PhenylketonuriaPRISM303NCT02468570
A Phase 3 Substudy to Evaluate Executive Function in Adults With PKU Who Are Participating in the Phase 3 Study, 165-302
An observational study of Phenylketonuria, run by BioMarin Pharmaceutical at 4 sites in United States.
Trial summary
A Phase 3 substudy to evaluate executive function in adults with phenylketonuria who are participating in the phase 3 Study, 165-302. Approximately 100 subjects, aged ≥ 18 to ≤ 70 years old, with PKU will be enrolled. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- Administration of CANTAB and Subject Global Assessment
- How many people
- 9 participants
- Where
- 4 sitesUnited States
- Study dates
- 5 Aug 2015to 1 Feb 2017
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Subjects with PKU who are currently enrolled in 165-302 Part 2.
Who may be able to join
- Are currently participating in Part 1 of Study 165-302 and meet the criteria for participation in Part 2 of 165-302
- Are willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any research-related procedures.
- Have the ability to complete the CANTAB and subject global assessment.
- Are willing and able to comply with all study procedures.
Who cannot join
- Any condition that, in the view of the investigator, places the subject at high risk of poor compliance or terminating early from the study
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Kentucky Medical Center
Lexington, Kentucky, 40536
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Oregon Health and Science University
Portland, Oregon, 97239
About this study
Official title: A Phase 3 Substudy to Evaluate Executive Function in Adults With Phenylketonuria Who Are Participating in the Phase 3 Study, 165-302
A Phase 3 substudy to evaluate executive function in adults with phenylketonuria who are participating in the phase 3 Study, 165-302. Approximately 100 subjects, aged ≥ 18 to ≤ 70 years old, with PKU will be enrolled.
Read the detailed description
Study 165-303, is a Phase 3 substudy enrolling approximately 100 subjects, aged ≥ 18 to ≤ 70 years old, with PKU who are participating in the Phase 3 study, 165-302.
Per the 165-303 protocol, the investigator does not assign a specific intervention to the study participants. In accordance with the protocol for Study 165-303, subjects were asked to perform selected set of three tasks from the CANTAB tool (Rapid Visual Processing [RVP], Spatial Working Memory [SWM], and Stop Signal Task [SST]) to assess executive function and each subject's self perception of their current state was measured using a subject global assessment questionnaire that contains seven questions about current state perception of attention, energy level, tiredness, confusion, sadness, anger and tension.
The time points for administering the above tools are as follows, which coincide with time points in part 2 and part 4 of Study 165-302: screening (entry into Part 2 165-302 Day 1 of Week 1), baseline visit (Part 2 Week 8), and 3 additional study visits at different time points in the Part 4 of 165-302 study.
- Conditions
- Phenylketonuria
- Being tested
- Administration of CANTAB and Subject Global Assessment
- Keywords
- PKU, PEG-PAL, Pegvaliase, BMN 165, rAv-PAL PEG, PRISM 302, PRISM 303, BioMarin, 165-302
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Administration of CANTAB and Subject Global AssessmentOther
At designated visits, subject will perform the CANTAB tasks and complete the Subject Global Assessment Questionnaire
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Rapid Visual Processing (RVP) Mean Response Latency (CANTAB Task)
The RVP task measures sustained attention. In this task, a series of random digits continuously appears in the middle of the screen. Subjects are asked to recognize a specific sequence of digits and are asked to press a button on the screen whenever this specific sequence of digits appears within this series of continuous digits.
RVP mean latency is the mean response latency during assessment sequence blocks where the subject responded correctly (Latency units are milliseconds). Lower scores represent better performance.
Observed range for Pooled Active: -103.1 to 65.5 (change from baseline) Observed range for Pooled Placebo: -10.4 to 39.0 (change from baseline)
Measured: Baseline to Part 2 Week 8
Change From Baseline in Spatial Working Memory (SWM) Between Errors 4-8 Boxes (CANTAB Task)
The SWM task measures visuospatial working memory. During this task, a number of boxes appears on a screen. The objective of the task is to find a token under a box and to place this token in a designated area. There is only one token under one box during each round and the location of the token rotates in each round to a different box, other than a box within which the token was found in previous rounds. The subject is therefore asked to remember which boxes previously contained tokens so as to better the chances and speed of finding tokens under boxes which did not previously contain tokens.
SWM between errors measures the total number of times the subject revisits a box in which a token has previously been found in the same problem (calculated for assessed problems only).
Observed range for Pooled Active: -8 to 1 (change from baseline) Observed range for Pooled Placebo: -5 to 12 (change from baseline)
Lower scores represent better performance.
