A Study to
compare the efficacy and safety of PZN-128 in treatment chronic
idiopathic thrombocytopenic purpura.
Scientific Title of Study
A randomized, international, multicenter double-blind study to
compare the efficacy,safety, and immunogenicity of PZN-128 powder for solution for subcutaneous injection 250 µg (Pharmasyntez Nord JSC, Russia) versus Ñomparator drug in patients with chronic
idiopathic (immune) thrombocytopenic purpura.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
PZN-128_Protocol version 2.0, dated 04.05.2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Umakanta Sahoo
Designation
Managing Director
Affiliation
GCT Pharma Research (India) Pvt. Ltd.
Address
GCT Pharma Research (India) Pvt. Ltd.
7th Floor, Wing-B, Vatika Business Center, Supreme Business Park,Hiranandani
Mumbai MAHARASHTRA 400076 India
Phone
912242369729
Fax
912242019191
Email
U.Sahoo@gctrials.com
Details of Contact Person Scientific Query
Name
Dr Umakanta Sahoo
Designation
Managing Director
Affiliation
GCT Pharma Research (India) Pvt. Ltd.
Address
GCT Pharma Research (India) Pvt. Ltd.
7th Floor, Wing-B, Vatika Business Center, Supreme Business Park,Hiranandani
MAHARASHTRA 400076 India
Phone
912242369729
Fax
912242019191
Email
U.Sahoo@gctrials.com
Details of Contact Person Public Query
Name
Dr Umakanta Sahoo
Designation
Managing Director
Affiliation
GCT Pharma Research (India) Pvt. Ltd.
Address
GCT Pharma Research (India) Pvt. Ltd.
7th Floor, Wing-B, Vatika Business Center, Supreme Business Park,Hiranandani
MAHARASHTRA 400076 India
Phone
912242369729
Fax
912242019191
Email
U.Sahoo@gctrials.com
Source of Monetary or Material Support
GCT Pharma Research (India) Pvt. Ltd.
7th Floor, Wing-B, Vatika Business Centre, Supreme Business Park, Hiranandani
Gardens, Powai, Mumbai-400076
Primary Sponsor
Name
PHARMASYNTEZ-NORD JSC
Address
74 Doroga v Kamenku, office 1–H, Saint-Petersburg, 194356, Russia
Department of Medicine, Datta Meghe Institute of Higher Education & Research, JNMC, Sawangi Meghe, Wardha- 442004, Maharashtra, India
Wardha MAHARASHTRA
9673288892 9673288892 drshilpagaidhane@gmail.com
Dr Utpal Chaudhuri
AMRI Hospital, Mukundapur
Department of hematology, 223 & 230, Barakhola, Jadavpur, Mukundapur, Kolkata, West Bengal 700099
Kolkata WEST BENGAL
9831043608 9831043608 uchaudhuri@gmail.com
Dr Shilpa Gupta
Bhaktivedanta Hospital and Research Institute
Department of hematology, Srishti complex, Bhaktivedanta Swami Marg, opp ISKON Temple, Mira Road, (E) Thane- 401107
Thane MAHARASHTRA
9820803843 9820803843 shilpagupta0707@gmail.com
Dr Vinay Bohara
Care CHL-Hospitals
Department of Hematology,Near LIG Square, A. B. Road, Indore, Madhya Pradesh, India- 452008
Indore MADHYA PRADESH
9104497595 9104497595 drvinaybohara@gmail.com
Dr Ambanna Gowda
Citizen Hospital
Department of hematology,,14, 2"d Main, Dispensary Road, Kalasipalya, Banglore-560002
Bangalore KARNATAKA
9845270377 9845270377 dr.ambanagowda@gmail.com
Dr Seema Bhatwadekar
Haemato Oncology Care Centre (HOCC)
Department of hematology, Kedar New India Mill compound, Jetralpur Road, behind swadia Patel Hospital, Vadodara, Gujarat, 390020
Vadodara GUJARAT
9099511709 9099511709 ssbkar16@gmail.com
Dr Shriram Kane
Hematology and Oncology Clinic
Department of hematology, Abhyankar Nagar Road, Balraj Marg Junction, Dhantoli, Nagpur, Maharashtra, India- 440012
Nagpur MAHARASHTRA
9823012851 9823012851 shriramkane@gmail.com
Dr Rajat Bajaj
Meditrina Institute of Medical Science
Department of hematology, Meditrina Institute of Medical Science, 278, Central Bazar Road, Ramdaspeth, Nagpur, Maharashta-440012, India.
Nagpur MAHARASHTRA
7387732732 7387732732 drrajatrbajaj@gmail.com
Dr Gautam Ganvir
Meera Hospital
Department of hematology, Devi Bhavan, Beside Dr. Acharya Hospital, Near Zojhwala Petrol Pump, Bail Bazar, Kalyan (W)- 421301
Mumbai MAHARASHTRA
9619183559 9619183559 gautamganvir914@gmail.com
Dr Tuphan Kanti Dolai
Nil Ratan Sircar Medical College and Hospital
Department of Hematology, Nil Ratan Sircar Medical College and Hospital, 138 AJC Bose Road, Kolkata- 700014
Kolkata WEST BENGAL
9874890275 9874890275 tkdolai@hotmail.com
Dr Ankit Raiyani
Rudraksha Multispeciality Hospital
Department of hematology, 1st floor, Rajmandir Complex, Off to Bareja Fly over, Bareja-382425, Ahmedabad, Gujarat, India
Ahmadabad GUJARAT
7798438250 7798438250 adraiyani@gmail.com
Dr Hasmukh Balar
Shalby Hospital
Department of hematology, Near Navyug College, RanderRoad, Adajan, Surat- 395005
Surat GUJARAT
7030022663 7030022663 hasmukhbalar@gmail.com
DrManjunath U
Sri. Lakshmi Multi Speciality Hospital
Department of hematology, 301, 3rd Main Road, Near Indane Gas, V B Layout, Old Extension, Krishnarajapura, Bengaluru, Karnataka 560036
Bangalore KARNATAKA
9742797117 9742797117 crsrilakshmi1@gmail.com
Dr Aman Vij
Venkateshwar Hospital
Department of hematology, Venkateshwar Hospital Sector 18 A, Dwarka, New Delhi-110075
North East DELHI
Institutional Ethics Committee, Nil Ratan Sircar Medical College and Hospital
Approved
Institutional Ethics Committee- Rughvani Child Health Care Centre
Approved
Integrity Ethics Committee
Approved
Meditrina Institute Ethics Committee
Approved
Meera Institutional Ethics Committee
Approved
Parikh Institutional Ethics Committee
Approved
Pranav DiabetesCentre Ethics Committee
Approved
Rudraksha Hospital Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: D758||Other specified diseases of bloodand blood-forming organs,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Placebo
The safety and efficacy of romiplostim was evaluated in two placebo-controlled, double-blind
studies: a phase 3 study with 24 weeks of romiplostim treatment and a phase 3 study with 12 weeks
of romiplostim treatment (up to 16 weeks for eligible responders who entered a 4-week pharmacokinetic assessment period). Both studies enrolled paediatric subjects (≥ 1 year to 18 years of
age) with thrombocytopenia (defined by a mean of 2 platelet counts ≤ 30 x 109
/L with neither
count 35 x 109
/L in both studies) with ITP, regardless of splenectomy status.
Intervention
PZN-128
Romiplostim
The safety and efficacy of romiplostim have been evaluated for up to 5 years of continuous treatment. In clinical trials, treatment with Romiplostim resulted in dose-dependent increases in platelet
count. Time to reach the maximum effect on platelet count is approximately 10-14 days, and is
independent of the dose. After a single subcutaneous dose of 1 to 10 μg/kg romiplostim in ITP
patients, the peak platelet count was 1.3 to 14.9 times greater than the baseline platelet count over
a 2 to 3 weeks period and the response was variable among patients.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
60.00 Year(s)
Gender
Both
Details
1. Informed consent to participate in the study.
2. Patients of both genders aged from 18 years.
3. Patients with diagnosed chronic idiopathic (autoimmune) thrombocytopenic purpura resistant to the first-line therapy.
4. Platelet count at the time of screening ≤ 30 x 10â¹/L.
5. Patients agreed to use a reliable method of contraception during the study up to its completion (for the subjects with reproductive potential).
