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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05936359




Registration number
NCT05936359
Ethics application status
Date submitted
21/06/2023
Date registered
7/07/2023

Titles & IDs
Public title
A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms
Scientific title
A Phase 1, Open-Label, Multicenter Study of INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms
Secondary ID [1] 0 0
2022-502514-86-00
Secondary ID [2] 0 0
INCA 33989-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myeloproliferative Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - INCA033989
Treatment: Drugs - Ruxolitinib

Experimental: Part 1a Dose Escalation Cohort Disease Group A - with MF - INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles as monotherapy to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with myelofibrosis (MF) will enroll in this group.

Experimental: Part 1a Dose Escalation Cohort Disease Group A - with ET - INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles as monotherapy to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with with essential thrombocythemia (ET) will enroll in this group.

Experimental: Part 1a: Dose Escalation Cohort Disease Group B - with TGB-MF SubOpt R - INCA033989 will be administered at a protocol defined starting regimen in 28- day cycles and will allow for the evaluation of INCA033989 in combination with ruxolitinib to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with myelofibrosis (MF) exhibiting suboptimal response (SubOpt R) will enroll in this group.

Experimental: Part 1b: Dose Expansion - with MF - INCA033989 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) myelofibrosis MF will enroll in this group.

Experimental: Part 1b: Dose Expansion - with TGB-MF SubOpt R - INCA033989 will be administered as an add-on therapy in combination with ruxolitinibat at the RDE(s) identified during Part 1a. Participants with treatment Group B (TGB) MF SubOpt R will enroll in this group.

Experimental: Part 1b: Dose Expansion - with ET - INCA033989 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) essential thrombocythemia (ET) will enroll in this group.

Experimental: Part 1c: Dose Expansion - INCA033989 will be administered at the dose level found to exhibit an overall positive benefit/risk as monotherapy or as combination therapy with Ruxolitinib. Participants with myelofibrosis (MF) will enroll in this group. The participants enrolled in the monotherapy arm will be offered the option to crossover to combination therapy with ruxolitinib if a suboptimal response to monotherapy is observed after 12 weeks.


Treatment: Drugs: INCA033989
INCA033989 will be administered at protocol defined dose.

Treatment: Drugs: Ruxolitinib
Rux will be administered according to Prescribing Information/SmPC.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Up to 28 days
Primary outcome [2] 0 0
Number of participants with Treatment-emergent Adverse Events (TEAEs)
Timepoint [2] 0 0
Up to 3 years and 60 days
Primary outcome [3] 0 0
Number of participants with TEAEs leading to dose modification or discontinuation
Timepoint [3] 0 0
Up to 3 years and 60 days
Secondary outcome [1] 0 0
Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF
Timepoint [1] 0 0
Up to 3 years and 60 days
Secondary outcome [2] 0 0
Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol
Timepoint [2] 0 0
Up to 3 years and 60 days
Secondary outcome [3] 0 0
Participants with MF with symptomatic anemia: Anemia Response
Timepoint [3] 0 0
Up to 3 years and 60 days
Secondary outcome [4] 0 0
Participants With ET: Response Rate
Timepoint [4] 0 0
Up to 3 years and 60 days
Secondary outcome [5] 0 0
Participants With ET: Mean change from baseline of total symptom score (TSS)
Timepoint [5] 0 0
Up to 3 years and 60 days
Secondary outcome [6] 0 0
Mean change in disease-related allele burden
Timepoint [6] 0 0
Up to 3 years and 60 days
Secondary outcome [7] 0 0
Pharmacokinetics Parameter: Cmax of INCA33989
Timepoint [7] 0 0
Up to 3 years and 60 days
Secondary outcome [8] 0 0
Pharmacokinetics Parameter: Tmax of INCA033989
Timepoint [8] 0 0
Up to 3 years and 60 days
Secondary outcome [9] 0 0
Pharmacokinetics Parameter: Cmin of INCA33989
Timepoint [9] 0 0
Up to 3 years and 60 days
Secondary outcome [10] 0 0
Pharmacokinetics Parameter: AUC(0-t) of INCA33989
Timepoint [10] 0 0
Up to 3 years and 60 days
Secondary outcome [11] 0 0
Pharmacokinetics Parameter: AUC 0-8 of INCA33989
Timepoint [11] 0 0
Up to 3 years and 60 days
Secondary outcome [12] 0 0
Pharmacokinetics Parameter: CL/F of INCA33989
Timepoint [12] 0 0
Up to 3 years and 60 days
Secondary outcome [13] 0 0
Pharmacokinetics Parameter: Vz/F of INCA33989
Timepoint [13] 0 0
Up to 3 years and 60 days
Secondary outcome [14] 0 0
Pharmacokinetics Parameter: t1/2 of INCA33989
Timepoint [14] 0 0
Up to 3 years and 60 days

