Amyotrophic Lateral SclerosisPhase 2CL211NCT00931944

Open-Label, Safety and Tolerability Extension Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS) (CL211)

A Phase 2 study testing KNS-760704 in people with Amyotrophic Lateral Sclerosis, run by Knopp Biosciences at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is an open-label, multi-center study designed to extend the evaluation of the safety, tolerability, and clinical effects of oral administration of KNS-760704 in patients with ALS. Read more about this study

Who is it for?: Ages 21 to 80 years
Conditions the study is for: Amyotrophic Lateral Sclerosis
What is being tested?: KNS-760704
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 74 participants
Where: 19 sitesUnited States
Study dates: Jul 2009to Jul 2013
Phase: Phase 2
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 21 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patient has provided signed informed consent for this trial before the commencement of any study-related procedure
Patient is actively participating in Knopp Protocol KNS-760704-CL201 and has completed the Part 2 Week 28 visit in that study or patient is actively receiving RTPB under Research IND #60,948

Who cannot join

Patient did not participate in Knopp Protocol KNS-760704-CL201 or patient did not receive RTPB under Research IND #60,948.
Patient discontinued from KNS-760704-CL201 for any reason other than enrollment into this study (applies to patients enrolled in KNS-760704-CL201 only)
Patient was not taking RTPB under Research IND #60,948 prior to April 30, 2009 (applies to patients enrolled under Research IND #60,948 only)

Trial locations and contacts

19 sites in 1 country.

City, postcode or hospital

19 sites in 1 country

United States19 sites

Johns Hopkins University School of Medicine
Baltimore, Maryland, 21228
Massachusettes General Hospital
Boston, Massachusetts, 02129
University of Virginia Health System
Charlottesville, Virginia, 22908
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033
University of Kansas Medical Center
Kansas City, Kansas, 66160
Bryan LGH Medical Center East
Lincoln, Nebraska, 68506
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
UCLA, Dept. of Neurology - Neuromuscular/ALS Research Center
Los Angeles, California, 90095
University of Miami Miller School of Medicine
Miami, Florida, 33136
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Columbia University, Lou Gehrig MDA/ALS Research Center
New York, New York, 10032
Drexel University College Of Medicine
Philadelphia, Pennsylvania, 19102
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania, 15213
University of Utah
Salt Lake City, Utah, 84132
University of Texas Health Sciences Center of San Antonio
San Antonio, Texas, 78229
The Forbes Norris MDA/ALS Research Center
San Francisco, California, 94115
University of Washington
Seattle, Washington, 98195
Washington University School of Medicine
St Louis, Missouri, 63110
SUNY Upstate Medical University
Syracuse, New York, 13210

Other trials in United States

About this study

Official title: An Open-Label, Safety and Tolerability, Study Evaluating KNS-760704 in Patients With Amyotrophic Lateral Sclerosis (ALS)

This is an open-label, multi-center study designed to extend the evaluation of the safety, tolerability, and clinical effects of oral administration of KNS-760704 in patients with ALS.

Read the detailed description

Patients who complete the Part 2 Week 28 visit in study KNS-760704-CL201 and patients with ALS who were actively receiving RTPB [(6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazolediamine dihydro-chloride monohydrate] under Research IND #60,948 were eligible to participate in this study.

Eligible patients received 1 tablet of KNS-760704 (150 mg) every 12 hours (Q12H) (300 mg total daily dose) for up to 180 weeks.

Conditions: Amyotrophic Lateral Sclerosis
Being tested: KNS-760704
Keywords: ALS, Amyotrophic Lateral Sclerosis, Lou Gehrig, Lou Gehrig's, Lou Gehrig's disease, Motor Neuron Disease, Nervous System Diseases, KNS-760704, RTPB
Medical subject headings: Amyotrophic Lateral Sclerosis, Motor Neuron Disease, Nervous System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

KNS-760704Drug
Also called dexpramipexole
150 mg Q12H KNS-760704 given orally (300 mg total daily dose)

Study groups in NCT00931944
Study group	Role	What they receive
KNS-760704 300 mg/day	Experimental	Open-label KNS-760704 (150 mg Q12H) Receives: Drug: KNS-760704

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Potentially Clinically Significant Hematology Results
Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Measured: 180 weeks
Number of Participants With Potentially Clinically Significant Liver Enzyme Abnormalities
Number of participants with potentially clinically significant liver enzyme abnormalities for the safety population are presented. Percentages are based on the number of patients with at least one non-missing, post-baseline value for each parameter.
Measured: 180 weeks
Number of Participants With Potentially Clinically ECG Abnormalities
Number of participants with potentially clinically significant ECG abnormalities for the safety population are presented. Percentages are based on the number of patients in the safety population who had at least one non-missing, post-baseline value.
Measured: 180 weeks
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities
Number of participants with potentially clinically significant vital sign abnormalities for the safety population are presented. Percentages are based on the number of patients with at least one non-missing, post-baseline value for each parameter.
Measured: 180 weeks

Secondary outcomes (10)

Change in ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) Total Score From Baseline to Week 12
The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48. Therefore, the score ranges from 0 to 48 with higher scores representing better function.
Measured: 12 weeks
Change in ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) Total Score From Baseline to Week 24
The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48. Therefore, the score ranges from 0 to 48 with higher scores representing better function.
Measured: 24 weeks
Change in ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) Total Score From Baseline to Week 48
The ALSFRS-R (ALS functional rating scale with respiratory component) is a validated scale which measures 4 functional domains, comprising respiratory function, bulbar function, gross motor skills, and fine motor skills. There are a total of 12 questions, each scored from 0 to 4 for a total possible score of 48. Therefore, the score ranges from 0 to 48 with higher scores representing better function.
Measured: 48 weeks
Change in Upright Vital Capacity From Baseline to Week 12
Change in Percent Predicted Upright Vital Capacity from Baseline to Week 12. A negative change indicates clinical worsening.
Measured: 12 weeks
Change in Upright Vital Capacity From Baseline to Week 24
Change in Percent Predicted Upright Vital Capacity from Baseline to Week 24. A negative change indicates clinical worsening.
Measured: 24 weeks
Change in Upright Vital Capacity From Baseline to Week 48
Change in Percent Predicted Upright Vital Capacity from Baseline to Week 48. A negative change indicates clinical worsening.
Measured: 48 weeks
Change in McGill Single-Item Scale (SIS) From Baseline to Week 12
The McGill SIS consists of a single question designed to assess the improvement of or the rate of deterioration of the subject's quality-of-life. Subjects rated their quality of life over the prior 2 days on a scale of 0 (very bad) to 10 (excellent). Decreases from Baseline indicate deterioration of a subject's quality of life.
Measured: 12 weeks
Change in McGill Single-Item Scale (SIS) From Baseline to Week 24
The McGill SIS consists of a single question designed to assess the improvement of or the rate of deterioration of the subject's quality-of-life. Subjects rated their quality of life over the prior 2 days on a scale of 0 (very bad) to 10 (excellent). Decreases from Baseline indicate deterioration of a subject's quality of life.
Measured: 24 weeks
Change in McGill Single-Item Scale (SIS) From Baseline to Week 48
The McGill SIS consists of a single question designed to assess the improvement of or the rate of deterioration of the subject's quality-of-life. Subjects rated their quality of life over the prior 2 days on a scale of 0 (very bad) to 10 (excellent). Decreases from Baseline indicate deterioration of a subject's quality of life.
Measured: 48 weeks
Number of Subjects With Feeding Tube Placed During the Study.
Number of participants who had a feeding tube placed during the study.
Measured: 144 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2009Jul 2013

First posted2 Jul 2009 (estimated)
Study startJul 2009
Primary completionJul 2013
Study completionJul 2013

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 Amyotrophic Lateral SclerosisStudies 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 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 74 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00931944
Sponsor's protocol ID: KNS-760704-CL211
Acronym: CL211
Status last verified: Jul 2021
First submitted: 30 Jun 2009
Last updated: 16 Aug 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Amyotrophic Lateral Sclerosis trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label, Safety and Tolerability, Study Evaluating KNS-760704 in Patients With Amyotrophic Lateral Sclerosis (ALS)
ClinicalTrials.gov ID: NCT00931944
Acronym / sponsor ID: CL211 / KNS-760704-CL211
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS, Amyotrophic Lateral Sclerosis, Lou Gehrig, Lou Gehrig's, Lou Gehrig's disease, Motor Neuron Disease, Nervous System Diseases, KNS-760704
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 74 participants (actual)
Lead sponsor: Knopp BiosciencesIndustry (pharma, biotech, devices)
Study start: Jul 2009
Primary completion: Jul 2013 (actual)
Study completion: Jul 2013 (actual)
First posted: 2 Jul 2009 (estimated)
Results: Posted 16 Aug 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This is an open-label, multi-center study designed to extend the evaluation of the safety, tolerability, and clinical effects of oral administration of KNS-760704 in patients with ALS.

Detailed description

Eligible patients received 1 tablet of KNS-760704 (150 mg) every 12 hours (Q12H) (300 mg total daily dose) for up to 180 weeks.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
KNS-760704 300 mg/day	Experimental	Drug: KNS-760704Open-label KNS-760704 (150 mg Q12H)

Who may qualify

Ages: 21 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Patient has provided signed informed consent for this trial before the commencement of any study-related procedure
Patient is actively participating in Knopp Protocol KNS-760704-CL201 and has completed the Part 2 Week 28 visit in that study or patient is actively receiving RTPB under Research IND #60,948

Key exclusion criteria (3 listed)

Patient did not participate in Knopp Protocol KNS-760704-CL201 or patient did not receive RTPB under Research IND #60,948.
Patient discontinued from KNS-760704-CL201 for any reason other than enrollment into this study (applies to patients enrolled in KNS-760704-CL201 only)
Patient was not taking RTPB under Research IND #60,948 prior to April 30, 2009 (applies to patients enrolled under Research IND #60,948 only)

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
KNS-760704Also: dexpramipexole150 mg Q12H KNS-760704 given orally (300 mg total daily dose)	Drug	KNS-760704 300 mg/day

Primary outcome

Number of Participants With Potentially Clinically Significant Hematology Results
Time frame: 180 weeks
Number of Participants with Potentially Clinically Significant Hematology Results by Treatment Group. Percentages based on number of patients with at least one non-missing post-baseline value in each treatment group. Patients are only counted once per criterion per laboratory test.
Number of Participants With Potentially Clinically Significant Liver Enzyme Abnormalities
Time frame: 180 weeks
Number of participants with potentially clinically significant liver enzyme abnormalities for the safety population are presented. Percentages are based on the number of patients with at least one non-missing, post-baseline value for each parameter.
Number of Participants With Potentially Clinically ECG Abnormalities
Time frame: 180 weeks
Number of participants with potentially clinically significant ECG abnormalities for the safety population are presented. Percentages are based on the number of patients in the safety population who had at least one non-missing, post-baseline value.
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities
Time frame: 180 weeks
Number of participants with potentially clinically significant vital sign abnormalities for the safety population are presented. Percentages are based on the number of patients with at least one non-missing, post-baseline value for each parameter.

10 secondary outcomes

Change in ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) Total Score From Baseline to Week 12
Time frame: 12 weeks
Change in ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) Total Score From Baseline to Week 24
Time frame: 24 weeks
Change in ALSFRS-R (ALS Functional Rating Scale With Respiratory Component) Total Score From Baseline to Week 48
Time frame: 48 weeks
Change in Upright Vital Capacity From Baseline to Week 12
Time frame: 12 weeks
Change in Upright Vital Capacity From Baseline to Week 24
Time frame: 24 weeks
Change in Upright Vital Capacity From Baseline to Week 48
Time frame: 48 weeks
Change in McGill Single-Item Scale (SIS) From Baseline to Week 12
Time frame: 12 weeks
Change in McGill Single-Item Scale (SIS) From Baseline to Week 24
Time frame: 24 weeks
Change in McGill Single-Item Scale (SIS) From Baseline to Week 48
Time frame: 48 weeks
Number of Subjects With Feeding Tube Placed During the Study.
Time frame: 144 weeks

Results and safety

Results posted to the registry on 16 Aug 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
300 mg Per Day	74	19

Primary outcome: Number of Participants With Potentially Clinically Significant Hematology Results

Time frame: 180 weeks. Count of participants. Unit: Participants

Measure	KNS-760704 300 mg/Day n = 74
WBC (<3.0 x 10^9/L)	5
WBC (>=16.0 x 10^9/L)	2
Neutrophils (<1.5 x 10^9/L)	3
Neutrophils (>13.5 x 10^9/L)	4

Population analysed: Number of subjects evaluated is the number of subjects who had a baseline assessment and at least one post-baseline assessment.

Primary outcome: Number of Participants With Potentially Clinically Significant Liver Enzyme Abnormalities

Time frame: 180 weeks. Count of participants. Unit: Participants

Measure	KNS-760704 300 mg/Day n = 74
Alkaline phosphatase >2.5 times ULN (upper limit of the 'normal' reference range)	1
ALT >3 times ULN	5
AST >3 times ULN	2
Total Bilirubin >1.5 times ULN	3
Creatinine >1.5 times ULN	0
ALT or AST >3 times ULN and total bilirubin >2 times ULN (Hy's Law)	0

Population analysed: Number of subjects evaluated is the number of subjects who had a baseline assessment and at least one post-baseline assessment.

Primary outcome: Number of Participants With Potentially Clinically ECG Abnormalities

Time frame: 180 weeks. Count of participants. Unit: Participants

Measure	KNS-760704 300 mg/Day n = 74
Axis - LEFT AXIS DEVIATION	5
Axis - RIGHT AXIS DEVIATION	1
Conduction - LEFT ANTERIOR HEMIBLOCK	2
Conduction - RSR' SUGGESTS RIGHT VENTRICULAR CONDUCTION DELAY	3
Conduction - SHORT P-R INTERVAL	3
Morphology - LEFT ATRIAL ENLARGEMENT	2
Morphology - LEFT VENTRICULAR HYPERTROPHY BY VOLTAGE CRITERIA ONLY	2
Morphology - LEFT VENTRICULAR HYPERTROPHY WITH REPOLARIZATION ABNORMALITIES	1

Population analysed: Number of subjects evaluated is the number of subjects who had a baseline assessment and at least one post-baseline assessment.

Primary outcome: Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities

Time frame: 180 weeks. Count of participants. Unit: Participants

Measure	KNS-760704 300 mg/Day n = 74
Temperature - >38 degree C. post-baseline and an increase from baseline of at least 1 degree Celsius	4
Pulse Rate - >120 bpm post-baseline or an increase from baseline of >20 bpm	26
Pulse Rate - >120 bpm post-baseline and an increase from baseline of >20 bpm	1
Pulse Rate - <50 bpm post-baseline or a decrease from baseline of >20 bpm	9
Pulse Rate - <50 bpm post-baseline and a decrease from baseline of >20 bpm	0
Systolic Blood Pressure - >180 mmHg post-baseline or an increase from baseline of >40 mmHg	3
Systolic Blood Pressure - >180 mmHg post-baseline and an increase from baseline of >40 mmHg	1
Systolic Blood Pressure - <90 mmHg post-baseline or a decrease from baseline of >30 mmHg	11

Population analysed: Number of subjects evaluated is the number of subjects in the Safety Population who had a baseline assessment and at least one post-baseline assessment.

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were monitored and reported from the first dose through 30 days following the last dose.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
300 mg Per Day	48 of 74 (64.9%)	74 of 74 (100%)	38 of 74

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Merit Cudkowicz, M.D., MSc principal investigator

NeuroClinical Trials Unit (Massachusetts General Hospital)

19 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing KNS-760704 in people with Amyotrophic Lateral Sclerosis, run by Knopp Biosciences at 19 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 2 inclusion and 3 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 16 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 16 Aug 2021). 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?

Number of Participants With Potentially Clinically Significant Hematology Results (time frame: 180 weeks). The study lists 4 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 NCT00931944.

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 16 Aug 2021.