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
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|ClinicalTrials.gov Identifier: NCT04454658|
Recruitment Status : Recruiting
First Posted : July 1, 2020
Last Update Posted : September 11, 2020
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 dosing 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.
|Condition or disease||Intervention/treatment||Phase|
|Myelofibrosis (MF)||Drug: ABBV-744 Drug: Navitoclax Drug: Ruxolitinib||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||130 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1b Study Of ABBV-744 Alone Or In Combination With Ruxolitinib Or Navitoclax In Subjects With Myelofibrosis|
|Actual Study Start Date :||August 19, 2020|
|Estimated Primary Completion Date :||November 22, 2022|
|Estimated Study Completion Date :||November 22, 2022|
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.
Other Name: ABT-263
Experimental: Segment D: ABBV-744 + Ruxolitinib
Participants who have never received JAKi will receive ABBV-744 and ruxolitinib.
- Percentage of Participants With Adverse Events [ Time Frame: Up to Approximately 1 year from start of study ]An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. The investigator assesses the relationship of each event to the use of study drug.
- Percentage Of Participants Who Achieve Spleen Volume Reduction Of 35% Or Greater (SVR35) [ Time Frame: Up To Week 24 ]Reduction in spleen volume is measured by magnetic resonance imaging (MRI).
- Maximum Observed Plasma Concentration (Cmax) of ABBV-744 [ Time Frame: Up To Week 12 ]Maximum observed plasma concentration (Cmax) of ABBV-744.
- Time To Cmax (Tmax) Of ABBV-744 [ Time Frame: Up To Week 12 ]The amount of time taken to reach Cmax.
- Area Under The Concentration Versus Time Curve (AUC) Of ABBV-744 [ Time Frame: Up To Week 12 ]AUC of ABBV-744 will be calculated.
- Half-Life (t1/2) Of ABBV-744 [ Time Frame: Up To Week 12 ]Half-life of ABBV-744 will be calculated.
- Accumulation Ratio Of ABBV-744 [ Time Frame: Up To Week 12 ]Pharmacokinetic parameters will include accumulation ratio of ABBV-744.
- Apparent Clearance (CL/F) Of ABBV-744 [ Time Frame: Up To Week 12 ]CL/F of ABBV-744 will be calculated.
- Apparent Volume Of Distribution (Vd/F) Of ABBV-744 [ Time Frame: Up To Week 12 ]Vd/F of ABBV-744 will be calculated.
- Percentage Of Participants With >= 50% Reduction In Total Symptom Score (TSS) [ Time Frame: Week 24 ]TSS is assessed using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. MFSAF v4.0 measures the burden of myelofibrosis-related symptoms. The symptoms are assessed on a 11-point numeric rating scale (NRS) anchored from 0 (absent) to 10 (worst imaginable).
- Objective Response Rate (ORR) [ Time Frame: Week 24 ]ORR is defined as the sum of rates of complete remission (CR) and of partial remission (PR).
- Maximum Observed Plasma Concentration (Cmax) Of Navitoclax [ Time Frame: Up To Week 12 ]Maximum Observed Plasma Concentration (Cmax) Of Navitoclax.
- Time To Cmax (Tmax) Of Navitoclax [ Time Frame: Up To Week 12 ]The amount of time taken to reach Cmax.
- Area Under The Concentration Versus Time Curve (AUC) Of Navitoclax [ Time Frame: Up To Week 12 ]AUC of Navitoclax will be calculated.
- Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib [ Time Frame: Up To Week 12 ]Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib.
- Time To Cmax (Tmax) Of Ruxolitinib [ Time Frame: Up To Week 12 ]The amount of time taken to reach Cmax.
- Area Under The Concentration Versus Time Curve (AUC) Of Ruxolitinib [ Time Frame: Up To Week 12 ]AUC of Ruxolitinib will be calculated.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04454658
|Contact: ABBVIE CALL CENTERemail@example.com|
|United States, California|
|UC Davis Comprehensive Cancer Center - Main /ID# 221790||Not yet recruiting|
|Sacramento, California, United States, 95817|
|United States, New York|
|Roswell Park Comprehensive Cancer Center /ID# 222557||Not yet recruiting|
|Buffalo, New York, United States, 14263|
|The Mount Sinai Hospital /ID# 221549||Not yet recruiting|
|New York, New York, United States, 10029|
|United States, Ohio|
|Gabrail Cancer Center Research /ID# 222802||Recruiting|
|Canton, Ohio, United States, 44718|
|United States, Oregon|
|Oregon Health and Science Univ /ID# 221801||Not yet recruiting|
|Portland, Oregon, United States, 97239|
|Sheba Medical Center /ID# 222151||Not yet recruiting|
|Ramat Gan, Israel, 5239424|
|Tel Aviv Sourasky Medical Center /ID# 223548||Not yet recruiting|
|Tel Aviv-Yafo, Israel, 6423906|
|Study Director:||AbbVie Inc.||AbbVie|