Eligibility
Key inclusion criteria
* Life expectancy > 6 months.
* Willingness to undergo a pretreatment and regular on-study BM biopsies and aspirates (as appropriate to disease).
* Existing documentation from a qualified local laboratory of CALR exon-9 mutation.
* Participants with MF and ET as defined in the protocol.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Presence of any hematological malignancy other than ET, PMF, or post-ET MF.
* Active invasive malignancy over the previous 2 years.
* Active HBV/HCV, HIV.
* History of clinically significant or uncontrolled cardiac disease.
* Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned.
* Laboratory values outside the Protocol-defined ranges.
* Participants undergoing treatment with G-CSF, GM-CSF, or TPO-R agonists at any time within 4 weeks before the first dose of study treatment.
* Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment.
* Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating agent used to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
* For TGBs only: Undergoing treatment with a potent/strong inhibitor or inducer of CYP 3A4/5 within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment, or expected to receive such treatment during the study.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Royal Brisbane and Women'S Hospital - Herston
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
04029 - Herston
Recruitment postcode(s) [2] 0 0
05000 - Adelaide
Recruitment postcode(s) [3] 0 0
03000 - Melbourne
Recruitment postcode(s) [4] 0 0
03004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Ontario
Country [2] 0 0
Canada
State/province [2] 0 0
Quebec
Country [3] 0 0
Denmark
State/province [3] 0 0
Odense C
Country [4] 0 0
Denmark
State/province [4] 0 0
Roskilde
Country [5] 0 0
Denmark
State/province [5] 0 0
Vejle
Country [6] 0 0
France
State/province [6] 0 0
Bordeaux
Country [7] 0 0
France
State/province [7] 0 0
Nimes
Country [8] 0 0
France
State/province [8] 0 0
Paris
Country [9] 0 0
France
State/province [9] 0 0
Villejuif Cedex
Country [10] 0 0
Germany
State/province [10] 0 0
Aachen
Country [11] 0 0
Germany
State/province [11] 0 0
Halle
Country [12] 0 0
Germany
State/province [12] 0 0
ULM
Country [13] 0 0
Italy
State/province [13] 0 0
Bologna
Country [14] 0 0
Italy
State/province [14] 0 0
Firenze
Country [15] 0 0
Italy
State/province [15] 0 0
Milan
Country [16] 0 0
Japan
State/province [16] 0 0
Chiba
Country [17] 0 0
Japan
State/province [17] 0 0
Kagoshima
Country [18] 0 0
Japan
State/province [18] 0 0
Osaka
Country [19] 0 0
Japan
State/province [19] 0 0
Tokyo
Country [20] 0 0
Japan
State/province [20] 0 0
TSU
Country [21] 0 0
Spain
State/province [21] 0 0
Madrid
Country [22] 0 0
Spain
State/province [22] 0 0
Valencia
Country [23] 0 0
United Kingdom
State/province [23] 0 0
London
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Manchester
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Incyte Corporation
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Incyte Medical Monitor
Address 0 0
Incyte Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Incyte Corporation Call Center (US)
Address 0 0
Country 0 0
Phone 0 0
1.855.463.3463
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.