Clinical trial NCT02255656: Phase IIIB-IV Long-Term Follow-up Study for Patients Who Participated in CAMMS03409
Official title: A Long-term Follow-up Study for Multiple Sclerosis Patients Who Have Completed the Alemtuzumab Extension Study (CAMMS03409)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Relapsing Remitting Multiple Sclerosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2014-10-02
Enrollment: 1062
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: The total duration per participants was up to 5.6 years.

As per Study Investigator discretion, participants can be treated with additional courses of alemtuzumab or any commercialized DMTs.

All participants who completed CAMMS03409 were allowed into the study, which might include specific vulnerable populations. If the investigator decided to treat a participant with a course of alemtuzumab, appropriate cautionary measures were applied as indicated in the approved labelling, or, in ex-European Union countries where Lemtrada was not approved, according to the investigator's brochure.

Eligibility criteria: Inclusion criteria:

Participant had completed at least 48 months of the Extension Study CAMMS03409. Signed written informed consent form.

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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: From Baseline until the end of the study (up to a maximum duration of 5.6 years)
measure: Number of Participants With Infusion-Associated Reactions (IAR)
timeFrame: Within 24 hours of any alemtuzumab infusion
measure: Number of Participants With Adverse Events of Special Interest (AESI)
timeFrame: From Baseline until the end of the study (up to a maximum duration of 5.6 years)
measure: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
timeFrame: From Baseline until the end of the study (up to a maximum duration of 5.6 years)
Secondary outcomes:
measure: Annualized Relapse Rate
timeFrame: Up to a maximum duration of 5.6 years
measure: Proportion of Participants Who Were Relapse Free
timeFrame: Up to a maximum duration of 5.6 years
measure: Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
timeFrame: Baseline (Month 0 of LPS13649), Month 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60
measure: Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Gadolinium Enhancing (Gd-enhancing) Lesions Per MRI Scan
timeFrame: Up to a maximum duration of 5.6 years
measure: Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan
timeFrame: Up to a maximum duration of 5.6 years
measure: Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New T1 (and New Hypointense T1) Lesions Per MRI Scan
timeFrame: Up to a maximum duration of 5.6 years
measure: Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T1 Lesions at Months 12, 24, 36, 48, and 60
timeFrame: Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
measure: Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T2 Lesions at Months 12, 24, 36, 48, and 60
timeFrame: Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
measure: Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Brain Parenchymal Fraction (BPF) at Month 12, 24, 36, 48, and 60
timeFrame: Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
measure: 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
timeFrame: Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
measure: Change From Baseline in Functional Assessment of Multiple Sclerosis (FAMS) Score at Month 12, 24, 36, 48, and 60
timeFrame: Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
measure: Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Score: Utility Scores at Month 12, 24, 36, 48, and 60
timeFrame: Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
measure: Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores at Month 12, 24, 36, 48, and 60
timeFrame: Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
measure: 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
timeFrame: Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
measure: Modified HRUQ: Number of Participants Who Reported Other Changes/Changes in Lifestyle Due to Multiple Sclerosis
timeFrame: Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
measure: Health Related Productivity Questionnaire (HRPQ): Number of Participants Reporting Current Employment Status (Part Time/Full Time/Not Employed) Due to Multiple Sclerosis
timeFrame: Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
measure: HRPQ: Total Scheduled Working Hours and Number of Hours Missed From Work Due to Multiple Sclerosis
timeFrame: Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
measure: HRPQ: Percentage Impact on Work Output Due to Multiple Sclerosis
timeFrame: Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
measure: HRPQ: Total Scheduled Household Chores Hours; Number of Hours Missed From Household Chores Due to Multiple Sclerosis
timeFrame: Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
measure: HRPQ: Percentage Impact on Work Output for Household Chores Due to Multiple Sclerosis
timeFrame: Baseline (Month 0 of LPS13649), Month 12, Month 24, Month 36, Month 48 and Month 60
measure: HRPQ: Duration of Disease (in Months) Since Development of Multiple Sclerosis
timeFrame: Baseline up to end of the study (up to a maximum duration of 5.6 years)
measure: HRPQ: Number of Participants Who Reported Impact on Work Due to Multiple Sclerosis
timeFrame: Baseline up to end of the study (up to a maximum duration of 5.6 years)
Other outcomes:
Locations:
city: Cullman
country: United States
facility: Investigational Site Number 1086
state: Alabama
city: Phoenix
country: United States
facility: Investigational Site Number 1031
state: Arizona
city: Phoenix
country: United States
facility: Investigational Site Number 1171
state: Arizona
city: Tucson
country: United States
facility: Investigational Site Number 1090
state: Arizona
city: Berkeley
country: United States
facility: Investigational Site Number 1040
state: California
city: Fullerton
country: United States
facility: Investigational Site Number 1152
state: California
city: Pasadena
country: United States
facility: Investigational Site Number 1093
state: California
city: Fort Collins
country: United States
facility: Investigational Site Number 1027
state: Colorado
city: Jacksonville
country: United States
facility: Investigational Site Number 1078
state: Florida
city: Maitland
country: United States
facility: Investigational Site Number 1059
state: Florida
city: Sarasota
country: United States
facility: Investigational Site Number 1173
state: Florida
city: Sunrise
country: United States
facility: Investigational Site Number 1034
state: Florida
city: Tampa
country: United States
facility: Investigational Site Number 1005
state: Florida
city: Tampa
country: United States
facility: Investigational Site Number 1049
state: Florida
city: Northbrook
country: United States
facility: Investigational Site Number 1008
state: Illinois
city: Fort Wayne
country: United States
facility: Investigational Site Number 1001
state: Indiana
city: Indianapolis
country: United States
facility: Investigational Site Number 1024
state: Indiana
city: Des Moines
country: United States
facility: Investigational Site Number 1017
state: Iowa
city: Kansas City
country: United States
facility: Investigational Site Number 1022
state: Kansas
city: Lenexa
country: United States
facility: Investigational Site Number 1083
state: Kansas
city: Lexington
country: United States
facility: Investigational Site Number 1039
state: Kentucky
city: Louisville
country: United States
facility: Investigational Site Number 1021
state: Kentucky
city: Wellesley
country: United States
facility: Investigational Site Number 1061
state: Massachusetts
city: Worcester
country: United States
facility: Investigational Site Number 1028
state: Massachusetts
city: Ann Arbor
country: United States
facility: Investigational Site Number 1025
state: Michigan
city: Detroit
country: United States
facility: Investigational Site Number 1020
state: Michigan
city: Traverse City
country: United States
facility: Investigational Site Number 1054
state: Michigan
city: Kansas City
country: United States
facility: Investigational Site Number 1084
state: Missouri
city: Saint Louis
country: United States
facility: Investigational Site Number 1092
state: Missouri
city: Teaneck
country: United States
facility: Investigational Site Number 1073
state: New Jersey
city: Albuquerque
country: United States
facility: Investigational Site Number 1014
state: New Mexico
city: Mineola
country: United States
facility: Investigational Site Number 1081
state: New York
city: New York
country: United States
facility: Investigational Site Number 1026
state: New York
city: Patchogue
country: United States
facility: Investigational Site Number 1160
state: New York
city: Rochester
country: United States
facility: Investigational Site Number 1015
state: New York
city: Syracuse
country: United States
facility: Investigational Site Number 1053
state: New York
city: Chapel Hill
country: United States
facility: Investigational Site Number 1095
state: North Carolina
city: Winston-Salem
country: United States
facility: Investigational Site Number 1082
state: North Carolina
city: Cleveland
country: United States
facility: Investigational Site Number 1035
state: Ohio
city: Uniontown
country: United States
facility: Investigational Site Number 1058
state: Ohio
city: Oklahoma City
country: United States
facility: Investigational Site Number 1067
state: Oklahoma
city: Allentown
country: United States
facility: Investigational Site Number 1097
state: Pennsylvania
city: Providence
country: United States
facility: Investigational Site Number 1057
state: Rhode Island
city: Cordova
country: United States
facility: Investigational Site Number 1163
state: Tennessee
city: Franklin
country: United States
facility: Investigational Site Number 1055
state: Tennessee
city: Knoxville
country: United States
facility: Investigational Site Number 1009
state: Tennessee
city: Nashville
country: United States
facility: Investigational Site Number 1042
state: Tennessee
city: Houston
country: United States
facility: Investigational Site Number 1018
state: Texas
city: Round Rock
country: United States
facility: Investigational Site Number 1002
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 1046
state: Texas
city: Vienna
country: United States
facility: Investigational Site Number 1037
state: Virginia
city: Seattle
country: United States
facility: Investigational Site Number 1068
state: Washington
city: Caba
country: Argentina
facility: Investigational Site Number 03208
city: Auchenflower
country: Australia
facility: Investigational Site Number 2013
city: Heidelberg
country: Australia
facility: Investigational Site Number 2001
city: Hobart
country: Australia
facility: Investigational Site Number 2011
city: Kogarah
country: Australia
facility: Investigational Site Number 2012
city: Melbourne
country: Australia
facility: Investigational Site Number 2003
city: Parkville
country: Australia
facility: Investigational Site Number 2002
city: Southport
country: Australia
facility: Investigational Site Number 2005
city: Sydney
country: Australia
facility: Investigational Site Number 2009
city: Westmead
country: Australia
facility: Investigational Site Number 2006
city: Bruxelles
country: Belgium
facility: Investigational Site Number 5005
city: Esneux
country: Belgium
facility: Investigational Site Number 5004
city: Leuven
country: Belgium
facility: Investigational Site Number 5001
city: Porto Alegre
country: Brazil
facility: Investigational Site Number 3006
city: Recife
country: Brazil
facility: Investigational Site Number 3002
city: São Paulo
country: Brazil
facility: Investigational Site Number 3001
city: São Paulo
country: Brazil
facility: Investigational Site Number 3003
city: Calgary
country: Canada
facility: Investigational Site Number 1102
city: Gatineau
country: Canada
facility: Investigational Site Number 1105
city: Greenfield Park
country: Canada
facility: Investigational Site Number 1104
city: Kingston
country: Canada
facility: Investigational Site Number 1109
city: London
country: Canada
facility: Investigational Site Number 1110
city: Ottawa
country: Canada
facility: Investigational Site Number 1101
city: Vancouver
country: Canada
facility: Investigational Site Number 1106
city: Brno
country: Czechia
facility: Investigational Site Number 4803
city: Hradec Kralove
country: Czechia
facility: Investigational Site Number 4804
city: Praha 2
country: Czechia
facility: Investigational Site Number 4801
city: Teplice
country: Czechia
facility: Investigational Site Number 4802
city: Aarhus N
country: Denmark
facility: Investigational Site Number 5302
city: København Ø.
country: Denmark
facility: Investigational Site Number 5301
city: Berlin
country: Germany
facility: Investigational Site Number 4602
city: Dresden
country: Germany
facility: Investigational Site Number 4607
city: Frankfurt am Main
country: Germany
facility: Investigational Site Number 4634
city: Hamburg
country: Germany
facility: Investigational Site Number 4622
city: Hannover
country: Germany
facility: Investigational Site Number 4605
city: Hennigsdorf
country: Germany
facility: Investigational Site Number 4609
city: München
country: Germany
facility: Investigational Site Number 4608
city: Rostock
country: Germany
facility: Investigational Site Number 4610
city: Wermsdorf
country: Germany
facility: Investigational Site Number 4613
city: Ramat Gan
country: Israel
facility: Investigational Site Number 5501
city: Tel Aviv
country: Israel
facility: Investigational Site Number 5505
city: Cagliari
country: Italy
facility: Investigational Site Number 4112
city: Gallarate (VA)
country: Italy
facility: Investigational Site Number 4102
city: Orbassano (TO)
country: Italy
facility: Investigational Site Number 4106
city: Roma
country: Italy
facility: Investigational Site Number 4110
city: Chihuahua
country: Mexico
facility: Investigational Site Number 3105
city: Mexico
country: Mexico
facility: Investigational Site Number 3102
city: Sittard-Geleen
country: Netherlands
facility: Investigational Site Number 4202
city: Krakow
country: Poland
facility: Investigational Site Number 4902
city: Lodz
country: Poland
facility: Investigational Site Number 4901
city: Lublin
country: Poland
facility: Investigational Site Number 4903
city: Poznan
country: Poland
facility: Investigational Site Number 4904
city: Warszawa
country: Poland
facility: Investigational Site Number 4905
city: Kazan
country: Russian Federation
facility: Investigational Site Number 6009
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6005
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6003
city: Nizhny Novgorod
country: Russian Federation
facility: Investigational Site Number 6006
city: Pyatigorsk
country: Russian Federation
facility: Investigational Site Number 6010
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6002
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6004
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6008
city: Samara
country: Russian Federation
facility: Investigational Site Number 6013
city: Ufa
country: Russian Federation
facility: Investigational Site Number 6016
city: Barcelona
country: Spain
facility: Investigational Site Number 4301
city: Madrid
country: Spain
facility: Investigational Site Number 4303
city: Málaga
country: Spain
facility: Investigational Site Number 4305
city: Sevilla
country: Spain
facility: Investigational Site Number 4304
city: Göteborg
country: Sweden
facility: Investigational Site Number 4701
city: Umeå
country: Sweden
facility: Investigational Site Number 4702
city: Kharkov
country: Ukraine
facility: Investigational Site Number 6102
city: Kiev
country: Ukraine
facility: Investigational Site Number 6104
city: Lviv
country: Ukraine
facility: Investigational Site Number 6103
city: Bristol
country: United Kingdom
facility: Investigational Site Number 4004
city: Cambridge
country: United Kingdom
facility: Investigational Site Number 4001
city: Cardiff
country: United Kingdom
facility: Investigational Site Number 4005
city: London
country: United Kingdom
facility: Investigational Site Number 4006
city: Salford
country: United Kingdom
facility: Investigational Site Number 4008
city: Sheffield
country: United Kingdom
facility: Investigational Site Number 4007
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Kuhle J, Daizadeh N, Benkert P, Maceski A, Barro C, Michalak Z, Sormani MP, Godin J, Shankara S, Samad TA, Jacobs A, Chung L, Rӧsch 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.