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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02255656




Registration number
NCT02255656
Ethics application status
Date submitted
30/09/2014
Date registered
2/10/2014
Date last updated
28/03/2022

Titles & IDs
Public title
Phase IIIB-IV Long-Term Follow-up Study for Patients Who Participated in CAMMS03409
Scientific title
A Long-term Follow-up Study for Multiple Sclerosis Patients Who Have Completed the Alemtuzumab Extension Study (CAMMS03409)
Secondary ID [1] 0 0
2013-003884-71
Secondary ID [2] 0 0
LPS13649
Universal Trial Number (UTN)
Trial acronym
TOPAZ
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsing Remitting Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - alemtuzumab GZ402673

Experimental: Alemtuzumab - All Participants who completed the study CAMMS03409 (extension study of CAMMS223 \[NCT00050778\], CAMMS323 \[NCT00530348\], or CAMMS324 \[NCT00548405\]) and received alemtuzumab within 48 months prior to enrollment were included in this LPS13649 study. Participants received alemtuzumab, intravenous infusion of 12 milligram per day (mg/day) for 3 consecutive days, at the study investigators' discretion; and at least 12 months after the prior treatment course in the current study (LPS13649).


Treatment: Drugs: alemtuzumab GZ402673
Pharmaceutical form:concentrate for solution for infusion Route of administration: intravenous
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)
Timepoint [1] 0 0
From Baseline until the end of the study (up to a maximum duration of 5.6 years)
Primary outcome [2] 0 0
Number of Participants With Infusion-Associated Reactions (IAR)
Timepoint [2] 0 0
Within 24 hours of any alemtuzumab infusion
Primary outcome [3] 0 0
Number of Participants With Adverse Events of Special Interest (AESI)
Timepoint [3] 0 0
From Baseline until the end of the study (up to a maximum duration of 5.6 years)
Primary outcome [4] 0 0
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Timepoint [4] 0 0
From Baseline until the end of the study (up to a maximum duration of 5.6 years)
Secondary outcome [1] 0 0
Annualized Relapse Rate
Timepoint [1] 0 0
Up to a maximum duration of 5.6 years
Secondary outcome [2] 0 0
Proportion of Participants Who Were Relapse Free
Timepoint [2] 0 0
Up to a maximum duration of 5.6 years
Secondary outcome [3] 0 0
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
Timepoint [3] 0 0
Baseline (Month 0 of LPS13649), Month 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
Secondary outcome [4] 0 0
Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Gadolinium Enhancing (Gd-enhancing) Lesions Per MRI Scan
Timepoint [4] 0 0
Up to a maximum duration of 5.6 years
Secondary outcome [5] 0 0
Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan
Timepoint [5] 0 0
Up to a maximum duration of 5.6 years
Secondary outcome [6] 0 0
Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New T1 (and New Hypointense T1) Lesions Per MRI Scan
Timepoint [6] 0 0
Up to a maximum duration of 5.6 years
Secondary outcome [7] 0 0
Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T1 Lesions at Months 12, 24, 36, 48, and 60
Timepoint [7] 0 0
Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
Secondary outcome [8] 0 0
Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T2 Lesions at Months 12, 24, 36, 48, and 60
Timepoint [8] 0 0
Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
Secondary outcome [9] 0 0
Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Brain Parenchymal Fraction (BPF) at Month 12, 24, 36, 48, and 60
Timepoint [9] 0 0
Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
Secondary outcome [10] 0 0
Change From Baseline in Self-reported Quality of Life (QoL) as Assessed by the Medical Outcome Study (MOS) 36-Item Short-Form Health Survey (SF-36): Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Month 12, 24, 36, 48, and 60
Timepoint [10] 0 0
Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
Secondary outcome [11] 0 0
Change From Baseline in Functional Assessment of Multiple Sclerosis (FAMS) Score at Month 12, 24, 36, 48, and 60
Timepoint [11] 0 0
Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
Secondary outcome [12] 0 0
Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Score: Utility Scores at Month 12, 24, 36, 48, and 60
Timepoint [12] 0 0
Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
Secondary outcome [13] 0 0
Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores at Month 12, 24, 36, 48, and 60
Timepoint [13] 0 0
Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
Secondary outcome [14] 0 0
Modified Healthcare Resource Utilization Questionnaire (HRUQ): Number of Participants Who Reported Change in Employment Situation, Availing of Sick Leaves, Admissions and Stays in Hospital, Rehabilitation Centers or Nursing Homes Due to Multiple Sclerosis
Timepoint [14] 0 0
Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
Secondary outcome [15] 0 0
Modified HRUQ: Number of Participants Who Reported Other Changes/Changes in Lifestyle Due to Multiple Sclerosis
Timepoint [15] 0 0
Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
Secondary outcome [16] 0 0
Health Related Productivity Questionnaire (HRPQ): Number of Participants Reporting Current Employment Status (Part Time/Full Time/Not Employed) Due to Multiple Sclerosis
Timepoint [16] 0 0
Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
Secondary outcome [17] 0 0
HRPQ: Total Scheduled Working Hours and Number of Hours Missed From Work Due to Multiple Sclerosis
Timepoint [17] 0 0
Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
Secondary outcome [18] 0 0
HRPQ: Percentage Impact on Work Output Due to Multiple Sclerosis
Timepoint [18] 0 0
Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
Secondary outcome [19] 0 0
HRPQ: Total Scheduled Household Chores Hours; Number of Hours Missed From Household Chores Due to Multiple Sclerosis
Timepoint [19] 0 0
Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
Secondary outcome [20] 0 0
HRPQ: Percentage Impact on Work Output for Household Chores Due to Multiple Sclerosis
Timepoint [20] 0 0
Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
Secondary outcome [21] 0 0
HRPQ: Duration of Disease (in Months) Since Development of Multiple Sclerosis
Timepoint [21] 0 0
Baseline up to end of the study (up to a maximum duration of 5.6 years)
Secondary outcome [22] 0 0
HRPQ: Number of Participants Who Reported Impact on Work Due to Multiple Sclerosis
Timepoint [22] 0 0
Baseline up to end of the study (up to a maximum duration of 5.6 years)

Eligibility
Key inclusion criteria
Inclusion criteria:

Participant had completed at least 48 months of the Extension Study CAMMS03409. Signed written informed consent form.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

Participant participating in another investigational interventional study.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/01/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/07/2020
Sample size
Target
Accrual to date
Final
1062
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 2013 - Auchenflower
Recruitment hospital [2] 0 0
Investigational Site Number 2001 - Heidelberg
Recruitment hospital [3] 0 0
Investigational Site Number 2011 - Hobart
Recruitment hospital [4] 0 0
Investigational Site Number 2012 - Kogarah
Recruitment hospital [5] 0 0
Investigational Site Number 2003 - Melbourne
Recruitment hospital [6] 0 0
Investigational Site Number 2002 - Parkville
Recruitment hospital [7] 0 0
Investigational Site Number 2005 - Southport
Recruitment hospital [8] 0 0
Investigational Site Number 2009 - Sydney
Recruitment hospital [9] 0 0
Investigational Site Number 2006 - Westmead
Recruitment postcode(s) [1] 0 0
4066 - Auchenflower
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
7000 - Hobart
Recruitment postcode(s) [4] 0 0
2217 - Kogarah
Recruitment postcode(s) [5] 0 0
3065 - Melbourne
Recruitment postcode(s) [6] 0 0
3050 - Parkville
Recruitment postcode(s) [7] 0 0
4215 - Southport
Recruitment postcode(s) [8] 0 0
- Sydney
Recruitment postcode(s) [9] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Iowa
Country [9] 0 0
United States of America
State/province [9] 0 0
Kansas
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
New Jersey
Country [15] 0 0
United States of America
State/province [15] 0 0
New Mexico
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Ohio
Country [19] 0 0
United States of America
State/province [19] 0 0
Oklahoma
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
Rhode Island
Country [22] 0 0
United States of America
State/province [22] 0 0
Tennessee
Country [23] 0 0
United States of America
State/province [23] 0 0
Texas
Country [24] 0 0
United States of America
State/province [24] 0 0
Virginia
Country [25] 0 0
United States of America
State/province [25] 0 0
Washington
Country [26] 0 0
Argentina
State/province [26] 0 0
Caba
Country [27] 0 0
Belgium
State/province [27] 0 0
Bruxelles
Country [28] 0 0
Belgium
State/province [28] 0 0
Esneux
Country [29] 0 0
Belgium
State/province [29] 0 0
Leuven
Country [30] 0 0
Brazil
State/province [30] 0 0
Porto Alegre
Country [31] 0 0
Brazil
State/province [31] 0 0
Recife
Country [32] 0 0
Brazil
State/province [32] 0 0
São Paulo
Country [33] 0 0
Canada
State/province [33] 0 0
Calgary
Country [34] 0 0
Canada
State/province [34] 0 0
Gatineau
Country [35] 0 0
Canada
State/province [35] 0 0
Greenfield Park
Country [36] 0 0
Canada
State/province [36] 0 0
Kingston
Country [37] 0 0
Canada
State/province [37] 0 0
London
Country [38] 0 0
Canada
State/province [38] 0 0
Ottawa
Country [39] 0 0
Canada
State/province [39] 0 0
Vancouver
Country [40] 0 0
Czechia