6. Patients, in the Investigator’s opinion, understand the requirements which should be fulfilled for the participation in the study and are ready to follow them
ExclusionCriteria
Details
1. Withdrawal of informed consent.
2. Erroneous inclusion (violation of inclusion and non-inclusion criteria).
3. The Investigator’s or Sponsor’s decision to exclude a patient from the study due to clinically significant deviation from/violation of the protocol.
4. Serious adverse events or adverse events (e.g. allergy) not meeting the seriousness criteria
with the development of which, in the Investigator’s opinion, the further participation in
the study will be detrimental for the patient’s health or well-being.
5. Any adverse event (may be not drug related) requiring observation, procedures and/or drug
treatment prohibited by this study protocol.
6. Loss of contact with a patient and loss to the visit.
7. The need of the therapy prohibited by the protocol.
8. Patient became pregnant.
Method of Generating Random Sequence
Adaptive randomization, such as minimization
Method of Concealment
Alternation
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
Percentage of patients who required emergency therapy to prevent clinically significant
bleeding.
Number (percentage) of patients with persistent response to treatment determined as platelet count 50 × 109
/L for 6 weeks of last 8-week therapy period in the absence of emergency therapy for relief of hemorrhagic synd
Secondary Outcome
Outcome
TimePoints
Number (percentage) of patients with platelet counts ≥ 250 × 109
/L for ≥ 8 weeks
Median time 7 weeks with a platelet response (i.e., the time when platelet counts were ≥
250 × 109
/L during the therapy).
• Percentage of patients who required emergency therapy to prevent clinically significant
bleeding.
Target Sample Size
Total Sample Size="203" Sample Size from India="183" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
ITP is an autoimmune disease characterized by production of antibodies to the membrane structures of platelets and their precursors – megakaryocytes (MKC) causing increased destruction of
platelets, inadequate thrombocytopoiesis characterized by isolated thrombocytopenia < 100*109
/L
and presence or absence of haemorrhagic syndrome of various severity. Ethiopathogenetic
mechanisms of ITP development are unknown. ITP morbidity varies from 1.6 to 12.5 cases per
100,000 population per year; the average morbidity value among female patients is higher
than in male patients (3.03 per 100,000 persons against 2.77 per 100,000 population, respectively).
The main ITP therapy aim – management of haemorrhagic syndrome and increase of platelet count
up to safe level – not less than 50.0 × 109
/L, which provides good quality of life of a patient with
no hematostaxic.
Treatment of patients with ITP should be based on individual approach, which is determined by
the severity of haemorrhagic syndrome, but not by platelet count. Comorbidity, patient’s life style,
complications of previous treatment, planned surgeries, etc. are of value at the therapy selection.
No therapy types capable of providing complete recovery are available at present, however an
adequate therapy improves the patient’s quality of life with severe chronic – recurrent and refractory forms of the disease. It allows to preserve the ability to work, to perform surgical procedures and surgeries with correct preparation of a patient, allows female patients to become pregnant and to deliver healthy children.
One of the most effective and safe therapeutic approaches in the treatment of ITP is based on the
use of thrombopoietin receptor agonists – romiplostim. Thrombocytic response while using
romiplostim is achieved by 93% of patients, while this drug product may be efficient as
second line therapy with contraindications to splenectomy or third line therapy after splenectomy
failure. Romiplostim (Nplate) is much more effective in patients with chronic ITP as compared to
rituximab and standard therapy.
The developer of the drug product and the Sponsor of the study, Pharmasyntez-Nord JSC, Russia,
conducted a phase I clinical trial "Double-blind, randomized, cross-over clinical study of comparative pharmacokinetics, pharmacodynamics and safety of the study drug product Romiplostim,
(romiplostim, powder for solution for subcutaneous injection, 250 µg, manufacturer is Pharmasyntez-Nord JSC) and the reference drug product Nplate, (romiplostim, powder for solution for subcutaneous injection 250 µg (Amgen Europe B.V., Netherlands) with a single subcutaneous injection to healthy volunteers.
44 healthy volunteers were randomized into the study, of which all study participants completed
the study protocol.