Avatrombopag for the Treatment of Chemotherapy-Induced Thrombocytopenia in Adults With Active Non-Hematological Cancers

• ClinicalTrials.gov Identifier: NCT03471078
• Recruitment Status: Completed
• First Posted: March 20, 2018
• Results First Posted: November 24, 2021
• Last Update Posted: April 20, 2023
• Sponsor: Sobi, Inc.
• Information provided by (Responsible Party): Sobi, Inc.

Tracking Information

• First Submitted Date: March 7, 2018
• First Posted Date: March 20, 2018
• Results First Submitted Date: September 10, 2021
• Results First Posted Date: November 24, 2021
• Last Update Posted Date: April 20, 2023
• Actual Study Start Date: October 12, 2018
• Actual Primary Completion Date: August 28, 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 8, 2021): Percentage of Subjects Who do Not Require Platelet Transfusion, Dose Reduction in Chemotherapy by 15%, or Chemotherapy Delay by >=4 Days [ Time Frame: Randomization up to 33 days ]

Original Primary Outcome Measures (submitted: March 13, 2018)

Evaluate the efficacy of avatrombopag in proportion of responders [ Time Frame: Randomization up to 33 days ]

Proportion of subjects who do not require platelet transfusion, dose reduction in chemotherapy by 15%, or chemotherapy delay by >=4 days

Current Secondary Outcome Measures (submitted: October 8, 2021)

• Duration of Severe Thrombocytopenia Defined as a Platelet Count <50 x 10^9/L [ Time Frame: Randomization up to 33 days ]
  The duration of severe thrombocytopenia is defined as the total number of days with a platelet count <50×10^9/L during the period after post-chemotherapy study drug treatment in Cycle X+1 through Chemotherapy Day of Cycle X+2.
• Change in Platelet Count From Baseline (Nadir) [ Time Frame: Randomization up to 33 days ]
  Comparison of avatrombopag 60 mg vs. placebo, adjusted for the number of chemotherapy agents currently receiving per IWRS (1, ≥2). Cycle X nadir is defined as the lowest platelet count value prior to the first dose of study drug; Cycle X+1 nadir is defined as the lowest platelet count value during the period after post-chemotherapy study drug treatment in Cycle X+1 through Chemotherapy Day in Cycle X+2.
• Percentage of Subjects Who Did Not Have Major or Non-major Clinically Relevant Bleeding During the Period After Post-chemotherapy Study Drug Treatment in Cycle X+1 Through Chemotherapy Day of Cycle X+2. [ Time Frame: Randomization up to 33 days ]

Original Secondary Outcome Measures (submitted: March 13, 2018)

• Duration of severe thrombocytopenia defined as a platelet count <50 x 109/L [ Time Frame: Randomization up to 33 days ]
• Change in platelet count from baseline (nadir) [ Time Frame: Randomization up to 33 days ]
• Proportion of subjects without major or non-major clinically relevant bleeding [ Time Frame: Randomization up to 33 days ]
• Incidence of Adverse Events [ Time Frame: Up to 26 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Avatrombopag for the Treatment of Chemotherapy-Induced Thrombocytopenia in Adults With Active Non-Hematological Cancers
• Official Title: Randomized, Double-Blind, Placebo-Controlled Study With Open-Label Extension to Evaluate the Efficacy and Safety of Avatrombopag for the Treatment of Chemotherapy-Induced Thrombocytopenia in Subjects With Active Non-Hematological Cancers
• Brief Summary: Phase 3 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of avatrombopag in subjects with chemotherapy-induced thrombocytopenia receiving chemotherapy for the treatment of ovarian, lung (small cell and non-small cell) and bladder cancer.
• Detailed Description: Subjects will receive placebo controlled test treatment for one cycle of chemotherapy followed by an observational cycle. Subjects will have the option to continue into an open label extension period for all remaining chemotherapy cycles within the current regimen. After the follow-up visit, all subjects will continue to a long-term safety follow-up period.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Supportive Care
• Condition: Chemotherapy-induced Thrombocytopenia

Intervention

• Drug: Avatrombopag
  Oral avatrombopag tablet
• Drug: Placebo Oral Tablet
  Placebo comparator tablet

Study Arms

• Experimental: Avatrombopag
  Study is 2:1 randomization ratio (avatrombopag to placebo). Investigational product administered orally once daily for 5 days prior to chemotherapy and 5 days following chemotherapy treatment.
  Intervention: Drug: Avatrombopag
• Placebo Comparator: Placebo
  Study is 2:1 randomization ratio (avatrombopag to placebo). Investigational product administered orally once daily for 5 days prior to chemotherapy and 5 days following chemotherapy treatment.
  Intervention: Drug: Placebo Oral Tablet

• Publications *: Al-Samkari H, Kolb-Sielecki J, Safina SZ, Xue X, Jamieson BD. Avatrombopag for chemotherapy-induced thrombocytopenia in patients with non-haematological malignancies: an international, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2022 Mar;9(3):e179-e189. doi: 10.1016/S2352-3026(22)00001-1.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 20, 2020): 122
• Original Estimated Enrollment (submitted: March 13, 2018): 120
• Actual Study Completion Date: January 31, 2023
• Actual Primary Completion Date: August 28, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Men and women greater than or equal to 18 years of age;
• A diagnosis of ovarian, lung (small cell or non-small cell) or bladder cancer requiring systemic chemotherapy

• Participant receiving a chemotherapy regimen given in a 21 or 28-day cycle, including 1 or more of the following agents or class of agents:

  • Nucleoside analog, including gemcitabine and fluorouracil;
  • Carboplatin or cisplatin;
  • Anthracycline; or
  • Alkylating agent;
• Participant experienced severe thrombocytopenia, defined as 2 platelet counts <50 x 109/L measured at least 24 hours apart, during the qualifying chemotherapy cycle, of their current chemotherapy regimen
• ECOG performance status <=2

Exclusion Criteria:

• Participant has experienced >=Grade 2 CIT other than during the current chemotherapy treatment regimen within 6 months of Screening;
• Participant has any history of hematologic malignancies, including leukemia, myeloma, myeloproliferative disease, lymphoma, or myelodysplastic diseases;
• Participant has received >2 previous lines of chemotherapy or is receiving whole brain radiation during the study treatment period;
• Participant has a known medical history of genetic prothrombotic syndromes
• Participant has a history of arterial or venous thrombosis within 3 months of screening;
• Use of vitamin K antagonists;
• Participant has previously received a thrombopoietin receptor agonist or recombinant human thrombopoietin for the treatment of CIT within 3 months of screening

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China, Hungary, Poland, Russian Federation, Serbia, Ukraine, United States

Administrative Information

• NCT Number: NCT03471078
• Other Study ID Numbers: AVA-CIT-330
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sobi, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Sobi, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Sobi, Inc.
• Verification Date: April 2023