Mucopolysaccharidosis VI
Conditions
Interventions
This is a randomized, double-blind, placebo-controlled, pilot study to evaluate the safety and tolerability of Pentosan Polysulfate Sodium (PPS) in the treatment of research participants with Mucopoly
Sponsors
Hospital de Clínicas de Porto Alegre da Universidade Federal do Rio Grande do Sul
Hospital Universitário Alcides Carneiro da Universidade Federal de Campina Grande
Universidade Federal de São Paulo
Eligibility
Age
5 Years to No maximum
Inclusion criteria
Inclusion criteria: Male and female subjects greater than or equal to 5 years of age; confirmed diagnosis by genetic testing and/or enzyme activity of Mucopolysaccharidosis (MPS) Type VI (N-acetylgalactosamine-4-sulfatase deficiency and a second normal sulfatase enzyme); must be on enzyme replacement therapy (ERT) for greater than or equal to 1 year; must be on at stable dose of enzyme replacement therapy (ERT) for 3 months prior to baseline; must have a mean pain score of a minimum of 3 and a maximum of 9 on the Faces Pain Scale-Revised (FPS-R) taken from the first 5 consecutive measurements at screening; able to walk 30 metres with or without use of an assistive device; 6MWT less than or equal to 70% (percent) predicted of normative mean value for age; participant demonstrates an impairment of ROM in at least one shoulder; participant or parent, or legally acceptable representative sufficiently able to understand the purposes and risks of the study and able to provide written informed consent or in the case of participants age less then 18 years, provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures or study assessment; if applicable, participants must be willing to comply with the medically acceptable contraceptive requirements of the study from screening to at least 28 days after the last investigational product (IP) administration; participants should not be pregnant or breastfeeding at the time of study entry; participants must be willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures
Exclusion criteria
Exclusion criteria: Documented or reported history of increased bleeding tendency in the presence or absence of anticoagulant or antiplatelet drugs; history of heparin induced thrombocytopenia; current treatment with anticoagulants or antiplatelet drugs, excluding aspirin less than or equal to 100 mg per day; absence of limitation in upper extremity fine motor skills; absence of shoulder joint Range of Motion (ROM) limitations; participant taking opioids within 2 weeks of Day 1 or unwilling to stop the treatment opioids throughout the study; parenteral iloprost from 12 weeks before Day 1 and throughout the study; parenteral bisphosphonates from 12 months before Day 1 and throughout the study; currently active or recent history (within preceding 12 months) of a gastric or duodenal ulcer, or suspicion of gastrointestinal (GI) tract bleeding; coagulation parameters or platelets outside laboratory reference range, liver function tests greater than or equal to 1.5 × upper limit of normal (ULN), or estimated glomerular filtration rate (eGFR) less then 30 mL per min at Screening; hepatic synthetic insufficiency (including Gilbert’s Syndrome); history of bone marrow transplant or haematopoietic stem cell transplant; history or evidence of chondrocalcinosis or fibromyalgia; history or evidence of HIV, hepatitis B or hepatitis C; major surgery within 12 weeks preceding Day 1 or anticipated surgery in the study period; medical history or evidence of any clinically significant active or chronic condition involving the musculoskeletal system, which in the opinion of the Investigator may impact assessment of safety or efficacy parameters or the validity of study results; current or recent immunosuppressive or immunomodulatory systemic therapy; currently hospitalised; any acute illness within 2 weeks of baseline; a history of drug or alcohol abuse and/or dependence as documented by participant/caregiver reporting within the 12 months preceding screening; participation in another clinical trial or administration of any investigational product or experimental product within 12 weeks or five half-lives (whichever is longer) preceding Day 1; history of significant hypersensitivity to pentosan polysulfate sodium (PPS) or drugs of a similar chemical or pharmacological class; any clinically significant abnormalities as judged by the Investigator at screening; history of or current clinically significant gastrointestinal (GI), hepatic, renal, cardiovascular, respiratory, endocrine, oncological, immunological, neurological, ophthalmological (including existing pigmentary maculopathy), haematological or psychiatric disorder or any other condition (with the exception of signs and symptoms relating to MPS VI), which in the opinion of the Investigator or Sponsor would jeopardize the safety of the subject or the validity of the study results; an employee of the Sponsor or research site personnel directly affiliated with this study or their immediate family members defined as a spouse, parent, sibling, or child, whether biological or legally adopted
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Observed Primary Endpoint 1: The study met the primary endpoint of safety and tolerability. Safety analysis: Safety analysis was performed on all participants who received at least 1 injection of PPS. A total of 13 participants (8 PPS-treated and 5 placebo-treated) were included in the safety summaries. The number and percentage of participants experiencing any TEAEs, SAEs, and AEs overall was tabulated at each visit, up to the end of study visit. Exposure data: The mean number of doses and exposure in days was similar between PPS with 23.9 doses (standard deviation [SD]: 0.35) and 161.6 days (SD: 1.06), and placebo with 24 doses (SD: 0.00) and 160.8 days (SD: 1.10). The mean compliance percentage of the PPS group was 99.48% (SD: 1.473) versus 100% (SD: 0.00) for the placebo group. Adverse events: Seven (7) out of 8 PPS participants (87.5%) and all the placebo participants 5/5 (100%) reported at least one TEAE. The majority of TEAEs were considered mild; with 7/8 participants (87.5%) in the PPS group and 5/5 participants (100%) in the placebo treatment group reporting mild TEAEs. One (1) participant in the PPS group (12.5%) and 2 participants in the placebo group (40%) had a TEAE that was considered moderate. No participants had a severe TEAE. The most frequently reported system organ classes (SOC) in the PPS group were general disorders and administration site conditions with 6/8 participants (75%), gastrointestinal disorders reported in 5/8 participants (62.5%), and infections and infestations reported in 4/8 participants (40%). The most frequently reported preferred term (PT) in the PPS group was vomiting reported in 4/8 participants (50%), and then injection site pain, injection site reaction, nausea, and headache, each reported in 3/8 participants (37.5%). All other PTs were not reported in more than 2 PPS participants. The most frequently reported SOC in the placebo group was also general disorders and administration site conditions, as well as gastrointestina | — |
Secondary
| Measure | Time frame |
|---|---|
| Expected Secondary Endpoint 3: To evaluate the effect of PPS on the change from baseline in pain intensity at the end of 6, 12, and 24 weeks as measured by the Faces Pain Scale-Revised assessment (FPS-R). Pain intensity analysis using a visual analogue scale (VAS) was also performed. Absolute and percentage change from baseline results at each assessment were assessed. ;Observed Secondary Endpoint 3: Timepoints measured for this endpoint are shown at the maximum visit timepoint window of 7, 13, and 25 weeks, which were within the tolerance as specified in the protocol. FPS-R pain responses improved (decreased FPS-R) in both groups over time, but the treatment difference was not significantly different between PPS and placebo at weeks 7, 13, and 25. Average VAS pain (calculated over 7 days) at baseline and after 25 weeks showed improvement (decreased VAS) in both groups, but the treatment difference was not significantly different between PPS and placebo at weeks 7, 13, and 25.;Expected Secondary Endpoint 4: To evaluate the effect of PPS on the change from baseline in upper extremity function via the NIH Toolbox 9-Hole Pegboard Dexterity Test (9-HPT) at 6, 12, and 24 weeks. Absolute and percentage change from baseline for the time to complete the NIH Toolbox 9-HPT at each assessment were assessed. ;Observed Secondary Endpoint 4: Timepoints measured for this endpoint are shown at the maximum visit timepoint window of 7, 13, and 25 weeks, which were within the tolerance as specified in the protocol. The NIH Toolbox 9-HPT measures fine motor dexterity and is reported for both the dominant hand and the non-dominant hand. The 9-HPT showed improvement (decreased time) for both dominant and non-dominant hand function in the PPS compared to the placebo group. There was a significant treatment difference of 4.4% improvement in favour of PPS in the non-dominant hand at week 13 (p<0.05). The PPS group had an 8.4% and 11% decrease in time taken to complete the test (improveme | — |
Countries
Brazil
Contacts
Public ContactMariane Carradore
CTI Clinical Brasil Serviços de Pesquisa Clínicas Ltda
Outcome results
None listed