Efficacy and Safety of P1101 in Polycythemia Vera Patients for Whom the Standard of Treatment is Difficult to Apply

Phase 2 Single Arm Study of Efficacy and Safety of P1101 for Polycythemia Vera (PV) Patients for Whom the Current Standard of Treatment is Difficult to Apply

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04182100

Enrollment

Registered

2019-12-02

Start date

2019-12-20

Completion date

2021-03-08

Last updated

2025-09-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Polycythemia Vera (PV)

Keywords

Myeloproliferative Neoplasms

Brief summary

This is a Phase 2 single arm study to investigate efficacy and safety of P1101 for adult Japanese patients with PV.

Detailed description

Eligible patients will be treated with P1101, starting at 100 μg (or 50 μg in patients under another cytoreductive therapy). The dose should be gradually increased by 50 μg every two weeks (in parallel, other cytoreductive therapy should be decreased gradually, as appropriate) until stabilization of the hematological parameters is achieved (hematocrit \<45%, platelets \<400 x 10\^9/L and leukocytes \<10 x 10\^9/L). The maximum recommended single dose is 500 μg injected every two weeks. At week 36 (month 9) and week 52 (month 12), the primary study endpoint, phlebotomy-free CHR, will be analyzed. After completion of the 52-week study duration, provision and administration of P1101, collection of the long-term follow up information (blood parameters, molecular and cytogenetic data, safety parameters and as also the optional bone marrow data) will be continued until the drug becomes commercially available for all study subjects..

Interventions

DRUGP1101

P1101 (ropeginterferon alfa-2b) will be administered subcutaneously every 2 weeks at the starting dose of 100 μg every two weeks (or 50 μg in patients under another cytoreductive therapy). The dose should be gradually increased by 50 μg every two weeks (in parallel, other cytoreductive therapy should be decreased gradually, as appropriate) until stabilization of the hematological parameters is achieved (hematocrit \<45%, platelets \<400 x 10\^9/L and leukocytes \<10 x 10\^9/L). The maximum recommended single dose is 500 μg injected every two weeks. The dose will be maintained at the highest level which can be tolerated and delivers best possible disease response.

DRUGLow-dose aspirin

Low-dose aspirin (acetylsalicylic acid) (75-150 mg/day) will be given as background therapy during the 12 months of study treatment, unless contraindicated.

PROCEDUREPhlebotomy

Phlebotomy is performed aiming at a hematocrit \< 45%. When the hematocrit value is 45% or higher, phlebotomy is performed. The volume of phlebotomy per procedure should be 200 to 400 mL while monitoring the circulatory dynamics such as blood pressure and pulse. In the elderly and patients with cardiovascular disorders, a small volume (100-200 mL) should be considered to avoid rapid changes in hemodynamics.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Conventional treatment based on phlebotomies, low-dose aspirin (acetylsalicylic acid, 75-150 mg/day) plus the subcutaneous administration of P1101 (ropeginterferon alfa-2b) once every 2 weeks

Eligibility

Sex/Gender

ALL

Age

20 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Male or female patients ≥20 years old 2. Patients diagnosed with PV according to the WHO 2008 or WHO 2016 criteria 3. PV patients for whom the current standard of treatment is difficult to apply. (Patients with a documented history of refractory to HU are excluded.) * Younger patients (long-term treatment is anticipated) * Patients who are categorized as low risk, but cytoreduction is recommended due to disease-related signs and symptoms (headache, dizziness, pruritus, night sweats, fatigue, erythromelalgia, vision disorders, scintillating scotoma, early satiety, abdominal distension). * Patients with HU intolerance 4. Total HU treatment duration shorter than 3 years (cumulatively) at screening 5. For cytoreduction naïve patients only: PV in need of cytoreductive treatment, defined by fulfilling as one or more of the following criteria at baseline: * at least one previous well documented major cardiovascular PV-related event in the medical history * poor tolerance of phlebotomy (defined as a phlebotomy/ procedure-related adverse event causing significant adverse impact on the patient and limiting ability to apply phlebotomy with the intention to keep Hct \<45%) * frequent need of phlebotomy (more than one phlebotomy within last month prior entering the study) * platelet counts greater than 1000 x 10\^9/L (for two measurements within the month prior treatment start) * leukocytosis (WBC\>10 x 10\^9/L for two measurements within the month prior treatment start) 6. Adequate hepatic function defined as bilirubin ≤1.5 x upper limit normal (ULN), international normalized ratio (INR) ≤1.5 x ULN, albumin \>3.5 g/dL, alanine aminotransferase (ALT) ≤2.0 x ULN, aspartate aminotransferase (AST) ≤2.0 x ULN at screening 7. Hemoglobin (HGB) ≥10 g/dL at screening 8. Neutrophil count ≥1.5 x 10\^9/L at screening 9. Serum creatinine ≤1.5 x ULN at screening 10. Hospital Anxiety and Depression Scale (HADS) score 0-7 on both subscales (Patients with a borderline of HADS score \[score 7 but \<10\] or patients with necessity \[expected benefits are higher than the risks\] based on investigators' discretion are required to receive following assessment by psychiatric specialist to confirm the eligibility for IFNα therapy.). 11. Males and females of childbearing potential, as well as all women \<2 years after the onset of menopause, must agree to use an acceptable form of birth control until 28 days following the last dose of the study drug 12. Written informed consent obtained from the patient or the patient's legal representative, and ability for the patient to comply with the requirements of the study

Exclusion criteria

1. Patients with symptomatic splenomegaly 2. Previous use of IFNα for any indication 3. Any contraindications or hypersensitivity to interferon-alfa 4. Co-morbidity with severe or serious conditions which may impact patient participation in the study in investigator's opinion 5. History of major organ transplantation 6. Pregnant or lactating females 7. Patients with any other medical conditions, which in the opinion of the Investigator would compromise the results of the study or may impair compliance with the requirements of the protocol 7-1. History or presence of thyroid dysfunction (clinical symptoms of hyper- or hypo-thyroidism) of the autoimmune origin, except late stages cases on the oral thyroid substitution therapy, where potential exacerbation under interferon therapy will not constitute any further harm to the patient 7-2.Documented autoimmune disease (e.g., hepatitis, idiopathic thrombocytopenic purpura \[ITP\], scleroderma, psoriasis, or any autoimmune arthritis) 7-3. Clinically relevant pulmonary infiltrates and pneumonitis at screening, patients with a history of interstitial pulmonary disease 7-4. Active infections with systemic manifestations (e.g., bacterial, fungal, hepatitis B \[HBV\], hepatitis C \[HCV\], or human immunodeficiency virus \[HIV\]) at screening) 7-5. Evidence of severe retinopathy (e.g., cytomegalovirus retinitis \[CMV\], macular degeneration) or clinically relevant ophthalmological disorder (due to diabetes mellitus or hypertension) based on the ophthalmological assessment by specialists. 7-6. Uncontrolled depression 7-7. Previous suicide attempts or at any risk of suicide at screening 8. Uncontrolled diabetes mellitus (HbA1c level of \> 7% at baseline) 9. History of any malignancy within for the past 5 years 10. History of alcohol or drug abuse within the last year 11. History or evidence of post polycythemia vera-myelofibrosis (PPV-MF), essential thrombocythemia, or any non-PV MPN 12. Presence of circulating blasts in the peripheral blood within the last 3 months 13. Use of any investigational drug(s), or investigational drug combinations \<4 weeks prior to the first dose of study drug or not recovered from effects of prior administration of any investigational agent

Design outcomes

Primary

Measure	Time frame	Description
Proportion of Subjects Who Achieved Durable Phlebotomy-free Complete Hematological Response (CHR) at Month 12	12 months	The primary efficacy endpoint was the phlebotomy-free CHR rate at Months 9 and 12. The phlebotomy-free CHR rate was defined as the proportion of patients who achieved phlebotomy-free CHR at both Months 9 and 12 without phlebotomies during the previous 3 months. A responder in sense of the primary endpoint was a patient who met all of the following criteria at Months 9 and 12: Hematocrit \<45% phlebotomy-free (absence of phlebotomy during the previous 3 months) Platelet count ≤400 × 10\^9/L Leukocyte count ≤10 × 10\^9/L

Secondary

Measure	Time frame	Description
Changes in WBC Count From Baseline	Baseline, 3 months, 6 months, 9 months and 12 months	WBC count will be recorded every 3 months.
Changes in Plt Count From Baseline	Baseline, 3 months, 6 months, 9 months and 12 months	Plt count will be recorded every 3 months.
Changes in Spleen Size From Baseline	Baseline, 3 months, 6 months, 9 months and 12 months	Spleen size will be recorded every 3 months.
Time to Requiring no Phlebotomy	Up to 12 months	Time to requiring no phlebotomy is recorded.
Time Required to First Response	Up to 12 months	Time required to first response is defined as time to achieve complete hematological response (CHR) without phlebotomy.
Changes in Hct From Baseline	Baseline, 3 months, 6 months, 9 months and 12 months	Hct will be recorded every 3 months.
Proportion of Subjects Without Thrombotic or Hemorrhagic Events	Up to 12 months	Thrombotic or hemorrhagic events will be recorded any time during the study. The proportion of subjects without thrombotic or hemorrhagic events is defined as the proportion of subjects experienced no thrombotic and hemorrhagic events during the study period (12 months).
Change of JAK2 Mutant Allelic Burden Over Time vs. Baseline	Baseline, 3 months, 6 months, 9 months and 12 months	Quantitative JAK2 measurements at screening, Months 3, 6, 9 and 12 (central laboratory) for subjects who signed consent form. Change of JAK2 allelic burden over time will be assessed.
PK of P1101	Up to 12 months	Trough concentration is the measured concentration of a drug at the end of a dosing interval at steady state every 2 weeks. Additionally, serum concentration is measured at hours 0, 24, 48, 96 and 168 after administration at Week 0 and Week 28.
Duration of Response Maintenance	Up to 12 months	Duration of maintained complete hematologic response (CHR) since first achievement of CHR after administration of the study drug will be calculated.

Other

Measure	Time frame	Description
Status of Bone Marrow Histological Remission (Optional)	0 month, 12 months	Status of bone marrow histological remission defined as the disappearance of hypercellularity (age-adjusted), trilineage growth (panmyelosis) and absence of \>grade 1 reticulin fibrosis

Countries

Japan

Participant flow

Recruitment details

Study was initiated at 8 sites in 1 country.

Pre-assignment details

Eligible patients were to be treated with P1101, starting at 100 μg (or 50 μg in patients under another cytoreductive therapy). The dose was to be gradually increased by 50 μg every 2 weeks (in parallel, other cytoreductive therapy should be decreased gradually, as appropriate) until stabilization of the hematological parameters is achieved (hematocrit \<45%, platelet count ≤400 × 10\^9/L, and leukocyte count ≤10 × 10\^9/L). The maximum recommended single dose is 500 μg injected every 2 weeks.

Participants by arm

Arm	Count
P1101 The dose was to be gradually increased by 50 μg every 2 weeks (in parallel, other cytoreductive therapy should be decreased gradually, as appropriate) until stabilization of the hematological parameters is achieved (hematocrit \<45%, platelet count ≤400 × 10\^9/L, and leukocyte count ≤10 × 10\^9/L). The maximum recommended single dose is 500 μg injected every 2 weeks.	29
Total	29

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	P1101
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	7 Participants
Age, Categorical Between 18 and 65 years	22 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	29 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Region of Enrollment Japan	29 participants
Sex: Female, Male Female	16 Participants
Sex: Female, Male Male	13 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 29
other Total, other adverse events	29 / 29
serious Total, serious adverse events	0 / 29

Outcome results

Primary

Proportion of Subjects Who Achieved Durable Phlebotomy-free Complete Hematological Response (CHR) at Month 12

The primary efficacy endpoint was the phlebotomy-free CHR rate at Months 9 and 12. The phlebotomy-free CHR rate was defined as the proportion of patients who achieved phlebotomy-free CHR at both Months 9 and 12 without phlebotomies during the previous 3 months. A responder in sense of the primary endpoint was a patient who met all of the following criteria at Months 9 and 12: Hematocrit \<45% phlebotomy-free (absence of phlebotomy during the previous 3 months) Platelet count ≤400 × 10\^9/L Leukocyte count ≤10 × 10\^9/L

Time frame: 12 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
P1101	Proportion of Subjects Who Achieved Durable Phlebotomy-free Complete Hematological Response (CHR) at Month 12	8 Participants

Secondary

Change of JAK2 Mutant Allelic Burden Over Time vs. Baseline

Quantitative JAK2 measurements at screening, Months 3, 6, 9 and 12 (central laboratory) for subjects who signed consent form. Change of JAK2 allelic burden over time will be assessed.