Phase I / IIa clinical study (FIH study) to investigate the safety and efficacy of high-purity mesenchymal stem cell (REC-01) transplantation in pediatric patients with hypophosphatasia

JRCT ID: jRCT2063210019

Registered date:23/06/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: severe hypophosphatasia
• Date of first enrollment: 23/06/2021
• Target sample size: 3
• Study type: Interventional
• Intervention(s): Transplantation of high-purity mesenchymal stem cells (REC-01)

Outcome(s)

• Primary Outcome: Safety: Adverse events, malfunctions

Key inclusion & exclusion criteria

• Age minimum: >= 3age old
• Age maximum: < 12age old
• Gender: Both

Include criteria

[Registration (1)] Immediately after obtaining consent, confirm that the following criteria (1) to (5) are met.
[Registration (2)] When the bone marrow fluid and cord blood can be arranged from a suitable donor (selection criteria (6) and (7)) and the REC-01 production schedule from the bone marrow fluid is in sight, cord blood transplantation and cord blood are available. Schedule REC-01 for the first dose and confirm that it conforms to (1) to (5) again within 1 month before the scheduled date and during the screening period before starting the pretreatment for cord blood transplantation.
1) Patients who have voluntarily obtained consent from the subject's substitute (guardian) based on the explanation / consent document approved by the clinical trial review committee.
(2) Patients diagnosed with hypophosphatasia according to the diagnostic criteria for pediatric specific chronic diseases Note 1
Note 1: Diagnostic criteria established by the Ministry of Health, Labor and Welfare Grant-in-Aid for Scientific Research to Overcome Intractable Diseases "Basic and Clinical Study for Individually Optimized Treatment of Hypophosphatasia Disease" group (Research Leader: Keiichi Ozono) ..
[Main symptoms] 1. Bone calcification disorder: Simple X-ray findings of bone include low calcification of bone, deformation of long canal bone, and rickets-like metaphyseal irregularity.
2. Early loss of deciduous teeth (dropout under 4 years old)
[Main laboratory findings] 1. Low serum alkaline phosphatase (ALP) level (Note the normal value by age: Judging by the normal value by age at each institution, the serum ALP value of growing children is 100 IU / L. If less than, you need to doubt your true nature)
(3) Patients with severe HPP defined below who have been administered ashotase alpha at the time of obtaining consent and whose symptoms have been stable after a sufficient administration period (6 months to several years).
Definition of severe illness: Those who meet all of the following: Having developed before 6 months of age, having respiratory disorders (Note 2), and ALPL gene mutation showing ALP activity of 50% or less compared to healthy subjects Have (Note 3)
Note 2: Respiratory disorders are those who have received or have received oxygen administration or mechanical ventilation management (including non-invasive positive pressure ventilation therapy).
Note 3: The specific activity per amount of ALP enzyme protein is 50% or less compared to healthy subjects.
(4) Patients whose consent date is 3 to 12 years old
(5) Patients who do not have the following obstacles that interfere with transplantation
ECOG performance status score at enrollment is 3 or less, total bilirubin level is 2.0 mg / dL or less, serum creatine is below the upper limit of normal age, or creatine clearance (measured value) is 60 mL / min or more. No ECG abnormalities requiring treatment, BNP 100 pg / mL or less, and left ventricular ejection fraction 50% or more.
(6) As a bone marrow fluid donor for the production of REC-01, a donor that matches 3 or more of the HLA 6 loci (-A, -B, -DRB1) between the bone marrow fluid donor and the subject can be found.
(7) According to the usual cord blood transplantation, a donor with 4 or more of the 6 HLA loci (-A, -B, -DRB1) matching can be found between the cord blood donor and the subject.
(8) Pregnant female patients should be admitted to this clinical trial only if the pregnancy test confirms that they are not pregnant and that the patient directly receives an informal cent and consistently and correctly understands and agrees to contraception. You can participate.

Exclude criteria

[Registration (1)] Immediately after obtaining consent, confirm that it does not violate any of the following criteria (1) to (10).
(1) History of heart failure requiring treatment.
(2) History of renal failure.
(3) Uncontrollable infectious diseases: Infectious diseases in which signs and symptoms related to infection continue and no improvement is observed even with appropriate treatment.
(4) Uncontrollable diabetes: Coexisting uncontrolled diabetes with HbA1c of 8% or more despite appropriate treatment.
(5) Coexisting cirrhosis.
(6) Coexistence of severe mental disorders that interfere with treatment performance.
(7) The brain wave is a flat brain wave.
(8) Patients who have had a cord blood transplant before obtaining consent.
(9) Patients who have been treated for mesenchymal stem cell transplantation in the past.
(10) Patients with hypersensitivity to bovine and human serum-derived proteins and antibiotics.
(11) In addition, patients who are judged by the investigator or investigator to be ineligible as subjects.

Related Information

• Primary Sponsor: Taketani Takeshi
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development (AMED)