Clinical trial NCT04278924: A Study of TAK-079 in Adults With Persistent/Chronic Primary Immune Thrombocytopenia
Official title: A Phase 2, Randomized, Double-blind, Placebo-Controlled Study to Evaluate Safety, Tolerability, and Efficacy of TAK-079 in Patients With Persistent/Chronic Primary Immune Thrombocytopenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Immune Thrombocytopenia
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2020-02-20
Enrollment: 41
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: Primary immune thrombocytopenia (ITP) is a rare disease that results in low levels of platelets - the cells that help blood clot.

The main aim of the study is to check for side effects from taking TAK-079 at three different dose levels. Another aim is to learn if TAK-079 can increase the platelet count in people with ITP.

In addition to receiving stable background therapy for ITP, participants will receive an injection of either TAK-079 or a placebo once a week for 2 months. A placebo looks like TAK-079 but will not have any medicine in it. After treatment, all participants will be followed-up for another 2 months.

Then, participants who received TAK-079 will continue to be followed-up for an extra 4 months. Participants who received the placebo and would like to receive TAK-079 may be able to do this in an extension period in the study.

Detailed description: The drug being tested in this study is called TAK-079. TAK-079 is being tested to treat people who have primary immune thrombocytopenia (ITP). This study will evaluate the safety and biologic activity of TAK-079 or matching placebo in combination with stable ITP background therapy.

The study will enroll approximately 36 to 54 participants. In Part A of the study, participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups. Those who received placebo in this period will have the choice to receive TAK-079 after a safety follow-up period and will be randomized to one of the two open-label TAK-079 treatment arms. An unblinded safety review will take place once a minimum of 24 evaluable participants are available for analysis in Part A to decide whether to open enrollment into Part B.

In Part B participants will be randomly assigned to one of two treatment groups. Those who received placebo in this period will have the choice to receive study drug after a safety follow-up period in a single open-label TAK-079 treatment arm.

This multi-center trial will be conducted worldwide. All participants will be followed for at least 8 weeks in a Safety Follow-up Period, and a 16-week Long-term Follow-up Period after the 8 weeks of treatment.

Eligibility criteria: Inclusion Criteria:

1. Diagnosed with ITP that has persisted for ≥3 months, diagnosed in accordance to The American Society of Hematology 2011 Evidence-based Practice Guideline for Immune Thrombocytopenia or the International Consensus Report on The Investigation and Management of Primary Immune Thrombocytopenia as locally applicable.
2. Has a mean platelet count of \<30,000/μL (and individually ≤35,000/μL) on at least 2 measurements at least 1 week apart during screening.
3. Diagnosis of ITP supported by a prior response to an ITP therapy (other than a thrombopoietin receptor agonists \[TPO-RA\]) that achieved a platelet count of ≥50,000/μL.
4. If receiving standard background treatment for ITP, treatment should be stable in dose and frequency for at least 4 weeks before dosing.

   1. Permitted standard background treatments may include: 1 oral corticosteroid; ±1 immunosuppressant from the following list: azathioprine, danazol, dapsone, cyclosporine, mycophenolate mofetil, mycophenolate sodium; ±1 TPO-RA (romiplostim, eltrombopag, avatrombopag); ±fostamatinib. Corticosteroids, including dexamethasone, must be given as oral, daily or every-other-day therapy as opposed to pulse therapy.
   2. The dose of any permitted standard background therapy must be expected to remain stable through the study, unless dose reduction is required because of toxicities.

Exclusion Criteria:

1. Use of anticoagulants or any drug with antiplatelet effect (such as aspirin) within 3 weeks before screening.
2. Has a history of any thrombotic or embolic event within 12 months before screening.
3. Has a history of splenectomy within 3 months before screening.
4. Use of intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin or anti-D immunoglobulin treatment within 4 weeks of screening, or an expectation that any therapy besides the participant's standard background therapies may be used for treatment of thrombocytopenia (e.g., a rescue therapy) between screening and dosing.
5. Diagnosed with chronic obstructive pulmonary disease (COPD) or asthma, and a prebronchodilatory forced expiratory volume in 1 second (FEV1) \<50% of predicted normal.
6. Use of rituximab or any monoclonal antibody (mAb) for immunomodulation within 4 months before first dosing. Note: Participants with prior exposure to rituximab must have cluster of differentiation (CD) 19 counts within the normal range at screening.
7. Use of immunosuppressants (such as cyclophosphamide, vincristine) other than permitted oral immunosuppressants within 6 months before first dosing.
8. Has been diagnosed with myelodysplastic syndrome.
9. Has received a live vaccine within 4 weeks before screening or has any live vaccine planned during the study.

10 Has had an opportunistic infection ≤12 weeks before initial study dosing or is currently undergoing treatment for a chronic opportunistic infection, such as tuberculosis (TB), pneumocystis pneumonia, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria.

Primary outcomes:
measure: Percentage of Participants With at Least One Grade 3 or Higher Treatment Emergent Adverse Event (TEAE), Treatment Emergent Serious Adverse Event (SAE), and TEAEs Leading to TAK-079 Discontinuation
timeFrame: Up to Week 32 in each Period of the study
Secondary outcomes:
measure: Percentage of Participants With Platelet Response at Weeks 16 and 32
timeFrame: At Weeks 16 and 32
measure: Percentage of Participants With Complete Platelet Response at Weeks 16 and 32
timeFrame: At Weeks 16 and 32
measure: Percentage of Participants With Clinically Meaningful Platelet Response at Weeks 16 and 32
timeFrame: At Weeks 16 and 32
measure: Percentage of Participants With Hemostatic Platelet Response at Weeks 16 and 32
timeFrame: At Weeks 16 and 32
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Clinical Research Center - Hunt - PPDS
state: Arizona
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Peoria
country: United States
facility: Bleeding and Clotting Disorders Institute
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Greenville
country: United States
facility: Leo W. Jenkins Cancer Center
state: North Carolina
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda
state: Sofia-Grad
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Sofiamed OOD
state: Sofia-Grad
city: Pleven
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski EAD
city: Plovdiv
country: Bulgaria
facility: University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Sv Ivan Rilski EAD
city: Sofia
country: Bulgaria
facility: Military Medical Academy Multiprofile Hospital for Active Treatment - Sofia
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Tianjin
country: China
facility: Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
state: Tianjin
city: Osijek
country: Croatia
facility: Clinical Hospital Centre Osijek
city: Zagreb
country: Croatia
facility: Klinicki bolnicki centar Zagreb
city: Zagreb
country: Croatia
facility: University Hospital Merkur
city: Frankfurt am Main
country: Germany
facility: Universitatsklinikum Frankfurt
state: Hessen
city: Berlin
country: Germany
facility: Onkologische Schwerpunktpraxis Kurfurstendamm
city: Marburg
country: Germany
facility: OnkoNet Marburg GmbH
city: Munchen
country: Germany
facility: Rotkreuzklinikum Munchen
city: Patra
country: Greece
facility: University General Hospital of Patras
state: Achaia
city: Athens
country: Greece
facility: General Hospital of Athens - George Gennimatas
state: Attiki
city: Thessaloniki
country: Greece
facility: Georgios Papanikolaou General Hospital of Thessaloniki
city: Trieste
country: Italy
facility: Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI)
state: Friuli-Venezia Giulia
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
state: Lombardia
city: Catania
country: Italy
facility: Azienda Ospedaliera Di Rilievo Nazionale E Di Alta Specializzazione Garibaldi
state: Sicilia
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Novara
country: Italy
facility: A.O.U. Maggiore della Carita
city: Roma
country: Italy
facility: Azienda Policlinico Umberto I
city: Itabashi
country: Japan
facility: Nihon University Itabashi Hospital
state: Tokyo
city: Minato-Ku
country: Japan
facility: Saiseikai Central Hospital
state: Tokyo
city: Ljubljana
country: Slovenia
facility: Univerzitetni klinicni Center Ljubljana
city: Maribor
country: Slovenia
facility: University Clinical Centre Maribor
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
state: Barcelona
city: Meco
country: Spain
facility: Hospital Universitario Principe de Asturias
state: Madrid
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Burgos
country: Spain
facility: C.A.U de Burgos - Hospital Universitario de Burgos
city: Madrid
country: Spain
facility: Hospital Universitario Quironsalud Madrid
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Malaga
country: Spain
facility: Hospital Universitario Virgen del Rocio - PPDS
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Mykolaiv
country: Ukraine
facility: Municipal Non-profit Enterprise Mykolayiv Regional Clinical Hospital the Mykolayiv Regional Council
state: Mykolaivs'ka Oblast
city: Ternopil
country: Ukraine
facility: Municipal Non-profit Enterprise Ternopil Regional Clinical Hospital of Ternopil Regional Council
state: Ternopil's'ka Oblast
city: Zhytomyr
country: Ukraine
facility: MNE Regional Clinical Hospital n a O F Herbachevskyi of Zhytomyr Regional Council
state: Zhytomyrs'ka Oblast
city: Dnipro
country: Ukraine
facility: Municipal Non-profit Enterprise "City Clinical Hospital # 4" of Dnipro City Council - PPDS
city: Kyiv
country: Ukraine
facility: Medical Center OK!Clinic+LLC International Institute of Clinical Research
city: Kyiv
country: Ukraine
facility: CNE Kyiv City Clinical Hospital #9 of Exec. Body of Kyiv City Council Kyiv City State Admin
city: Lviv
country: Ukraine
facility: State Institution Institute of Blood Pathology and Transfusion Medicine of NAMS of Ukraine
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: