A Long-term Safety Study of Esketamine Nasal Spray in Treatment-resistant Depression

NCT ID: NCT02782104

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1148 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-09
• Study Completion Date: 2022-12-30

Brief Summary

The purpose of this study is to assess the safety and tolerability of esketamine nasal spray in participants with treatment-resistant depression (TRD).

Detailed Description

This is an open-label (the researchers and participants know the treatment the participant is receiving) long-term extension study. The study will consist of 2 open-label Phases: 4-week Induction phase (if applicable) and Open-Label Optimization/Maintenance phase (variable). Participants will enter the study Induction Phase from ESKETINTRD3001 (NCT02417064), ESKETINTRD3002 (NCT02418585), ESKETINTRD3003 (NCT02493868), ESKETINTRD3005 (NCT02422186) and ESKETINTRD3006 (US sites only). Participants will enter the study Open-Label Optimization/Maintenance phase from ESKETINTRD3001 (NCT02417064), ESKETINTRD3002 (NCT02418585), ESKETINTRD3003 (NCT02493868) (if appropriate at week 16) or ESKETINTRD3006 (US sites only). In the Open-Label Induction Phase, participants will self-administer flexibly-dosed esketamine nasal spray. During first 4 weeks in Optimization/Maintenance Phase responder participants from the induction phase of study 54135419TRD3008, will continue on the same dose of esketamine nasal spray from the induction phase and have a weekly intranasal treatment session frequency. Participants entering the optimization/maintenance phase from study ESKETINTRD3005 will also have a weekly intranasal treatment session frequency. However, as the ESKETINTRD3005 intranasal study medication is blinded at the time of entry into the current study, the dose of esketamine nasal spray will be administered as outlined in protocol. Participants entering the optimization/maintenance phase from study ESKETINTRD3003 (Direct Entry) or ESKETINTRD3004 who were ongoing in the Optimization, Maintenance, or Optimization/Maintenance phase, respectively, will have the option to have their current intranasal dosing frequency adjusted at the time of entry into 54135419TRD3008 study and should remain on the selected frequency from week 1 to week 4. A one-time dose change will be permitted at study entry. After 4 weeks, esketamine nasal spray treatment sessions will be individualized to either once weekly or once every other week at the fixed 2-week interval (based on clinical global impression - severity [CGI-S] performed at that visit), and every 4 weeks for participants dosed at the 4 week interval. Participants safety will be monitored throughout the study.

Conditions

Depressive Disorder, Treatment-Resistant

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Esketamine Nasal Spray

Open-Label Induction Phase: Participants will self-administer with esketamine nasal spray twice per week for 4 weeks as a flexible dose regimen (56 milligram \[mg\] or 84 mg for those \< 65 years; 28 mg, 56 mg or 84 mg for those \>= 65 years). Participants \>= 65 years old will start at a dose of 28 mg on Day 1. Optimization/Maintenance Phase: Participants entering from studies ESKETINTRD3001 (NCT02417064), ESKETINTRD3002 (NCT02418585), ESKETINTRD3003 (NCT02493868), ESKETINTRD3004 (NCT02497287), or ESKETINTRD3006 (US sites only) will self-administer esketamine nasal spray (same dose) once weekly. Participants entering from study ESKETINTRD3005 (NCT02422186) will self-administer esketamine nasal spray (28 mg in week 1; 28 or 56 mg in week 2; and 28, 56 or 84 mg in week 3 and 4) once weekly. After Week 4 (starting at Week 5), based on the Investigator's clinical judgment, the dose of esketamine for all participants can be adjusted based upon efficacy and tolerability.

Group Type: EXPERIMENTAL

Esketamine Nasal Spray

Intervention Type: DRUG

Open-Label Induction Phase: Participants will self-administer with esketamine nasal spray twice per week for 4 weeks as a flexible dose regimen (56 milligram \[mg\] or 84 mg for those \< 65 years; 28 mg, 56 mg or 84 mg for those \>= 65 years). Participants \>= 65 years old will start at a dose of 28 mg on Day 1. Optimization/Maintenance Phase: Participants entering from studies ESKETINTRD3001 (NCT02417064), ESKETINTRD3002 (NCT02418585) or ESKETINTRD3006 (US sites only) will self-administer esketamine nasal spray (same dose) once weekly. Participants entering from study ESKETINTRD3005 (NCT02422186) will self-administer esketamine nasal spray (28 mg in week 1; 28 or 56 mg in week 2; and 28, 56 or 84 mg in week 3 and 4) once weekly. After Week 4 (starting at Week 5), based on the Investigator's clinical judgment, the dose of esketamine for all participants can be adjusted based upon efficacy and tolerability.

Interventions

Esketamine Nasal Spray

Open-Label Induction Phase: Participants will self-administer with esketamine nasal spray twice per week for 4 weeks as a flexible dose regimen (56 milligram \[mg\] or 84 mg for those \< 65 years; 28 mg, 56 mg or 84 mg for those \>= 65 years). Participants \>= 65 years old will start at a dose of 28 mg on Day 1. Optimization/Maintenance Phase: Participants entering from studies ESKETINTRD3001 (NCT02417064), ESKETINTRD3002 (NCT02418585) or ESKETINTRD3006 (US sites only) will self-administer esketamine nasal spray (same dose) once weekly. Participants entering from study ESKETINTRD3005 (NCT02422186) will self-administer esketamine nasal spray (28 mg in week 1; 28 or 56 mg in week 2; and 28, 56 or 84 mg in week 3 and 4) once weekly. After Week 4 (starting at Week 5), based on the Investigator's clinical judgment, the dose of esketamine for all participants can be adjusted based upon efficacy and tolerability.

Intervention Type: DRUG

Other Intervention Names

JNJ-54135419

Eligibility Criteria

Inclusion Criteria

• Based on the prior study the participant is entering 54135419TRD3008 from: a) From ESKETINTRD3001 (NCT02417064) or ESKETINTRD3002 (NCT02418585) study: Participant has completed the induction phase and the 2-weeks follow up phase visit; or Participants completed the induction phase and was a responder and study ESKETINTRD3003 is terminated.; b) From ESKETINTRD3003 (NCT02493868) study: (1) Participant relapsed during the maintenance phase; or (2) Participant was in the induction phase of the ESKETINTRD3003 study when the study was terminated and, after completion of the induction phase, was determined to be a responder; or (3) Participant was in the optimization or maintenance phases at the time the study was terminated; or (4) or (5) Participants was in the induction phase and after completion of induction phase was determined to not meet response criteria (1) Participant completed ESKETINTRD3004 study (optimization/maintenance phase); or (2) Participant was in the induction phase of the ESKETINTRD3004 study when the study was terminated and, after completion of the induction phase, was determined to be a responder; or (3) Participant was in the optimization/maintenance phase at the time the study was terminated; (4) Participant was in the induction phase and did not meet criteria for response may be eligible for to be rolled over into 54135419TRD3008. d) From ESKETINTRD3005 (NCT02422186) study: Participant was in the induction phase of the ESKETINTRD3005 study at the time enrollment into the ESKETINTRD3004 study was closed and, after completion of the induction phase, was determined to be a responder or did not meet the criteria for response. e) From ESKETINTRD3006 study (US Study sites only) (1) Participant completed the induction phase and was a responder.

Exclusion Criteria

• Participant must be medically stable according to the investigator's judgment and knowledge of the subject's medical stability in the parent study. This determination must be documented.
• A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [b-hCG]) predose on the day of the first intranasal treatment session
• During the study (that is, from the first intranasal treatment session) and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of intranasal study medication, a man who is sexually active with a woman of childbearing potential must be practicing a highly effective method of contraception with his female partner c) must agree not to donate sperm.

• The evaluation of the benefit versus risk of continued esketamine nasal spray treatment is not favorable for the participant in the opinion of the investigator
• Since the last study visit in the participant's prior study, participant has suicidal ideation with intent to act per the investigator's clinical judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS) [corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) in the suicidal ideation module of the C-SSRS] or suicidal behavior per the investigator's clinical judgment or based on the C-SSRS (corresponding to any score higher than 0 in the suicidal behavior module of the C-SSRS)
• Participant has positive test result(s) for drugs of abuse (including barbiturates, methadone, opiates, cocaine, phencyclidine, and amphetamine/methamphetamine) predose on the day of the first intranasal treatment session
• Participant has any anatomical or medical condition that, per the investigator's clinical judgment based on assessment, may impede delivery or absorption of intranasal study drug
• Participant has taken any prohibited therapies that would not permit administration of the first intranasal treatment session

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Birmingham, Alabama, United States

Little Rock, Arkansas, United States

Garden Grove, California, United States

Glendale, California, United States

Oakland, California, United States

Orange, California, United States

San Diego, California, United States

San Rafael, California, United States

Hartford, Connecticut, United States

New Haven, Connecticut, United States

Gainesville, Florida, United States

Miami, Florida, United States

Orlando, Florida, United States

Atlanta, Georgia, United States

Chicago, Illinois, United States

Hoffman Estates, Illinois, United States

Joliet, Illinois, United States

Maywood, Illinois, United States

Skokie, Illinois, United States

Iowa City, Iowa, United States

Wichita, Kansas, United States

Lake Charles, Louisiana, United States

Shreveport, Louisiana, United States

Baltimore, Maryland, United States

Gaithersburg, Maryland, United States

Boston, Massachusetts, United States

New Bedford, Massachusetts, United States

Watertown, Massachusetts, United States

Worcester, Massachusetts, United States

Rochester Hills, Michigan, United States

O'Fallon, Missouri, United States

Saint Charles, Missouri, United States

Omaha, Nebraska, United States

Cedarhurst, New York, United States

New York, New York, United States

Staten Island, New York, United States

Hickory, North Carolina, United States

Cincinnati, Ohio, United States

Oklahoma City, Oklahoma, United States

Allentown, Pennsylvania, United States

Media, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Lincoln, Rhode Island, United States

