RALPID

Phase 2

Recruiting

• Conditions: Primary immunodeficiency; PID, ALPS, APDS, CTLA4, IPEX, lymphoproliferative disease, enterocolitis, cytopenia; D000081207

• Registration Number: JPRN-jRCT2031210309
• Lead Sponsor: Endo Akifumi

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-09-13
• Last Update Posted: 17 October 2023

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

(1) Individuals enrolled in PIDJ who were diagnosed with any of the following diseases by flow cytometry or genetic testing
1) Activated PI3K-delta (APDS)
2) CTLA4 haploinsufficiency
3) LRBA deficiency
4) IPEX's syndrome, IPEX-like
5) Autoimmune lymphoproliferative syndrome (ALPS), ALPS-like
6) Common Variable Immunodeficiency (CVID)
7) Other Primary Immunodeficiencies
-6), 7) Only patients judged by the Disease Assessment Committee to have an over-activated mTOR pathway background will be included.
(2) Patients with any of the following symptoms who have been treated with steroids for at least 3 months with inadequate response or who are undesirable to continue steroid therapy due to side effects
1) Patients with evaluable lymphoproliferative symptoms;
-Hepatomegaly: palpable 3.0 cm or more under the costal arch
-Splenomegaly: palpable
-Measurable nodal or extranodal disease: CT or MRI > 2.0cm in major axis
2) Patients with enterocolitis (>=16 years: CDAI score >=220, <16 years: wPCDAI score >=40)
3) Patients with at least two of following autoimmune cytopenias:
-Hemoglobin concentration < 10.0g/dL
-Neutrophil count<1,500/microliter
-Platelet count<75,000/microliter
Autoimmune cytopenias: cytopenias without decreased cytopoiesis, with a history of treatment response to immunosuppressive agents or with autoantibodies
(3) Patients aged 0 years and older than 2 months at the time of informed consent
(4) Patients who can take granules or tablets
(5) Patients who are able to comply with protocol requirements, such as handling and management of investigational products.
(6) Patients for whom written informed consent has been obtained from the patients themselves or their legally acceptable representative to participate in the clinical trial.

Exclusion Criteria

(1) Patients with secondary immunodeficiency
(2) Patients with idiopathic interstitial pneumonia
(3) Patients with uncontrolled hyperlipidemia or uncontrolled diabetes
(4) Patients with clinically significant signs and symptoms of infection (e.g., infections requiring iv such as antibiotics)
(5) Patients with serum creatinine > 3 times the upper reference limit at screening
(6) HBsAg-positive patients, HBs antibody or HBc antibody-positive patients with detectable HBV-DNA, or patients with active hepatitis C (except for HCV antibody-positive patients who are inactive and have normal liver function).
(7) QFT/T-SPOT positive patients
(8) Patients who have undergone surgery (invasion of the body cavity or surgery requiring suturing 3 or more needles, including biopsy) within 2 weeks before enrollment.
(9) Patients scheduled to undergo surgery during the study treatment period.
(10) Patients undergoing hematopoietic stem cell transplantation
(11) Patients who received a blood transfusion within 12 weeks before enrollment in the study.
(12) Patients who received G-CSF products within 1 week prior to enrollment in the study (within 4 weeks for persistent G-CSF products)
(13) Patients taking angiotensin-converting enzyme inhibitors within 4 weeks before enrollment in the study.
(14) Patients who took other investigational products within 4 weeks before enrollment in the study
(15) Patients who have previously taken mTOR inhibitors or PI3K-delta inhibitors
(16) Patients who received a live vaccine within 4 weeks prior to enrollment in the study
(17) Patients with NYHA class II-IV congestive heart failure
(18) Patients with a history of myocardial infarction in the 6 months prior to enrollment.
(19) Patients with symptomatic arrhythmias requiring treatment
(20) Patients with active malignancy at screening
(21) Patients with a history of hypersensitivity to sirolimus, sirolimus ingredients, or sirolimus derivatives (everolimus, temsirolimus)
(22) Patients who are of childbearing potential or have a partner of childbearing potential and who are unable to provide adequate contraception from the time of obtaining informed consent to 12 weeks after the last dose of the investigational product
(23) Patients who are pregnant, breastfeeding, or possibly pregnant
(24) Other patients who are judged by the principal investigator or a sub-investigator to be ineligible for the study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified