Clinical trial NCT04993885: Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
Official title: Efficacy and Safety of Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies Fail to Eltrombopag or Herombopag Treatment: a Single-center, Prospective, One-arm Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Immune Thrombocytopenia
Autoantibodies
Evan Syndrome
Connective Tissue Diseases
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2021-08-06
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This prospective, open-label, single-center, one-arm clinical trial aims at evaluating the efficacy and safety of avatrombopag in Chinese adult Immune Thrombocytopenia (ITP) patients with autoantibodies fail (due to intolerance or resistance) to eltrombopag or herombopag treatment.

Detailed description: This prospective, open-label, single-center, one-arm clinical trial aims at evaluating the efficacy and safety of avatrombopag in Chinese adult ITP patients with autoantibodies fail (due to intolerance or resistance) to eltrombopag or herombopag treatment.

The subjects include ITP secondary to connective tissue diseases (including but not limited to systemic lupus erythematosus, Sjogren's syndrome and rheumatoid arthritis), primary ITP with positive antinuclear antibody but not up to the diagnostic criteria of connective tissue diseases, primary Evans syndrome, Evans syndrome secondary to connective tissue diseases, and primary ITP with positive Coomb's test but not up to the diagnostic criteria of Evans syndrome.

Fifty-two eligible subjects will be enrolled in this study. The dose will be adjusted according to the platelet count during the period from week 1 to week 12.

Eligibility criteria: Inclusion Criteria:

* The patients have provided written informed consent prior to enrollment.
* Men and women greater than or equal to 18 years of age.
* Diagnosed as ITP secondary to connective tissue diseases (including but not limited to systemic lupus erythematosus, Sjogren's syndrome and rheumatoid arthritis), primary ITP with positive antinuclear antibody but not up to the diagnostic criteria of connective tissue diseases, primary Evans syndrome, Evans syndrome secondary to connective tissue diseases, and primary ITP with positive Coomb's test but not up to the diagnostic criteria of Evans syndrome.
* Platelet count\<30 ×10\^9/L at screening.
* Patients who have previously failed to receive Eltrombopag or Herombopag \[poor efficacy (Eltrombopag 75 mg/d or Herombopag 7.5 mg/D, at least 4 weeks), or the efficacy cannot be maintained\], or who have contraindications, can not tolerate or refuse Eltrombopag or Herombopag treatment.
* Treatment for ITP (including but not limited to glucocorticoids, recombinant human thrombopoietin, and other thrombopoietin receptor agonists other than Avatrombopag) must be completed before enrollment, or the dose must be stable or in a phase of reduction within 2 weeks before enrollment.
* Effective contraceptive measures will be taken during the clinical trial.

Exclusion Criteria:

* Patients with active thyroid disease requiring treatment.
* Patients with any prior history of arterial or venous thrombosis within 3 months, and with any of the following risk factors: cancer, Factor V Leiden, ATIII deficiency, or patients who are using anticoagulants or antiplatelet drugs at the beginning of screening.
* Those who had received rituximab within 3 months.
* Patients who had failed to respond to the previous use of Avatrombopag (40mg once a day for more than 4 weeks).
* Subjects known to be allergic to Avatrombopag or any of its excipients.
* Patients who had received splenectomy within 3 months or have splenectomy plan within 3 months.
* Patients with lupus encephalopathy or lupus nephritis.
* Patients with cataract.
* Patients with infectious fever (including but not limited to pulmonary infection) within 1 month or with active infection during screening.
* Existing hepatitis B virus, hepatitis C virus replication or HIV infection.
* Severe liver dysfunction (alanine aminotransferase or glutamic oxaloacetic transaminase \> 3×ULN).
* Patients with severe cardiac or pulmonary dysfunction.
* Severe renal damage (creatinine clearance \< 30 ml/min).
* There are surgical planners during the study.
* History of psychiatric disorder.
* Pregnant or lactating women or those planning to be pregnant during the trial.
* Patients with a history of drug/alcohol abuse (within 2 years before the study).
* Patients that had participated in other experimental researches within one month before enrollment.
* Any other circumstances that the investigator considers that the patient is not suitable to participate in the trial.

Primary outcomes:
measure: Platelet response
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
Secondary outcomes:
measure: Platelet response
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
measure: Platelet response
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
measure: Duration of platelet response
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
measure: Platelet response
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
measure: Time to platelet response
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
measure: Duration of platelet response
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
measure: Proportion of patients receiving remedial treatment.
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
measure: Bleeding score
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
measure: Changes of disease activity index in patients with systemic lupus erythematosus
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
measure: The improvement of symptoms
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
measure: Improvement in immune indexes
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
measure: Discontinuation rate of glucocorticoids
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
measure: Functional assessment of chronic illness therapy-fatigue
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
measure: ITP-Patient Assessment Questionnaire
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
Other outcomes:
measure: Incidence of Toxicity
timeFrame: From the start of study treatment (Day 1) up to the end of week 12.
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Lei Zhang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: