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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04655118




Registration number
NCT04655118
Ethics application status
Date submitted
24/11/2020
Date registered
7/12/2020
Date last updated
10/05/2024

Titles & IDs
Public title
Study of TL-895 in Subjects With Myelofibrosis or Indolent Systemic Mastocytosis
Scientific title
A Phase 2 Multicenter Study of TL-895 in Subjects With Relapsed/Refractory Myelofibrosis, Janus Kinase Inhibitor Intolerant Myelofibrosis, Janus Kinase Inhibitor Treatment Ineligible Myelofibrosis, or Indolent Systemic Mastocytosis
Secondary ID [1] 0 0
TL-895-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis 0 0
Indolent Systemic Mastocytosis 0 0
Condition category
Condition code
Skin 0 0 0 0
Other skin conditions
Blood 0 0 0 0
Other blood disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TL-895
Treatment: Drugs - Placebo

Experimental: Cohort 1a, Relapsed/Refractory Myelofibrosis - 150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.

Experimental: Cohort 1b, Relapsed/Refractory Myelofibrosis - 300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.

Experimental: Cohort 1c, Relapsed/Refractory Myelofibrosis - 300 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.

Experimental: Cohort 1d, Relapsed/Refractory Myelofibrosis - 450 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.

Experimental: Cohort 2a, JAKi Intolerant Myelofibrosis - 150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.

Experimental: Cohort 2b, JAKi Intolerant Myelofibrosis - 300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.

Experimental: Cohort 3a, JAKi Ineligible Myelofibrosis with platelet count of = 25 and < 50 × 109/L - 150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.

Experimental: Cohort 3b, JAKi Ineligible Myelofibrosis with platelet count of = 25 and < 50 × 109/L - 300 mg of TL-895 will be administered orally, once daily (QD) continuously starting on Day 1 in a 28-day cycle.

Experimental: Cohort 5a, Indolent Systemic Mastocytosis - TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with best supportive care (BSC).

Experimental: Cohort 5b, Indolent Systemic Mastocytosis - TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.

Experimental: Cohort 5c, Indolent Systemic Mastocytosis - TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.

Experimental: Cohort 5d, Indolent Systemic Mastocytosis - TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.

Placebo comparator: Cohort 5e, Indolent Systemic Mastocytosis - Placebo to match TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle in combination with BSC.


Treatment: Drugs: TL-895
TL-895 is an experimental tyrosine kinase inhibitor drug taken by mouth.

Treatment: Drugs: Placebo
Placebo to match TL-895
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohorts 1-3: Determine the RP2D of TL-895
Timepoint [1] 0 0
9 months
Primary outcome [2] 0 0
Cohort 5: Determine the RP2D of TL-895
Timepoint [2] 0 0
Week 24
Secondary outcome [1] 0 0
Cohorts 1-3: Spleen volume reduction (SVR) rate
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Cohort 5: Changes in patient reported symptoms
Timepoint [2] 0 0
Week 12

Eligibility
Key inclusion criteria
Cohorts 1-3

Key

* Adults =18 years of age
* Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO) criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of =2
* Adequate hematologic, hepatic, and renal functions
* MF symptoms as defined by having at least 2 symptoms with an average baseline (Day -7 to Day -1) score of at least 1 for each of the 2 symptoms per MFSAF v4.0
* Cohort 3 only: Ineligibility for JAKi treatment with a platelet count of = 25 and < 50 x 10^9/L

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with any BTK or BMX inhibitors
* Prior treatment with JAKi within 28 days prior to study treatment
* Prior splenectomy or splenic irradiation within 24 weeks prior to first dose of study treatment

Cohort 5

Key Inclusion Criteria:

* Adults =18 years of age
* Confirmed diagnosis of ISM as defined by WHO diagnostic criteria based on review of bone marrow biopsy pathology report results
* Subject must have moderate-to-severe symptoms

Key

* Prior treatment with any BTK or BMX inhibitors
* Prior treatment with Avapritinib, bezuclastinib, or BLU-263/elenestinib
* Diagnosis with another myeloproliferative disorder

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
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
22/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
121
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Border Medical Oncology - East Albury
Recruitment hospital [2] 0 0
Southern Oncology Specialists - Kogarah
Recruitment hospital [3] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [4] 0 0
St Vincent's Hospital Sydney - Sydney
Recruitment postcode(s) [1] 0 0
- East Albury
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment postcode(s) [4] 0 0
2010 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Minnesota
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Belgium
State/province [5] 0 0
Liège
Country [6] 0 0
Belgium
State/province [6] 0 0
Woluwe-Saint-Lambert
Country [7] 0 0
Brazil
State/province [7] 0 0
São Paulo
Country [8] 0 0
Bulgaria
State/province [8] 0 0
Sofia
Country [9] 0 0
France
State/province [9] 0 0
Le Mans
Country [10] 0 0
France
State/province [10] 0 0
Nantes
Country [11] 0 0
France
State/province [11] 0 0
Nice
Country [12] 0 0
Germany
State/province [12] 0 0
Dresden
Country [13] 0 0
Germany
State/province [13] 0 0
Düsseldorf
Country [14] 0 0
Germany
State/province [14] 0 0
Halle
Country [15] 0 0
Germany
State/province [15] 0 0
Jena
Country [16] 0 0
Germany
State/province [16] 0 0
Koblenz
Country [17] 0 0
Hungary
State/province [17] 0 0
Debrecen
Country [18] 0 0
Hungary
State/province [18] 0 0
Eger
Country [19] 0 0
Hungary
State/province [19] 0 0
Nyíregyháza
Country [20] 0 0
Hungary
State/province [20] 0 0
Székesfehérvár
Country [21] 0 0
Italy
State/province [21] 0 0
Catania
Country [22] 0 0
Italy
State/province [22] 0 0
Meldola
Country [23] 0 0
Italy
State/province [23] 0 0
Milano
Country [24] 0 0
Italy
State/province [24] 0 0
Novara
Country [25] 0 0
Italy
State/province [25] 0 0
Perugia
Country [26] 0 0
Italy
State/province [26] 0 0
Ravenna
Country [27] 0 0
Italy
State/province [27] 0 0
Reggio Calabria
Country [28] 0 0
Italy
State/province [28] 0 0
Roma
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Daegu
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Seoul
Country [31] 0 0
Poland
State/province [31] 0 0
Bydgoszcz
Country [32] 0 0
Poland
State/province [32] 0 0
Gdansk
Country [33] 0 0
Poland
State/province [33] 0 0
Kraków
Country [34] 0 0
Poland
State/province [34] 0 0
Wroclaw
Country [35] 0 0
Spain
State/province [35] 0 0
Barcelona
Country [36] 0 0
Spain
State/province [36] 0 0
Madrid
Country [37] 0 0
Spain
State/province [37] 0 0
Salamanca
Country [38] 0 0
Spain
State/province [38] 0 0
Zaragoza
Country [39] 0 0
Taiwan
State/province [39] 0 0
Kaohsiung City
Country [40] 0 0
Taiwan
State/province [40] 0 0
Kaohsiung
Country [41] 0 0
Taiwan
State/province [41] 0 0
Taichung
Country [42] 0 0
Taiwan
State/province [42] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Telios Pharma, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study evaluates TL-895, a potent, orally-available and highly selective irreversible tyrosine kinase inhibitor for the treatment of Myelofibrosis (Cohorts 1-3) or Indolent Systemic Mastocytosis (Cohort 5). Participants must be diagnosed with Myelofibrosis and be relapsed/refractory (e.g., having failed prior therapy), intolerant, or ineligible to receive JAKi treatment, or be diagnosed with Indolent Systemic Mastocytosis.
Trial website
https://clinicaltrials.gov/study/NCT04655118
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
John Mei
Address 0 0
Country 0 0
Phone 0 0
650-542-0136
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04655118