A Multicenter Open-Label Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Pegunigalsidase Alfa (PRX-102) in Japanese Patients with Fabry Disease (RISE)
Study to Evaluate the Safety, PK, PD, and Efficacy of PRX-102 in Japanese Patients With Fabry Disease (RISE)
Stokes Andrew
Chiesi Farmaceutici S.p.A.
4-1-3 Kyuutaromachi, Chuo-ku, Osaka, 541-0056, Japan
+81-6-4560-2001
Japan-Chiken@iconplc.com
Clinical trial contact
ICON Clinical Research GK
4-1-3 Kyutaro-cho, Chuuou-ku, Osaka-city, Osaka, 541-0056, Japan
+81-6-4560-2001
Japan-Chiken@iconplc.com
Recruiting
May. 17, 2023
Aug. 25, 2023
18
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
All subjects
1. Must have been born in Japan and have their biological parents and all 4 grandparents of Japanese descent
2. A documented diagnosis of Fabry disease, as determined by the following:
- Males: Plasma and/or leukocyte alfa-galactosidase-A activity (by activity assay) that is =<5% of mean normal laboratory levels, or, if the enzymatic activity is above the 5% limit but still under the normal level, a confirmed disease-causing mutation of the GLA gene
- Females: Historical genetic test results consistent with Fabry mutations, or, in the case of novel mutations, a first-degree male relative with Fabry disease
- All subjects: At least one of the following characteristic features of Fabry disease: neuropathic pain, cornea verticillata, and/or clustered angiokeratoma
c. Agree to use one of the following highly reliable methods of contraception from the day of the informed consent signature until 30 days after the last infusion received. The following methods are acceptable:
- Placement of an intrauterine device (IUD) or intrauterine releasing system (IUS)
- Combined (both estrogen and progestogen) hormonal contraception (oral) associated with inhibition of ovulation, supplemented with a barrier method (preferably male condom)
- Bilateral tubal occlusion
- Sexual abstinence, defined as refraining from heterosexual intercourse during the entire study period
- Partner vasectomy, provided that the partner is the sole sexual partner and has received medical verification of the surgical success
Be of non-childbearing potential, defined as one of the following:
- Post-menopausal (12 consecutive months of amenorrhea), OR
- Permanently sterile following hysterectomy, bilateral salpingectomy, or bilateral oophorectomy (supporting evidence required)
Additional inclusion criteria for subjects in Cohort A
- Aged =>18 to =< 70 years
- Treatment with agalsidase beta or agalsidase alfa for at least the last 12 months Prior to
screening, with the dose stable (defined as having received at least 80% of the labelled dose) for at least the last 6 months
- Diagnosis of kidney impairment, defined as a linear slope of eGFR more negative than or equal to -2 mL/min/1.73 m~2/year. The historical slope will be calculated based on at least 3 serum creatinine values obtained over the 9 to 24 months prior to screening, using the JPN-CKD-EPI Creatinine equation (2009). It is preferable if all 3 samples assessed were done at the same center using the same laboratory; however, the results of samples that were assessed by different laboratories will be accepted. This criterion will be confirmed at screening by calculating the screening eGFR slope using historical and screening serum creatinine values. Both historical and screening eGFR slopes will be used for the diagnosis of kidney impairment.
Additional inclusion criterion for subjects in Cohort B
- Aged =>18 to =< 70 years
Additional inclusion criteria for subjects in Cohort C
- Aged =>13 to <18 years
- Subjects who have previously received or are currently receiving ERT treatment, must be negative for anti-drug antibodies to PRX-102
The presence of any of the following will exclude a prospective subject from study enrolment:
1. Administration of previous treatment for Fabry disease within 14 days before baseline, substrate reduction therapy for
Fabry disease within 3 days before
baseline, or chaperone therapy for Fabry disease within 3 days before baseline
2. History of severe type I hypersensitivity reactions (anaphylactic or anaphylactoid life-threatening reaction) to other ERT treatment for Fabry disease or to any component of the study drug
3. Cohort A only: eGFR value of >90 to =<120 mL/min/1.73 m^2 at screening, and a historical eGFR value >120 mL/min/1.73 m^2 in the 9 to 24 months before screening, indicating absence of renal impairment, eGFR to be calculated using the JPN-CKD-EPI creatinine equation (2009).
4. Urine protein to creatinine ratio (UPCR) >0.5 g/g (0.5 mg/mg or 500 mg/g) if not treated with an ACE inhibitor or ARB
5. Initiation of treatment, or a change in dose to ongoing treatment, with an angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in the 4 weeks prior to screening
6. Currently taking another investigational drug for any condition
7. Carry only known non-pathogenic Fabry mutations
8. History of renal dialysis or kidney transplantation
9. History of acute kidney injury in the 12 months prior to screening, including specific kidney diseases (e.g., acute interstitial nephritis, acute glomerular and renal vasculitis); non-specific conditions (e.g., ischemia, toxic injury); or extrarenal pathology (e.g., prerenal azotemia, and acute postrenal obstructive nephropathy
10. History of (current) malignancy requiring treatment; the one exception is a prior history of resected basal cell carcinoma
11. Severe cardiomyopathy or significant unstable cardiac disease within 6 months prior to screening
12. A positive test for Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) within 3 months prior to Screening, using a validated molecular assay or validated antigen assay
13. Females: Pregnant or lactating or of childbearing potential with a fertile male partner and unwilling to use a highly reliable method of contraception from the informed consent signature until 30 days after the last infusion received
14. Presence of any medical, emotional, behavioral, or psychological condition that in the judgment of the Investigator could interfere with the subjects compliance with the requirements of the study
15. Previous treatment with cellular therapy or gene therapy for any condition
13age old over
70age old under
Both
Fabry disease
Experimental: PRX-102 1 mg/kg every 2 weeks or PRX-102 2 mg/kg every 4 weeks
1. Incidence of Treatment Emergent Adverse Events (TEAEs)
2. Incidence of Infusion Related Reactions (IRRs)
3. Incidence of Injection site reactions (ISRs)
4. Change of laboratory tests' results
5. Change in in body weight in kilograms
6. Change in height in centimeters
7. Change in Tanner stage
8. Change from baseline of 12-lead ECG quantitative parameters
9. Incidence of Anti-Drug Antibodies (ADAs) against PRX-102
10. ADA status change from baseline
11. Incidence of premedication use at each visit and change of infusion premedications from baseline
12. Change from baseline of Maximum plasma concentration (Cmax)
13. Change from baseline of Time to maximum plasma concentration (tmax)
14. Change from baseline of Area under the plasma concentration-time curve from time 0 to time t (AUC0 t)
15. Change from baseline of Area under the curve from time 0 to 2 weeks (AUC0-2wk)
16. Change from baseline of Area under the curve from time 0 to infinity (AUCinf)
17. Change from baseline of Terminal half-life (t1/2)
18. Change from baseline of Area under the curve over a dosing interval (AUCtau)
19. Change from baseline of Observed drug concentration at the end of the dosing interval (Ctau)
20. Change from baseline of Clearance (Cl)
21. Change from baseline of Volume of distribution (Vz)
Chiesi Farmaceutici S.p.A. (ICCC: ICON Clinical Research GK)
The Jikei University Hospital Institutional Review Board
