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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04454658




Registration number
NCT04454658
Ethics application status
Date submitted
30/06/2020
Date registered
1/07/2020
Date last updated
18/06/2024

Titles & IDs
Public title
Safety and Tolerability Study of Oral ABBV-744 Tablet Alone or in Combination With Oral Ruxolitinib Tablet or Oral Navitoclax Tablet in Adult Participants With Myelofibrosis
Scientific title
A Phase 1b Study Of ABBV-744 Alone Or In Combination With Ruxolitinib Or Navitoclax In Subjects With Myelofibrosis
Secondary ID [1] 0 0
2020-001225-32
Secondary ID [2] 0 0
M20-247
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis (MF) 0 0
Condition category
Condition code
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 - ABBV-744
Treatment: Drugs - Navitoclax
Treatment: Drugs - Ruxolitinib

Experimental: Segment A: ABBV-744 Dose Identification and Optimization - Participants who have been previously treated with Janus Kinase inhibitor(s) (JAKi) and stopped such therapy, will receive different dosing regimens and schedules of ABBV-744 to identify the safe dosing regimen and schedule.

Experimental: Segment A: ABBV-744 Monotherapy - Participants will receive the identified safe dosing regimen of ABBV-744 as monotherapy.

Experimental: Segment B: Ruxolitinib + ABBV-744 "Add on" Therapy - Participants whose disease (myelofibrosis) is inadequately controlled by ongoing ruxolitinib therapy will receive ruxolitinib and ABBV-744 as "add-on" therapy.

Experimental: Segment C: ABBV-744 + Navitoclax - Participants who have previously been exposed to JAKi, and stopped such therapy, will receive ABBV-744 and navitoclax.

Experimental: Segment D: ABBV-744 + Ruxolitinib - Participants who have never received JAKi will receive ABBV-744 and ruxolitinib.


Treatment: Drugs: ABBV-744
Tablet; Oral

Treatment: Drugs: Navitoclax
Tablet; Oral

Treatment: Drugs: Ruxolitinib
Tablet; Oral
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Adverse Events
Timepoint [1] 0 0
Up to Approximately 1 year from start of study
Secondary outcome [1] 0 0
Percentage Of Participants Who Achieve Spleen Volume Reduction Of 35% Or Greater (SVR35)
Timepoint [1] 0 0
Up To Week 24
Secondary outcome [2] 0 0
Maximum Observed Plasma Concentration (Cmax) of ABBV-744
Timepoint [2] 0 0
Up To Week 12
Secondary outcome [3] 0 0
Time To Cmax (Tmax) Of ABBV-744
Timepoint [3] 0 0
Up To Week 12
Secondary outcome [4] 0 0
Area Under The Concentration Versus Time Curve (AUC) Of ABBV-744
Timepoint [4] 0 0
Up To Week 12
Secondary outcome [5] 0 0
Half-Life (t1/2) Of ABBV-744
Timepoint [5] 0 0
Up To Week 12
Secondary outcome [6] 0 0
Accumulation Ratio Of ABBV-744
Timepoint [6] 0 0
Up To Week 12
Secondary outcome [7] 0 0
Apparent Clearance (CL/F) Of ABBV-744
Timepoint [7] 0 0
Up To Week 12
Secondary outcome [8] 0 0
Apparent Volume Of Distribution (Vd/F) Of ABBV-744
Timepoint [8] 0 0
Up To Week 12
Secondary outcome [9] 0 0
Percentage Of Participants With >= 50% Reduction In Total Symptom Score (TSS)
Timepoint [9] 0 0
Up to Week 24
Secondary outcome [10] 0 0
Objective Response Rate (ORR)
Timepoint [10] 0 0
Week 24
Secondary outcome [11] 0 0
Maximum Observed Plasma Concentration (Cmax) Of Navitoclax
Timepoint [11] 0 0
Up To Week 12
Secondary outcome [12] 0 0
Time To Cmax (Tmax) Of Navitoclax
Timepoint [12] 0 0
Up To Week 12
Secondary outcome [13] 0 0
Area Under The Concentration Versus Time Curve (AUC) Of Navitoclax
Timepoint [13] 0 0
Up To Week 12
Secondary outcome [14] 0 0
Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib
Timepoint [14] 0 0
Up To Week 12
Secondary outcome [15] 0 0
Time To Cmax (Tmax) Of Ruxolitinib
Timepoint [15] 0 0
Up To Week 12
Secondary outcome [16] 0 0
Area Under The Concentration Versus Time Curve (AUC) Of Ruxolitinib
Timepoint [16] 0 0
Up To Week 12

Eligibility
Key inclusion criteria
* Laboratory values indicative of adequate bone marrow, renal, and hepatic function meeting protocol criteria.
* Completion of the Myelofibrosis System Assessment Form (MFSAF) on at least 4 out of the 7 days prior to Day 1 with at least 2 symptoms with a score >=3 or a total score of >=10.
* Documented diagnosis of intermediate or high-risk primary myelofibrosis (PMF), post-polycythemia vera MF (PPV-MF) or post-essential thrombocytopenia MF (PET-MF) as defined by the World Health Organization (WHO).
* Eastern Cooperative Oncology Group (ECOG) Performance Status of <= 2.
* Intermediate - 2, or High-Risk disease as defined by the Dynamic International Prognostic Scoring System (For Segment A only, Intermediate - 1 with palpable splenomegaly >=5 centimeters [cm] below costal margin are also eligible).
* Splenomegaly defined as spleen palpation measurement >= 5 cm below costal margin or spleen volume >= 450 cubic cms as assessed by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan (for Segments A and C, baseline spleen assessment must be obtained > 7 days after discontinuation of most recent Myelofibrosis (MF) therapy. If possible, this assessment should occur within 10 days of Cycle 1 Day 1).

Segment-Specific Prior Therapy Criteria:

* Segment A:

* Prior exposure to one or more Janus Kinase inhibitors (JAKi),[the most recent of which was discontinued > 14 days prior to Cycle 1 Day 1] and are intolerant, resistant, refractory or lost response to the JAKi.
* Segment B:

* Currently receiving ruxolitinib AND
* Willingness to reduce ruxolitinib dose (if on a higher dose); and on a stable dose for 14 days or longer prior to Cycle 1 Day 1; AND
* At least one of the following criteria (a, b, or c):

1. >= 24 weeks duration of current ruxolitinib course, with evidence of disease that is resistant, refractory, or has lost response to ruxolitinib therapy;
2. < 24 weeks duration of current ruxolitinib course with documented resistance, refractories, or loss of response, as defined by any of the following:

* Appearance of new splenomegaly that is palpable to at least 5 cm below the left costal margin (LCM), in participants with no evidence of splenomegaly prior to the initiation of ruxolitinib.
* >=100% increase in the palpable distance below the LCM, in participants with measurable spleen distance 5 - 10 cm prior to the initiation of ruxolitinib.
* >=50% increase in the palpable distance below the LCM, in participants with measurable spleen > 10 cm prior to the initiation of ruxolitinib.
* A spleen volume increase >= 25% (as assessed by MRI or CT) in participants with a spleen volume assessment available prior to the initiation of ruxolitinib.
3. Prior treatment with ruxolitinib for >= 28 days complicated by any of the following:

* Development of red blood cell transfusion requirement (at least 2 units/month for 2 months).
* Grade >= 3 adverse events of neutropenia and/or anemia while on ruxolitinib treatment, with improvement or resolution upon dose reduction.
* Segment C:

* Prior exposure to one or more JAKi (the most recent of which was discontinued > 14 days prior to Cycle 1 Day 1), and are intolerant, resistant, refractory or lost response to the JAKi.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Segment-Specific Prior Therapy Criteria:

* Segment A:

* Prior exposure to one or more Bromodomain and Extra-Terminal (BET) inhibitors.
* Segment B:

* Prior exposure to one or more BET inhibitors.
* Segment C:

* Prior exposure to one or more BET inhibitors and/or any B-Cell Lymphoma 2 (BCL)-2 and/or BCL- XL inhibitor, including navitoclax.
* Segment D:

* Prior exposure to JAKi and/or any BET inhibitor.

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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
2/11/2024
Actual
Sample size
Target
Accrual to date
Final
21
Recruitment in Australia
Recruitment state(s)
QLD,TAS,WA
Recruitment hospital [1] 0 0
Townsville University Hospital /ID# 225859 - Douglas
Recruitment hospital [2] 0 0
Royal Hobart Hospital /ID# 241677 - Hobart
Recruitment hospital [3] 0 0
Royal Perth Hospital /ID# 241678 - Perth
Recruitment postcode(s) [1] 0 0
4814 - Douglas
Recruitment postcode(s) [2] 0 0
7000 - Hobart
Recruitment postcode(s) [3] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
New Hampshire
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Oklahoma
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Argentina
State/province [9] 0 0
Buenos Aires
Country [10] 0 0
Argentina
State/province [10] 0 0
Ciudad Autonoma De Buenos Aires
Country [11] 0 0
Brazil
State/province [11] 0 0
Goias
Country [12] 0 0
Brazil
State/province [12] 0 0
Rio Grande Do Sul
Country [13] 0 0
Brazil
State/province [13] 0 0
Sao Paulo
Country [14] 0 0
Brazil
State/province [14] 0 0
Rio de Janeiro
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Sofia
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Varna
Country [17] 0 0
Chile
State/province [17] 0 0
Region Metropolitana De Santiago
Country [18] 0 0
Chile
State/province [18] 0 0
Temuco
Country [19] 0 0
Hungary
State/province [19] 0 0
Heves
Country [20] 0 0
Hungary
State/province [20] 0 0
Budapest
Country [21] 0 0
Israel
State/province [21] 0 0
Tel-Aviv
Country [22] 0 0
Israel
State/province [22] 0 0
Yerushalayim
Country [23] 0 0
Italy
State/province [23] 0 0
Milan
Country [24] 0 0
Japan
State/province [24] 0 0
Fukuoka
Country [25] 0 0
Japan
State/province [25] 0 0
Hokkaido
Country [26] 0 0
Japan
State/province [26] 0 0
Osaka
Country [27] 0 0
Japan
State/province [27] 0 0
Yamanashi
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Busan Gwang Yeogsi
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Sweden
State/province [31] 0 0
Orebro Lan
Country [32] 0 0
Sweden
State/province [32] 0 0
Uppsala Lan
Country [33] 0 0
Turkey
State/province [33] 0 0
Ankara
Country [34] 0 0
Turkey
State/province [34] 0 0
Istanbul

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

Ethics approval
Ethics application status

Summary
Brief summary
Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body. MF disturbs the body's normal production of blood cells, causing extensive scarring in the bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. The purpose of this study is to see how safe and tolerable ABBV-744 is, when given alone, and in combination with ruxolitinib or navitoclax, for adult participants with MF.

ABBV-744 is an investigational drug being developed for the treatment of MF. The study has 4 segments - A, B, C, and D. In Segment A, the safe dosing regimen of ABBV-744 is identified and then, given alone as monotherapy. In Segment B, C, and D, combination therapies of ABBV-744 with either ruxolitinib or navitoclax are given. Adult participants with a diagnosis of MF will be enrolled. Around 130 participants will be enrolled in 60 sites worldwide.

In Segment A, participants will receive different doses and schedules of oral ABBV-744 tablet to identify safe dosing regimen. Additional participants will be enrolled at the identified monotherapy dosign regimen. In Segment B, participants will receive oral ruxolitinib and ABBV-744 will be given as "add-on" therapy. In Segment C, participants will receive ABBV-744 and oral navitoclax. In Segment D, participants will receive ABBV-744 and ruxolitinib. Participants will receive treatment until disease progression or the participants are not able to tolerate the study drugs.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow tests, checking for side effects, and completing questionnaires.
Trial website
https://clinicaltrials.gov/study/NCT04454658
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04454658