HU-F-AIM - A prospective, interventional clinical study to evaluate hydroxyurea (HU) resistance in patients with polycythaemia vera who meet prediction parameters identified in the PV-AIM project using artificial intelligence

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Jul 2023 → 26 Feb 2026

Decision date (initial)

2023-05-17

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Evaluation of HU-resistance/intolerance in PV patients who meet the predictive risk factors identified in the machine learning project PV-AIM (referred to as: PV-AIM HU-resistance predictors) at start of their regular HU-treatment.

Secondary objectives 3

1. Evaluation of patients who are eligible for de novo HU therapy and simultaneously meet the PV-AIM HU-resistance predictors before start of HU treatment.
2. Evaluate the development of HU resistance/intolerance at any time within the study period, including correlation with the PV-AIM HU-resistance predictors.
3. To describe the therapies given after confirmation of HU-resistance/intolerance including the rationale for continuing treatment with HU or switching.

Conditions and MedDRA coding

Polycythemia vera

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Signed informed consent must be obtained prior to participation in the study
2. Patients ≥ 18 years
3. Confirmed diagnosis of Polycythemia vera (according to WHO 2008, 2016, or 2022 criteria)
4. Eastern Cooperative Oncology Group (ECOG) ≤ 2
5. No previous pharmacologic cytoreductive therapy (including investigational drugs)
6. No phlebotomy in last 14 days
7. HU-eligible • High-risk: age ≥ 60 years and/or prior history of thrombosis • Low-risk: showing at least one of the defined criteria o Signs of disease progression (myeloproliferation) o Increasing risk of thromboembolism and bleeding
8. Female participants of childbearing potential should have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study treatment.

Exclusion criteria 9

1. Patients with post- polycythemia vera myelofibrosis (post-PV MF) or accelerated phase/ blast phase myeloproliferative neoplasm acute myeloid leukemia (AP/BP-MPN AML)
2. Patients with a contraindication to HU according to the SmPC (severe bone marrow depression, leukopenia (< 2.5 x 10^9 leukocytes/l), thrombocytopenia (< 100 x 10^9 platelets/L), severe anemia (< 10 g/dL HGB)
3. Patients with rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption in their past medical history
4. Active uncontrolled infection that is considered by the Investigator as a reason for exclusion
5. Active malignancies (except for carcinoma in situ; prostate cancer and breast cancer in remission and – where necessary - ongoing hormonal therapy)
6. Inadequate renal function as demonstrated by Modification of Diet in Renal Disease estimate glomerular filtration rate (MDRDeGFR) < 30 mL/min/1.73m2 or on dialysis
7. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotrophin (hCG) laboratory test.
8. Sexually active males unwilling to use a condom during intercourse while taking study treatment and for at least 3 months after stopping study treatment.
9. HIV patients treated with nucleoside reverse transcriptase inhibitors like didanosine and stavudine

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of PV patients with HU-resistance/intolerance within 6-9 months after start of de novo HU- treatment in presence of the PV-AIM HU-resistance predictors at the start of HU treatment.

Secondary endpoints 4

1. Proportion of PV patients who meet the PV-AIM HU-resistance predictors before start of HU-treatment
2. Proportion of patients developing HU resistance/intolerance at any time within the maximum treatment period of 15 months
3. Proportion of patients developing HU resistance/intolerance at any time within the maximum treatment period of 15 months in presence or absence of the PV-AIM HU-resistance predictors at start of HU treatment.
4. For all patients who develop HU resistance/intolerance according to (European LeukemiaNet) ELN criteria at any time during the maximum treatment period of 15 months • Proportion of “non-switchers” (i.e., patients remaining on HU despite they meet the HU-resistance/intolerance criteria) compared to “switchers” • Timepoint of therapy switch (after confirmation of HU resistance/intolerance) • Reasons for therapy switch / non-switch • Therapies applied during follow-up period

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma GmbH

Sponsor organisation

Novartis Pharma GmbH

Address

Sophie-Germain-Strasse 10, Gostenhof Gostenhof

City

Nuremberg

Postcode

90443

Country

Germany

Scientific contact point

Organisation

Novartis Pharma GmbH

Contact name

Medizinischer InfoService (MCC)

Public contact point

Organisation

Novartis Pharma GmbH

Contact name

Medizinischer InfoService (MCC)

Third parties 2

Sponsor responsibilities

Article 77 implementation

Novartis Pharma GmbH

Locations

1 EU/EEA country · 33 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications