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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01769001




Registration number
NCT01769001
Ethics application status
Date submitted
31/08/2012
Date registered
5/09/2012
Date last updated
13/09/2023

Titles & IDs
Public title
Dose-ranging Study of PRX-102 in Adult Fabry Disease Patients
Scientific title
A Phase 1/2, Open Label, Dose Ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Exploratory Efficacy Parameters of PRX-102 Administered by Intravenous Infusion Every 2 Weeks for 12 Months to Adult Fabry Patients
Secondary ID [1] 0 0
PB-102-F01 & PB-102-F02
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fabry Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cytarabine
Treatment: Drugs - Dasatinib
Treatment: Drugs - Daunorubicin Hydrochloride
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Drugs - Etoposide
Treatment: Drugs - Hydrocortisone Sodium Succinate
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Leucovorin Calcium
Treatment: Drugs - Mercaptopurine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Pegaspargase
Treatment: Drugs - Prednisone
Treatment: Other - Radiation Therapy
Treatment: Drugs - Thioguanine
Treatment: Drugs - Vincristine Sulfate

Experimental: 0.2 mg/kg - PRX-102 0.2 mg/kg every 2 weeks

Experimental: 1 mg/kg - PRX-102 1 mg/kg every 2 weeks

Experimental: 2 mg/kg - PRX-102 2 mg/kg every 2 weeks


Treatment: Drugs: Cytarabine
Given IT, IV, or SC

Treatment: Drugs: Dasatinib
Given PO

Treatment: Drugs: Daunorubicin Hydrochloride
Given IV

Treatment: Drugs: Dexamethasone
PO or IV

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Drugs: Hydrocortisone Sodium Succinate
Given IT

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Leucovorin Calcium
Given PO or IV

Treatment: Drugs: Mercaptopurine
Given PO

Treatment: Drugs: Methotrexate
Given IT and IV

Treatment: Drugs: Pegaspargase
Given IV

Treatment: Drugs: Prednisone
Given PO or IV

Treatment: Other: Radiation Therapy
Undergo radiation therapy

Treatment: Drugs: Thioguanine
Given PO

Treatment: Drugs: Vincristine Sulfate
Given IV
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse Events
Timepoint [1] 0 0
12 months
Primary outcome [2] 0 0
DFS of Non-DS HR Post-induction Patients Receiving Intrathecal (IT) Methotrexate (MTX) Compared With Patients Receiving Intrathecal Triple Therapy (ITT) on a Modified Berlin-Frankfurt-Munster (MBFM) Interim Maintenance High-dose Methotrexate Backbone
Timepoint [2] 0 0
At 5 years
Primary outcome [3] 0 0
DFS of Non-DS VHR Post-Induction Patients Who Receive a Modified MBFM-IMHDM Regimen That Contains a Second IM (Control Arm) Compared to Patients Receive the Cyclophosphamide + Etoposide Containing Regimen (Experimental Arm 1)
Timepoint [3] 0 0
At 4 years
Secondary outcome [1] 0 0
Toxicity and Tolerability of Post-induction Age-adjusted ITT Compared to Age-adjusted IT MTX in Children With HR B-ALL
Timepoint [1] 0 0
Up to 10 years
Secondary outcome [2] 0 0
Toxicity and Tolerability of Experimental Arm 1 and Control Arm in Patients With VHR B-ALL
Timepoint [2] 0 0
Up to 10 years
Secondary outcome [3] 0 0
Induction Mortality in Patients With DS and HR B-ALL Treated With Modified Induction
Timepoint [3] 0 0
At 1 month
Secondary outcome [4] 0 0
5-year DFS in Patients With Down Syndrome (DS) and HR B-ALL Treated With Modified Induction and Post-Induction Therapy Regimen With MBFM-IMIDM
Timepoint [4] 0 0
At 5 years
Secondary outcome [5] 0 0
DFS for Children and Young Adults With Ph-like B-ALL and a Predicted Tyrosine Kinase Inhibitor (TKI)-Sensitive Mutation Treated With Dasatinib Plus MBFM-IMHDM
Timepoint [5] 0 0
Up to 4 years
Secondary outcome [6] 0 0
Toxicity and Tolerability of MBFM-interim Maintenance Intermediate Dose Methotrexate (IMIDM) in Children With Down Syndrome
Timepoint [6] 0 0
Up to 10 years
Secondary outcome [7] 0 0
Overall Survival (OS) Rate for HR B-ALL Patients, Overall and by Randomized Arm
Timepoint [7] 0 0
At 5 years
Secondary outcome [8] 0 0
Overall Survival (OS) Rate for VHR B-ALL Patients, Overall and by Randomized Arm.
Timepoint [8] 0 0
At 4 years
Secondary outcome [9] 0 0
Incidence of Osteonecrosis (ON) Defined by Magnetic Resonance (MR) Imaging in Children, Adolescents, and Young Adults 10 Years of Age and Greater
Timepoint [9] 0 0
Up to 10 years
Secondary outcome [10] 0 0
The Prevalence of Cognitive Deficits Measured by CogState (Domain: Working Memory), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy
Timepoint [10] 0 0
Up to 10 years
Secondary outcome [11] 0 0
The Prevalence of Cognitive Deficits Measured by CogState (Domain: Executive Function), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy
Timepoint [11] 0 0
Up to 10 years
Secondary outcome [12] 0 0
The Prevalence of Cognitive Deficits Measured by CogState (Domain: Visual Learning), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy
Timepoint [12] 0 0
Up to 10 years
Secondary outcome [13] 0 0
The Prevalence of Cognitive Deficits Measured by CogState (Domain: Processing Speed), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy
Timepoint [13] 0 0
Up to 10 years
Secondary outcome [14] 0 0
The Prevalence of Cognitive Deficits Measured by CogState (Domain: Visual Attention), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy
Timepoint [14] 0 0
Up to 10 years

Eligibility
Key inclusion criteria
* Symptomatic adult Fabry patients (=18 yrs)
* Males: plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than lower limit of normal (LLN in plasma=3.2 nmol/hr/ml, LLN in leucocytes=32 nmol/hr/mg/protein)
* Females: historical genetic test results consistent with Fabry mutations
* Globotriaosylceramide (Gb3) concentration in urine > 1.5 times upper normal limit
* Patients who have never received enzyme replacement therapy (ERT) in the past, or patients who have not received ERT in the past 6 months and have a negative anti alpha galactosidase antibody test
* eGFR = 60 mL/min/1.73m2
* The patient signs informed consent
* Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically acceptable method of contraception, not including the rhythm method
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participation in any trial of an investigational drug within 30 days prior to study screening
* Chronic kidney disease stages 3-5 (CKD 3-5) (Appendix 7)
* History of dialysis or renal transplantation
* Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
* Severe myocardial fibrosis by MRI (=2 late-enhancement [LE] positive left ventricular segments) (Weidemann et al. 2009)
* History of clinical stroke
* Pregnant or nursing
* Presence of HIV and/or HBsAg and/or Hepatitis C infections
* Known allergies to ERT
* Known allergy to Gadolinium based contrast agents
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/03/2016
Sample size
Target
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Melbourne Hospital - Victoria Park
Recruitment hospital [2] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [4] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [5] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [6] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [7] 0 0
Monash Medical Center-Clayton Campus - Clayton
Recruitment hospital [8] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [9] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [10] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
3050 - Victoria Park
Recruitment postcode(s) [2] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
5006 - North Adelaide
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment postcode(s) [7] 0 0
3052 - Parkville
Recruitment postcode(s) [8] 0 0
6008 - Perth
Recruitment postcode(s) [9] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
Paraguay
State/province [10] 0 0
Asuncion
Country [11] 0 0
Serbia
State/province [11] 0 0
Belgrade
Country [12] 0 0
Spain
State/province [12] 0 0
Zaragoza
Country [13] 0 0
United Kingdom
State/province [13] 0 0
London
Country [14] 0 0
United States of America
State/province [14] 0 0
Alabama
Country [15] 0 0
United States of America
State/province [15] 0 0
Alaska
Country [16] 0 0
United States of America
State/province [16] 0 0
Arizona
Country [17] 0 0
United States of America
State/province [17] 0 0
Arkansas
Country [18] 0 0
United States of America
State/province [18] 0 0
Colorado
Country [19] 0 0
United States of America
State/province [19] 0 0
Connecticut
Country [20] 0 0
United States of America
State/province [20] 0 0
Delaware
Country [21] 0 0
United States of America
State/province [21] 0 0
District of Columbia
Country [22] 0 0
United States of America
State/province [22] 0 0
Florida
Country [23] 0 0
United States of America
State/province [23] 0 0
Hawaii
Country [24] 0 0
United States of America
State/province [24] 0 0
Idaho
Country [25] 0 0
United States of America
State/province [25] 0 0
Illinois
Country [26] 0 0
United States of America
State/province [26] 0 0
Indiana
Country [27] 0 0
United States of America
State/province [27] 0 0
Kentucky
Country [28] 0 0
United States of America
State/province [28] 0 0
Louisiana
Country [29] 0 0
United States of America
State/province [29] 0 0
Maine
Country [30] 0 0
United States of America
State/province [30] 0 0
Massachusetts
Country [31] 0 0
United States of America
State/province [31] 0 0
Michigan
Country [32] 0 0
United States of America
State/province [32] 0 0
Minnesota
Country [33] 0 0
United States of America
