臨床研究等提出・公開システム

A Phase 3 Study in Patients with Chronic Idiopathic Thrombocytopenic Purpura in R788

A Clinical Study in Patients with Chronic Idiopathic Thrombocytopenic Purpura in R78

34

The background of the subjects in the R788 group and the placebo group was as follows: Male, 18.2% (4/22 subjects) and 33.3% (4/12 subjects); female, 81.8% (18/22 subjects) and 66.7% (8/12 subjects); age, 61 years (25 to 81 years) and 64 years (31 to 76 years) (median [range], the same applies hereinafter); baseline platelet count, 19000/uL (3000 to 28000/uL) and 18000/uL (1000 to 27000/uL); duration of ITP, 12 years (1 to 41 years) and 12 years (1 to 38 years); and history of splenectomy, 22.7% (5/22 subjects) and 16.7% (2/12 subjects), respectively. The number of prior ITP medications (number of categories) was 2 (1 to 5) and 2 (1 to 6) in the R788 group and the placebo group, respectively. The disposition (including overlaps) was corticosteroids in 95.5% (21/22 subjects) and 100.0% (12/12 subjects), rituximab in 4.5% (1/22 subjects) and 33.3% (4/12 subjects), and TPO receptor agonists in 50.0% (11/22 subjects) and 58.3% (7/12 subjects).

Seventy-two subjects provided their written informed consent. Of these, 34 subjects considered eligible for the study were randomized to receive the investigational products. The number of subjects in Period I were 22 in the R788 group and 12 in the placebo group. 30 subjects transitioned to Period II and 22 subjects transitioned to Period III. R788 was administered to 33 subjects (except 1 subject in the placebo group who discontinued the study in Period I) in this study. Across the entire period of R788 treatment, 11 subjects (33.3%) were discontinued.

[R788 treatment period] 1) The incidence of adverse events was 100.0% (33/33 subjects). Adverse events that occurred in >=10% of subjects were diarrhoea observed in 39.4% (13/33 subjects), hypertension observed in 33.3% (11/33 subjects), COVID-19 observed in 18.2% (6/33 subjects), constipation and eczema observed in 15.2% (5/33 subjects) each, and nasopharyngitis and liver function test increased observed in 12.1% (4/33 subjects) each. 2) The incidence of adverse drug reactions was 72.7% (24/33 subjects). Adverse drug reactions that occurred in >=10% of subjects were diarrhoea and hypertension observed in 30.3% (10/33 subjects) each. 3) There was no death. Serious adverse events excluding deaths were observed in 24.2% (8/33 subjects), and adverse events leading to study drug withdrawal occurred in 15.2% (5/33 subjects).

[Period I] Stable platelet response was achieved in 36.4% (8/22 subjects) in the R788 group and 0.0% (0/12 subjects) in the placebo group: The rate was significantly higher in the R788 group than in the placebo group (Fisher's exact test, P = 0.030; difference in percentage [R788 - placebo], 36.4%; 95% CI, 3.1%, 59.3%). [R788 treatment period] Duration of platelet response was observed in 16 of 33 subjects, and the median duration of platelet response was 392 days (range: 106 to 946 days). Duration of platelet response was continued for 4 subjects at the end of the post-marketing clinical study.

R788 was found to be effective in increasing the platelet count that is significantly superior to the placebo in Japanese patients with chronic ITP (Period I). As a result of administration of R788 to 33 subjects for up to 1184 days (median: 771 days), the duration of platelet response was observed in 16 of 33 subjects. The median duration of platelet response was 392 days (range: 106 to 946 days), confirming the maintenance of platelet increasing effect.

No

Kissei Pharmaceutical Co., Ltd.

3-1-3, Koishikawa, Bunkyo-ku, Tokyo

rinsyousiken@pharm.kissei.co.jp

Kissei Pharmaceutical Co., Ltd.

3-1-3, Koishikawa, Bunkyo-ku, Tokyo

+81-120-007-622

rinsyousiken@pharm.kissei.co.jp

completed

Dec. 24, 2019

Interventional

A placebo-controlled, multicenter, randomized, double-blind, parallelgroup study and a multicenter, open-label study

treatment purpose

3

- Patients diagnosed with ITP at least 6 months before acquisition of consent
- Patients with a platelet count average of < 30000/uL during screening period and with each platelet count < 35000/uL
- Patients who have used and failed at least 1 of the typical ITP medications before informed consent

- Patients with thrombocytopenia associated with other diseases
- Patients with autoimmune hemolytic anemia
- Patients with poor blood pressure control
- Patients with or with a history of a history of coagulopathy

Both

Idiopathic Thrombocytopenic Purpura

investigational material(s)
Generic name etc :
INN of investigational material : Fostamatinib
Therapeutic category code : 399 Agents affecting metabolism, n.e.c.
Dosage and Administration for Investigational material :

control material(s)
Generic name etc :
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material :

efficacy
Achievement rate of stable platelet response (subjects who achieve a platelet count of >= 50000/uL on at least 4 of the 6 visits from Weeks 14 to 24 are considered as a responder and the percentage of responders will be evaluated)

efficacy
Achievement rate of overall response (subjects who achieve a platelet count of >= 50000/uL during at least 1 of the 6 visits from Weeks 2 to 12 are considered as a responder and the percentage of responders will be evaluated)
efficacy
Duration of maintained platelet count since first achievement of a platelet count >= 50000/uL after administration of the study drug
efficacy
Achievement rate of a platelet count of >= 50000/uL at the specified evaluation time point
efficacy
Achievement rate of a platelet count of >= 30000/uL at the specified evaluation time points and platelet count increase at least 20000/uL above baseline

Oct. 15, 2019