AutismPhase 2NCT02947048
Safety of L1-79 in Adolescent and Adult Males With Autism
A Phase 2 study testing L1-79 in people with Autism, run by Yamo Pharmaceuticals LLC at 2 sites in United States.
Trial summary
This is a five-arm designed to assess the safety of L1-79 that incorporates 15 prospectively randomized, placebo controlled patients and 5 open label patients at either 100 tid (three times daily) or 200 tid dosing for 28 days. Read more about this study
- Who is it for?
- Ages 12 to 21 years, men only
- Conditions the study is for
- Autism
- What is being tested?
- L1-79
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2016to 1 Feb 2018
- 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 12 to 21 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Males who are not sexually active
- 12 and 21 years of age
- Signed informed consent
- Normal clinical laboratory values
- DSM-5 compliant diagnosis of autism spectrum disorder, confirmed by the Autistic Diagnosis Interview Review (ADIR), and by the Autism Diagnosis Observation Schedule (ADOS) score consistent with a diagnosis of autism
- No more than one concomitant medication for the treatment of autism, on a stable for at least 2 weeks prior to enrollment and no planned changes in psychosocial interventions during the trial
- No medications for any other pathology
Who cannot join
- Any co-morbidities, including Fragile-X syndrome, epilepsy, Retts syndrome, ADHD, or other disease or syndrome aside from autism that requires treatment
- Any other psychiatric disorder, or out of range lab values
- DSM-5 diagnosis of schizophrenia, schizoaffective disorder, alcohol use disorder
- Active medical problems: unstable seizures (>2 in past month)
- Concomitant physical illness
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Eric Bartky MD, Bartky Health Care Center
Livingston, New Jersey, 07039
F. Peter Halas MD, Sea Girt Pediatrics
Sea Girt, New Jersey, 07850
About this study
Official title: A Randomized, Placebo-controlled Phase 2 Study With Open-Label and Double-Blind Portions to Evaluate the Safety of L1-79 in Adolescent and Young Adult Males With Autism
This is a five-arm designed to assess the safety of L1-79 that incorporates 15 prospectively randomized, placebo controlled patients and 5 open label patients at either 100 tid (three times daily) or 200 tid dosing for 28 days. The open label patients will be assessed for the purpose of understanding PK/PD and to determine if there are any EKG changes associated with the administration of L1-79. Additional safety information will be provided by the 30 patients randomized 2:1 active:placebo.
Read the detailed description
Protocol Number: HT 02-121
Protocol Title: Phase 2 Safety Study of L1-79 for the Treatment of Autism Study Phase: 2
The first cohort of 20 patients to be enrolled will all receive L1-79 100 mg t.i.d., and will be comprised of 3 groups of patients. The first group of patients to receive 100 mg will differ from the others in that they will get blood samples drawn for PK analysis and EKGs will be taken. The safety and PK data from this group will be submitted for FDA review and acceptance before the 200 mg t.i.d. cohort will be enrolled. The remaining 15 patients in this cohort will be randomized to receive either L1-79 100 mg t.i.d. or placebo on a 2:1 basis (2 L1-79 patients for each placebo patient). While the FDA is reviewing the data from the first 5 patients all 100 mg t.i.d. patients will continue to be treated.
The second cohort is identical to the first. The initial 5 patients to be enrolled will differ from the others in that they will get blood samples drawn for PK analysis and EKGs will be taken. The remaining 15 patients in this cohort will be randomized to receive either L1-79 200 mg t.i.d. or placebo on a 2:1 active:placebo.
Sample Size: N=40
- Group 1 (n=5) open100mg L1-79 (1x100mg capsule+1 placebo capsule)
- Group 2 (n=10) blind100mg L1-79 (1x100mg capsule+1 placebo capsule)
- Group 3 (n=5) open200 mg L1-79 (2x100 mg capsules)
- Group 4 (n=10) blind200 mg L1-79 (2x100 mg capsules)
- Group 5 (n=10) Placebo (2 placebo capsules) All Groups will receive the assigned study drug three-times daily
Study Population: Male subjects with autism between the ages of 13 and 21 years of age who meet the entry criteria and who are able to complete standardized measures allowing them to participate in this study.
Evaluation Schedule: Subjects will be evaluated within one week prior to study accession, and weekly throughout the dosing period, and again 4 weeks after the cessation of treatment. The Assigned Dosage Groups (Groups 1 and 3) will have PK blood draws and EKG the randomized group will not have.
Safety Measures: All Groups will have regularly scheduled complete history and physical examination that includes orthostatic blood pressure measurements, vital signs, CBC, differential, platelet counts, urine analysis, and serum analytes including: total protein, albumin, glucose, BUN, creatinine, direct and total bilirubin, alkaline phosphatase, phosphorous, calcium, AST, ALT, sodium, potassium, chloride, bicarbonate, T4, TSH, and adverse events assessments. The Assigned Groups (1 and 3) will also have electrocardiograms taken at the study screening visit and weekly throughout the treatment interval.
- Conditions
- Autism
- Being tested
- L1-79, Placebo
- Medical subject headings
- Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L1-79Drug
Also called D,L-α-Methyltyrosine
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 100 mg open | Experimental | open-label lead-in 100 mg L1-79 t.i.d. Receives: Drug: L1-79 |
| 100 mg blinded | Experimental | blinded and randomized 100 mg L1-79 t.i.d. Receives: Drug: L1-79 |
| 200 mg open | Experimental | open-label lead-in 200 mg L1-79 t.i.d. Receives: Drug: L1-79 |
| 200 mg blinded | Experimental | blinded and randomized 200 mg L1-79 t.i.d. Receives: Drug: L1-79 |
| Placebo | Placebo comparator | placebo t.i.d. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Number of Participants with On-treatment Adverse Events.
To be conservative, it was pre-specified that all placebo data be combined (open-label, first cohort, and second cohort) for the safety population. For the efficacy population open-label data was excluded due to potential bias and placebo arms from the first and second cohort were presented separately due to differences in efficacy questionnaires completion in the first and second cohorts. Theses differences were not relevant to the adverse event data.
Measured: 4 weeks
Secondary outcomes (7)
Change From Baseline in Clinical Global Impression Scale (CGI)
The Clinical Global Impression (CGI) has two components: the CGI-Severity (CGI-S), which rates illness severity, and the CGI-Improvement (CGI-I), which rates the change in illness severity from baseline.
The CGI-S is rated on the following seven-point scale with 1 being normal and 7 being among the most extremely ill subjects. The CGI-I score is rated on a seven-point scale with 1 being very much improved and 7 being very much worse.
Higher values of the CGI-S score indicate a "worse" state. CGI-I scores of 5 or greater indicate decline, CGI I scores of 3 or lower indicate improvement, and a CGI-I score of 4 indicates no change.
Measured: Week 0 and Week 4
Change From Baseline in Vineland Adaptive Behavior Scale - 2nd Edition Socialization Standard Score
The Vineland Adaptive Behavior Scales, Second Edition (VABS-II) indicates adaptive functioning and consists of four major domains. Only the communication and socialization domains were done in this study. The VABS-II data is comprised of Socialization.
Socialization Standard Scores may range from 20 to 160, with a population mean of 100 and a standard deviation of 15. Lower Vineland Adaptive Behavior Socialization Standard Scores indicate a "worse" state. A positive value of change from baseline indicates improvement.
Measured: Day 0 and Week 4
Change From Baseline in Vineland Adaptive Behavior Scale - 2nd Edition Communication Standard Score
The Vineland Adaptive Behavior Scales, Second Edition (VABS-II) indicates adaptive functioning and consists of four major domains. Only the communication and socialization domains were done in this study. The VABS-II is comprised of Communication.
Communication Standard Scores may range from 20 to 160, with a population mean of 100 and a standard deviation of 15. Lower Vineland Adaptive Behavior Communication Standard Scores indicate a "worse" state. A positive value of change from baseline indicates improvement.
Measured: Week 0 and Week 4
Change From Baseline in the Autism Diagnostic Observation Schedule 2nd Edition (ADOS-2) Overall Total Score
The Autism Diagnostic Observation Schedule 2nd Edition (ADOS-2) is the "Gold Standard" for assessing severity of ASD and position on the autism spectrum. The ADOS-2 is a semi-structured, standardized assessment of: Communication, Social interaction, Play, and Restricted and repetitive behaviors. The total scores range from 15 to 60, and the cut-off score to determine autism is 30. More specifically, a score of <30 is classified as non-autism, a score of 30-36 is classified as mild to moderate autism, and a score of ≥37 is classified as severe autism.
A higher ADOS-2 value indicates a "worse" state. A negative value of change from baseline indicates an improvement.
Measured: Day 0 and Week 4
Change From Baseline in the Social Responsiveness Scale - 2nd Edition (SRS-2) Total T-score
Social Responsiveness Scale - 2nd edition (SRS-2) identifies social impairment associated with ASD and quantifies its severity. Raw and T-scores will be collected for SRS-2 Total, Social Awareness, Social Cognition, Social Communication, Social Motivation, Restricted Interest and Repetitive Behavior, DSM-5 Social Communication, and DSM-5 Restrictive Interest and Repetitive Behavior. Each domain has a varied but similar ranges of possible scores from 32 points-114 points. All T-scores have a mean of 50 points with a standard deviation of 10 points.
