Safety and Efficacy of SOD1 Inhibition By Pyrimethamine in Familial (ALS)

• Register: EUCTR
• Last refreshed on: 27 October 2014
• Main ID: EUCTR2011-004798-99-DE
• Date of registration: 27/12/2012
• Prospective Registration: Yes
• Primary sponsor: Weill Medical College of Cornell University
• Public title: Safety and Efficacy of SOD1 Inhibition By Pyrimethamine in Familial (ALS)
• Scientific title: Safety and Efficacy of SOD1 Inhibition By Pyrimethamine in Familial (ALS) - Pyrimethamine In Familial ALS
• Date of first enrolment: 27/02/2013
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004798-99
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes 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 Number of treatment arms in the trial: 1

Countries of recruitment

Germany, Italy, United States

Contacts

• Name: Albert C. Ludolph
• Affiliation: Klinik für Neurologie der Universität Ulm

• Name: Albert C. Ludolph
• Affiliation: Klinik für Neurologie der Universität Ulm

Key inclusion & exclusion criteria

Inclusion criteria:
1. ALS diagnosed as probable, laboratory supported probable or definite according to the World Federation of Neurology El Escorial criteria
2. Age 18 or older
3. Capable of providing informed consent and complying with trial procedures
4. SOD1 mutation confirmation by study team
5. Not taking Riluzole (Rilutek) or on a stable dose for 30 days
6. Not taking Coenzyme QR10R or on a stable dose and brand for 30 days

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

Exclusion criteria:
1. History or evidence of malabsorption syndromes
2. Exposure to any experimental agent within 30 days of onset of this protocol
3. Women who are pregnant or planning to become pregnant
4. Women of childbearing potential not practicing contraception
5. Women who are breastfeeding
6. Enrollment in another research study within 30 days of or during this trial
7. Alcoholism
8. Patients taking phenytoin (Dilantin) or other therapy affecting folate levels
9. Dementia (MMSE <22)
10. Seizure disorder
11. Folate deficiency
12. Megaloblastic anemia
13. Cardiovascular disorder/arrhythmia
14. Impaired kidney function, defined as creatinine levels of 2.5 x ULN
15. Impaired liver function, defined as AST or ALT of 3 X ULN
16. Advanced ALS patients, defined as those with any of the following: forced vital capacity <60%
(use of BIPAP is allowed); traecheostomy; or mechanical ventilation
17. Use of any of the following medications: cytosine, arabinoside, methotrexate, daunorubicin,
sulfonamides, zidovudine, lorazapam, coumadin, sulfamethoxazole, and trimethoprim
18. Patients taking Lithium within 30 days of or during this trial
19. Incapable of providing informed consent and complying with trial procedures


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

Health Condition(s) or Problem(s) studied

Familial amyotrophic lateral sclerosis (FALS)
MedDRA version: 14.1 Level: LLT Classification code 10036704 Term: Primary lateral sclerosis System Organ Class: 100000004852

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

Intervention(s)

Trade Name: Daraprim
Pharmaceutical Form: Tablet
INN or Proposed INN: PYRIMETHAMINE
CAS Number: 58-14-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Primary end point(s): reduction of SOD1 protein for 15 % in the cerebrospinal fluid in patients with FALS with pyrimethamin

Main Objective: To evaluate the ability of pyrimethamine to reduce SOD1 protein by 15% in the cerebrospinal fluid in patients with FALS at doses of 75 mg or less.

Secondary Objective: To evaluate the safety and tolerability of pyrimethamine in patients with FALS.

Timepoint(s) of evaluation of this end point: last visit (week 36)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Safety and tolerability will be assessed every week, either during the study visit or by phone interview.

Secondary end point(s): Safety and tolerability of pyrimethan in patients with FALS due to measure safety and tolerability by adverse events, laboratory data,
and ability to remain on assigned treatment.

Secondary ID(s)

0903010259

Source(s) of Monetary Support

Muscular Dystrophy Association