State/province [33] 0 0
Mississippi
Country [34] 0 0
United States of America
State/province [34] 0 0
Missouri
Country [35] 0 0
United States of America
State/province [35] 0 0
Nebraska
Country [36] 0 0
United States of America
State/province [36] 0 0
Nevada
Country [37] 0 0
United States of America
State/province [37] 0 0
New Hampshire
Country [38] 0 0
United States of America
State/province [38] 0 0
New Jersey
Country [39] 0 0
United States of America
State/province [39] 0 0
New Mexico
Country [40] 0 0
United States of America
State/province [40] 0 0
New York
Country [41] 0 0
United States of America
State/province [41] 0 0
North Dakota
Country [42] 0 0
United States of America
State/province [42] 0 0
Ohio
Country [43] 0 0
United States of America
State/province [43] 0 0
Oklahoma
Country [44] 0 0
United States of America
State/province [44] 0 0
Oregon
Country [45] 0 0
United States of America
State/province [45] 0 0
Rhode Island
Country [46] 0 0
United States of America
State/province [46] 0 0
South Carolina
Country [47] 0 0
United States of America
State/province [47] 0 0
South Dakota
Country [48] 0 0
United States of America
State/province [48] 0 0
Tennessee
Country [49] 0 0
United States of America
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Utah
Country [50] 0 0
United States of America
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Vermont
Country [51] 0 0
United States of America
State/province [51] 0 0
Washington
Country [52] 0 0
United States of America
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West Virginia
Country [53] 0 0
United States of America
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Wisconsin
Country [54] 0 0
Canada
State/province [54] 0 0
Alberta
Country [55] 0 0
Canada
State/province [55] 0 0
British Columbia
Country [56] 0 0
Canada
State/province [56] 0 0
Manitoba
Country [57] 0 0
Canada
State/province [57] 0 0
Newfoundland and Labrador
Country [58] 0 0
Canada
State/province [58] 0 0
Nova Scotia
Country [59] 0 0
Canada
State/province [59] 0 0
Ontario
Country [60] 0 0
Canada
State/province [60] 0 0
Quebec
Country [61] 0 0
Canada
State/province [61] 0 0
Saskatchewan
Country [62] 0 0
Ireland
State/province [62] 0 0
Co Dublin
Country [63] 0 0
New Zealand
State/province [63] 0 0
Auckland
Country [64] 0 0
New Zealand
State/province [64] 0 0
Christchurch
Country [65] 0 0
Puerto Rico
State/province [65] 0 0
San Juan
Country [66] 0 0
Switzerland
State/province [66] 0 0
Geneva
Country [67] 0 0
Switzerland
State/province [67] 0 0
Lausanne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Protalix
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Chiesi Farmaceutici S.p.A.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is the first human treatment with PRX-102, an enzyme being developed as a long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease (alpha galactosidase deficiency). The safety, tolerability, and exploratory efficacy will be evaluated in this study of increasing doses. Patients will be treated with infusions every two weeks for 12 months.
Trial website
https://clinicaltrials.gov/study/NCT01769001
Trial related presentations / publications
Schiffmann R, Goker-Alpan O, Holida M, Giraldo P, Barisoni L, Colvin RB, Jennette CJ, Maegawa G, Boyadjiev SA, Gonzalez D, Nicholls K, Tuffaha A, Atta MG, Rup B, Charney MR, Paz A, Szlaifer M, Alon S, Brill-Almon E, Chertkoff R, Hughes D. Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: A 1-year Phase 1/2 clinical trial. J Inherit Metab Dis. 2019 May;42(3):534-544. doi: 10.1002/jimd.12080. Epub 2019 Apr 8.
Salzer WL, Burke MJ, Devidas M, Dai Y, Hardy KK, Kairalla JA, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Impact of Intrathecal Triple Therapy Versus Intrathecal Methotrexate on Disease-Free Survival for High-Risk B-Lymphoblastic Leukemia: Children's Oncology Group Study AALL1131. J Clin Oncol. 2020 Aug 10;38(23):2628-2638. doi: 10.1200/JCO.19.02892. Epub 2020 Jun 4.
Public notes

Contacts
Principal investigator
Name 0 0
Einat Almon, PhD
Address 0 0
Protalix Biotherapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01769001