A higher SRS-2 total T-score indicates greater impairment. A negative change from baseline indicates improvement.
Measured: Week 0 and Week 4
Change From Baseline in Aberrant Behavior Checklist - Community (ABC-C)
The Aberrant Behavior Checklist - Community (ABC-C) is a 58-symptom checklist for assessing problem behaviors of children and adults with developmental disabilities (intellectual disability, ASD, cerebral palsy, epilepsy) that resolve onto five subscales. The subscales and the respective number of items are as follows: (a) irritability (15 items, scores range from 0-45), (b) lethargy/social withdrawal (16 items, scores range from 0-48), (c) stereotypic behavior (7 items, scores range from 0-21), (d) hyperactivity/noncompliance (16 items, scores range from 0-48), and (e) inappropriate speech (4 items, scores range from 0-12).
Higher ABC-C subscale scores indicates a "worse" outcome. A negative value of change from baseline indicates improvement.
Measured: Week 0 to Week 4
Change From Baseline in the Repetitive Behavior Scale - Revised (RBS-R) Total Score
The RBS-R is a 43-item self-report questionnaire that is used to measure the breadth of repetitive behavior in children, adolescents, and adults with Autism Spectrum disorders. Behaviors are rated on a 4-point scale: 0-Behavior does not occur, 1-Behavior occurs and is a mild problem, 2-Behavior occurs and is a moderate problem, 3-Behavior occurs and is a severe problem. The total score is the sum of all 6 subscale scores and ranges from 0-127, stereotypic behavior ranges from 0-18, self-injurious behavior ranges from 0-24, compulsive behavior ranges from 0-24, ritualistic behavior ranges from 0-18, sameness behavior ranges from 0-33 and restricted behaviors ranges from 0-12.
A higher RBS-R score indicates a "worse" state. A negative value of change from baseline indicates an improvement.
Measured: Week 0 and Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2016 (estimated)
- Study startOct 2016
- Primary completionDec 2017
- Study completion1 Feb 2018
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 AutismStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yamo Pharmaceuticals LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John Rothman, PhD, Study director, Yamo Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02947048
- Sponsor's protocol ID
- HT 02-121
- Status last verified
- Jul 2024
- First submitted
- 25 May 2016
- Last updated
- 21 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled Phase 2 Study With Open-Label and Double-Blind Portions to Evaluate the Safety of L1-79 in Adolescent and Young Adult Males With Autism
- ClinicalTrials.gov ID
- NCT02947048
- Acronym / sponsor ID
- HT 02-121
- Conditions
- Autism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Yamo Pharmaceuticals LLCIndustry (pharma, biotech, devices)
- Study start
- Oct 2016
- Primary completion
- Dec 2017 (actual)
- Study completion
- 1 Feb 2018 (actual)
- First posted
- 27 Oct 2016 (estimated)
- Results
- Posted 21 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a five-arm designed to assess the safety of L1-79 that incorporates 15 prospectively randomized, placebo controlled patients and 5 open label patients at either 100 tid (three times daily) or 200 tid dosing for 28 days. The open label patients will be assessed for the purpose of understanding PK/PD and to determine if there are any EKG changes associated with the administration of L1-79. Additional safety information will be provided by the 30 patients randomized 2:1 active:placebo.
Detailed description
Protocol Number: HT 02-121
Protocol Title: Phase 2 Safety Study of L1-79 for the Treatment of Autism Study Phase: 2
The first cohort of 20 patients to be enrolled will all receive L1-79 100 mg t.i.d., and will be comprised of 3 groups of patients. The first group of patients to receive 100 mg will differ from the others in that they will get blood samples drawn for PK analysis and EKGs will be taken. The safety and PK data from this group will be submitted for FDA review and acceptance before the 200 mg t.i.d. cohort will be enrolled. The remaining 15 patients in this cohort will be randomized to receive either L1-79 100 mg t.i.d. or placebo on a 2:1 basis (2 L1-79 patients for each placebo patient). While the FDA is reviewing the data from the first 5 patients all 100 mg t.i.d. patients will continue to be treated.
The second cohort is identical to the first. The initial 5 patients to be enrolled will differ from the others in that they will get blood samples drawn for PK analysis and EKGs will be taken. The remaining 15 patients in this cohort will be randomized to receive either L1-79 200 mg t.i.d. or placebo on a 2:1 active:placebo.
Sample Size: N=40
- Group 1 (n=5) open100mg L1-79 (1x100mg capsule+1 placebo capsule)
- Group 2 (n=10) blind100mg L1-79 (1x100mg capsule+1 placebo capsule)
- Group 3 (n=5) open200 mg L1-79 (2x100 mg capsules)
- Group 4 (n=10) blind200 mg L1-79 (2x100 mg capsules)
- Group 5 (n=10) Placebo (2 placebo capsules) All Groups will receive the assigned study drug three-times daily
Study Population: Male subjects with autism between the ages of 13 and 21 years of age who meet the entry criteria and who are able to complete standardized measures allowing them to participate in this study.
Evaluation Schedule: Subjects will be evaluated within one week prior to study accession, and weekly throughout the dosing period, and again 4 weeks after the cessation of treatment. The Assigned Dosage Groups (Groups 1 and 3) will have PK blood draws and EKG the randomized group will not have.
Safety Measures: All Groups will have regularly scheduled complete history and physical examination that includes orthostatic blood pressure measurements, vital signs, CBC, differential, platelet counts, urine analysis, and serum analytes including: total protein, albumin, glucose, BUN, creatinine, direct and total bilirubin, alkaline phosphatase, phosphorous, calcium, AST, ALT, sodium, potassium, chloride, bicarbonate, T4, TSH, and adverse events assessments. The Assigned Groups (1 and 3) will also have electrocardiograms taken at the study screening visit and weekly throughout the treatment interval.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 100 mg open | Experimental | Drug: L1-79open-label lead-in 100 mg L1-79 t.i.d. |
| 100 mg blinded | Experimental | Drug: L1-79blinded and randomized 100 mg L1-79 t.i.d. |
| 200 mg open | Experimental | Drug: L1-79open-label lead-in 200 mg L1-79 t.i.d. |
| 200 mg blinded | Experimental | Drug: L1-79blinded and randomized 200 mg L1-79 t.i.d. |
| Placebo | Placebo comparator | Drug: Placeboplacebo t.i.d. |
Who may qualify
- Ages
- 12 to 21 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Males who are not sexually active
- 12 and 21 years of age
- Signed informed consent
- Normal clinical laboratory values
- DSM-5 compliant diagnosis of autism spectrum disorder, confirmed by the Autistic Diagnosis Interview Review (ADIR), and by the Autism Diagnosis Observation Schedule (ADOS) score consistent with a diagnosis of autism
Key exclusion criteria (5 listed)
- Any co-morbidities, including Fragile-X syndrome, epilepsy, Retts syndrome, ADHD, or other disease or syndrome aside from autism that requires treatment
- Any other psychiatric disorder, or out of range lab values
- DSM-5 diagnosis of schizophrenia, schizoaffective disorder, alcohol use disorder
- Active medical problems: unstable seizures (>2 in past month)
- Concomitant physical illness
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 |
|---|---|---|
| L1-79Also: D,L-α-Methyltyrosine | Drug | 100 mg blinded, 100 mg open, 200 mg blinded, 200 mg open |
| Placebo | Drug | Placebo |
Primary outcome
Adverse Events
Time frame: 4 weeks
Number of Participants with On-treatment Adverse Events. To be conservative, it was pre-specified that all placebo data be combined (open-label, first cohort, and second cohort) for the safety population. For the efficacy population open-label data was excluded due to potential bias and placebo arms from the first and second cohort were presented separately due to differences in efficacy questionnaires completion in the first and second cohorts. Theses differences were not relevant to the adverse event data.
7 secondary outcomes
Change From Baseline in Clinical Global Impression Scale (CGI)
Time frame: Week 0 and Week 4
Change From Baseline in Vineland Adaptive Behavior Scale - 2nd Edition Socialization Standard Score
Time frame: Day 0 and Week 4
Change From Baseline in Vineland Adaptive Behavior Scale - 2nd Edition Communication Standard Score
Time frame: Week 0 and Week 4
Change From Baseline in the Autism Diagnostic Observation Schedule 2nd Edition (ADOS-2) Overall Total Score
Time frame: Day 0 and Week 4
Change From Baseline in the Social Responsiveness Scale - 2nd Edition (SRS-2) Total T-score
Time frame: Week 0 and Week 4
Change From Baseline in Aberrant Behavior Checklist - Community (ABC-C)
Time frame: Week 0 to Week 4
Change From Baseline in the Repetitive Behavior Scale - Revised (RBS-R) Total Score
Time frame: Week 0 and Week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
John Rothman, PhD study director
Yamo Pharmaceuticals
2 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 L1-79 in people with Autism, run by Yamo Pharmaceuticals LLC at 2 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 7 inclusion and 5 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 21 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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. 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 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 21 Aug 2024). 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?
Adverse Events (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Aug 2024.