Pantothenate Kinase-Associated NeurodegenerationPhase 3PKANNCT03041116
Efficacy and Safety Study of Fosmetpantotenate (RE-024) in PKAN Participants
A Phase 3 study testing Fosmetpantotenate in people with Pantothenate Kinase-Associated Neurodegeneration, run by Travere Therapeutics, Inc. at 20 sites in 9 countries.
Trial summary
This study investigated whether fosmetpantotenate (RE-024), a phosphopantothenate replacement therapy, was safe and effective in treating participants with PKAN. Read more about this study
- Who is it for?
- Ages 6 to 65 years
- Conditions the study is for
- Pantothenate Kinase-Associated Neurodegeneration
- What is being tested?
- Fosmetpantotenate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 20 sitesin 9 countries
- Study dates
- 17 Jul 2017to 30 Dec 2019
- Phase
- Phase 3
- 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 6 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The participant had a diagnosis of PKAN as indicated by confirmed mutations in the pantothenate kinase 2 gene.
- The participant was male or female aged 6 to 65 years, inclusive.
- The participant had a score of ≥ 6 on the PKAN-specific activities of daily living measure.
Who cannot join
- The participant had required regular or intermittent invasive ventilatory support to maintain vital signs within 24 weeks prior to randomization.
- The participant had a deep brain stimulation device implanted within 6 months prior to screening.
- The participant had taken deferiprone within 30 days prior to screening.
- The participant was unable to maintain stable doses of allowed concomitant medications for the first 24 weeks of the study.
Trial locations and contacts
20 sites in 9 countries.
20 sites in 9 countries
United States9 sites
Travere Investigational Site
Boston, Massachusetts, 02114
Travere Investigational Site
Chicago, Illinois, 60612
Travere Investigational Site
Decatur, Georgia, 30033
Travere Investigational Site
Houston, Texas, 77030
Travere Investigational Site
Irvine, California, 92697
Travere Investigational Site
Miami, Florida, 33155
Travere Investigational Site
New York, New York, 10032
Travere Investigational Site
Pittsburgh, Pennsylvania, 15224
Travere Investigational Site
Washington D.C., District of Columbia, 20010
Canada2 sites
Travere Investigational Site
Toronto, Ontario, M5G1X8
Travere Investigational Site
Toronto, Ontario, M5T 2S8
France2 sites
Travere Investigational Site
Montpellier, Languedoc-Rousillon
Travere Investigational Site
Paris, Île-de-France Region
Spain2 sites
Travere Investigational Site
Barcelona, Catalonia, 08035
Travere Investigational Site
Barcelona
About this study
Official title: Efficacy, Safety, and Tolerability of Fosmetpantotenate (RE-024), a Phosphopantothenate Replacement Therapy, in Pantothenate Kinase-Associated Neurodegeneration (PKAN) Patients: A Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label Extension
This study investigated whether fosmetpantotenate (RE-024), a phosphopantothenate replacement therapy, was safe and effective in treating participants with PKAN.
- Being tested
- Fosmetpantotenate, Placebo
- Keywords
- PKAN
- Medical subject headings
- Pantothenate Kinase-Associated Neurodegeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FosmetpantotenateDrug
Also called RE-024
Daily dosing
PlaceboDrug
Daily dosing
| Study group | Role | What they receive |
|---|---|---|
| Fosmetpantotenate | Experimental | Administered as powder for reconstitution. Receives: Drug: Fosmetpantotenate |
| Placebo | Placebo comparator | Administered as powder for reconstitution. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline In The Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living (PKAN-ADL) Total Score To The End Of The 24-week Double-blind Period
Change from baseline to Week 24 activities of daily living was assessed on the PKAN-ADL scale based on the Unified Parkinson's Disease Rating Scale (UPDRS) Part II. The PKAN-ADL is a validated measure of the participant's ability to complete ADL that are impacted by the diffuse motor manifestations of PKAN. It consists of 12 items related to activities of daily living, including eating, dressing, and walking. Each item has responses ranging from 0-4, with a higher value indicating greater disability in the given activity. To compute the total score, responses are summed across the 12 items. The available range of total scores on the PKAN-ADL scale was from 0 (no ADL affected) to 48 (ADL highly affected). The reported least square mean (LSM) was adjusted for baseline score and age group from the Type III analysis. A decrease in score indicates improvement in symptoms.
Measured: Baseline (Day -1), Week 24
Number Of Participants With At Least 1 (≥1) Treatment-emergent Adverse Event (TEAE) And Treatment-emergent Serious Adverse Event (TESAE) During The 24-week Double-blind Period
An adverse event (AE) is any untoward medical occurrence associated with the use of the investigational product (IP; active or placebo) in a participant, without regard to possibility of causal relationship with IP. A serious adverse event (SAE) is an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of death from AE); persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious medical events. The TEAEs in the double-blind period are defined as AEs that are new or are a worsening of an existing condition that begins from day of first dose of IP until day after last dose for double-blind treatment period.
Measured: From Screening until end of Week 24
Secondary outcomes (1)
Absolute Change From Baseline In The UPDRS Part 3 (UPDRS-III) Total Score To The End Of The 24-week Double-blind Period
The UPDRS is a comprehensive assessment of the burden and severity of signs and symptoms of Parkinsonism captured via systematic interview and neurological examination. The UPDRS-III is a standardized neurological examination that evaluates the performance of movements commonly affected in Parkinson's disease, PKAN, and other movement disorders. Part III of the UPDRS consists of 27 items, which correspond to 14 domains related to motor abilities such as tremor, stability, and bradykinesia. Each item has responses ranging from 0-4. To compute the UPDRS-III total score, responses are summed across the 27 items, and accordingly, range from 0-108. For domain totals, responses are summed across all of the items in a given domain (when domain corresponds to multiple items). An increase in score indicates greater disability. The reported LSM was adjusted for baseline score and age group from the Type III analysis.
Measured: Baseline (Day -1), Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2017 (estimated)
- Study start17 Jul 2017
- Primary completion30 Dec 2019
- Study completion30 Dec 2019
Why it stopped: The study was terminated since fosmetpantotenate did not show statistically significant effects or clinical benefits during the double-blind period.
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pantothenate Kinase-Associated NeurodegenerationStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Travere Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Thomas Klopstock, MD, Principal investigator, LMU Klinikum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03041116
- Sponsor's protocol ID
- 024PKAN15004
- Acronym
- PKAN
- Status last verified
- Jan 2021
- First submitted
- 2 Dec 2016
- Last updated
- 26 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Klopstock T, Escolar ML, Marshall RD, Perez-Duenas B, Tuller S, Videnovic A, Greblikas F. The FOsmetpantotenate Replacement Therapy (FORT) randomized, double-blind, Placebo-controlled pivotal trial: Study design and development methodology of a novel primary efficacy outcome in patients with pantothenate kinase-associated neurodegeneration. Clin Trials. 2019 Aug;16(4):410-418. doi: 10.1177/1740774519845673. Epub 2019 May 6.
PubMed 31055958
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy, Safety, and Tolerability of Fosmetpantotenate (RE-024), a Phosphopantothenate Replacement Therapy, in Pantothenate Kinase-Associated Neurodegeneration (PKAN) Patients: A Randomized, Double-Blind, Placebo-Controlled Study With an Open-Label Extension
- ClinicalTrials.gov ID
- NCT03041116
- Acronym / sponsor ID
- PKAN / 024PKAN15004
- Keywords
- PKAN
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated since fosmetpantotenate did not show statistically significant effects or clinical benefits during the double-blind period.
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Travere Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 17 Jul 2017 (actual)
- Primary completion
- 30 Dec 2019 (actual)
- Study completion
- 30 Dec 2019 (actual)
- First posted
- 2 Feb 2017 (estimated)
- Results
- Posted 29 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study investigated whether fosmetpantotenate (RE-024), a phosphopantothenate replacement therapy, was safe and effective in treating participants with PKAN.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fosmetpantotenate | Experimental | Drug: FosmetpantotenateAdministered as powder for reconstitution. |
| Placebo | Placebo comparator | Drug: PlaceboAdministered as powder for reconstitution. |
Who may qualify
- Ages
- 6 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- The participant had a diagnosis of PKAN as indicated by confirmed mutations in the pantothenate kinase 2 gene.
- The participant was male or female aged 6 to 65 years, inclusive.
- The participant had a score of ≥ 6 on the PKAN-specific activities of daily living measure.
Key exclusion criteria (4 listed)
- The participant had required regular or intermittent invasive ventilatory support to maintain vital signs within 24 weeks prior to randomization.
- The participant had a deep brain stimulation device implanted within 6 months prior to screening.
- The participant had taken deferiprone within 30 days prior to screening.
- The participant was unable to maintain stable doses of allowed concomitant medications for the first 24 weeks of 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 |
|---|---|---|
| FosmetpantotenateAlso: RE-024Daily dosing | Drug | Fosmetpantotenate |
| PlaceboDaily dosing | Drug | Placebo |
Primary outcome
Change From Baseline In The Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living (PKAN-ADL) Total Score To The End Of The 24-week Double-blind Period
Time frame: Baseline (Day -1), Week 24
Change from baseline to Week 24 activities of daily living was assessed on the PKAN-ADL scale based on the Unified Parkinson's Disease Rating Scale (UPDRS) Part II. The PKAN-ADL is a validated measure of the participant's ability to complete ADL that are impacted by the diffuse motor manifestations of PKAN. It consists of 12 items related to activities of daily living, including eating, dressing, and walking. Each item has responses ranging from 0-4, with a higher value indicating greater disability in the given activity. To compute the total score, responses are summed across the 12 items. The available range of total scores on the PKAN-ADL scale was from 0 (no ADL affected) to 48 (ADL highly affected). The reported least square mean (LSM) was adjusted for baseline score and age group from the Type III analysis. A decrease in score indicates improvement in symptoms.
Number Of Participants With At Least 1 (≥1) Treatment-emergent Adverse Event (TEAE) And Treatment-emergent Serious Adverse Event (TESAE) During The 24-week Double-blind Period
Time frame: From Screening until end of Week 24
An adverse event (AE) is any untoward medical occurrence associated with the use of the investigational product (IP; active or placebo) in a participant, without regard to possibility of causal relationship with IP. A serious adverse event (SAE) is an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of death from AE); persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious medical events. The TEAEs in the double-blind period are defined as AEs that are new or are a worsening of an existing condition that begins from day of first dose of IP until day after last dose for double-blind treatment period.
1 secondary outcome
Absolute Change From Baseline In The UPDRS Part 3 (UPDRS-III) Total Score To The End Of The 24-week Double-blind Period
Time frame: Baseline (Day -1), Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31055958Klopstock T, Escolar ML, Marshall RD, Perez-Duenas B, Tuller S, Videnovic A, Greblikas F. The FOsmetpantotenate Replacement Therapy (FORT) randomized, double-blind, Placebo-controlled pivotal trial: Study design and development methodology of a novel primary efficacy outcome in patients with pantothenate kinase-associated neurodegeneration. Clin Trials. 2019 Aug;16(4):410-418. doi: 10.1177/1740774519845673. Epub 2019 May 6.
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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.
Thomas Klopstock, MD principal investigator
LMU Klinikum
20 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fosmetpantotenate in people with Pantothenate Kinase-Associated Neurodegeneration, run by Travere Therapeutics, Inc. at 20 sites in 9 countries.
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 3 inclusion and 4 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: stopped early, as of the sponsor's last update on 26 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Canada, France, Spain, Czechia and 4 more countries. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 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 The Pantothenate Kinase-Associated Neurodegeneration-Activities of Daily Living (PKAN-ADL) Total Score To The End Of The 24-week Double-blind Period (time frame: Baseline (Day -1), Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03041116, which also lists 1 linked publication.
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 26 Jan 2021.