A clinical trial to test the safety, dosing, effect and activity of PRN1008 in patients with Relapsed Immune Thrombocytopenia

Phase 1

• Conditions: Immune Thrombocytopenia; MedDRA version: 23.0Level: LLTClassification code 10074667Term: Immune thrombocytopenic purpuraSystem Organ Class: 100000004851; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2017-004012-19-NL
• Lead Sponsor: Principia Biopharma, a Sanofi Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-02-05
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 83

Inclusion Criteria

Part A:
1. Male or female patients, aged 18 to 80 years old (Czech Republic and Norway only: 18 to 65 years old)
2. Immune-related ITP (both primary and secondary)
3. Refractory or relapsed patients with no available and approved therapeutic options with a platelet count of <30,000/µL on two occasions no less than 7 days apart in the 15 days prior to beginning study treatment.
4. A history of response (two or more platelet counts = 50,000/µL with an increase of at least 20,000/µL) to at least one prior line of therapy (with splenectomy being considered a line of therapy)
5. Adequate hematologic, hepatic, and renal function (absolute
neutrophil count =1.5 × 109/L, hemoglobin [Hgb] >9 g/dL, AST/ALT =
1.5 × ULN, albumin =3 g/dL, total bilirubin =1.5 × ULN, estimated
glomerular filtration rate [eGFR] > 60 mL/min (Cockcroft and Gault
method) (C1D1 pre-dose may be checked up to Day -3 prior to C1D1)
6. Female patients who are of reproductive potential must agree for the duration of active treatment in the study to use a highly effective means of contraception (hormonal contraception methods
that inhibits ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal ligation, vasectomized partner,
sexual abstinence when this is in line with the preferred and usual lifestyle of the patient). Unless surgically sterile, postmenopausal females should have menopause confirmed by FSH testing.
7. Able to provide written informed consent and agreeable to the schedule of assessments

Part B:
1. Male or female patients, aged 18 to 80 years old
2. Patients with immune-related ITP (both primary and secondary) as
defined by current guidelines with at least 3 months duration
3. Patients who had a response (achievement of platelet count =
50,000/µL) to IVIg/anti-D or corticosteroid that was not sustained and
failed at least one other ITP therapy (that was not IVIg or
corticosteroid)
4. Patients with a platelet count of < 30,000/µL on two occasions no less
than 7 days apart in the 15 days before treatment begins, and no
platelet count above 35,000/µL on Study Day 1.
5. Patients with adequate hematologic, hepatic, and renal function
(absolute neutrophil count =1.5 × 109/L, Hgb >9 g/dL, AST/ALT =1.5 ×
ULN, albumin =3 g/dL, total bilirubin =1.5 × ULN, eGFR >50 mL/min
(Cockcroft and Gault method) (pre-dose may be checked up to Day -3)
6. Female patients who are of reproductive potential must agree for the
duration of active treatment in the study to use a highly effective means
of contraception (hormonal contraception methods that inhibits
ovulation, intrauterine device, intrauterine hormonereleasing system,
bilateral tubal ligation, vasectomized partner, or true-abstinence; when
this is in line with the preferred and usual lifestyle of the patient).
Unless surgically sterile, postmenopausal females should have
menopause confirmed by FSH testing.
7. Able to provide written informed consent and agreeable to the
schedule of assessments
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 67
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

Exclusion Criteria

Part A:
1. Pregnant or lactating women
2. ECG findings of QTcF > 450 msec (males) or > 470 msec (females), poorly controlled atrial fibrillation (i.e., symptomatic patients or a ventricular rate above 100 beats/min on ECG), or other
clinically significant abnormalities
3. History of current, active malignancy requiring or likely to require chemotherapeutic or surgical treatment during the trial, with the exception of non-melanoma skin cancer
4. Transfusion with blood or blood products or plasmapheresis within 2 weeks before Day 1
5. Change in corticosteroid and/or TPO agonist dose within 2 weeks prior to Day 1 (more than 10% variation from Day 1 daily doses)
6. Use of rescue medications other than corticosteroids or TPO in Exclusion Criterion #5 in the two weeks before Day 1
7. Immunosuppressant drugs other than corticosteroids – these drugs should be discontinued for at least 14 days before Day 1
8. Treatment with rituximab or splenectomy within the 3 months prior to Day 1
9. Ongoing need for the use of proton pump inhibitor drugs such as omeprazole and esomeprazole (it is acceptable to change patient to H2 receptor blocking drugs prior to Day 1)
10. Concomitant use of known strong-to-moderate inducers or inhibitors of CYP3A within 3 days or 5 half-lives (whichever is longer) of Day 1
11. Use of CYP3A-sensitive substrate drugs with a narrow therapeutic index within 3 days or 5 half-lives (whichever is longer) of study drug dosing including, but not limited to, alfentanil, astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or terfenadine
12. Planned or concomitant use of any anticoagulants and platelet aggregation inhibiting drugs such as aspirin, non-steroidal anti
inflammatory
drugs (NSAIDs), thienopyridenes (within 14 days of planned dosing through end of
follow-up).
13. Has received any investigational drug within the 30 days before receiving the first dose of study medication, or at least 5 times elimination half-life of the drug (whichever is longer); patient
should not be using an investigational device at the time of dosing
14. Current drug or alcohol abuse
15. Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate study drug absorption
16. History of solid organ transplant
17. Positive for screening for HIV, hepatitis B (surface antigen and core antibodies unrelated to vaccination), or hepatitis C (anti-HCV antibody confirmed with HCV RNA)
18. History of serious infections requiring intravenous therapy within the last 3 months before Day 1
19. Clinically significant cognitive dysfunction (= Grade 1) or medical history suggestive of increased risk for cognitive dysfunction during the study
20. Live vaccine within 28 days prior to Day 1 or plan to receive one during the study
21. Planned surgery in the time frame of the dosing period
22. Any other clinically significant disease, condition, or medical history that, in the opinion of the Investigator, would interfere with patient safety, study evaluations, and/or study procedures

Part B:
1. Pregnant or lactating women
2. ECG findings of QTcF > 450 msec (males) or > 470 msec (females),
poorly controlled atrial fibrillation (i.e., symptomatic patients or a
ventricular rate above 100 beats/min on ECG), or other clinically
significant abnormalities
3. History (within 5 years of SD1) or current, active malignancy requiring or likely to r

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified