the safety profile and risk-benefit.
Firstreceived Results Disposition Date
N/A
Study Design Info
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
September 30, 2015
Study First Submitted Qc
October 1, 2015
Study First Posted
October 2, 2015
Last Update Submitted
March 21, 2019
Last Update Submitted Qc
March 21, 2019
Last Update Posted
March 25, 2019
ClinicalTrials.gov processed this data on December 12, 2019
Conditions
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conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.