An Open-Label Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of OV101 in Individuals With Angelman Syndrome (ELARA)

• ClinicalTrials.gov Identifier: NCT03882918
• Recruitment Status: Terminated
• First Posted: March 20, 2019
• Last Update Posted: February 4, 2022
• Sponsor: Ovid Therapeutics Inc.
• Information provided by (Responsible Party): Ovid Therapeutics Inc.

Study Description

Brief Summary:

This open-label study (OV101-18-002) will evaluate the long-term (52 weeks) safety of OV101 in subjects with AS and provide additional OV101 treatment to those subjects who completed Study OV101-15-001 (NCT02996305). Subjects with AS who completed the pharmacokinetic Study OV101-16-001 (NCT03109756) will also be permitted to participate, provided they meet all entry criteria.

Condition or disease	Intervention/treatment	Phase
Angelman Syndrome	Drug: OV101	Phase 3

Detailed Description:

This will be an open-label, long-term safety study for evaluation of further treatment with OV101 in subjects with AS who have completed previous Ovid studies (OV101-15-001 or OV101-16-001). There will be no placebo treatment. As this study will enroll subjects who have completed previous AS studies for different periods of time before entering this study, subjects will be required to complete screening and baseline visits before receiving OV101 under this protocol.The secondary objective of this study is to evaluate the long-term efficacy of OV101 treatment assessed by changes in behavior, sleep, and functioning in individuals with AS.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 125 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of OV101 in Individuals With Angelman Syndrome
• Actual Study Start Date: January 31, 2019
• Actual Primary Completion Date: June 4, 2021
• Actual Study Completion Date: June 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: OV101; once daily at bedtime (gaboxadol)	Drug: OV101; Each subject will be titrated to his or her maximal tolerated daily dose, up to a maximum daily dose of 15 mg at bedtime.; Other Name: gaboxadol

Outcome Measures

Primary Outcome Measures :

1. Incidence of adverse events in active treatment group [ Time Frame: Change from baseline to Week 52 ]
   Safety assessments related to the primary study objective of evaluating safety and tolerability of OV101 will include frequency, severity, and causality of AEs (including SAEs and AEs leading to study discontinuation), clinical assessment of suicidality, vital sign measurements, physical examinations, and EEG evaluations.

Eligibility Criteria

• Ages Eligible for Study: 13 Years to 49 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Each subject must meet all the following criteria to be enrolled in this study:

1. Has completed the OV101-15-001 or OV101-16-001 study up to the EOS.
2. Is male or female and 13 to 49 years old (inclusive) at the time of inclusion in the OV101-15-001 or OV101-16-001 study.
3. Has a previous diagnosis of AS with molecular confirmation from the OV101-15-001 or OV101-16-001 study.
4. Has an LAR/caregiver capable of providing informed consent and able to attend all scheduled study visits, oversee the administration of study drug, and provide feedback regarding the subject's symptoms and performance as described in the protocol.
5. Provides assent to the protocol (to the extent possible and in accordance with local institutional review board (IRB) and regulatory requirements) and has an LAR/caregiver who will provide written informed consent. Subjects providing assent must do so at the same visit as LAR/caregiver written informed consent is provided.
6. Can swallow study drug capsules or ingest the contents of study drug capsules after sprinkling the capsule contents onto 1 spoon of applesauce or low-fat yogurt.
7. Is currently receiving a stable dose of concomitant medications such as anti-epileptic medication, gabapentin, clonidine, trazadone, melatonin, and special diets for at least 4 weeks prior to Baseline.
8. Agrees to remain sexually abstinent from the first day of screening until 30 days after the last dose of study treatment.
9. Has LAR/caregiver(s) who agree not to post any of the subject's personal medical data or information related to the study on any website or social media site (eg, Facebook, Instagram, Twitter) until notified that the study is completed.

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from the study:

1. Discontinued from the OV101-15-001 or OV101-16-001 study due to safety reasons causally related to OV101.
2. Has a concomitant disease (eg, gastrointestinal, renal, hepatic, endocrine, respiratory, or cardiovascular system disease) or condition or any clinically significant finding at Screening that could interfere with the conduct of the study or that would pose an unacceptable risk to the subject in this study.
3. Has poorly controlled seizures defined as > 3 seizures lasting < 3 minutes per week or > 1 seizure episode lasting more than 3 minutes per week or as per medical monitor judgment.
4. Has clinically significant clinical laboratory abnormalities or vital signs at the time of screening (eg, alanine aminotransferase or aspartate aminotransferase > 2.5 × upper limit of normal; total bilirubin or creatinine > 1.5 × upper limit of normal). Retesting of clinical laboratory parameters may be allowed after consultation with the medical monitor or designee.
5. Current use of benzodiazepines, zolpidem, zaleplon, zopiclone, eszopiclone, barbiturates, or ramelteon for sleep within the 4 weeks prior to Day 1. Benzodiazepines administered for situational anxiety related to occasional procedures or events are permitted.
6. Has a history of suicidal behavior or is considered by the investigator to be at increased risk of suicide.
7. Has any condition or circumstance that, in the opinion of the investigator, makes the subject unsuitable for enrollment.
8. Has enrolled in any clinical trial or used any investigational agent or device, or has participated in any investigational procedure, within the 30 days before screening or does so concurrently with this study.
9. Is a family member of the investigator or of study site staff.

Contacts and Locations

Locations

United States, Arizona

Ovid Therapeutics Investigative Site

Phoenix, Arizona, United States, 85006

United States, California

Ovid Therapeutics Investigative Site

San Diego, California, United States, 32123

United States, Georgia

Ovid Therapeutics Investigative Site

Atlanta, Georgia, United States, 30322

United States, Illinois

Ovid Therapeutics Investigative Site

Chicago, Illinois, United States, 60612

United States, Massachusetts

Ovid Therapeutics Investigative Site

Boston, Massachusetts, United States, 02115

Ovid Therapeutics Investigative Site

Lexington, Massachusetts, United States, 02421

United States, Ohio

Ovid Therapeutics Investigative Site

Cincinnati, Ohio, United States, 45229

United States, Pennsylvania

Ovid Therapeutics Investigative Site

Media, Pennsylvania, United States, 19063

United States, Tennessee

Ovid Therapeutics Investigative Site

Nashville, Tennessee, United States, 37212

United States, Washington

Ovid Therapeutics Investigative Site

Tacoma, Washington, United States, 98405

Israel

Ovid Therapeutics Investigative Site

Ramat Gan, Israel, 52621

Sponsors and Collaborators

Ovid Therapeutics Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Heussler HS. Emerging Therapies and challenges for individuals with Angelman syndrome. Curr Opin Psychiatry. 2021 Mar 1;34(2):123-128. doi: 10.1097/YCO.0000000000000674. Erratum In: Curr Opin Psychiatry. 2021 Sep 1;34(5):514.

• Responsible Party: Ovid Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT03882918
• Other Study ID Numbers: OV101-18-002
• First Posted: March 20, 2019
• Last Update Posted: February 4, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Angelman Syndrome; Syndrome; Disease; Pathologic Processes; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Gaboxadol; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anticonvulsants; GABA Agonists; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action