Irritable MoodPhase 2NCT02507284
Tolerability, Safety, and Activity of SRX246 in Irritable Subjects With Huntington's Disease
A Phase 2 study testing SRX246 in people with Irritable Mood and Huntington's Disease, run by Azevan Pharmaceuticals at 22 sites in United States.
Trial summary
This study evaluates the tolerability, safety and activity of SRX246 in the treatment of irritability in patients with Huntington's disease. Two-thirds of all participants will receive SRX246, while the other third will receive a placebo. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Irritable Mood, Huntington's Disease
- What is being tested?
- SRX246
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 22 sitesUnited States
- Study dates
- 10 May 2016to 21 Dec 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female Subjects aged 18 years or older
- Subjects must have clinical features of HD, which can include motor, cognitive, or behavioral symptoms
- A confirmatory family history of HD; OR CAG repeat expansion ≥ 37
- Total Functional Capacity (TFC) score of 5-13
- Evidence of irritability; a score of at least 2 or greater on the severity measure of either the UHDRS Irritability question (30b) or Aggression question (Disruptive or Aggressive Behavior, 31b)
- Women of childbearing potential (i.e., those not postmenopausal or surgically sterile) must have a negative pregnancy test, be non-lactating and use adequate contraception methods during the study. Adequate birth control includes: abstinence; oral, implanted or injected contraceptives, e.g., birth control pills; intra-uterine device; barrier (vaginal ring or diaphragm/cervical cap with spermicide); transdermal patch. Reliable contraception must have been in use 30 days prior to the Baseline Visit. Partner(s) contraception (e.g., male partner with vasectomy or other surgical contraception) is acceptable.
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- Men must agree not to father a child during the study and one month after and to use contraception. Barrier with spermicide or surgical contraception is acceptable. Partner(s) contraception (e.g., female partner taking birth control pills or surgically sterile) is acceptable.
- Subjects must be able to swallow study drug capsules whole.
- Sufficient English skills to complete all assessments without assistance of an English language interpreter. Subjects with HD who cannot read or write might qualify for enrollment in the study. Site PIs will have to decide in each case whether the Subject can understand and fully participate with help from his/her Informant.
- Availability of a responsible Informant (referred to as a "study partner" in the consent document) who has good English skills, is familiar with the Subject, and is able and willing to comply with all required study procedures, ensuring that the patient attends all study visits and takes the study medicine as instructed. The study partner must spend time with the patient a minimum of 4 times per week on 4 separate days, and must monitor the patient's compliance and adverse events, participate in caregiver assessments, and use the eDiary.
- Subject has provided written, informed consent or, if Subject lacks the capacity to provide informed consent (as determined by an independent assessment by a qualified healthcare provider not directly involved in other study activities), a legally authorized representative (LAR) has provided written informed consent and the Subject has provided assent.
Who cannot join
- Any significant neurologic disease other than HD at Screening.
- Severe psychotic features or other severe psychiatric symptoms within the last three months which could lead to difficulty complying with the protocol.
- History of active alcohol or substance abuse within the past two years or Subject is unable to refrain from substance abuse throughout the study.
- Any chronic disability, significant systemic illness or unstable medical condition at Screening or Baseline that could lead to difficulty complying with the protocol.
- Use of any investigational drugs within 30 days of Screening.
- Subject has known allergy to any of the components of study medication.
- Subject is currently pregnant, breast-feeding and/or lactating.
- Subject acknowledges present use of illicit drugs at Screening.
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
United States22 sites
Emory University
Atlanta, Georgia, 30329
University of Colorado Hospital Translational Research Center
Aurora, Colorado, 80045
University of Alabama
Birmingham, Alabama, 35233
Massachusetts General Hospital
Charlestown, Massachusetts, 02129
University of Virginia Health System, Department of Neurology
Charlottesville, Virginia, 22908
Northwestern Out-Patient Neurology Clinic
Chicago, Illinois, 60611
University Medical Arts Building
Cincinnati, Ohio, 45219
Ohio State University, Wexner Medical Center, Department of Neurology
Columbus, Ohio, 43221
UT Southwestern Medical Center
Dallas, Texas, 75390
SUNY Stony Brook Clinical Research Center, Department of Neurology
East Setauket, New York, 11733
University of Kansas Medical Center
Kansas City, Kansas, 66160
UCLA, Neurology Clinic
Los Angeles, California, 90095
University of Miami, Miller School of Medicine, Jackson Behavioral Health Hospital
Miami, Florida, 33136
Vanderbilt Clinical Research Center
Nashville, Tennessee, 37232
Columbia University Medical Center, New York Presbyterian Hospital
New York, New York, 10032
University of Pittsburgh Medical Center, Department of Neurology
Pittsburgh, Pennsylvania, 15213
Oregon Health and Science University
Portland, Oregon, 97239
University of Rochester Medical Center
Rochester, New York, 14618
UC Davis Medical Center, Department of Neurology, CTSC Clinical Research Center
Sacramento, California, 95817
University of Utah, Department of Neurology
Salt Lake City, Utah, 84108
Swedish Neuroscience Institute
Seattle, Washington, 98122
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: An Exploratory Phase II Study to Determine the Tolerability, Safety, and Activity of a Novel Vasopressin 1a Receptor Antagonist (SRX246) in Irritable Subjects With Huntington's Disease (HD)
This study evaluates the tolerability, safety and activity of SRX246 in the treatment of irritability in patients with Huntington's disease. Two-thirds of all participants will receive SRX246, while the other third will receive a placebo.
Read the detailed description
SRX246 is a first-in-class vasopressin 1a (V1a) receptor antagonist that crosses the blood-brain barrier following oral administration. The molecule exhibits high affinity and high selectivity for its target receptor. Preclinical pharmacology studies have demonstrated significant CNS effects in models of irritability, including impulsive aggression, depression, and anxiety. In an experimental medicine fMRI study in healthy volunteers, SRX246 treatment significantly attenuated the effect of intranasal AVP in brain circuits known to modulate emotional responses to stimuli that elicit aggression/fear. Together, these findings suggest that SRX246 has potential as a novel therapeutic agent for major neuropsychiatric symptoms seen in HD patients.
This is a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12 week, dose escalation study of SRX246 in irritable Subjects with early symptomatic HD.
Following an initial screening visit, Subjects fulfilling the study inclusion and exclusion criteria will enter a pre-treatment screening phase to permit evaluations to confirm eligibility for inclusion into the study. This screening phase will be no longer than 30 days. At the completion of the screening period, eligible Subjects will be randomized at baseline visit to receive either placebo or final doses of SRX246 of 120 mg twice daily or 160 mg twice daily during the double-blind treatment phase. At baseline, Subjects in the active groups will receive 80 mg twice daily for 2 weeks, then escalate to 120 mg twice daily for 4 weeks. Then one group of Subjects will continue to take 120 mg of SRX246 twice daily for an additional 6 weeks, and the second group of Subjects will increase their dose to 160 mg of SRX246 twice daily for 6 weeks. Total dosing duration is 12 weeks.
Subjects in the placebo group will receive a similar number of capsules that are identical in appearance to the capsules that contain SRX246 during the trial, in order to preserve the blind.
In all groups, dose escalation will occur (stepwise) if patients have not experienced dose-limiting adverse effects. Patients who cannot tolerate their final dose of drug (or placebo) can have this dose reduced without compromising the blinding.
Subjects will have periodic visits either "in-person" or by "telephone", to assess tolerability, safety, and several measures of irritability and other problem behaviors, and clinical assessments for activity signals.
- Conditions
- Irritable Mood, Huntington's Disease
- Being tested
- SRX246, Placebo
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SRX246Drug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| SRX246 120mg BID | Experimental | SRX246 capsules, administered orally, in divided doses twice daily Receives: Drug: SRX246 |
| SRX246 160mg BID | Experimental | SRX246 capsules, administered orally, in divided doses twice daily Receives: Drug: SRX246 |
| Placebo | Placebo comparator | Placebo capsules, administered orally, in divided doses twice daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerability of SRX246
The primary endpoint, tolerability of SRX246, was assessed by the number of completers in each group.
Measured: 12 weeks
Secondary outcomes (1)
Safety of SRX246
The Safety of SRX246 was assessed by the number of participants who experience an adverse event.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2015 (estimated)
- Study start10 May 2016
- Primary completion10 Sep 2018
- Study completion21 Dec 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 Irritable MoodStudies 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
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azevan Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), NeuroNEXT Network
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02507284
- Sponsor's protocol ID
- AVN011
- Other IDs
- 1U44NS090616-01A1
- Status last verified
- Jul 2023
- First submitted
- 22 Jul 2015
- Last updated
- 20 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Phase II Study to Determine the Tolerability, Safety, and Activity of a Novel Vasopressin 1a Receptor Antagonist (SRX246) in Irritable Subjects With Huntington's Disease (HD)
- ClinicalTrials.gov ID
- NCT02507284
- Acronym / sponsor ID
- AVN011
- Conditions
- Irritable Mood, Huntington's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Azevan PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), NeuroNEXT Network
- Study start
- 10 May 2016 (actual)
- Primary completion
- 10 Sep 2018 (actual)
- Study completion
- 21 Dec 2018 (actual)
- First posted
- 23 Jul 2015 (estimated)
- Results
- Posted 20 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the tolerability, safety and activity of SRX246 in the treatment of irritability in patients with Huntington's disease. Two-thirds of all participants will receive SRX246, while the other third will receive a placebo.
Detailed description
SRX246 is a first-in-class vasopressin 1a (V1a) receptor antagonist that crosses the blood-brain barrier following oral administration. The molecule exhibits high affinity and high selectivity for its target receptor. Preclinical pharmacology studies have demonstrated significant CNS effects in models of irritability, including impulsive aggression, depression, and anxiety. In an experimental medicine fMRI study in healthy volunteers, SRX246 treatment significantly attenuated the effect of intranasal AVP in brain circuits known to modulate emotional responses to stimuli that elicit aggression/fear. Together, these findings suggest that SRX246 has potential as a novel therapeutic agent for major neuropsychiatric symptoms seen in HD patients.
This is a 3-arm, multicenter, randomized, placebo-controlled, double-blind, 12 week, dose escalation study of SRX246 in irritable Subjects with early symptomatic HD.
Following an initial screening visit, Subjects fulfilling the study inclusion and exclusion criteria will enter a pre-treatment screening phase to permit evaluations to confirm eligibility for inclusion into the study. This screening phase will be no longer than 30 days. At the completion of the screening period, eligible Subjects will be randomized at baseline visit to receive either placebo or final doses of SRX246 of 120 mg twice daily or 160 mg twice daily during the double-blind treatment phase. At baseline, Subjects in the active groups will receive 80 mg twice daily for 2 weeks, then escalate to 120 mg twice daily for 4 weeks. Then one group of Subjects will continue to take 120 mg of SRX246 twice daily for an additional 6 weeks, and the second group of Subjects will increase their dose to 160 mg of SRX246 twice daily for 6 weeks. Total dosing duration is 12 weeks.
Subjects in the placebo group will receive a similar number of capsules that are identical in appearance to the capsules that contain SRX246 during the trial, in order to preserve the blind.
In all groups, dose escalation will occur (stepwise) if patients have not experienced dose-limiting adverse effects. Patients who cannot tolerate their final dose of drug (or placebo) can have this dose reduced without compromising the blinding.
Subjects will have periodic visits either "in-person" or by "telephone", to assess tolerability, safety, and several measures of irritability and other problem behaviors, and clinical assessments for activity signals.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SRX246 120mg BID | Experimental | Drug: SRX246SRX246 capsules, administered orally, in divided doses twice daily |
| SRX246 160mg BID | Experimental | Drug: SRX246SRX246 capsules, administered orally, in divided doses twice daily |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo capsules, administered orally, in divided doses twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male and female Subjects aged 18 years or older
- Subjects must have clinical features of HD, which can include motor, cognitive, or behavioral symptoms
- A confirmatory family history of HD; OR CAG repeat expansion ≥ 37
- Total Functional Capacity (TFC) score of 5-13
- Evidence of irritability; a score of at least 2 or greater on the severity measure of either the UHDRS Irritability question (30b) or Aggression question (Disruptive or Aggressive Behavior, 31b)
Key exclusion criteria (8 listed)
- Any significant neurologic disease other than HD at Screening.
- Severe psychotic features or other severe psychiatric symptoms within the last three months which could lead to difficulty complying with the protocol.
- History of active alcohol or substance abuse within the past two years or Subject is unable to refrain from substance abuse throughout the study.
- Any chronic disability, significant systemic illness or unstable medical condition at Screening or Baseline that could lead to difficulty complying with the protocol.
- Use of any investigational drugs within 30 days of Screening.
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 |
|---|---|---|
| SRX246 | Drug | SRX246 120mg BID, SRX246 160mg BID |
| Placebo | Drug | Placebo |
Primary outcome
Tolerability of SRX246
Time frame: 12 weeks
The primary endpoint, tolerability of SRX246, was assessed by the number of completers in each group.
1 secondary outcome
Safety of SRX246
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2023.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
22 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 SRX246 in people with Irritable Mood and Huntington's Disease, run by Azevan Pharmaceuticals at 22 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 11 inclusion and 8 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 20 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 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 20 Jul 2023). 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?
Tolerability of SRX246 (time frame: 12 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 20 Jul 2023.