Measured: Baseline to Part 2 Week 8
Change From Baseline in Stop Signal Task (SST) Stop Signal Reaction T (CANTAB Task)
The SST task measures inhibitory control and cognitive flexibility. The SST is a 2-part task. During part 1, an arrow appears on the screen and subjects are asked to press an arrow button on the screen corresponding with the direction of the arrow displayed. During part 2 of the task, subjects follow the same instructions as in part 1; however, they are asked to withhold their response (do not press an arrow button) if they hear an auditory signal (beep) when the arrow is displayed.
SST stop signal delay is the length of time between the go stimulus and the stop stimulus at which the subject is able to successfully inhibit their response on 50% of trials. Lower time represents better performance.
Observed range for Pooled Active: -31.6 to 48.7 (change from baseline) Observed range for Pooled Placebo: 47.8 to 72.5 (change from baseline)
Measured: Baseline to Part 2 Week 8
Secondary outcomes (3)
Change From Baseline in RVP A Prime - Signal Detection Measure of Sensitivity to the Target (CANTAB Task)
The RVP task measures sustained attention. In this task, a series of random digits continuously appears in the middle of the screen. Subjects are asked to recognize a specific sequence of digits and are asked to press a button on the screen whenever this specific sequence of digits appears within this series of continuous digits.
RVP A prime represents the signal detection measure of sensitivity to the target, regardless of response tendency. In essence, measure of how good the subject is at detecting target sequences.
Observed range for Pooled Active: -0.004 to 0.030 (change from baseline) Observed range for Pooled Placebo: -0.057 to -0.001 (change from baseline)
A higher score on the test represents a better performance.
Measured: Baseline to Part 2 Week 8
Change From the Baseline in SWM Strategy 6-8 Boxes - Number of Distinct Boxes Used by the Subject to Begin a New Search for a Token(CANTAB Task)
The SWM task measures visuospatial working memory. During this task, a number of boxes appears on a screen. The objective of the task is to find a token under a box and to place this token in a designated area. There is only one token under one box during each round and the location of the token rotates in each round to a different box, other than a box within which the token was found in previous rounds. The subject is therefore asked to remember which boxes previously contained tokens so as to better the chances and speed of finding tokens under boxes which did not previously contain tokens.
For assessed problems with six boxes or more, SWM strategy is the number of distinct boxes used by the subject to begin a new search for a token (within the same problem). A high score represents poor use of this strategy and a low score equates to effective use.
Observed range for Pooled Active: -3 to 3 (change from baseline) Observed range for Pooled Placebo: -3 to 1(change from baseline)
Measured: Baseline to Part 2 Week 8
Change From Baseline in SST Proportion of Successful Stops - Measures the Proportion of Completed Stop Trials That Were Successful Stops (CANTAB Task)
The SST task measures inhibitory control and cognitive flexibility. The SST is a 2-part task. During part 1, an arrow appears on the screen and subjects are asked to press an arrow button on the screen corresponding with the direction of the arrow displayed. During part 2 of the task, subjects follow the same instructions as in part 1; however, they are asked to withhold their response (do not press an arrow button) if they hear an auditory signal (beep) when the arrow is displayed. SST stop signal delay is the length of time between the go stimulus and the stop stimulus at which the subject is able to successfully inhibit their response on 50% of trials.
SST proportion of successful stops measures the proportion of completed stop trials that were successful stops. A higher score on the test represents a better performance.
Observed range for Pooled Active: -0.1 to 0.05 (change from baseline) Observed range for Pooled Placebo: 0.0 to 0.0 (change from baseline)
Measured: Baseline to Part 2 Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2015 (estimated)
- Study start5 Aug 2015
- Primary completion1 Feb 2017
- Study completion1 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Debra Lounsbury, Study director, Principal Scientist/Medical Monitor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02468570
- Sponsor's protocol ID
- 165-303
- Acronym
- PRISM303
- Status last verified
- May 2020
- First submitted
- 3 Jun 2015
- Last updated
- 4 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Substudy to Evaluate Executive Function in Adults With Phenylketonuria Who Are Participating in the Phase 3 Study, 165-302
- ClinicalTrials.gov ID
- NCT02468570
- Acronym / sponsor ID
- PRISM303 / 165-303
- Conditions
- Phenylketonuria
- Keywords
- PKU, PEG-PAL, Pegvaliase, BMN 165, rAv-PAL PEG, PRISM 302, PRISM 303, BioMarin
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- 5 Aug 2015 (actual)
- Primary completion
- 1 Feb 2017 (actual)
- Study completion
- 1 Feb 2017 (actual)
- First posted
- 11 Jun 2015 (estimated)
- Results
- Posted 4 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase 3 substudy to evaluate executive function in adults with phenylketonuria who are participating in the phase 3 Study, 165-302. Approximately 100 subjects, aged ≥ 18 to ≤ 70 years old, with PKU will be enrolled.
Detailed description
Study 165-303, is a Phase 3 substudy enrolling approximately 100 subjects, aged ≥ 18 to ≤ 70 years old, with PKU who are participating in the Phase 3 study, 165-302.
Per the 165-303 protocol, the investigator does not assign a specific intervention to the study participants. In accordance with the protocol for Study 165-303, subjects were asked to perform selected set of three tasks from the CANTAB tool (Rapid Visual Processing [RVP], Spatial Working Memory [SWM], and Stop Signal Task [SST]) to assess executive function and each subject's self perception of their current state was measured using a subject global assessment questionnaire that contains seven questions about current state perception of attention, energy level, tiredness, confusion, sadness, anger and tension.
The time points for administering the above tools are as follows, which coincide with time points in part 2 and part 4 of Study 165-302: screening (entry into Part 2 165-302 Day 1 of Week 1), baseline visit (Part 2 Week 8), and 3 additional study visits at different time points in the Part 4 of 165-302 study.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects with PKU who are currently enrolled in 165-302 Part 2.
Key inclusion criteria (4 listed)
- Are currently participating in Part 1 of Study 165-302 and meet the criteria for participation in Part 2 of 165-302
- Are willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any research-related procedures.
- Have the ability to complete the CANTAB and subject global assessment.
- Are willing and able to comply with all study procedures.
Key exclusion criteria (1 listed)
- Any condition that, in the view of the investigator, places the subject at high risk of poor compliance or terminating early from the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Administration of CANTAB and Subject Global AssessmentAt designated visits, subject will perform the CANTAB tasks and complete the Subject Global Assessment Questionnaire | Other | – |
Primary outcome
Change From Baseline in Rapid Visual Processing (RVP) Mean Response Latency (CANTAB Task)
Time frame: Baseline to Part 2 Week 8
The RVP task measures sustained attention. In this task, a series of random digits continuously appears in the middle of the screen. Subjects are asked to recognize a specific sequence of digits and are asked to press a button on the screen whenever this specific sequence of digits appears within this series of continuous digits. RVP mean latency is the mean response latency during assessment sequence blocks where the subject responded correctly (Latency units are milliseconds). Lower scores represent better performance. Observed range for Pooled Active: -103.1 to 65.5 (change from baseline) Observed range for Pooled Placebo: -10.4 to 39.0 (change from baseline)
Change From Baseline in Spatial Working Memory (SWM) Between Errors 4-8 Boxes (CANTAB Task)
Time frame: Baseline to Part 2 Week 8
The SWM task measures visuospatial working memory. During this task, a number of boxes appears on a screen. The objective of the task is to find a token under a box and to place this token in a designated area. There is only one token under one box during each round and the location of the token rotates in each round to a different box, other than a box within which the token was found in previous rounds. The subject is therefore asked to remember which boxes previously contained tokens so as to better the chances and speed of finding tokens under boxes which did not previously contain tokens. SWM between errors measures the total number of times the subject revisits a box in which a token has previously been found in the same problem (calculated for assessed problems only). Observed range for Pooled Active: -8 to 1 (change from baseline) Observed range for Pooled Placebo: -5 to 12 (change from baseline) Lower scores represent better performance.
Change From Baseline in Stop Signal Task (SST) Stop Signal Reaction T (CANTAB Task)
Time frame: Baseline to Part 2 Week 8
The SST task measures inhibitory control and cognitive flexibility. The SST is a 2-part task. During part 1, an arrow appears on the screen and subjects are asked to press an arrow button on the screen corresponding with the direction of the arrow displayed. During part 2 of the task, subjects follow the same instructions as in part 1; however, they are asked to withhold their response (do not press an arrow button) if they hear an auditory signal (beep) when the arrow is displayed. SST stop signal delay is the length of time between the go stimulus and the stop stimulus at which the subject is able to successfully inhibit their response on 50% of trials. Lower time represents better performance. Observed range for Pooled Active: -31.6 to 48.7 (change from baseline) Observed range for Pooled Placebo: 47.8 to 72.5 (change from baseline)
3 secondary outcomes
Change From Baseline in RVP A Prime - Signal Detection Measure of Sensitivity to the Target (CANTAB Task)
Time frame: Baseline to Part 2 Week 8
Change From the Baseline in SWM Strategy 6-8 Boxes - Number of Distinct Boxes Used by the Subject to Begin a New Search for a Token(CANTAB Task)
Time frame: Baseline to Part 2 Week 8
Change From Baseline in SST Proportion of Successful Stops - Measures the Proportion of Completed Stop Trials That Were Successful Stops (CANTAB Task)
Time frame: Baseline to Part 2 Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BioMarin Pharmaceutical WebsiteLink provided by the sponsor.
- BioMarin sponsored PKU educational/community websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Debra Lounsbury study director
Principal Scientist/Medical Monitor
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Phenylketonuria, run by BioMarin Pharmaceutical at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Rapid Visual Processing (RVP) Mean Response Latency (CANTAB Task) (time frame: Baseline to Part 2 Week 8). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2020.