An international open label trial of deferiprone in patients with iron storage brain disorders - an extension to TIRCON2012V1 (a randomised controlled trial of deferiprone in patients with iron storage brain disorders).

• Register: EUCTR
• Last refreshed on: 28 May 2018
• Main ID: EUCTR2014-001427-79-GB
• Date of registration: 05/11/2015
• Prospective Registration: Yes
• Primary sponsor: ApoPharma Inc
• Public title: An international open label trial of deferiprone in patients with iron storage brain disorders - an extension to TIRCON2012V1 (a randomised controlled trial of deferiprone in patients with iron storage brain disorders).
• Scientific title: Long-term Safety and Efficacy Study of Deferiprone in Patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN) - TIRCON2012V1-EXT
• Date of first enrolment: 30/12/2015
• Target sample size: 89
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001427-79
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; 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

Germany, Italy, United Kingdom, United States

Contacts

• Name: Morrison
• Affiliation: Newcastle University

• Name: Morrison
• Affiliation: Newcastle University

Key inclusion & exclusion criteria

Inclusion criteria:
1. Completed study TIRCON2012V1
2. Sexually active females of childbearing potential, including those who are perimenopausal (defined as less than 2 years since last menstrual period) must have a negative pregnancy test result at Visit 1 (if applicable; in cases where the investigator determines there is no reasonable risk of pregnancy because of significant incapacity, pregnancy testing will not be performed). In addition, if applicable, they must meet at least one of the following criteria:
? Use an effective method of contraception during the study and within 30 days following their last dose of study medication, OR
? Participate in a non-heterosexual lifestyle, OR
? Have a male sexual partner who has been sterilized (supporting evidence required)
Approved methods of contraception will consist of the following or must follow local requirements:
? Oral contraceptive used in conjunction with condom, diaphragm, or spermicide
? Hormonal implant used in conjunction with condom, diaphragm, or spermicide
? Injectable contraceptive used in conjunction with condom, diaphragm, or spermicide
? Diaphragm or condom used with spermicide
? Abstinence, which must be true abstinence that is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal,post-ovulation methods) and withdrawal are not acceptable methods of contraception.
If a hormonal contraception is used, it should have a Pearl index <1%.
Female patients who meet any of the following criteria are not of childbearing potential and therefore do not need to practice contraception:
? Post-menopausal (last menstrual period > 2 years ago)
? Had a tubal ligation (supporting evidence required)
? Had a hysterectomy or oophorectomy (supporting evidence required)

3. Fertile heterosexual males and/or their partners must agree to use an effective method of contraception (as defined in criterion # 2) during the study and for 30 days following the last dose of study medication

4. Patients and/or their authorized legal representatives must provide signed and dated written informed consent prior to the first study intervention, and patients must be able to adhere to study restrictions, appointments, and evaluation schedules. Patients who are minors must sign an assent form as per local regulatory requirements.
Are the trial subjects under 18? yes
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 6
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1. Withdrew from the study TIRCON2012V1 for reasons of safety

2. Plan to participate in another clinical trial at any time from the day of enrolment until 30 days post-treatment in the current study

3. Presence of any medical, psychological, or psychiatric condition which in the opinion of the investigator would cause participation in the study to be unwise.

4. Pregnant, breastfeeding, or planning to become pregnant during the study period.


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Pantothenate Kinase-Associated Neurodegeneration (PKAN)
MedDRA version: 18.1 Level: PT Classification code 10053643 Term: Neurodegenerative disorder System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: Ferriprox
Product Name: Deferiprone 80 mg/mL oral solution
Pharmaceutical Form: Oral solution
INN or Proposed INN: Deferiprone
CAS Number: 30652-11-0
Other descriptive name: Deferiprone
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 80-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Timepoints:

Baseline, 12m, 18m

Main Objective: To evaluate the long-term safety and tolerability of the drug deferiprone in patients with pantothenate kinase-associated neurodegeneration (PKAN).

Primary end point(s): Adverse events (AEs): Frequency, severity, time to onset, duration, and relatedness to study product
- Serious adverse events (SAEs): Frequency, severity, time to onset,
duration, and relatedness to study product
- Number of discontinuations due to AEs
- Hematology assessments
- Blood chemistry assessments
- ECG assessments

Secondary Objective: To evaluate the change in severity of dystonia (a state of abnormal muscle tone resulting in muscular spasm and abnormal posture, typically due to neurological disease) over time in patients with PKAN treated with deferiprone.
?
To evaluate global improvement over time in patients with PKAN treated
with deferiprone

Secondary Outcome(s)

Secondary end point(s): All patients:
Change in the BAD total score from baseline (defined as prior to the start of
deferiprone therapy) to Visit 4, as assessed by central evaluation of videotapes

Proportion of patients with improved or unchanged BAD scale total score between
baseline and Visit 4 (responder analysis)

Change from baseline to Visit 4 in BAD scale score per body region (eyes, mouth,
neck, trunk, and each upper and lower extremity), as assessed by central evaluation of videotapes

Change in score on the PGI-I from baseline to Visit 4

Proportion of patients showing an improvement on PGI-I at Visit 4 (responder analysis)
The time points for these efficacy endpoints are defined as follows:
?
For patients who received deferiprone in the earlier study, the baseline visit of that
study will be treated as the baseline visit of TIRCON2012V1-EXT as well. Thus,
Visit 1 of the extension study (Week 0) will be Year 1.5, and Visit 4 (Week 78) will
be Year 3.
?
For patients who received placebo in the earlier study, Visit 1 of the extension study
(Week 0) will be the baseline visit. Thus, Visit 4 (Week 78) will be Year 1.5.


Patients who received placebo in initial study:
For this group only, for each measure, the changes seen between the start and completion of study TIRCON2012V1 (i.e., following 18 months on placebo) will be compared against the changes seen between the start and completion of study TIRCON2012V1-EXT (i.e.,following 18 months on deferiprone), as follows:

Comparison of change in BAD total score from baseline to completion of the initial
study vs. change in BAD total score from baseline to completion of the extension study
?
Comparison of the proportion of patients with improved or unchanged BAD scale
total score between baseline and completion of the initial study vs. the proportion
with improved or unchanged BAD scale total score from baseline to completion of
the extension study (responder analysis)

Comparison of the change in BAD score per body region between baseline and
completion of the initial study vs. change in BAD score per body region between
baseline and completion of the extension study

Comparison of change in PGI-I score from baseline to completion of the initial study
vs. change in PGI-I score from baseline to completion of the extension study

Comparison of the proportion of patients showing an improvement on PGI-I at
completion of the initial study vs. the proportion showing an improvement at
completion of the extension study (responder analysis)

Timepoint(s) of evaluation of this end point: See above.

Secondary ID(s)

NCT02174848

TIRCON2012V1-EXT

2014-001427-79-DE

Source(s) of Monetary Support

ApoPharma Inc (sponsor and funder including cost of the IMP)