Open label safety study of tasimelteon indicated in the treatment of blind individuals with no light perception having problems synchronizing their internal clock with the 24- hour light-dark cycle.

2024-516721-31-00 Protocol VP-VEC-162-3202 Therapeutic confirmatory (Phase III) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 2 sites · Protocol VP-VEC-162-3202

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Authorised, recruitment pending
Participants planned 140
Countries 1
Sites 2

Non-24 Hour Sleep-Wake Disorder

To characterize the effect of tasimelteon on standard measures of patient's safety.

Key facts

Sponsor
Vanda Pharmaceuticals Inc.
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nervous System Diseases [C10]
Decision date (initial)
2024-12-03
Transition trial
Yes
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
Yes
Funding sources
Vanda Pharmaceuticals Inc.

External identifiers

EU CT number
2024-516721-31-00
EudraCT number
2010-020912-12
ClinicalTrials.gov
NCT01218789

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Therapy, Pharmacodynamic, Pharmacogenomic, Efficacy, Safety

To characterize the effect of tasimelteon on standard measures of patient's safety.

Secondary objectives 3

  1. To assess the effect of tasimelteon on patient reported nighttime sleep as measured by a Patient Global Impression of Change (PGI-C).
  2. To assess the effect of tasimelteon on daytime naps as measured by Patient Global Impression of Change (PGI-C).
  3. To assess the effects of tasimelteon as measured by a Clinical Global Impression of Change (CGI-C).

Conditions and MedDRA coding

Non-24 Hour Sleep-Wake Disorder

VersionLevelCodeTermSystem organ class
20.0 SOC 10029205 Nervous system disorders 8

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

  1. Ability and acceptance to provide informed consent.
  2. Men or women ≥ 18 years.
  3. Body Mass Index (BMI) of ≥ 18 and ≤ 40 kg/m2 (BMI = weight (kg)/ [height (m)]2).
  4. Males, non-fecund females, or females of child-bearing potential (defined as less than 1 year post-menopausal or not surgically sterile) must be using an acceptable method of birth control (e.g., oral contraceptives, patch, intrauterine device [IUD], diaphragm or condom with spermicidal jelly or foam or abstinence, or cervical cap) for a period of 35 days before the first dosing and must have a negative pregnancy test at the screening and baseline visits.
  5. Willing and able to comply with study requirements and restrictions.
  6. No perception of light.
  7. History (within the last 3 months) of trouble sleeping at night (difficulty initiating sleep or staying asleep), difficulty awakening in the morning, or daytime sleepiness as determined by answering yes to at least one question in the Sleep Complaint Questionnaire.
  8. Affiliated with or beneficiary of a social security system.

Exclusion criteria 18

  1. Have a probable diagnosis of a current sleep disorder other than N24HSWD that is the primary cause of the sleep disturbance based on clinical investigator medical judgment.
  2. History (within the 12 months prior to screening) of psychiatric disorders including Major Depressive Disorder, Generalized Anxiety Disorder, Axis II Disorders, delirium or any other psychiatric disorder that in the opinion of the clinical investigator would affect participation in the study or full compliance with study procedures unless currently controlled and stable.
  3. History of intolerance and/or hypersensitivity to melatonin or melatonin agonists.
  4. History of drug or alcohol abuse as defined in DSM-IV, Diagnostic Criteria for Drug and Alcohol Abuse, within the 12 months prior to screening and/or regular consumption of alcoholic drinks (> 40g/day).
  5. Patients having any current suicidal ideation of type 4 or 5 on the C-SSRS at Screening or Baseline.
  6. Patient is at risk of suicide, in the opinion of the Investigator. Evidence of suicide risk could include any suicide attempt within the past year or any other suicidal behavior within the past year.
  7. Current clinically significant cardiovascular, respiratory, neurologic, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction unless currently controlled and stable.
  8. Patients who have estimated creatinine clearance (CLcr; based on the Cockcroft-Gault equation) ≤ to 55 mL/min.
  9. Clinically significant deviation from normal in clinical laboratory results, vital signs measurements, or physical examination findings at screening or baseline as determined by the clinical investigator.
  10. Indication of impaired liver function (values for AST, ALT or bilirubin > 2 times Upper Limit of Normal).
  11. Pregnant or lactating females.
  12. A positive test for drugs of abuse at the screening visit.
  13. Smoke more than 10 cigarettes/day.
  14. Participation in a previous tasimelteon (aka VEC-162 or BMS-214778) trial.
  15. Exposure to any investigational drug, including placebo, within 30 days, 5 half-lives, or the exclusion period given by a previous study in which the patient has participated in, whichever of the three scenarios is longer.
  16. Unwilling or unable to discontinue usage of medication listed in Section 8.2.1
  17. Current use of melatonin or melatonin agonist.
  18. Any other sound medical reason as determined by the clinical investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Adverse events (AEs) including suicidal ideation or behavior, changes in vital signs, clinical laboratory evaluations, electrocardiograms (ECGs) and physical exam findings during treatment.

Secondary endpoints 3

  1. Patient Global Impression-Change (PGI-C) for nighttime sleep.
  2. Patient Global Impression-Change (PGI-C) for daytime naps.
  3. Clinical Global Impression-Change (CGI-C).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

HETLIOZ 20 mg hard capsules

PRD8431741 · Product

Active substance
Tasimelteon
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL USE
Max daily dose
20 mg milligram(s)
Max total dose
20 mg milligram(s)
Max treatment duration
676 Week(s)
Authorisation status
Authorised
ATC code
N05CH03 — -
Marketing authorisation
EU/1/15/1008/001
MA holder
VANDA PHARMACEUTICALS NETHERLANDS B.V.
MA country
EU
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/10/841
Modified vs. Marketing Authorisation
No

Tasimelteon

SUB166225 · Substance

Active substance
Tasimelteon
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL USE
Max daily dose
20 mg milligram(s)
Max total dose
20 mg milligram(s)
Max treatment duration
676 Week(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/10/841
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vanda Pharmaceuticals Inc.

5 Total trials 3 Recruiting 1 Ended
Commercial
Sponsor organisation
Vanda Pharmaceuticals Inc.
Address
2200 Pennsylvania Avenue Northwest Suite 300
City
Washington
Postcode
20037-1709
Country
United States

Scientific contact point

Organisation
Vanda Pharmaceuticals Inc.
Contact name
Vanda Pharmaceuticals, Inc.

Public contact point

Organisation
Vanda Pharmaceuticals Inc.
Contact name
Vanda Pharmaceuticals, Inc.

Third parties 4

OrganisationCity, countryDuties
Creapharm Clinical Supplies
ORG-100020131
 Reims, France Code 14
United BioSource (Suisse) S.A.
ORG-100008646
 Vernier, Switzerland Code 8
Medpace Finland Oy
ORG-100009147
 Helsinki, Finland On site monitoring, Code 10, Code 11, Code 12, Code 13, Other, Code 2, Laboratory analysis, Data management
Oracle America Inc.
ORG-100039874
 Redwood City, United States E-data capture

Locations

1 EU/EEA country · 2 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Authorised, recruitment pending 140 2
Rest of world — 0 —

Investigational sites

France

2 sites · Authorised, recruitment pending
Hospital Hotel Dieu
Centre du Sommeil, 1 Parvis Notre Dame Place Jean Paul II, 75004, Paris
Centre Hospitalier Universitaire De Montpellier
Unité des Troubles du Sommeil, 80 Avenue Augustin Fliche, 34295, Montpellier Cedex 5

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Urgent safety measure US-73005

Event date
2025-02-28
Submission date
2025-03-03
In response to
OTHER
Member states affected
France
Event description
Protocol Amendment 18 (Amd 18) to the VP-VEC-162-3202 study was submitted to the French RA and EC for review and approval on 31/01/2025 as part of a substantial modification (ID: SM-1). SM-1 was validated on 06/02/2025. French RA review of Part I was concluded as “acceptable” on 25/02/2025. Until EC feedback is received, Amd 18 cannot be implemented. Participant 500-1002 is currently at a serious risk of a lapse in IMP treatment under the currently approved Protocol Amendment 17. The participant has been enrolled in VP-VEC-162-3202 since January 2011 and has been taking daily open-label study medication since January 2012.

The participant is scheduled to require additional IMP on 02/03/2025. A site visit and associated re-supply of IMP to this participant would be out of scope of the currently approved Protocol Amendment 17. This is the only participant in the VP-VEC-162-3202 study affected by this timeline lapse.
Measures taken
The below measure has been deemed appropriate and necessary to prevent a lapse in treatment for participant 500-1002. To maintain this participant on their current daily dose of tasimelteon capsules, Vanda has, in agreement with MedPace (study primary CRO), approved the shipment of IMP to participant 500-1002 to continue their treatment until Protocol Amendment 18 (Amd 18) is approved by the French RA and EC. Once Amd 18 is fully implemented in France, the participant will conduct a standard on-site visit.

As of March 2024, over 2,000 subjects have received at least one dose of tasimelteon in thirty-three clinical trials. 1,572 subjects were a part of a Phase II or Phase III trial and 190 with Non-24-Hour Sleep-Wake Disorder. Throughout the course of clinical development of tasimelteon, there have been relatively few SAE’s. Of the 500 plus tasimelteon-treated subjects in placebo-controlled studies shorter than 28 days, there was one observed unrelated SAE attributed to an undiagnosed condition. No SAE’s were observed in open-label studies that were shorter than 28 days.

In two tasimelteon studies over 20 weeks long, VP-VEC-162-3201 and VP-VEC-162-3203, treatment with tasimelteon 20 mg capsules was safe and well tolerated by totally blind subjects with Non-24-Hour Disorder. Although the VP-VEC-162-3202 study is ongoing, interim results (cut off date 31-OCT-2013) supported that long-term daily use of tasimelteon is safe and well-tolerated.

The European Commission granted a marketing authorisation valid throughout the European Union for tasimelteon (HETLIOZ®) capsules on 3 July 2015 for the treatment of Non-24 in totally blind adults. Additionally, tasimelteon (HETLIOZ®) capsules have received market authorization by the FDA for the treatment of Non-24 in adults in 2014 and nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) in patients 16 years of age and older in 2020.

Participant 500-1002 started treatment in January 2011. Although it is possible the first 52 weeks of treatment were with placebo, they have been on an open label daily dose of Hetlioz 20 MG since, at the latest, 2012. During this time, the participant presented with four SAE’s, all of which resolved and were not related to study drug. All SAE’s for this participant were determined by the investigator to be attributed to an intercurrent disease or underlying disease/pre-existing condition.

Given overall long-term safety profile of tasimelteon, absence of drug-related AE’s for this participant, and stable dose relative to previous years in this study the clinical team feels it is safe to proceed with IMP administration prior to the formal implementation of Amd 18.

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol 2024-516721-31-00 19
Recruitment arrangements (for publication) K1_Recruitment arrangements NA
Subject information and informed consent form (for publication) L1_SIS and ICF_Main Consent Form_Vanda Pharmaceuticals Inc_redacted 12
Subject information and informed consent form (for publication) L1_SIS and ICF_Main Information Sheet_Vanda Pharmaceuticals Inc_redacted 12
Summary of Product Characteristics (SmPC) (for publication) E1_SmPC Hetlioz NA
Synopsis of the protocol (for publication) D1_Protocol synopsis_FR_2024-516721-31_Vanda Pharmaceuticals redacted 19

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-16 France Acceptable
2024-11-28
 2024-12-03
2 SUBSTANTIAL MODIFICATION SM-1 2025-01-31 France Acceptable
2025-02-25
 2025-03-10
3 SUBSTANTIAL MODIFICATION SM-2 2025-10-20 France Acceptable
2026-01-19
 2026-01-23