State/province [40] 0 0
Brno
Country [41] 0 0
Czechia
State/province [41] 0 0
Hradec Kralove
Country [42] 0 0
Czechia
State/province [42] 0 0
Praha 2
Country [43] 0 0
Czechia
State/province [43] 0 0
Teplice
Country [44] 0 0
Denmark
State/province [44] 0 0
Aarhus N
Country [45] 0 0
Denmark
State/province [45] 0 0
København Ø.
Country [46] 0 0
Germany
State/province [46] 0 0
Berlin
Country [47] 0 0
Germany
State/province [47] 0 0
Dresden
Country [48] 0 0
Germany
State/province [48] 0 0
Frankfurt am Main
Country [49] 0 0
Germany
State/province [49] 0 0
Hamburg
Country [50] 0 0
Germany
State/province [50] 0 0
Hannover
Country [51] 0 0
Germany
State/province [51] 0 0
Hennigsdorf
Country [52] 0 0
Germany
State/province [52] 0 0
München
Country [53] 0 0
Germany
State/province [53] 0 0
Rostock
Country [54] 0 0
Germany
State/province [54] 0 0
Wermsdorf
Country [55] 0 0
Israel
State/province [55] 0 0
Ramat Gan
Country [56] 0 0
Israel
State/province [56] 0 0
Tel Aviv
Country [57] 0 0
Italy
State/province [57] 0 0
Cagliari
Country [58] 0 0
Italy
State/province [58] 0 0
Gallarate (VA)
Country [59] 0 0
Italy
State/province [59] 0 0
Orbassano (TO)
Country [60] 0 0
Italy
State/province [60] 0 0
Roma
Country [61] 0 0
Mexico
State/province [61] 0 0
Chihuahua
Country [62] 0 0
Mexico
State/province [62] 0 0
Mexico
Country [63] 0 0
Netherlands
State/province [63] 0 0
Sittard-Geleen
Country [64] 0 0
Poland
State/province [64] 0 0
Krakow
Country [65] 0 0
Poland
State/province [65] 0 0
Lodz
Country [66] 0 0
Poland
State/province [66] 0 0
Lublin
Country [67] 0 0
Poland
State/province [67] 0 0
Poznan
Country [68] 0 0
Poland
State/province [68] 0 0
Warszawa
Country [69] 0 0
Russian Federation
State/province [69] 0 0
Kazan
Country [70] 0 0
Russian Federation
State/province [70] 0 0
Moscow
Country [71] 0 0
Russian Federation
State/province [71] 0 0
Nizhny Novgorod
Country [72] 0 0
Russian Federation
State/province [72] 0 0
Pyatigorsk
Country [73] 0 0
Russian Federation
State/province [73] 0 0
Saint-Petersburg
Country [74] 0 0
Russian Federation
State/province [74] 0 0
Samara
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Ufa
Country [76] 0 0
Spain
State/province [76] 0 0
Barcelona
Country [77] 0 0
Spain
State/province [77] 0 0
Madrid
Country [78] 0 0
Spain
State/province [78] 0 0
Málaga
Country [79] 0 0
Spain
State/province [79] 0 0
Sevilla
Country [80] 0 0
Sweden
State/province [80] 0 0
Göteborg
Country [81] 0 0
Sweden
State/province [81] 0 0
Umeå
Country [82] 0 0
Ukraine
State/province [82] 0 0
Kharkov
Country [83] 0 0
Ukraine
State/province [83] 0 0
Kiev
Country [84] 0 0
Ukraine
State/province [84] 0 0
Lviv
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Bristol
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Cambridge
Country [87] 0 0
United Kingdom
State/province [87] 0 0
Cardiff
Country [88] 0 0
United Kingdom
State/province [88] 0 0
London
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Salford
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Genzyme, a Sanofi Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

To evaluate long-term safety of alemtuzumab.

Secondary Objectives:

* To evaluate long term efficacy of alemtuzumab.
* To evaluate the safety profile of participants who received other Disease Modifying Treatment (DMT) following alemtuzumab treatment.
* To evaluate participant-reported Quality of Life (QoL) outcomes and health resource utilization of participant who received alemtuzumab.
* To evaluate as needed re-treatment with alemtuzumab and other DMTs.
Trial website
https://clinicaltrials.gov/study/NCT02255656
Trial related presentations / publications
Coles AJ, Jones JL, Vermersch P, Traboulsee A, Bass AD, Boster A, Chan A, Comi G, Fernandez O, Giovannoni G, Kubala Havrdova E, LaGanke C, Montalban X, Oreja-Guevara C, Piehl F, Wiendl H, Ziemssen T. Autoimmunity and long-term safety and efficacy of alemtuzumab for multiple sclerosis: Benefit/risk following review of trial and post-marketing data. Mult Scler. 2022 Apr;28(5):842-846. doi: 10.1177/13524585211061335. Epub 2021 Dec 9.
Kuhle J, Daizadeh N, Benkert P, Maceski A, Barro C, Michalak Z, Sormani MP, Godin J, Shankara S, Samad TA, Jacobs A, Chung L, R?sch N, Kaiser C, Mitchell CP, Leppert D, Havari E, Kappos L. Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing-remitting MS. Mult Scler. 2022 Apr;28(4):573-582. doi: 10.1177/13524585211032348. Epub 2021 Aug 11.
Bass AD, Arroyo R, Boster AL, Boyko AN, Eichau S, Ionete C, Limmroth V, Navas C, Pelletier D, Pozzilli C, Ravenscroft J, Sousa L, Tintore M, Uitdehaag BMJ, Baker DP, Daizadeh N, Choudhry Z, Rog D; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ investigators. Alemtuzumab outcomes by age: Post hoc analysis from the randomized CARE-MS studies over 8 years. Mult Scler Relat Disord. 2021 Apr;49:102717. doi: 10.1016/j.msard.2020.102717. Epub 2020 Dec 24.
Ziemssen T, Bass AD, Berkovich R, Comi G, Eichau S, Hobart J, Hunter SF, LaGanke C, Limmroth V, Pelletier D, Pozzilli C, Schippling S, Sousa L, Traboulsee A, Uitdehaag BMJ, Van Wijmeersch B, Choudhry Z, Daizadeh N, Singer BA; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ investigators. Efficacy and Safety of Alemtuzumab Through 9 Years of Follow-up in Patients with Highly Active Disease: Post Hoc Analysis of CARE-MS I and II Patients in the TOPAZ Extension Study. CNS Drugs. 2020 Sep;34(9):973-988. doi: 10.1007/s40263-020-00749-x.
Steingo B, Al Malik Y, Bass AD, Berkovich R, Carraro M, Fernandez O, Ionete C, Massacesi L, Meuth SG, Mitsikostas DD, Pardo G, Simm RF, Traboulsee A, Choudhry Z, Daizadeh N, Compston DAS; CAMMS223, CAMMS03409, and TOPAZ Investigators. Long-term efficacy and safety of alemtuzumab in patients with RRMS: 12-year follow-up of CAMMS223. J Neurol. 2020 Nov;267(11):3343-3353. doi: 10.1007/s00415-020-09983-1. Epub 2020 Jun 24.
Comi G, Alroughani R, Boster AL, Bass AD, Berkovich R, Fernandez O, Kim HJ, Limmroth V, Lycke J, Macdonell RA, Sharrack B, Singer BA, Vermersch P, Wiendl H, Ziemssen T, Jacobs A, Daizadeh N, Rodriguez CE, Traboulsee A; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ Investigators. Efficacy of alemtuzumab in relapsing-remitting MS patients who received additional courses after the initial two courses: Pooled analysis of the CARE-MS, extension, and TOPAZ studies. Mult Scler. 2020 Dec;26(14):1866-1876. doi: 10.1177/1352458519888610. Epub 2019 Nov 25.
Okai AF, Amezcua L, Berkovich RR, Chinea AR, Edwards KR, Steingo B, Walker A, Jacobs AK, Daizadeh N, Williams MJ; CARE-MS I, CARE-MS II, CAMMS03409, and TOPAZ Investigators. Efficacy and Safety of Alemtuzumab in Patients of African Descent with Relapsing-Remitting Multiple Sclerosis: 8-Year Follow-up of CARE-MS I and II (TOPAZ Study). Neurol Ther. 2019 Dec;8(2):367-381. doi: 10.1007/s40120-019-00159-2. Epub 2019 Oct 25.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02255656