Trial Outcomes & Findings for SOD1 Inhibition by Pyrimethamine in Familial Amyotrophic Lateral Sclerosis (ALS) (NCT NCT01083667)

NCT ID: NCT01083667

Last Updated: 2017-06-19

Results Overview

Reported change in mean SOD1 CSf from baseline to visit 6 (week 18) and end of study for all subjects who completed the measure

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 32 participants
• Primary outcome timeframe: baseline, Visit 6 week 18, end of study
• Results posted on: 2017-06-19

Participant Flow

Patient were recruited from all sites and referrals received from other physicians. Subjects also contacted sites from ClinicalTrials.gov posting

Participant milestones

Measure	Pyrimethamine Open label. Only one arm will receive the intervention. Pyrimethamine: Open Label, dose escalating,
Overall Study STARTED	32
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

SOD1 Inhibition by Pyrimethamine in Familial Amyotrophic Lateral Sclerosis (ALS)

Baseline characteristics by cohort

Measure	Pyrimethamine n=32 Participants Open label. Only one arm will receive the intervention. Pyrimethamine: Open Label, dose escalating,
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	31 Participants n=93 Participants
Age, Categorical >=65 years	1 Participants n=93 Participants
Age, Continuous	48 years n=93 Participants
Sex: Female, Male Female	16 Participants n=93 Participants
Sex: Female, Male Male	16 Participants n=93 Participants
Region of Enrollment United States	20 participants n=93 Participants
Region of Enrollment Italy	8 participants n=93 Participants
Region of Enrollment Germany	4 participants n=93 Participants

PRIMARY outcome

Timeframe: baseline, Visit 6 week 18, end of study

Population: 24 subjects completed up to visit 6 and 21 subjects for final study visit. Reported is the change in SOD1 CSF from baseline to week 36.

Reported change in mean SOD1 CSf from baseline to visit 6 (week 18) and end of study for all subjects who completed the measure

Outcome measures

Measure	Pyrimethamine n=22 Participants Open label. Only one arm will receive the intervention. Pyrimethamine: Open Label, dose escalating,
Mean Change in SOD1 CSF	6.8 ng/ml Interval 3.4 to 10.3

SECONDARY outcome

Timeframe: Week 0, 6, 18, and end of study

Population: 22 subjects completed to visit 9 and had a final score for Appel Score. Reported is the mean change from Baseline to week 36

an objective and timed measurement of strength and function of subjects including muscle testing, respiratory function and fine motor function, all summed together for a total value, and is measured at baseline, visit 2, visit 6 and end of study. The scale ranges from 30 in a healthy person to to 164 in a maximally impaired person; an increase in score indicates progression and is expected in disease progression.

Outcome measures

Measure	Pyrimethamine n=22 Participants Open label. Only one arm will receive the intervention. Pyrimethamine: Open Label, dose escalating,
Appel ALS Score	18 units on a scale Interval 12.0 to 24.0

Adverse Events

Pyrimethamine

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure

Pyrimethamine n=32 participants at risk Open label. Only one arm will receive the intervention. Pyrimethamine: Open Label, dose escalating,

Infections and infestations Pneumonia

3.1% 1/32 • Number of events 1 • AE's were collected over the course of the study and up to 30 days following the last dose taken. CTCAE version 4.0 was used to assess the severity of AE's experienced during the study. This uses a grading system (referring to the severity) to assess the AEs. The CTCAE v4.0 displays Grades 1-5 with unique clinical descriptions of severity for each AE based on this general guideline: G1 Mild AE, G2 Moderate AE, G3 Severe or medically significant but not immediately life-threatening, G4 Life-threatening, G5 Death related to AE. SAE reporting per criteria od clinicaltrials.gov

Other adverse events

Measure	Pyrimethamine n=32 participants at risk Open label. Only one arm will receive the intervention. Pyrimethamine: Open Label, dose escalating,
Nervous system disorders Headache	40.6% 13/32 • Number of events 13 • AE's were collected over the course of the study and up to 30 days following the last dose taken. CTCAE version 4.0 was used to assess the severity of AE's experienced during the study. This uses a grading system (referring to the severity) to assess the AEs. The CTCAE v4.0 displays Grades 1-5 with unique clinical descriptions of severity for each AE based on this general guideline: G1 Mild AE, G2 Moderate AE, G3 Severe or medically significant but not immediately life-threatening, G4 Life-threatening, G5 Death related to AE. SAE reporting per criteria od clinicaltrials.gov
Metabolism and nutrition disorders Nausea	43.8% 14/32 • Number of events 14 • AE's were collected over the course of the study and up to 30 days following the last dose taken. CTCAE version 4.0 was used to assess the severity of AE's experienced during the study. This uses a grading system (referring to the severity) to assess the AEs. The CTCAE v4.0 displays Grades 1-5 with unique clinical descriptions of severity for each AE based on this general guideline: G1 Mild AE, G2 Moderate AE, G3 Severe or medically significant but not immediately life-threatening, G4 Life-threatening, G5 Death related to AE. SAE reporting per criteria od clinicaltrials.gov
Metabolism and nutrition disorders Diarrhea	18.8% 6/32 • Number of events 6 • AE's were collected over the course of the study and up to 30 days following the last dose taken. CTCAE version 4.0 was used to assess the severity of AE's experienced during the study. This uses a grading system (referring to the severity) to assess the AEs. The CTCAE v4.0 displays Grades 1-5 with unique clinical descriptions of severity for each AE based on this general guideline: G1 Mild AE, G2 Moderate AE, G3 Severe or medically significant but not immediately life-threatening, G4 Life-threatening, G5 Death related to AE. SAE reporting per criteria od clinicaltrials.gov
Musculoskeletal and connective tissue disorders Pain	15.6% 5/32 • Number of events 5 • AE's were collected over the course of the study and up to 30 days following the last dose taken. CTCAE version 4.0 was used to assess the severity of AE's experienced during the study. This uses a grading system (referring to the severity) to assess the AEs. The CTCAE v4.0 displays Grades 1-5 with unique clinical descriptions of severity for each AE based on this general guideline: G1 Mild AE, G2 Moderate AE, G3 Severe or medically significant but not immediately life-threatening, G4 Life-threatening, G5 Death related to AE. SAE reporting per criteria od clinicaltrials.gov
Metabolism and nutrition disorders weight loss	9.4% 3/32 • Number of events 3 • AE's were collected over the course of the study and up to 30 days following the last dose taken. CTCAE version 4.0 was used to assess the severity of AE's experienced during the study. This uses a grading system (referring to the severity) to assess the AEs. The CTCAE v4.0 displays Grades 1-5 with unique clinical descriptions of severity for each AE based on this general guideline: G1 Mild AE, G2 Moderate AE, G3 Severe or medically significant but not immediately life-threatening, G4 Life-threatening, G5 Death related to AE. SAE reporting per criteria od clinicaltrials.gov
Infections and infestations Upper respiratory infection	12.5% 4/32 • Number of events 4 • AE's were collected over the course of the study and up to 30 days following the last dose taken. CTCAE version 4.0 was used to assess the severity of AE's experienced during the study. This uses a grading system (referring to the severity) to assess the AEs. The CTCAE v4.0 displays Grades 1-5 with unique clinical descriptions of severity for each AE based on this general guideline: G1 Mild AE, G2 Moderate AE, G3 Severe or medically significant but not immediately life-threatening, G4 Life-threatening, G5 Death related to AE. SAE reporting per criteria od clinicaltrials.gov
Metabolism and nutrition disorders decreased appetite	6.2% 2/32 • Number of events 2 • AE's were collected over the course of the study and up to 30 days following the last dose taken. CTCAE version 4.0 was used to assess the severity of AE's experienced during the study. This uses a grading system (referring to the severity) to assess the AEs. The CTCAE v4.0 displays Grades 1-5 with unique clinical descriptions of severity for each AE based on this general guideline: G1 Mild AE, G2 Moderate AE, G3 Severe or medically significant but not immediately life-threatening, G4 Life-threatening, G5 Death related to AE. SAE reporting per criteria od clinicaltrials.gov

Additional Information

Dale Lange

HSS/WCMC

Phone: 6467978917

Email: langed@hss.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place