Providence, Rhode Island, United States

Charleston, South Carolina, United States

Austin, Texas, United States

Dallas, Texas, United States

Houston, Texas, United States

Wichita Falls, Texas, United States

Charlottesville, Virginia, United States

Waukesha, Wisconsin, United States

Banfield, , Argentina

Buenos Aires, , Argentina

Córdoba, , Argentina

La Plata, , Argentina

Mendoza, , Argentina

Rosario, , Argentina

Caulfield, , Australia

Elizabeth Vale, , Australia

Frankston, , Australia

Vienna, , Austria

Aalst, , Belgium

Bruges, , Belgium

Brussels, , Belgium

Heusden-Zolder, , Belgium

Liège, , Belgium

Yvoir, , Belgium

Belo Horizonte, , Brazil

Curitiba, , Brazil

Fortaleza, , Brazil

Passo Fundo, , Brazil

Porto Alegre, , Brazil

Recife, , Brazil

Rio de Janeiro, , Brazil

São Bernardo do Campo, , Brazil

São Paulo, , Brazil

Burgas, , Bulgaria

Kardzhali, , Bulgaria

Pazardzhik, , Bulgaria

Pleven, , Bulgaria

Plovdiv, , Bulgaria

Rousse, , Bulgaria

Sofia, , Bulgaria

Varna, , Bulgaria

Vancouver, British Columbia, Canada

Kingston, Ontario, Canada

Ottawa, Ontario, Canada

Toronto, Ontario, Canada

Brno, , Czechia

Pilsen, , Czechia

Prague, , Czechia

Tallinn, , Estonia

Tartu, , Estonia

Kuopio, , Finland

Clermont-Ferrand, , France

Douai, , France

Nantes, , France

Nîmes, , France

Paris, , France

Poitiers, , France

Toulon, , France

Berlin, , Germany

Bochum, , Germany

Mainz, , Germany

Mittweida, , Germany

Oranienburg, , Germany

Pfaffenhofen, , Germany

Budapest, , Hungary

Debrecen, , Hungary

Győr, , Hungary

Pécs, , Hungary

Sopron, , Hungary

Szekszárd, , Hungary

Vác, , Hungary

Kaunas, , Lithuania

Kuala Lumpur, , Malaysia

Guadalajara, , Mexico

León, , Mexico

Mexico City, , Mexico

México, , Mexico

Monterrey, , Mexico

San Luis Potosí City, , Mexico

Bełchatów, , Poland

Bialystok, , Poland

Bydgoszcz, , Poland

Gdansk, , Poland

Leszno, , Poland

Lublin, , Poland

Warsaw, , Poland

Bratislava, , Slovakia

Liptovský Mikuláš, , Slovakia

Rimavská Sobota, , Slovakia

Rožňava, , Slovakia

Svidník, , Slovakia

Cape Town, , South Africa

Pretoria, , South Africa

Welgemoed, , South Africa

Gwangju, , South Korea

Seoul, , South Korea

Alcorcón, , Spain

Barcelona, , Spain

Bilbao, , Spain

Madrid, , Spain

Oviedo, , Spain

Palma, , Spain

Pamplona, , Spain

Sabadell, , Spain

Salamanca, , Spain

Sant Boi de Llobregat, , Spain

Torrevieja, , Spain

Vitoria-Gasteiz, , Spain

Zamora, , Spain

Halmstad, , Sweden

Lund, , Sweden

Skövde, , Sweden

Stockholm, , Sweden

Kaohsiung City, , Taiwan

New Taipei City, , Taiwan

Taichung, , Taiwan

Taipei, , Taiwan

Taoyuan District, , Taiwan

Adana, , Turkey (Türkiye)

Ankara, , Turkey (Türkiye)

Bursa, , Turkey (Türkiye)

Istanbul, , Turkey (Türkiye)

Kucukcekmece/Istanbul, , Turkey (Türkiye)

Oanakkale, , Turkey (Türkiye)

Samsun, , Turkey (Türkiye)

Chesterfield, , United Kingdom

Derby, , United Kingdom

London, , United Kingdom

Northampton, , United Kingdom

Oxford, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Bulgaria; Canada; Czechia; Estonia; Finland; France; Germany; Hungary; Lithuania; Malaysia; Mexico; Poland; Slovakia; South Africa; South Korea; Spain; Sweden; Taiwan; Turkey (Türkiye); United Kingdom

References

Zaki N, Chen LN, Lane R, Doherty T, Drevets WC, Morrison RL, Sanacora G, Wilkinson ST, Young AH, Lacerda ALT, Paik JW, Popova V, Fu DJ. Safety and efficacy with esketamine in treatment-resistant depression: long-term extension study. Int J Neuropsychopharmacol. 2025 Jun 6;28(6):pyaf027. doi: 10.1093/ijnp/pyaf027.

Reference Type: DERIVED

PMID: 40319349 (View on PubMed)

Castro M, Wilkinson ST, Al Jurdi RK, Petrillo MP, Zaki N, Borentain S, Fu DJ, Turkoz I, Sun L, Brown B, Cabrera P. Efficacy and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Who Completed a Second Induction Period: Analysis of the Ongoing SUSTAIN-3 Study. CNS Drugs. 2023 Aug;37(8):715-723. doi: 10.1007/s40263-023-01026-3. Epub 2023 Aug 9.

Reference Type: DERIVED

PMID: 37558912 (View on PubMed)

Zaki N, Chen LN, Lane R, Doherty T, Drevets WC, Morrison RL, Sanacora G, Wilkinson ST, Popova V, Fu DJ. Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study. Neuropsychopharmacology. 2023 Jul;48(8):1225-1233. doi: 10.1038/s41386-023-01577-5. Epub 2023 May 12.

Reference Type: DERIVED

PMID: 37173512 (View on PubMed)

Starr HL, Abell J, Larish A, Lewis S, DeMuro C, Gogate J, Jamieson C, Daly E, Zaki N, Kramer M. Self-reported review of the value of esketamine in patients with treatment-resistant depression: Understanding the patient experience in the STRIVE Study. Psychiatry Res. 2020 Nov;293:113376. doi: 10.1016/j.psychres.2020.113376. Epub 2020 Aug 8.

Reference Type: DERIVED

PMID: 32818917 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

54135419TRD3008

Identifier Type: OTHER

Identifier Source: secondary_id

2015-003578-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108149

Identifier Type: -

Identifier Source: org_study_id