Phase 3 Study of the Safety, Efficacy & PK of pegunigalsidase alfa (PRX-102) 2 mg/kg IV Administered Every 4 Weeks in Fabry Disease Patients (BRIGHT)

• Register: EUCTR
• Last refreshed on: 13 October 2020
• Main ID: EUCTR2017-001528-23-GB
• Date of registration: 28/06/2017
• Prospective Registration: Yes
• Primary sponsor: Protalix Ltd.
• Public title: Phase 3 Study of the Safety, Efficacy & PK of pegunigalsidase alfa (PRX-102) 2 mg/kg IV Administered Every 4 Weeks in Fabry Disease Patients (BRIGHT)
• Scientific title: A Phase 3, Open Label, Switch Over Study to Assess the Safety, Efficacy and Pharmacokinetics of pegunigalsidase alfa (PRX-102) 2 mg/kg Administered by Intravenous Infusion Every 4 Weeks for 52 weeks in Patients with Fabry Disease Currently Treated with Enzyme Replacement Therapy; Fabrazyme® (agalsidase beta) or Replagal™ (agalsidase alfa)
• Date of first enrolment: 18/10/2017
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001528-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Czech Republic, Denmark, Germany, Netherlands, Spain, Turkey, United Kingdom, United States

Contacts

• Name: Raul Chertkoff
• Affiliation: Protalix Ltd.

• Name: Raul Chertkoff
• Affiliation: Protalix Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age: 18-60 years
2. A documented diagnosis of Fabry disease
3. Males: plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than lower limit of normal according to the laboratory reference ranges and one or more of the characteristic features of Fabry disease
a. Neuropathic pain
b. Cornea verticillata
c. Clustered angiokeratoma
4. Females: historical genetic test results consistent with Fabry mutations, or in the case of novel mutations a first-degree male relative with Fabry disease, and one or more of the characteristic features of Fabry disease
a. Neuropathic pain
b. Cornea verticillata
c. Clustered angiokeratoma
5. Treatment with agalsidase alfa or agalsidase beta for at least 3 years and on a stable dose (>80% labelled dose/kg) for at least 6 months
6. eGFR = 30 mL/min/1.73 m2 by CKD-EPI equation at screening visit
7. Availability of at least 3 historical serum creatinine evaluations since starting agalsidase alfa or agalsidase beta treatment and not more than 2 years old
8. Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically accepted, highly effective method of contraception. These include combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, or sexual abstinence
9. Patients whose clinical condition, in the opinion of the Investigator, is suitable for treatment with ERT every 4 weeks.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1. History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase alfa or agalsidase beta
2. History of renal dialysis or transplantation
3. Linear negative slope of eGFR of = 2 mL/min/1.73 m2 based on at least 4 serum creatinine values over approximately 2 years (including the value obtained at the screening visit)
4. History of acute kidney injury in the 12 months prior to screening, including specific kidney diseases (e.g., acute interstitial nephritis, acute glomerular and vasculitic renal diseases); non-specific conditions (e.g., ischemia, toxic injury); as well as extrarenal pathology (e.g., prerenal azotemia and acute post renal obstructive nephropathy)
5. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
6. Urine protein to creatinine ratio (UPCR) at screening > 0.5 g/g or mg/mg or 500 mg/g and not treated with an ACE inhibitor or ARB
7. Females who are pregnant, planning to become pregnant during the study, or are breast feeding
8. Cardiovascular event (myocardial infarction, unstable angina) in the 6-month period before screening
9. Cerebrovascular event (stroke, transient ischemic attack) in the 6-month period before screening
10. Presence of any medical, emotional, behavioral, or psychological condition that, in the judgment of the Investigator and/or Medical Director, would interfere with the patient’s compliance with the requirements of the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Fabry disease (a-galactosidase A deficiency)
MedDRA version: 20.0 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

Intervention(s)

Product Name: Pegunigalsidase alfa
Product Code: PRX-102
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Pegunigalsidase alfa
CAS Number: 1333358-30-7
Current Sponsor code: PRX-102
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

Secondary Objective: Not applicable

Primary end point(s): SAFETY ENDPOINTS:
Changes from baseline in:
- Clinical laboratory tests
- Physical examination
- Assessment of the injection site
- Electrocardiogram
- Treatment-emergent adverse events
- Ability to taper off infusion premedication
- Requirement for use of premedication overall to manage infusion reactions
- Treatment-induced anti-pegunigalsidase alfa antibodies

EFFICACY EXPLORATORY ENDPOINTS:
- Estimated glomerular filtration rate (eGFRCKD-EPI)
- Left Ventricular Mass Index (g/m2) by echocardiogram
- Plasma Lyso-Gb3
- Plasma Gb3
- Urine Lyso-Gb3
- Protein/Creatinine ratio spot urine test
- Frequency of pain medication use
- Exercise tolerance (Stress Test)
- Short Form Brief Pain Inventory (BPI)
- Mainz Severity Score Index (MSSI)
- Quality of life EQ-5D-5L

Timepoint(s) of evaluation of this end point: As per protocol

Main Objective: To evaluate the safety, efficacy and pharmacokinetics of pegunigalsidase alfa (PRX-102) in patients with Fabry disease currently treated with currently commercially available ERT (agalsidase alfa or agalsidase beta).

Secondary Outcome(s)

Secondary end point(s): Not applicable

Timepoint(s) of evaluation of this end point: Not applicable

Secondary ID(s)

PB-102-F50

Source(s) of Monetary Support

Protalix Ltd.

Ethics review

Status: Approved
Approval date: 18/10/2017
Contact: