Polycythemia VeraPhase 3CONTI-PVNCT02218047
AOP2014 vs. BAT in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study.
A Phase 3 study testing Pegylated-Proline-interferon alpha-2b and Best available therapy (BAT) in people with Polycythemia Vera, run by AOP Orphan Pharmaceuticals AG at 47 sites in 12 countries.
Trial summary
Polycythemia Vera (PV) is a disease of bone marrow stem cells that manifests in a drastic increase of red blood cells and frequently also of white blood cells. The "thickening" of the blood in relation with a modified function of the cells has several consequences like increased blood pressure, pruritus of the skin… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Polycythemia Vera
- What is being tested?
- Pegylated-Proline-interferon alpha-2b and Best available therapy (BAT)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 47 sitesin 12 countries
- Study dates
- Nov 2014to 29 Apr 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who completed the 12 months AOP2014 treatment arm of the PROUD-PV study and at the "end-of-treatment visit" (EoT) of the PROUD-PV study who fulfill at least one of the following criteria:
- normalization of at least two out of three main blood parameters (Hct, PLTs and WBCs) if these parameters were moderately increased (Hct<50%, WBC<20 x 109/L, PLTs<600 x 109/L) at baseline of the PROUD-PV study, OR
- >35% decrease of at least two out of three main blood parameters (Hct, PLTs and WBCs) if these parameters were massively increased (Hct>50%, WBCs>20 x 109/L, PLTs>600 x 109/L), at baseline of the PROUD-PV study, OR
- normalization of spleen size, if spleen was enlarged at baseline of the PROUD-PV study, OR
- otherwise a clear, medically verified benefit from treatment with AOP2014 (e.g. normalization of disease-related micro-vasculatory symptoms, substantial decrease of JAK2 allelic burden).
- Signed written ICF.
Who cannot join
- Withdrawal criteria, as specified in the PROUD-PV study, which mandate treatment discontinuation:
- Non-recovery from the AOP2014 related toxicities to the grade (usually, Grade I) which allows continuation of the treatment.
- HADS score of 11 or higher on either or both of the subscales, and /or development or worsening of the clinically significant depression or suicidal thoughts.
- Progressive and clinically significant increase of liver enzyme levels despite dose reduction, or if such increase is accompanied by increased bilirubin level, any signs or symptoms of a clinically significant autoimmune disease.
- Clinically significant development of a new ophthalmologic disorder, or worsening of a pre-existing one, during the study.
- Loss of efficacy of AOP2014 or any comparable situation where no further benefits of treatment continuation are expected by the investigator.
- The main efficacy evaluation criterion will be disease response defined as Hct<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs<400 x 109/L, WBCs<10 x 109/L, and normal spleen size.
- The main efficacy endpoint will be the maintenance rate of disease response at assessment visits (every three months).
Trial locations and contacts
47 sites in 12 countries.
47 sites in 12 countries
Austria7 sites
LKH Graz
Graz
University Hospital Innsbruck
Innsbruck
Elisabethinen Hospital Linz
Linz
Salzburg Regional Hospital
Salzburg
Hanusch Hospital
Vienna
Medical University Vienna
Vienna
Hospital Wels-Grieskirchen
Wels
Hungary5 sites
St Istvan and St Laszlo Hospital of Budapest
Budapest
University of Debrecen
Debrecen
Bekes County Pandy Kalman Hospital, 1st Department of Medicine, Hematology
Gyula
Kaposi Mor County Teaching Hospital
Kaposvár
University of Szeged, Albert Szent-Gyorgyi Clinical Center, Koranyi fasor 6
Szeged
Poland5 sites
University Hospital in Cracow
Krakow
Independent Public Teaching Hospital No.1 in Lublin
Lublin
Fryderyk Chopin Provincial Specialized Hospital
Rzeszów
Nicolaus Copernicus Municipal Specialist Hospital
Torun
Institute of Hematology and Transfusion Medicine
Warsaw
Russia5 sites
Baranov Republican Hospital
Petrozavodsk
Samara Kalinin Regional Clinical Hospital
Samara
Komi Republican Oncology Center
Syktyvkar
Tula Regional Clinical Hospital
Tula
Yaroslavl Regional Clinical Hospital
Yaroslavl
Ukraine5 sites
Cherkasy Regional Oncology Center, Regional Treatment and Diagnostics Hematology Center
Cherkasy
Dnipropetrovsk City Multispecialty Clinical Hospital #4
Dnipropetrovsk
National Research Center for Radiation Medicine, Institute of Clinical Radiology
Kiev
Institute of Blood Pathology and Transfusion Medicine
Lviv
O.F. Herbachevskyi Regional Clinical Hospital
Zhytomyr
Bulgaria4 sites
University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv
Plovdiv
Specialized Hospital for Active Treatment of Hematological Diseases
Sofia
Multiprofile Hospital for Active Treatment "Sveta Marina", Varna
Varna
Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa, First Department of Internal Medicine
Vratsa
Czechia4 sites
University Hospital Brno
Brno
University Hospital Hradec Kralove
Hradec Králové
University Hospital Kralovske Vinohrady
Prague
University Hospital Motol
Prague
France3 sites
Institute Paoli-Calmettes
Marseille
Hospital Saint-Louis
Paris
Clinical Research Center CIC
Poitiers
Germany3 sites
Aachen University Hospital, Medical Clinic IV
Aachen
University Hospital Bonn, Center for Internal Medicine, Medical Clinic and Outpatient Clinic III
Bonn
University Hospital Carl Gustav Carus, Medical Clinic and Polyclinic I
Dresden
Romania3 sites
Emergency Clinical County Hospital Brasov
Brasov
Bucharest University Emergency Hospital
Bucharest
Coltea Clinical Hospital
Bucharest
Slovakia2 sites
University Hospital with Outpatient Clinic F.D. Roosevelt
Banská Bystrica
Saint Cyril and Metod University Hospital Bratislava
Bratislava
About this study
Official title: An Open-label, Multicenter, Phase IIIb Study Assessing the Long-term Efficacy and Safety of AOP2014 and Standard First Line Treatment (BAT) in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study
Polycythemia Vera (PV) is a disease of bone marrow stem cells that manifests in a drastic increase of red blood cells and frequently also of white blood cells. The "thickening" of the blood in relation with a modified function of the cells has several consequences like increased blood pressure, pruritus of the skin, fatigue, disturbed blood circulation in the brain as well as fingers and toes and an increased risk of arterial and venous thrombosis (thrombosis is the formation of a blood clot in a vessel); like stroke, cardiac infarction, deep vein thrombosis in the legs. In case of a strong increase of platelets there is an additional risk of bleedings. As the disease progresses the size of spleen and liver increased in most cases and the bone marrow shows signs of fibrosis. In some cases of PV a progression at a later time point to a leukemia (increased formation of white blood cells) can occur.
The aim of this study is to show that the study drug AOP2014 (pegylated proline interferon alpha-2b) has the long term efficacy and safety in controlling the disease. A comparison arm is receiving best available therapy as selected by the investigator. Response to the treatment is measured by several blood parameters as well as size of the spleen.
Interferon-alpha has been shown to be effective in controlling the blood parameters by immunologically influencing the blood building cells. This can lead to a suppression of the disease-causing stem cells and help healthy stem cells to proliferate. Through this mechanism it is possible that Interferon-alpha can avoid long-term damaging effects of the disease.
Read the detailed description
This is a Phase III, parallel-arm, open-label continuation of the PROUD-PV study performed in adults diagnosed with Polycythemia Vera (PV). Patients who received AOP2014 in the primary study, PROUD-PV will continue on AOP2014, patients who received HU in the PROUD-PV study will receive best available therapy as selected by the investigator. Only patients who completed PROUD-PV including the end of study visit will be enrolled into this continuation study.
- Conditions
- Polycythemia Vera
- Being tested
- Pegylated-Proline-interferon alpha-2b, Best available therapy (BAT)
- Keywords
- Pegylated-Proline-interferon alpha-2b (AOP2014), Polycythemia Vera, PROUD-PV, CONTINUATION-PV, AOP Orphan, Polycythemia, Hematologic Diseases, Myeloproliferative Disorders, Bone Marrow Diseases, Interferon-alpha, Peginterferon alfa-2b
- Medical subject headings
- Polycythemia Vera, Polycythemia, Hematologic Diseases, Myeloproliferative Disorders, Bone Marrow Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pegylated-Proline-interferon alpha-2bDrug
Also called AOP2014
Subjects will continue to receive the dosage which delivers the optimal disease response (hematocrit [Hct]<45%, platelets [PLTs]<400 x 109/L and leukocytes [WBCs]<10 x 109/L), as determined in the PROUD-PV study, preferably at the level of target blood values.
Best available therapy (BAT)Drug
Also called best available therapy
Best available therapy as selected by the investigator
| Study group | Role | What they receive |
|---|---|---|
| Best available therapy (BAT) | Active comparator | Best available therapy, as chosen by the investigator for patients who had been on HU in the 1 Year PROUD-PV study Receives: Drug: Best available therapy (BAT) |
| Pegylated-Proline-interferon alpha-2b | Experimental | AOP2014 for those patients who had been on AOP2014 in the PROUD-PV study Receives: Drug: Pegylated-Proline-interferon alpha-2b |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease response at quarterly assessment visits
The primary efficacy endpoint will be the rate of disease response at assessment visits (every 3 months).
The co-primary efficacy evaluation criterion will be (1) disease response defined as hematologic response: Hct<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs<400 x 109/L, WBCs<10 x 109/L, and normal spleen size, and (2) disease response defined as hematologic response (Hct<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs<400 x 109/L, WBCs<10 x 109/L), resolution and/or clinically improvement of disease-related signs (clinical significant splenomegaly) and disease-related symptoms (microvascular disturbances, pruritus, headache).
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2014 (estimated)
- Study startNov 2014
- Primary completion29 Apr 2021
- Study completion29 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycythemia VeraStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- AOP Orphan Pharmaceuticals AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PharmaEssentia Corporation (for the U.S.)
- Responsible party
- Sponsor
- Investigators
- Heinz Gisslinger, MD, Principal investigator, Med Uni Wien
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02218047
- Sponsor's protocol ID
- CONTINUATION-PV
- Other IDs
- 2014-001357-17, 2014
- Acronym
- CONTI-PV
- Status last verified
- May 2021
- First submitted
- 14 Aug 2014
- Last updated
- 1 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multicenter, Phase IIIb Study Assessing the Long-term Efficacy and Safety of AOP2014 and Standard First Line Treatment (BAT) in Patients With Polycythemia Vera Who Previously Participated in the PROUD-PV Study
- ClinicalTrials.gov ID
- NCT02218047
- Acronym / sponsor ID
- CONTI-PV / CONTINUATION-PV
- Conditions
- Polycythemia Vera
- Keywords
- Pegylated-Proline-interferon alpha-2b (AOP2014), Polycythemia Vera, PROUD-PV, CONTINUATION-PV, AOP Orphan, Polycythemia, Hematologic Diseases, Myeloproliferative Disorders
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 170 participants (actual)
- Lead sponsor
- AOP Orphan Pharmaceuticals AGIndustry (pharma, biotech, devices)
- Collaborators
- PharmaEssentia Corporation (for the U.S.)
- Study start
- Nov 2014 (actual)
- Primary completion
- 29 Apr 2021 (actual)
- Study completion
- 29 Apr 2021 (actual)
- First posted
- 15 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Polycythemia Vera (PV) is a disease of bone marrow stem cells that manifests in a drastic increase of red blood cells and frequently also of white blood cells. The "thickening" of the blood in relation with a modified function of the cells has several consequences like increased blood pressure, pruritus of the skin, fatigue, disturbed blood circulation in the brain as well as fingers and toes and an increased risk of arterial and venous thrombosis (thrombosis is the formation of a blood clot in a vessel); like stroke, cardiac infarction, deep vein thrombosis in the legs. In case of a strong increase of platelets there is an additional risk of bleedings. As the disease progresses the size of spleen and liver increased in most cases and the bone marrow shows signs of fibrosis. In some cases of PV a progression at a later time point to a leukemia (increased formation of white blood cells) can occur.
The aim of this study is to show that the study drug AOP2014 (pegylated proline interferon alpha-2b) has the long term efficacy and safety in controlling the disease. A comparison arm is receiving best available therapy as selected by the investigator. Response to the treatment is measured by several blood parameters as well as size of the spleen.
Interferon-alpha has been shown to be effective in controlling the blood parameters by immunologically influencing the blood building cells. This can lead to a suppression of the disease-causing stem cells and help healthy stem cells to proliferate. Through this mechanism it is possible that Interferon-alpha can avoid long-term damaging effects of the disease.
Detailed description
This is a Phase III, parallel-arm, open-label continuation of the PROUD-PV study performed in adults diagnosed with Polycythemia Vera (PV). Patients who received AOP2014 in the primary study, PROUD-PV will continue on AOP2014, patients who received HU in the PROUD-PV study will receive best available therapy as selected by the investigator. Only patients who completed PROUD-PV including the end of study visit will be enrolled into this continuation study.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Best available therapy (BAT) | Active comparator | Drug: Best available therapy (BAT)Best available therapy, as chosen by the investigator for patients who had been on HU in the 1 Year PROUD-PV study |
| Pegylated-Proline-interferon alpha-2b | Experimental | Drug: Pegylated-Proline-interferon alpha-2bAOP2014 for those patients who had been on AOP2014 in the PROUD-PV study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients who completed the 12 months AOP2014 treatment arm of the PROUD-PV study and at the "end-of-treatment visit" (EoT) of the PROUD-PV study who fulfill at least one of the following criteria:
- Signed written ICF.
Key exclusion criteria (8 listed)
- Withdrawal criteria, as specified in the PROUD-PV study, which mandate treatment discontinuation:
- Non-recovery from the AOP2014 related toxicities to the grade (usually, Grade I) which allows continuation of the treatment.
- HADS score of 11 or higher on either or both of the subscales, and /or development or worsening of the clinically significant depression or suicidal thoughts.
- Progressive and clinically significant increase of liver enzyme levels despite dose reduction, or if such increase is accompanied by increased bilirubin level, any signs or symptoms of a clinically significant autoimmune disease.
- Clinically significant development of a new ophthalmologic disorder, or worsening of a pre-existing one, during the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pegylated-Proline-interferon alpha-2bAlso: AOP2014Subjects will continue to receive the dosage which delivers the optimal disease response (hematocrit [Hct]<45%, platelets [PLTs]<400 x 109/L and leukocytes [WBCs]<10 x 109/L), as determined in the PROUD-PV study, preferably at the level of target blood values. | Drug | Pegylated-Proline-interferon alpha-2b |
| Best available therapy (BAT)Also: best available therapyBest available therapy as selected by the investigator | Drug | Best available therapy (BAT) |
Primary outcome
Disease response at quarterly assessment visits
Time frame: 3 years
The primary efficacy endpoint will be the rate of disease response at assessment visits (every 3 months). The co-primary efficacy evaluation criterion will be (1) disease response defined as hematologic response: Hct<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs<400 x 109/L, WBCs<10 x 109/L, and normal spleen size, and (2) disease response defined as hematologic response (Hct<45% without phlebotomy (at least 3 months since the last phlebotomy), PLTs<400 x 109/L, WBCs<10 x 109/L), resolution and/or clinically improvement of disease-related signs (clinical significant splenomegaly) and disease-related symptoms (microvascular disturbances, pruritus, headache).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heinz Gisslinger, MD principal investigator
Med Uni Wien
47 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pegylated-Proline-interferon alpha-2b and Best available therapy (BAT) in people with Polycythemia Vera, run by AOP Orphan Pharmaceuticals AG at 47 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 47 sites in Austria, Hungary, Poland, Russia, Ukraine and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease response at quarterly assessment visits (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2021.