Trial Title:
A Study to Access Efficacy and Safety of P1101 in Chinese PV Patients Who Are Intolerant or Resistance to HU
NCT ID:
NCT05485948
Condition:
Polycythemia Vera
Conditions: Official terms:
Polycythemia Vera
Polycythemia
Conditions: Keywords:
Ropeginterferon alpha-2b
Polycythemia Vera
Hydroxyurea
P1101
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Ropeginterferon alfa-2b
Description:
Initial dose of 250 µg at Week 0, a medium dose of 350 µg at Week 2, a target dose of 500
µg at Week 4, and a maintenance dose of 500 µg until Week 52.
Arm group label:
Treatment with P1101
Other name:
BESREMI
Summary:
This study is a phase II single-arm study designed to evaluate the efficacy and safety of
P1101 in Chinese PV patients who are intolerance or resistance to HU.
Detailed description:
Eligible subjects will be treated with P1101 at a starting dose of 250 µg at Week 0, a
medium dose of 350 µg at Week 2, a target dose of 500 µg at Week 4, and a maintenance
dose of 500 µg from the subsequent week until Week 52. At Week 24 (Month 6), the primary
study endpoint, i.e., the phlebotomy- or erythrocytapheresis-free CHR rate, will be
analyzed.
For subjects who switch from previous HU treatment to P1101 (for subjects who are
currently receiving HU treatment), the dose should be gradually reduced during the
screening period (adjusted by the investigator based on clinical practice); the HU
treatment should be ended within up to 4 weeks of P1101 treatment, and HU should be
prohibited after 4 weeks of P1101 treatment.
During the treatment period, subject visits are scheduled for once every 2 weeks. The end
of treatment (EOT) visit will be performed at Week 52 or early termination of the study,
and the end of study (EOS) visit will be performed at 28 days after the EOT visit.
Data analyses will be performed after all subjects complete 24 weeks of treatment, and a
clinical trial report written, and the new drug application is submitted accordingly. An
end-of-study statistical analysis will be performed after all the subjects have completed
all visits as per protocol.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Male or female patients aged ≥18 years at the time of signing the informed consent
form;
- Patients diagnosed with PV according to the 2016 World Health Organization (WHO)
criteria;
- According to the 2020 Guidelines of Chinese Society of Clinical Oncology (CSCO) on
Diagnosis and Treatment of Hematological Malignancies, PV patients who are HU
resistant or intolerant must meet at least one of the following criteria;
1. Drug resistance: 3 months of treatment at HU doses above 2 g/d
1. Phlebotomy is still required to maintain Hct <45%;
2. Failure to control the bone marrow proliferation (such as platelet count
>400x10^9/L and white blood cell count >10x10^9/L);
3. spleen shrinkage of less than >50%;
2. Intolerance
1. At the minimum dose of HU required to achieve complete or partial clinical
hematologic response, the absolute neutrophil count (ANC) <1x10^9/L or PLT
<100x10^9/L or HGB <100 g/L;
2. At any dose of HU treatment, the patient develops lower limb ulcers or
other intolerable non-hematologic toxicity, such as skin mucosal
manifestations (dark skin, teeth or nails; oral ulcers, mucositis; skin
ulcers, rash, and other symptoms), gastrointestinal complaints (nausea,
loss of appetite, indigestion, vomiting, abdominal pain, constipation, and
other symptoms), pneumonia, fever, etc.
- Have not received interferon therapy previously; or have negative anti-P1101 binding
antibody at screening, and the washout time between the last dose of interferon and
the first dose of the study drug should not be shorter than 14 days;
- With good liver function at screening, which is defined as total bilirubin ≤1.5 ×
upper limit of normal (ULN), international normalized ratio (INR) ≤1.5 × ULN,
albumin >3.5 g/dL, alanine aminotransferase (ALT) ≤2.0 × ULN, and aspartate
aminotransferase (AST) ≤2.0 × ULN;
- Hemoglobin (HGB) ≥10 g/dL for females, and hemoglobin (HGB) ≥11 g/dL for males at
screening;
- Neutrophil count ≥1.5x10^9/L at screening;
- Creatinine clearance rate ≥40 mL/min at screening (according to the Cockcroft-Gault
formula);
- Males and females of childbearing potential, as well as all the females with a
menopause duration of less than 2 years, must consent to use acceptable
contraceptive methods within 28 days after the last dose of the study drug;
- The patient or the patient's guardian signs the written informed consent, and the
patient is able to comply with the study requirements.
Exclusion Criteria:
- Patients with symptomatic splenomegaly;
- Any contraindications to interferon α or hypersensitivity to interferon α;
- With severe or serious diseases that the investigator determines may affect the
patient's participation in this study;
- History of major organ transplantation;
- Pregnant or breastfeeding women;
- Patients with any other diseases that the investigator determines will affect the
study results or may weaken the compliance to protocol, including but not limited
to:
1. Prior or current autoimmune thyroid disease, but patients with oral thyroxine
replacement therapy could be enrolled;
2. Other documented autoimmune diseases (such as hepatitis, immune
thrombocytopenia [ITP], scleroderma, psoriasis or any autoimmune arthritis);
3. Clinically significant pulmonary infiltration, infectious pneumonia and
non-infectious pneumonia, or a past history of interstitial pneumonia at
screening;
4. Active infection with systemic manifestations (e.g., presence of bacteria,
fungi and human immunodeficiency virus [HIV], excluding hepatitis B [HBV]
and/or hepatitis C [HCV] at screening);
5. With evidence of severe retinopathy (e.g., cytomegalovirus [CMV]-induced
retinitis, macular degeneration) or clinically significant eye diseases (due to
diabetes or hypertension);
6. With clinically significant depression or a history of depression;
7. Previously had suicidal attempts or has any risk for suicidal tendency at
screening.
- Poorly controlled diabetes;
- Thromboembolic complications caused by PV and active abdomina hemorrhage;
- History of any malignancy tumors (except stage 0 chronic lymphocytic leukemia [CLL],
cured basal cell carcinoma, squamous cell carcinoma and superficial melanoma) in the
past 5 years;
- History of alcohol or drug abuse in the past year;
- History or evidence of post polycythemia vera-myelofibrosis (PPV-MF), essential
thrombocythemia, or any non-PV MPN;
- Presence of blast cells in the peripheral blood in the past 3 months;
- Use any investigational drugs or investigational drug combinations within 4 weeks
before the first dose of the study drug, or have not yet recovered from the effects
caused by any previously administered investigational drug.
Unless with contraindications, acetylsalicylic acid will be considered as background
treatment of this study. The following are contraindications to low-dose acetylsalicylic
acid: history of allergies to Bayaspirin or any preparations of salicylic acid, peptic
ulcer, bleeding tendency, aspirin-induced asthma (asthma attack caused by non-steroidal
anti-inflammatory drugs, etc.) and its history. If any contraindications are found, other
prophylactic anti-thrombotic drugs can be used.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Peking Union Medical College Hospital
Address:
City:
Beijing
Country:
China
Facility:
Name:
Xiangya Hospital Central South University
Address:
City:
Changsha
Country:
China
Facility:
Name:
The First Affiliated Hospital of Chongqing Medical Universit
Address:
City:
Chongqing
Country:
China
Facility:
Name:
Nanfang Hospital affiliated to Southern Medical University
Address:
City:
Guangzhou
Country:
China
Facility:
Name:
Anhui Provincial Hospital
Address:
City:
Hefei
Country:
China
Facility:
Name:
Huashan Hospital affiliated to Fudan University
Address:
City:
Shanghai
Country:
China
Facility:
Name:
Ruijin Hospital affiliated to Shanghai Jiaotong University
Address:
City:
Shanghai
Country:
China
Facility:
Name:
Shenzhen Second People's Hospital
Address:
City:
Shenzhen
Country:
China
Facility:
Name:
The First Affiliated Hospital of Soochow University
Address:
City:
Suzhou
Country:
China
Facility:
Name:
Institute of Hematology &Blood Diseases Hospital ,Chinese Academy of medical science & Peking Union Medical College
Address:
City:
Tianjin
Country:
China
Facility:
Name:
The Second Hospital of Tianjin Medical University
Address:
City:
Tianjin
Country:
China
Facility:
Name:
Zhongnan Hospital affiliated to Wuhan University
Address:
City:
Wuhan
Country:
China
Facility:
Name:
The First Affiliated Hospital Zhejiang University of Medicine
Address:
City:
Zhejiang
Country:
China
Facility:
Name:
Henan Cancer Hospital
Address:
City:
Zhengzhou
Country:
China
Start date:
October 8, 2021
Completion date:
May 2025
Lead sponsor:
Agency:
PharmaEssentia
Agency class:
Industry
Source:
PharmaEssentia
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05485948
