Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma
Phase 3 Study Comparing Daratumumab, Bortezomib and Dexamethasone (DVd) vs Bortezomib and Dexamethasone (Vd) in Subjects With Relapsed or Refractory Multiple Myeloma
3 other identifiers
interventional
498
15 countries
105
Brief Summary
The purpose of this study is to assess the effects of administration of daratumumab when combined with VELCADE (bortezomib) and dexamethasone compared with bortezomib and dexamethasone alone, for participants with relapsed or refractory multiple myeloma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 multiple-myeloma
Started Aug 2014
Longer than P75 for phase_3 multiple-myeloma
105 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 1, 2014
CompletedFirst Posted
Study publicly available on registry
May 12, 2014
CompletedStudy Start
First participant enrolled
August 15, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 11, 2016
CompletedResults Posted
Study results publicly available
February 10, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
January 10, 2024
CompletedAugust 29, 2025
August 1, 2025
1.4 years
May 1, 2014
December 20, 2016
August 14, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS)
PFS was defined as duration from date of randomization to either progressive disease (PD)/death, whichever occurred first. PD was defined as meeting any one of following criteria: Increase of greater than equal to (\>=)25 percent (%) in level of serum M-protein from lowest response value and absolute increase must be \>=0.5 gram per deciliter (g/dL); Increase of \>=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be \>=200 mg/24hours; Only in participants without measurable serum and urine M-protein levels: increase of \>=25% in difference between involved and uninvolved FLC levels from lowest response value and absolute increase must be \>10 mg/dL; Definite increase in size of existing bone lesions or soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
From the date of randomization to either progressive disease or death, whichever occurred first (approximately 1 year 4 months)
Secondary Outcomes (5)
Time to Disease Progression (TTP)
From the date of randomization to the date of first documented evidence of progression or death due to PD whichever occurred first (approximately 6 years 9 months)
Percentage of Participants With a Very Good Partial Response (VGPR) or Better
Up to disease progression (approximately 6 years 9 months)
Overall Response Rate (ORR)
Up to disease progression (approximately 6 years 9 months)
Percentage of Participants With Negative Minimal Residual Disease (MRD)
Up to disease progression (approximately 6 years 9 months)
Overall Survival (OS)
Up to 6 years 9 months
Study Arms (2)
Daratumumab+VELCADE+dexamethasone
EXPERIMENTALDaratumumab, VELCADE and dexamethasone
VELCADE+dexamethasone
ACTIVE COMPARATORVELCADE and dexamethasone.
Interventions
Daratumumab will be administered as an IV infusion or 16 mg/kg weekly for the first 3 cycles, on Day 1 of Cycles 4-9, and then every 4 weeks thereafter. As per protocol amendment-6 participants receiving treatment with daratumumab IV will have the option to switch to daratumumab SC 1800 mg on Day 1 of any cycle, at the discretion of the investigator.
VELCADE will be administered at a dose of 1.3 mg/m2 subcutaneously (SC) on Days 1, 4, 8 and 11 of each 21-day cycle. Eight VELCADE treatment cycles are to be administered.
Dexamethasone will be administered orally at 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 of the first 8 VELCADE treatment cycles.
Eligibility Criteria
You may qualify if:
- Must have had documented multiple myeloma
- Must have received at least 1 prior line of therapy for multiple myeloma
- Must have had documented evidence of progressive disease as defined based on Investigator's determination of response of International Myeloma Working Group (IMWG) criteria on or after their last regimen
- Must have an Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
- Must have achieved a response (partial response \[PR\] or better based on investigator's determination of response by the IMWG criteria) to at least 1 prior regimen in the past
You may not qualify if:
- Has received daratumumab or other anti-CD38 therapies previously
- Is refractory to VELCADE or another PI, like ixazomib and carfilzomib (had progression of disease while receiving VELCADE therapy or within 60 days of ending VELCADE therapy or another PI therapy, like ixazomib and carfilzomib
- Is intolerant to VELCADE (ie, discontinued due to any adverse event while on VELCADE treatment)
- Has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 milligram per day \[mg/day\] for a maximum of 4 days) before treatment. A list of anti-myeloma treatments with the corresponding pharmacokinetic half-lives is provided in the Site Investigational Product Procedures Manual (IPPM).
- Has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization
- Has any concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (105)
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Birmingham, Alabama, United States
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Los Angeles, California, United States
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Stamford, Connecticut, United States
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Jacksonville, Florida, United States
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Atlanta, Georgia, United States
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Niles, Illinois, United States
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Topeka, Kansas, United States
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Westwood, Kansas, United States
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Marrero, Louisiana, United States
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Boston, Massachusetts, United States
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Lansing, Michigan, United States
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New York, New York, United States
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Chapel Hill, North Carolina, United States
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Portland, Oregon, United States
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Philadelphia, Pennsylvania, United States
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Providence, Rhode Island, United States
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Seattle, Washington, United States
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Adelaide, Australia
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Concord, Australia
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Fitzroy, Australia
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Hobart, Australia
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Melbourne, Australia
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Nedlands, Australia
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Woodville South, Australia
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Barretos, Brazil
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Porto Alegre, Brazil
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Salvador, Brazil
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São Paulo, Brazil
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Brno, Czechia
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Hradec Králové, Czechia
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Ostrava-Poruba, Czechia
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Prague, Czechia
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Bamberg, Germany
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Berlin, Germany
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Düsseldorf, Germany
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Freiburg im Breisgau, Germany
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Göttingen, Germany
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Hamburg, Germany
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Mainz, Germany
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München, Germany
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Stuttgart, Germany
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Tübingen, Germany
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Ulm, Germany
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Würzburg, Germany
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Budapest, Hungary
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Debrecen, Hungary
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Győr, Hungary
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Pécs, Hungary
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Veszprém, Hungary
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Huixquilucan, Mexico
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Monterrey, Mexico
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Alkmaar, Netherlands
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Amersfoort, Netherlands
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Dordrecht, Netherlands
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Groningen, Netherlands
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Leiden, Netherlands
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Maastricht, Netherlands
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Nijmegen, Netherlands
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The Hague, Netherlands
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Chorzów, Poland
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Katowice, Poland
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Krakow, Poland
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Poznan, Poland
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Warsaw, Poland
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Krasnodar, Russia
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Moscow, Russia
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Nizhny Novgorod, Russia
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Penza, Russia
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Pyatigorsk, Russia
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Ryazan, Russia
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Samara, Russia
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Sochi, Russia
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Syktyvkar, Russia
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Busan, South Korea
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Hwasun, South Korea
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Seoul, South Korea
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Suwon, South Korea
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Ulsan, South Korea
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Madrid, Spain
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Salamanca, Spain
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San Sebastián de los Reyes, Spain
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Toledo, Spain
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Valencia, Spain
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Linköping, Sweden
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Luleå, Sweden
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Lund, Sweden
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Örebro, Sweden
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Sundsvall, Sweden
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Umeå, Sweden
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Uppsala, Sweden
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Västerås, Sweden
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Ankara, Turkey (Türkiye)
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Istanbul, Turkey (Türkiye)
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Izmir, Turkey (Türkiye)
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Kayseri, Turkey (Türkiye)
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Kocaeli, Turkey (Türkiye)
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Malatya, Turkey (Türkiye)
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Cherkasy, Ukraine
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Dnipro, Ukraine
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Ivano-Frankivsk, Ukraine
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Kiev, Ukraine
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Lviv, Ukraine
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Poltava, Ukraine
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Vinnitsa, Ukraine
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Zaporizhzhya, Ukraine
Related Publications (9)
Almansour SA, Alqudah MAY, Abuhelwa Z, Al-Shamsi HO, Alhuraiji A, Semreen MH, Bustanji Y, Alzoubi KH, Modi ND, Mckinnon RA, Sorich MJ, Hopkins AM, Abuhelwa AY. Antithrombotic utilization, adverse events, and associations with treatment outcomes in multiple myeloma: pooled analysis of three clinical trials. Ther Adv Med Oncol. 2024 Sep 2;16:17588359241275387. doi: 10.1177/17588359241275387. eCollection 2024.
PMID: 39229471DERIVEDSpencer A, Moreau P, Mateos MV, Goldschmidt H, Suzuki K, Levin MD, Sonneveld P, Orlowski RZ, Yoon SS, Usmani SZ, Weisel K, Reece D, Ahmadi T, Pei H, Mayo WG, Gai X, Carey J, Bartlett JB, Carson R, Dimopoulos MA. Daratumumab for patients with myeloma with early or late relapse after initial therapy: subgroup analysis of CASTOR and POLLUX. Blood Adv. 2024 Jan 23;8(2):388-398. doi: 10.1182/bloodadvances.2023010579.
PMID: 38048391DERIVEDSonneveld P, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, Mark TM, Levin MD, Ahmadi T, Qin X, Garvin Mayo W, Gai X, Carey J, Carson R, Spencer A. Overall Survival With Daratumumab, Bortezomib, and Dexamethasone in Previously Treated Multiple Myeloma (CASTOR): A Randomized, Open-Label, Phase III Trial. J Clin Oncol. 2023 Mar 10;41(8):1600-1609. doi: 10.1200/JCO.21.02734. Epub 2022 Nov 22.
PMID: 36413710DERIVEDHe J, Berringer H, Heeg B, Ruan H, Kampfenkel T, Dwarakanathan HR, Johnston S, Mendes J, Lam A, Bathija S, Mackay EK. Indirect Treatment Comparison of Daratumumab, Pomalidomide, and Dexamethasone Versus Standard of Care in Patients with Difficult-to-Treat Relapsed/Refractory Multiple Myeloma. Adv Ther. 2022 Sep;39(9):4230-4249. doi: 10.1007/s12325-022-02226-x. Epub 2022 Jul 22.
PMID: 35876974DERIVEDCavo M, San-Miguel J, Usmani SZ, Weisel K, Dimopoulos MA, Avet-Loiseau H, Paiva B, Bahlis NJ, Plesner T, Hungria V, Moreau P, Mateos MV, Perrot A, Iida S, Facon T, Kumar S, van de Donk NWCJ, Sonneveld P, Spencer A, Krevvata M, Heuck C, Wang J, Ukropec J, Kobos R, Sun S, Qi M, Munshi N. Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA. Blood. 2022 Feb 10;139(6):835-844. doi: 10.1182/blood.2021011101.
PMID: 34289038DERIVEDAvet-Loiseau H, San-Miguel J, Casneuf T, Iida S, Lonial S, Usmani SZ, Spencer A, Moreau P, Plesner T, Weisel K, Ukropec J, Chiu C, Trivedi S, Amin H, Krevvata M, Ramaswami P, Qin X, Qi M, Sun S, Qi M, Kobos R, Bahlis NJ. Evaluation of Sustained Minimal Residual Disease Negativity With Daratumumab-Combination Regimens in Relapsed and/or Refractory Multiple Myeloma: Analysis of POLLUX and CASTOR. J Clin Oncol. 2021 Apr 1;39(10):1139-1149. doi: 10.1200/JCO.20.01814. Epub 2021 Jan 29.
PMID: 33513030DERIVEDWeisel K, Spencer A, Lentzsch S, Avet-Loiseau H, Mark TM, Spicka I, Masszi T, Lauri B, Levin MD, Bosi A, Hungria V, Cavo M, Lee JJ, Nooka A, Quach H, Munder M, Lee C, Barreto W, Corradini P, Min CK, Chanan-Khan AA, Horvath N, Capra M, Beksac M, Ovilla R, Jo JC, Shin HJ, Sonneveld P, Casneuf T, DeAngelis N, Amin H, Ukropec J, Kobos R, Mateos MV. Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. J Hematol Oncol. 2020 Aug 20;13(1):115. doi: 10.1186/s13045-020-00948-5.
PMID: 32819447DERIVEDMateos MV, Spencer A, Nooka AK, Pour L, Weisel K, Cavo M, Laubach JP, Cook G, Iida S, Benboubker L, Usmani SZ, Yoon SS, Bahlis NJ, Chiu C, Ukropec J, Schecter JM, Qin X, O'Rourke L, Dimopoulos MA. Daratumumab-based regimens are highly effective and well tolerated in relapsed or refractory multiple myeloma regardless of patient age: subgroup analysis of the phase 3 CASTOR and POLLUX studies. Haematologica. 2020 Jan 31;105(2):468-477. doi: 10.3324/haematol.2019.217448. Print 2020.
PMID: 31221782DERIVEDPalumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, Mark TM, Qi M, Schecter J, Amin H, Qin X, Deraedt W, Ahmadi T, Spencer A, Sonneveld P; CASTOR Investigators. Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Aug 25;375(8):754-66. doi: 10.1056/NEJMoa1606038.
PMID: 27557302DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Director, Clinical Research
- Organization
- Janssen R&D US
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical trial
Janssen Research & Development, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 1, 2014
First Posted
May 12, 2014
Study Start
August 15, 2014
Primary Completion
January 11, 2016
Study Completion
January 10, 2024
Last Updated
August 29, 2025
Results First Posted
February 10, 2017
Record last verified: 2025-08