Comprehensive Evaluation of Two Second-Line Therapeutic Approaches for Immune Thrombocytopenia (ITP) – a Pragmatic Randomized Controlled Trial - Holistic Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ostfold Hospital Trust

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

1 Jul 2025 → ongoing

Decision date (initial)

2024-01-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To compare in a randomized clinical trial (RCT) the efficacy of the oral TPO-RA, Avatrombopag, to Rituximab, in adult ITP patients who fail to achieve adequate response to a short course of corticosteroids.

Secondary objectives 12

1. The changes in the disease specific HRQoL during the study.
2. The changes in the level of fatigue during the study
3. The rates of Sustained Response Off-Treatment (SROT) at 78 weeks.
4. The rates of and time to treatment failure.
5. The cost-effectiveness during the first two study phases
6. The changes in the level of generic HRQoL
7. Patients’ satisfaction during the first two study phases
8. The duration of response in patients randomized to Avatrombopag or Rituximab
9. The rate and duration of overall response.
10. Consumption of corticosteroids and rescue therapy during the first phase of the study.
11. Bleeding complications during the first two phases of the study
12. The safety of treatment with Avatrombopag or Rituximab during all study phases

Conditions and MedDRA coding

Immune Thrombocytopenia (ITP)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male or female aged ≥18 years
2. Diagnosis of primary ITP of less than one-year duration and having a platelet count of < 30 x109/L measured within two weeks prior to inclusion with failure to achieve response or relapse after at least one cycle of dexamethasone (20-40 mg daily for 4 days) or prednisone /prednisolone (1 mg/kg for at least two weeks). Shorter courses or lower doses are allowed if discontinued or modified due to side effects
3. Failure to achieve response or relapse after at least one cycle of dexamethasone (20-40 mg daily for 4 days) or prednisone /prednisolone (1 mg/kg for at least two weeks). Shorter courses or lower doses are allowed if discontinued or modified due to side effects.
4. Clinical need for subsequent platelet elevating therapy assessed by the physician in charge
5. Signed and dated written informed consent.

Exclusion criteria 12

1. Previous treatment for ITP with: Rituximab, other immune suppressants (including mycophenolate mofetil, azathioprine, cyclosporine), dapsone, danazol, chemotherapy (apart from vincristine as rescue therapy) or splenectomy. Short treatment with any thrombopoietic agent is allowed if given for a limited duration of a maximum of 2 weeks as rescue therapy for quick elevation of platelet count in emergency situations e.g. bleeding
2. Presence of active malignancy unless deemed cured by adequate treatment. Participants with the following neoplastic conditions can be included: a. Monoclonal gammopathy of undetermined significance (MGUS) or monoclonal B lymphocytosis of undetermined significance (MBUS). b. Basal/squamous cell carcinoma of the skin c. Carcinoma in situ of the cervix d. Carcinoma in situ of the breast e. Incidental histological finding of prostate cancer (TNM stage T1a or T1b).
3. Patients with history of poor compliance or history of alcohol/drug abuse or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or any disease that might interfere with the ability to comply with the study protocol or give informed consent
4. Pregnancy or lactation.
5. Females of child-bearing potential refusing to follow effective contraceptive methods (as described in SmPC) for at least 12 months following the last administration of Rituximab or during treatment with Avatrombopag
6. Secondary ITP: ITP secondary to lymphoma or chronic lymphocytic leukemia; ITP secondary to the following autoimmune disorders: Systemic Lupus Erythematosus, or Antiphospholipid Syndrome; ITP secondary to Common Variable Immune Deficiency; ITP secondary the following viral infections: Human Immunodeficiency Virus or Hepatitis C Virus
7. Concomitant autoimmune hemolytic anemia
8. Active hepatitis B virus (positive HBsAg). Patients with HBsAg negative and HBV core antigen antibody positive (HBcAb) should accept to receive entecavir (Baraclude) for 12 months if they will be allocated to Rituximab. Monthly HBV DNA monitoring will be required while on treatment and for the 6 months after the last dose of the study drug
9. Presence of any serious comorbidity where the condition may worsen by and of the study drugs
10. Known allergy, sensitivity or contraindication to Rituximab or Avatrombopag
11. Patients in a severely immune compromised state
12. Any contraindication according to the SmPC of Rituximab (e.g. active serious infections (e.g. tuberculosis, opportunistic infections, sepsis) and serious heart failure (NYHAC IV) or serious uncontrolled heart disease) or of Avatrombopag (e.g. cirrhosis and/or severe hepatic impairment).”

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Occurrence of durable platelet response defined as achieving platelet counts > 50 X109/L in > 3 of the bi-weekly measurements between weeks 20 and 28 including the last count without having received any other platelet elevating agents after randomization apart from rescue therapy received before end of week 10.

Secondary endpoints 12

1. Change in ITP-PAQ (Overall Quality of Life scale) score from baseline to weeks 28 and 78.
2. Change in the FACIT-Fatigue score from baseline to weeks 28 and 78.
3. Occurrence of SROT defined as: 1. a platelet count > 50 X109/L in at least 3 of the 4 planned visits between weeks 36 and 78 including week 78 and; 2. no administration of platelet elevating agent between weeks 36 and 78.
4. Occurrence of treatment failure anytime during the 3 phases defined as: 1. switching to another platelet elevating agent after randomization to avatrombopag/ rituximab and; 2. thrombocytopenia (platelet count <30 X109/L), high risk of bleeding or intolerance of study drug.
5. Incremental treatment cost per incremental quality adjusted life-years (QALY) at end of study: Difference in average treatment cost per patient (use of pre-selected resource units collected for each patient, scaled with pertinent unit cost) per arm over entire study period. Difference in average QALYs per patient (SF-36 scores at baseline, weeks 28 and 78 transformed to utility weights multiplied with time under study: area under the curve method). Incremental cost-effectiveness ratio (ICER):
6. Change in summary scores of SF-36 (v2) questionnaires from baseline to weeks 28 and 78 in all randomized patient.
7. Change in the score of the Treatment Satisfaction Questionnaire for Medication from baseline to weeks 28 and to 78 weeks.
8. Cumulative number of weeks with platelet count > 50 X109/L between randomization and week 78 (including SROT in the Avatrombopag arm) or retreatment. A period of 2 weeks will be deducted after IVIG and 4 weeks after Dexamethasone or Prednisolone including the treatment period.
9. Occurrence of overall response in>3 of the bi-weekly measur between weeks 20 and 28 without the use of rescue therapy after week 10 where overall response is defined as a platelet count >30 X109/L and at least doubling of the lowest platelet count measured during the prescreening period of 2 weeks, in > 80% of the measurements between weeks 20 and 28 without the use of rescue therapy or corticosteroids after week 10
10. Cumulative dose of dexamethasone /prednisolone, cumulative dose of IVIG, number of platelet transfusions, from time of randomization to treatment failure or week 28.
11. Number and severity of WHO bleeding events. Change in Khellaf score from baseline to weeks 28 and 78.
12. Occurrence and severity of treatment emergent adverse events Occurrence and severity of adverse events of special interest including infections leading to hospitalization or death, arterial and venous thrombosis and bone marrow fibrosis (bone marrow biopsy showing MF2 or higher).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ostfold Hospital Trust

Sponsor organisation

Ostfold Hospital Trust

Address

P. O. Box 16

City

Fredrikstad

Postcode

1603

Country

Norway

Scientific contact point

Organisation

Ostfold Hospital Trust

Contact name

Waleed Ghanima

Public contact point

Organisation

Ostfold Hospital Trust

Contact name

Waleed Ghanima

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications