A Study to Evaluate the Safety and Effectiveness of ALKS 2680 in Subjects With Narcolepsy Type 1

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alkermes Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

17 Jan 2025 → 31 Jul 2025

Decision date (initial)

2024-08-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Alkermes, Inc.

External identifiers

EU CT number

2024-511112-24-00

ClinicalTrials.gov

NCT06358950

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of ALKS 2680 for the treatment of EDS in subjects with NT1

Secondary objectives 2

1. To evaluate the efficacy of ALKS 2680 for the treatment of EDS and cataplexy in subjects with NT1
2. To evaluate the safety and tolerability of ALKS 2680 in subjects with NT1

Conditions and MedDRA coding

Narcolepsy Type 1

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Is 18 to 70 years of age at the time of informed consent.
2. Is willing and able to provide informed consent before study participation, as required by local regulations and IEC requirements.
3. Has a BMI ≥18 and ≤40 kg/m 2 at Visit 1
4. Meets the diagnostic criteria of NT1 according to ICSD-3-TR guidelines (Section 10.11), confirmed by the diagnostic evaluations (PSG/MSLT, or CSF hypocretin-1 levels) within the last 10 years. Additionally, meets the following protocol requirements: a. Has residual EDS (ie, ESS total score >12 at Visit 4); b. Is HLA-DQB1*06:02-positive, confirmed historically or at Visit 1, or documented hypocretin-1 CSF levels ≤110 pg/mL; c. Has an average of >4 weekly cataplexy events during the last 2 weeks of the Screening Period; d. Has an MSL of ≤15 minutes across 4 MWT trials during the Screening Period. * If the past diagnostic PSG/MSLT was performed >10 years prior to Visit 1, or is otherwise not available, a repeat confirmatory assessment may be conducted by the study site during the Screening Period with the Sponsor’s prior authorization.
5. In the opinion of the Investigator can safely discontinue any medications prescribed for the management of narcolepsy symptoms for at least 14 days (or 5 half-lives, whichever is longer) prior to Day 1, and for the duration of study; is also experiencing an unsatisfactory clinical response and/or side effect(s) from any medications prescribed for the management of narcolepsy symptoms
6. Is willing and able, in the opinion of the Investigator, to understand and comply with protocol requirements, including: a. Lifestyle considerations and restrictions detailed in Section 5.3; b. Adherence to contraception guidance detailed in Section 10.4.2; c. Adherence to actigraphy and diary requirements (ie, ≥80% completion). d. If receiving treatment for OSA, adherence to primary OSA therapy over the 30 days prior to Visit 1, and throughout the study, including during overnight visits. Adherence is defined as: − PAP use for ≥4 hours/night on ≥70% of nights (≥5 of 7 nights/week), based on the Investigator’s review of PAP unit data, and ≥4 hours/night during an overnight visit − Oral appliance use on ≥70% of nights (≥5 of 7 nights/week) and during an overnight visit

Exclusion criteria 11

1. Has poorly controlled and clinically significant sleep-disordered breathing, at the most recent diagnostic PSG or at Visit 4 (in accordance with the AASM Scoring Manual [rule 1B]): a. Has AHI ≥15 per hour b. If receiving treatment for OSA, has an average AHI ≥10 per hour over the 30 days prior to Visit 1 based on the Investigator’s review of PAP unit data c. Has central apnea index >5 per hour
2. Has another comorbid sleep disorder or condition that may influence the sleep-wake cycle: a. Has symptoms of narcolepsy secondary to another medical condition (eg, central nervous system injury or lesion, craniopharyngioma, chronic fatigue syndrome) b. Has performed shift work (working nighttime hours) or is experiencing other life activities (eg, insufficient night sleep; consistently caring for a child who wakes in the night) that interfere with regular nighttime sleep in the past 30 days prior to Visit 4 c. Has an implanted hypoglossal nerve stimulation device (eg, the Inspire® Upper Airway Stimulation system) d. Has nicotine dependence that affects sleep (eg, a subject who routinely wakes at night to smoke). See Section 5.3 for restrictions during the study. e. Excessive caffeine use 1 week prior to Visit 4 or anticipated excessive caffeine use during the study, defined as >600 mg/day of caffeine. See Section 5.3 for restrictions during the study
3. Has a significant cardiovascular disease during the Screening Period, or within the last 2 years, including: a. Myocardial infarction, ischemic heart disease, cardiac failure, or arrhythmia; b. Atrial fibrillation or an abnormal ECG demonstrating clinically significant dysrhythmia(s), including having a corrected QTcF >450 msec if male and >470 msec if female. Left bundle branch block is not exclusionary if it is asymptomatic and is an isolated ECG finding without clinical significance, as determined by the Investigator; c. Idiopathic sinus tachycardia with a resting HR >100 beats per minute, confirmed on repeat testing within 30 minutes; d. Uncontrolled hypertension with systolic BP >130 or diastolic BP >90 mmHg during Visit 1. One retest is allowed. If the retest measurement is >130/90 mmHg the subject may be rescreened once, but only after their BP has been stabilized and is ≤130/90 mmHg for at least 30 days. See Section 8.3.4 for details on BP and HR collection.
4. Has a major psychiatric or substance use disorder established in accordance with DSM-5, including: a. Disorders of schizophrenia spectrum (ie, schizophrenia, schizophreniform, schizoaffective disorder, acute or chronic psychotic disorder); b. Bipolar disorder; c. Current or recent (within the last 6 months) major depressive episode; d. Current or past (within the last 2 years) diagnosis of a moderate or severe substance use disorder; e. The subject is at a current risk of suicidal behavior; or has a “Yes” to questions 4 or 5 on the C-SSRS and/or had a suicide attempt in the period within 12 months prior to Visit 1 and up to and including Visit 4.
5. Has a positive alcohol breath test or urine drug screen for drugs of potential abuse at Visit 4. See Section 10.2 for details.
6. Has a history or presence at Visit 1 of other clinically significant (treated or untreated) illness, disease, abnormality, or surgical procedure that, in the opinion of the Investigator, might compromise subject safety, interfere with any study assessment, or affect the subject’s ability to complete the study. This includes but is not necessarily limited to the following: a. Uncontrolled or unstable hypothyroidism or diabetes mellitus; b. Clinically significant hepatic or renal disease; c. Significant neurological disorder, including dementia, neurodegeneration, stroke, epilepsy, or seizures (excluding pediatric febrile seizures). d. Clinically significant findings on the baseline eye and vision examination (Section 8.3.2.1), or anticipated vision loss or eye surgery during the study.
7. Presence of the following laboratory abnormalities at Visit 1 (one repeat is allowed at the Investigator’s discretion), including: a. Elevated liver function tests (ALT, AST) >1.5 times the upper limit of normal; b. Positive serology test for HBsAg, hepatitis C antibody confirmed by RNA testing at Visit 1; c. Renal creatinine clearance (Cockcroft-Gault Equation) is ≤50 mL/min; d. HbA1c ≥6.5%.
8. Is currently taking (or is anticipated to take) any prohibited prescription or OTC medications listed in Section 5.3, or will not be able to comply with provided washout requirements.
9. Is currently pregnant, breastfeeding, or is planning to become pregnant during the study.
10. Is currently enrolled in another clinical study or used any investigational drug or device within 30 days prior to Visit 1.
11. Is employed by Alkermes, the CRO, or study site (permanent, temporary contract worker, or designee responsible for the conduct of the study) or is immediate family (ie, a spouse, parent, sibling, or child, whether biological or legally adopted) of an Alkermes, CRO, or study site employee

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in the MSL on MWT from baseline to Week 6 by dose level

Secondary endpoints 7

1. Change in ESS from baseline to Week 6 by dose level
2. Mean WCR as derived from the subject cataplexy diary over Weeks 5 and 6 by dose level
3. TEAEs by study period
4. Clinical laboratory assessments by study period
5. Vital signs by study period
6. Safety ECG by study period
7. C-SSRS by study period

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alkermes Inc.

Sponsor organisation

Alkermes Inc.

Address

900 Winter Street

City

Waltham

Postcode

02451-1449

Country

United States

Scientific contact point

Organisation

Alkermes Inc.

Contact name

ALKS Project Lead

Public contact point

Organisation

Alkermes Inc.

Contact name

ALKS Project Lead

Third parties 12

Locations

6 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 136 files

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

Application history

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