2-((4S)-6-(4-CHLOROPHENYL)-1-METHYL-4H-BENZO[C]ISOXAZOLO[4,5-E]AZEPIN-4-YL)ACETAMIDE MONOHYDRATE for Myelofibrosis|Myeloproliferative neoplasms|Essential thrombocythemia

Inclusion criteria

• {"criterion_text":"- Eligibility for Ongoing Pelabresib Treatment (criteria 1-6 ) 1. Capable of giving signed informed consent as described in Section 12.2.2, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol"}
• {"criterion_text":"- Eligibility for Survival Follow-up (4): Willingness and ability to comply with ongoing follow-up as indicated in this protocol"}
• {"criterion_text":"- Participant must be at least 18 years of age and the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the informed consent"}
• {"criterion_text":"- Was previously enrolled and is still receiving treatment with pelabresib in a parent clinical study"}
• {"criterion_text":"- Is receiving clinical benefit from treatment with pelabresib in the parent study, as assessed by the investigator"}
• {"criterion_text":"- Willingness and ability to comply with scheduled visits, treatment plans, and any other study procedures indicated in this protocol"}
• {"criterion_text":"- Agrees to avoid pregnancy or fathering children based on the criteria below: a. Male participants and their female partners of childbearing potential must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from the time of the eligibility check through 94 days after the last dose of pelabresib. Additionally, male participants must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy (Section 7.13.) should be communicated to the participants and their understanding confirmed. b. WOCBP must have a negative serum pregnancy test at the time of the eligibility check and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from the time of the eligibility check until the end of relevant systemic exposure (ie, through 184 days after the last dose of pelabresib). They must also agree to regular urine pregnancy testing through the study treatment period and monthly pregnancy testing up to 184 days after the last dose of pelabresib. They must also refrain from breastfeeding and donating oocytes during the course of study and for 184 days after the last dose of pelabresib. Permitted methods that are at least 99% effective in preventing pregnancy (Section 7.13) should be communicated to the participants and their understanding confirmed. c. Women without childbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR postmenopausal with ≥12 months of amenorrhea without an alternative medical cause) are eligible. NOTE: Female participants who have been amenorrheic for at least 12 months resulting from chemo/radiotherapy are considered of childbearing potential and should agree to use adequate contraceptive measures (Section 7.13)."}
• {"criterion_text":"- Eligibility for Survival Follow-up (1): Capable of giving signed informed consent as described in Section 12.2.2, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol"}
• {"criterion_text":"- Eligibility for Survival Follow-up (2) : Participant must be at least 18 years of age and the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the ICF"}
• {"criterion_text":"- Eligibility for Survival Follow-up (3): Participant was previously enrolled in a clinical study with pelabresib"}

Exclusion criteria

• {"criterion_text":"- Eligibility for Ongoing Pelabresib Treatment (criteria 1-14 ): 1. Participants who are legally institutionalized or under judicial protection"}
• {"criterion_text":"- Had systemic anticancer treatment or treatment with investigational agents, with the exception of the study drug in the parent study or hormonal therapy, less than 2 weeks (or 5 half-lives, whichever is longer) before the first dose of study drug (Section 7.10). NOTE: Hydroxyurea and anagrelide are permitted up to 24 hours prior to start of study drug."}
• {"criterion_text":"- Had hematopoietic growth factor (granulocyte growth factor, erythropoiesis stimulating agent, thrombopoietin mimetic) or androgenic steroids less than 4 weeks before the first dose of study drug (Section 7.10)"}
• {"criterion_text":"- Had a strong CYP3A4 inhibitor or inducer within 2 weeks prior to the first dose of study drug, including St. John’s wort (Section 7.10). Initiation of treatment or concomitant use of a strong CYP3A4 inhibitor or inducer during study treatment is prohibited."}
• {"criterion_text":"- Had immunosuppressive agents with systemic activity (>10 mg QD prednisone or equivalent) less than 4 weeks before the first dose of study drug. Participants who received topical, nasal, intra-articular, inhaled, and other forms of corticosteroids without systemic activity are eligible (Section 7.10 )."}
• {"criterion_text":"- Had a live vaccination within 30 days prior to the first dose of study drug, except for COVID-19 vaccination (Section 7.10)"}
• {"criterion_text":"- Participants who are unwilling or unable to comply with this study protocol or study requirements"}
• {"criterion_text":"- Concurrent enrollment in another interventional clinical trial (other than the parent study)"}
• {"criterion_text":"- History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical class"}
• {"criterion_text":"- Any other medical condition that, in the investigator’s opinion, makes the participant unsuitable for the study"}
• {"criterion_text":"- participant with an uncontrolled intercurrent illness or any concurrent condition that, in the investigator’s opinion, would jeopardize the safety of the participant or compliance with the protocol"}
• {"criterion_text":"- Female participants who are pregnant or breastfeeding or not on adequate contraceptive therapy specified in inclusion criteria"}
• {"criterion_text":"- A male participants who does not agree to use contraception as specified in the inclusion criteria during the treatment period and for at least 94 days after the last dose of pelabresib (if they have a heterosexual partner who is a WOCBP) and who does not refrain from donating sperm during this period"}
• {"criterion_text":"- Eligibility for Survival Follow-up : 1. participants who are legally institutionalized or under judicial protection"}
• {"criterion_text":"- Participants with impaired gastrointestinal function or gastrointestinal disease, including active IBD, that could significantly alter the absorption of study drug, including any unresolved nausea, vomiting, or diarrhea > Grade 1"}

Primary endpoints

• {"endpoint_text":"- Occurrence and severity of treatment-emergent adverse events (TEAEs) and serious TEAEs among patients who are receiving pelabresib","definition_or_measurement_approach":"Occurrence and severity of TEAEs and serious TEAEs among patients who are receiving pelabresib (as stated in endpoint text). No further measurement details provided in available source."}
• {"endpoint_text":"- Survival and leukemia-free survival","definition_or_measurement_approach":"Survival and leukemia-free survival (no further measurement definitions provided in available source)"}
• {"endpoint_text":"- Time-to-event endpoints (eg, duration of response, progression-free survival)","definition_or_measurement_approach":"Time-to-event endpoints including duration of response and progression-free survival (as examples provided); no additional measurement specifications available in source."}

Belgium

Earliest CTIS Part Ii Submission Date

15-08-2024

Latest Decision Or Authorization Date

29-10-2025

Processing Time Days

440

Number Of Sites

2

Number Of Participants

7

Netherlands

Earliest CTIS Part Ii Submission Date

15-08-2024

Latest Decision Or Authorization Date

10-11-2025

Processing Time Days

452

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

20-08-2024

Latest Decision Or Authorization Date

07-11-2025

Processing Time Days

444

Number Of Sites

3

Number Of Participants

26

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Harmony Clinical Research

Responsibilities

codes: 1,12,15 (Site contract negotiations),2

Name

Novotech (Australia) Pty Limited

Responsibilities

codes: 1,12,2,5

Name

Parexel International (IRL) Limited

Responsibilities

codes: 12,8

Name

Metronomia Clinical Research GmbH

Responsibilities

codes: 6

Name

PPD Development L.P.

Responsibilities

codes: 8

Name

Evidenze Health S.r.l.

Responsibilities

codes: 1,12,15 (Site contract negotiations),2

Name

Suvoda LLC

Responsibilities

codes: 3

Third parties

• {"country":"Belgium","full_name":"Harmony Clinical Research","duties_or_roles":"codes: 1,12,15 (Site contract negotiations),2","organisation_type":"Pharmaceutical company"}
• {"country":"Australia","full_name":"Novotech (Australia) Pty Limited","duties_or_roles":"codes: 1,12,2,5","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"codes: 12,8","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Metronomia Clinical Research GmbH","duties_or_roles":"codes: 6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development L.P.","duties_or_roles":"codes: 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"codes: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Italy","full_name":"Evidenze Health S.r.l.","duties_or_roles":"codes: 1,12,15 (Site contract negotiations),2","organisation_type":"Pharmaceutical company"}