Clinical trial NCT06552429: Peginterferon α-2b Injection for Hydroxyurea Resistant or Intolerant ET
Official title: A Phase 2 Multicenter, Randomized, Open-label Study to Evaluate the Pharmacokinetic, Safety and Efficacy of Peginterferon Alfa-2b Injection in Subjects With Essential Thrombocythemia Who Are Resistant to or Intolerant of Hydroxyurea.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Essential Thrombocythemia
Keywords: Essential Thrombocythemia
Peginterferon α-2b
hydroxyurea resistant
hydroxyurea intolerant
Lead sponsor: Xiamen Amoytop Biotech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-08-14
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, open-label Phase 2 clinical study. It is aimed to enroll 27 essential thrombocytopenia (ET) patients who are resistant to or intolerant of hydroxyurea(HU). Eligible patients will be randomized to receive either Peginterferon α-2b 135 mcg or Peginterferon α-2b 180 mcg at a ratio of 1:2, and all subjects will go through a target treatment period (Weeks 1 \~ Week 48), an extension treatment period (Weeks 49 \~ Week 96) and a follow-up period (Weeks 97 \~ Week 100). Pharmacokinetics, safety, efficacy will be evaluated.


Eligibility criteria: Inclusion Criteria:

* Male or female subjects, aged greater or equal to 18 years old at screening;
* Subjects diagnosed as high-risk ET according to the World Health Organization (WHO) 2016 criteria：1) who is older than 60 years and JAK2V617F positive at screening, 2) or who previously suffered from disease-related thrombosis or hemorrhage;
* Subjects who have previously received HU for ET, and the time interval between the last HU dose and the first dose of the study drug should not be less than 7 days;
* Interferon treatment-naïve, and for those who have previously received interferon the the time interval between the last dose of interferon and randomization should not be less than 1 month;
* Patients with confirmed hydroxyurea resistance or intolerant, as at least one of the following criteria is met:

  1. Platelet count remain greater than 600×10\^9 /L after at least 3 months of HU treatment at a dose ≥2g/d (dose ≥2.5 g/d if subject weight \> 80 kg);
  2. Platelet count greater than 400\*10\^9/L while white blood cell (WBC) count lower than 2.5\*10\^9/L, or platelet count greater than 400\*10\^9 /L while hemoglobin lower than 100 g/L at any dose of HU;
  3. Presence of HU-related toxicities at any dose of HU: e.g. ulcers in legs, or any unacceptable skin mucosal manifestations or fever;
* Platelet counts \> 450\*10\^9/L at screening;
* Neutrophil count ≥1.0\*10\^9/L at screening;
* Haemoglobin ≥11 g/dL at screening for males and 10 g/dL for females at screening;
* There is no serious function damage in liver and kidney: total bilirubin ≤1.5 upper limit of normal (ULN), alanine aminotransferase≤2.0 ULN, aspartate aminotransferase≤2.0 ULN, prothrombin time is prolonged by less than 4 seconds, Creatinine clearance ≥50 mL/min (according to Cockcroft-Gault formula) at screening;
* Both male and female subjects must agree take an appropriate contraceptive method, including:

  1. Male subjects: must agree to use reliable contraception from inform consent until 6 months following the last dose of the study drug.
  2. Female subjects: Must meet at least one of the following conditions:

  i) Women without childbearing potential; ii) Women of childbearing potential: no pregnant or breastfeed, negative in blood pregnancy test within 4 days prior to the first dosing, and must agree to use reliable contraception from inform consent until 6 months following the last dose of the study drug;
* Subjects understand the objective, characteristic, method and possible adverse reactions of the study, voluntarily participate in this study, and sign informed consent.

Exclusion Criteria:

* History of any other myeloproliferative tumors, or evidence of the presence of any other myeloproliferative tumors;
* Contraindications or hypersensitivities to interferons of any of its excipients;
* Severe medical conditions or serious comorbidities that the investigators determined could jeopardize the safety or protocol adherence, e.g. New York Heart Association \[NYHA\] Class III-IV, congestive heart failure, symptomatic arrhythmias，pulmonary hypertension;
* History of major organ transplantation;
* Documented autoimmune disease or history of autoimmune disease at screening, e.g. medication un-controlled thyroid dysfunction, autoimmune hepatitis, idiopathic thrombocytopenic purpura, scleroderma, psoriasis, or any autoimmune arthritis;
* Clinically significant pulmonary infiltration, infectious pneumonia, and non-infectious pneumonia at screening that, in the investigator's opinion, would jeopardize the safety of the subject or their compliance with the protocol;
* Infection with systemic clinical manifestations at screening, e.g., bacteria, fungi, human immunodeficiency virus, excluding hepatitis B and/or C;
* Evidence of severe retinopathy, e.g., cytomegalovirus retinitis, symptomatic macular degeneration, or clinically significant eye disease, e.g. due to diabetes mellitus or hypertension;
* Diagnosed clinically significant depression or a history of depression and, in the investigator's opinion, previous suicide attempts or at any risk of suicide at screening;
* Diagnosed clinically significant neurological disease or a history of clinically significant neurological disease, except for a history of stable cerebral thrombosis or cerebral hemorrhage;
* History of any malignancy within 5 years (except stage 0 chronic lymphocytic leukemia, basal cell carcinoma, squamous cell carcinoma, and superficial melanoma);
* A history of alcohol or drug abuse within 1 year;
* Have used any investigational drug within 4 weeks prior to first dose of investigational drug, or not recovered from the effects of prior investigational drug administration;
* Other situations that, in the investigator's opinion, not appropriate for inclusion.

Primary outcomes:
measure: Maximum concentration (Cmax)
timeFrame: week1,4, 8, 12, 24, 36, 48, 60, 72, 84, 96.
measure: Time to maximum concentration (Tmax)
timeFrame: week1,4, 8, 12, 24, 36, 48, 60, 72, 84, 96.
measure: Area under the plasma concentration-time curve
timeFrame: week1,4, 8, 12, 24, 36, 48, 60, 72, 84, 96.
measure: Apparent volume of distribution after oral administration (Vz/f)
timeFrame: week1,4, 8, 12, 24, 36, 48, 60, 72, 84, 96.
measure: Apparent plasma clearance (CL/F)
timeFrame: week1,4, 8, 12, 24, 36, 48, 60, 72, 84, 96.
measure: Plasma elimination half-life (t1/2)
timeFrame: week1,4, 8, 12, 24, 36, 48, 60, 72, 84, 96.
measure: Relationship between exposure and the effect (desired-effectiveness or undesirable-toxicity) in a pharmacokinetic model and pharmacodynamic model.
timeFrame: up to 96 weeks.
Secondary outcomes:
measure: Rate of complete hematological remission.
timeFrame: Week 24, 36, 48, 60, 72, 84, 96.
measure: Platelet counts change from baseline.
timeFrame: Week 12, 24, 36, 48, 60, 72, 84, 96.
measure: White blood cell counts change from baseline.
timeFrame: Week 12, 24, 36, 48, 60, 72, 84, 96.
measure: Complete remission rate.
timeFrame: Week 24, 36, 48, 60, 72, 84, 96.
measure: Time to complete remission from baseline.
timeFrame: Week 48, 96.
measure: Duration of complete remission.
timeFrame: Week 48, 96.
measure: Remission rate of bone marrow.
timeFrame: Week 48, 96.
measure: Incidence of disease progression.
timeFrame: Week 48, 96.
measure: Change of JAK2V617F mutations load from baseline.
timeFrame: Week 48, 96.
measure: Change of CALR mutations load from baseline.
timeFrame: Week 48, 96.
measure: Change of MPL mutations load from baseline.
timeFrame: Week 48, 96.
measure: Change of MPN-SAF TSS scores from baseline
timeFrame: Week 12, 24, 36, 48, 60, 72, 84,96.
measure: Change of spleen size from baseline
timeFrame: Week 12, 24, 36, 48, 60, 72, 84, 96.
measure: Rate of complete hematological remission maintenance in patients received dose-reduction extension therapy
timeFrame: Week 96.
measure: Duration of complete hematological remission in patients received dose-reduction extension therapy
timeFrame: Week 96.
measure: Change of 3-level Version of EuroQol Five Dimensions(EQ-5D-3L) scores from baseline.
timeFrame: Week 12, 24, 36, 48, 60, 72, 84, 96.
measure: Incidence of thrombotic and bleeding events.
timeFrame: through study completion, an average of 2 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Hospital, Chinese Academy of Medical Sciences
city: Beijing
country: China
facility: Peking University People's Hospital
city: Fujian
country: China
facility: Union Hospital affiliated to Fujian Medical University
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
city: Harbin
country: China
facility: Harbin First Hospital
city: Henan
country: China
facility: Henan Cancer Hospital
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
city: Zhejiang
country: China
facility: The First Affiliated Hospital of Zhejiang University School of Medicine
Study officials:
affiliation: Chinese Academy of Medical Sciences
name: Lei Zhang
role: PRINCIPAL_INVESTIGATOR
References: