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Phase IIIB-IV Long-Term Follow-up Study for Patients Who Participated in CAMMS03409 (TOPAZ)

Primary Purpose

Relapsing Remitting Multiple Sclerosis

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

alemtuzumab GZ402673

About this trial

This is an interventional treatment trial for Relapsing Remitting Multiple Sclerosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Alemtuzumab

Arm Description

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).

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)

An Adverse Event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have causal relationship with treatment. TEAEs were defined as AEs that developed/worsened during the 'treatment period (time from Baseline until the end of the study LPS13649 [i.e. up to a maximum of 5.6 years]). Serious adverse events (SAEs) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.

Number of Participants With Infusion-Associated Reactions (IAR)

Infusion-associated reactions (IAR) was defined as any adverse event occurring during and within 24 hours of alemtuzumab infusion.

Number of Participants With Adverse Events of Special Interest (AESI)

Adverse events of special interest included the following: hypersensitivity or anaphylaxis; pregnancy of a woman entered in the study; symptomatic overdose (serious or non-serious) with investigational medicinal Product (IMP); increase in alanine transaminase (ALT); autoimmune mediated conditions; hemophagocytic lymphohistiocytosis; progressive multifocal leukoencephalopathy; temporally associated AEs; serious infections; malignancy; and pneumonitis.

Number of Participants With Potentially Clinically Significant Laboratory Abnormalities

Criteria for potentially clinically significant laboratory abnormalities included: Hemoglobin (Hb): less than or equal to (<=)115 grams per liter (g/L)(Male [M]), <= 95 g/L (Female[ F]); greater than or equal to (>=)185 g/L (M), >= 165 g/L (F); Decrease From Baseline (DFB) >= 20 g/L. Hematocrit: <= 0.37 volume/volume (v/v) (M); <= 0.32 v/v (F); >= 0.55 v/v (M); >= 0.5 v/v (F). Red Blood Cells (RBCs): >=6 *10^12/L. Platelets: <100 *10^9/L; >=700 *10^9/L. As pre-specified, data collection and analysis for this outcome measure was done on the overall population along with 2 subgroups (DAT and IAT).

Secondary Outcome Measures

Annualized Relapse Rate

Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination. Annualized relapse rate was obtained from the total number of confirmed relapses that occurred during the treatment follow up time of all participants divided by the total years of follow-up for all participants. The annualized relapse rate was estimated using a negative binomial model with robust variance estimation.

Proportion of Participants Who Were Relapse Free

Relapse was defined as new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination. The proportion of participants who were relapse free (without event) were estimated using the Kaplan-Meier method.

Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60

EDSS is an ordinal scale in half-point increments that qualifies disability in participants with multiple sclerosis (MS). It consists of 8 ordinal rating scales assessing seven functional systems (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other). EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicated worst outcomes.

Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Gadolinium Enhancing (Gd-enhancing) Lesions Per MRI Scan

Number of Gd-enhancing lesions per scan was defined as the total number of Gd-enhancing lesions that occurred during the treatment period divided by the total number of scans performed during the treatment period. The adjusted cumulative count of lesions was estimated by a repeated negative binomial regression with generalized estimating equation (GEE) adjusted for analysis groups and geographic region as covariates.

Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan

Number of new or enlarged T2 lesions per scan was defined as the total number of new or enlarged T2 lesion that occurred during treatment period divided by the total number of scans performed during treatment period. The adjusted cumulative count of lesions was estimated by a repeated negative binomial regression with GEE adjusted for analysis groups and geographic region as covariates.

Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New T1 (and New Hypointense T1) Lesions Per MRI Scan

Number of new T1 lesions per scan was defined as the total number of new T1 lesion (and New Hypointense T1) that occurred during treatment period divided by the total number of scans performed during treatment period.The adjusted cumulative count of lesions was estimated by a repeated negative binomial regression with GEE adjusted for analysis groups and geographic region as covariates.

Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T1 Lesions at Months 12, 24, 36, 48, and 60

The total lesion volume (T1 lesions) was measured by MRI scan.

Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T2 Lesions at Months 12, 24, 36, 48, and 60

The total lesion volume (T2 lesions) was measured by MRI scan.

Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Brain Parenchymal Fraction (BPF) at Month 12, 24, 36, 48, and 60

The brain parenchymal fraction was measured by MRI scan.

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

The MOS SF-36 is an extensively validated and widely used measure of QoL that assesses participants' perceptions of health status and its impact on their lives. It consisted of 36 items organized into 8 scales (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health). Two summary measures of physical and mental health, the PCS and MCS, respectively, were derived from scale aggregates, and were reported in this outcome measure. The score range for each of these 2 summary scores was from 0 (worst) to 100 (best), higher scores indicated better QoL.

Change From Baseline in Functional Assessment of Multiple Sclerosis (FAMS) Score at Month 12, 24, 36, 48, and 60

The FAMS is a self-reported multidimensional index comprising a total of 58 items on 7 subscales: mobility (7 items); symptoms (7 items); emotional well-being (7 items); general contentment (7 items); thinking and fatigue (9 items); family/social well-being (7 items); and additional concerns (14 items, these are not scored). Each item (except those for "additional concerns") was rated on a 5-point scale of 0 (lower quality of life) to 4 (higher quality of life). Total FAMS score was the sum of 44 scored items, which ranged from 0 (poor) to 176 (best), with higher numbers reflecting a higher quality of life.

Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Score: Utility Scores at Month 12, 24, 36, 48, and 60

The EQ-5D is a generic, standardized instrument that provides a simple, descriptive profile and a single index value for health status used in the clinical and economic evaluation of health care as well as in population health surveys. The EQ-5D comprises 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension measured on 3 levels: some, moderate, and extreme problems. The 5 dimensional 3-level systems was converted into single index utility score ranges from 0 to 100, where 100=best health state; and 0=worst health state; higher scores indicated better outcome.

Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores at Month 12, 24, 36, 48, and 60

EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0 to 100), where 0=worst imaginable health state to 100=best imaginable health state, and higher score indicated better outcome.

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

Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRUQ) designed to evaluate the economic impact of MS. Questionnaire addresses the following content areas: employment situation and changes in employment situation due to MS;sick leaves,admissions and stays in hospital, rehabilitation centers, or nursing homes; typical MS-related investments (eg, stair and bed lift, ramps,rails) and devices (eg,walking aids,wheelchairs); assistance by community or social services (e.g. home nurse, transportation), or help from family or friends. Each question requires a binary answer (yes/no). Number of participants who reported "Yes" as an answer to "employment situation change; had sick leaves; had hospital admission; had spent time in rehabilitation center and had spent time in a nursing home or a similar institution" questions were reported in this outcome measure.

Modified HRUQ: Number of Participants Who Reported Other Changes/Changes in Lifestyle Due to Multiple Sclerosis

Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRUQ) designed to evaluate the economic impact of MS.Questionnaire addresses following content areas: employment situation and changes in employment situation due to MS; admissions and stays in hospital, rehabilitation centers, or nursing homes; typical MS-related investments(e.g.stair and bed lift,ramps,rails) and devices(e.g.walking aids,wheelchairs);assistance by community or social services(e.g.home nurse, transportation), or help from family or friends. Each question requires a binary answer (yes/no). Number of participants who reported other changes/changes in lifestyle due to MS, i.e."Yes" as an answer to "had made changes to your house, apartment, car or did you require any special equipment or aids; assistance required; other assistance required" questions were reported in this outcome measure.

Health Related Productivity Questionnaire (HRPQ): Number of Participants Reporting Current Employment Status (Part Time/Full Time/Not Employed) Due to Multiple Sclerosis

HRPQ: Total Scheduled Working Hours and Number of Hours Missed From Work Due to Multiple Sclerosis

HRPQ: Percentage Impact on Work Output Due to Multiple Sclerosis

HRPQ: Total Scheduled Household Chores Hours; Number of Hours Missed From Household Chores Due to Multiple Sclerosis

HRPQ: Percentage Impact on Work Output for Household Chores Due to Multiple Sclerosis

HRPQ: Duration of Disease (in Months) Since Development of Multiple Sclerosis

HRPQ: Number of Participants Who Reported Impact on Work Due to Multiple Sclerosis

Participants use of healthcare resources, non-medical resources, and informal care as well as their work capacity was assessed at scheduled study visits using a modified questionnaire (HRPQ) designed to evaluate the economic impact of MS. The questionnaire addresses the following content area: participant reported data regarding employment status, work productivity, impact on household chores due to MS. Number of participants who reported "Yes" as an answer to questions related to impact on work: "forced me to work part-time when I wanted to work full-time; kept me from having a job when I wanted to work full-time; kept me from having a job when I wanted to work part-time; none of the above" questions were reported in this outcome measure.

Full Information

NCT ID

NCT02255656

First Posted

September 30, 2014

Last Updated

March 21, 2022

Sponsor

Genzyme, a Sanofi Company

1. Study Identification

Unique Protocol Identification Number

NCT02255656

Brief Title

Phase IIIB-IV Long-Term Follow-up Study for Patients Who Participated in CAMMS03409

Acronym

TOPAZ

Official Title

A Long-term Follow-up Study for Multiple Sclerosis Patients Who Have Completed the Alemtuzumab Extension Study (CAMMS03409)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Completed

Study Start Date

January 7, 2015 (Actual)

Primary Completion Date

July 15, 2020 (Actual)

Study Completion Date

July 15, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Genzyme, a Sanofi Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Relapsing Remitting Multiple Sclerosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

1062 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Alemtuzumab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

alemtuzumab GZ402673

Intervention Description

Pharmaceutical form:concentrate for solution for infusion Route of administration: intravenous

Primary Outcome Measure Information:

Title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)

Description

Time Frame

From Baseline until the end of the study (up to a maximum duration of 5.6 years)

Title

Number of Participants With Infusion-Associated Reactions (IAR)

Description

Infusion-associated reactions (IAR) was defined as any adverse event occurring during and within 24 hours of alemtuzumab infusion.

Time Frame

Within 24 hours of any alemtuzumab infusion

Title

Number of Participants With Adverse Events of Special Interest (AESI)

Description

Time Frame

From Baseline until the end of the study (up to a maximum duration of 5.6 years)

Title

Number of Participants With Potentially Clinically Significant Laboratory Abnormalities

Description

Time Frame

From Baseline until the end of the study (up to a maximum duration of 5.6 years)

Secondary Outcome Measure Information:

Title

Annualized Relapse Rate

Description

Time Frame

Up to a maximum duration of 5.6 years

Title

Proportion of Participants Who Were Relapse Free

Description

Time Frame

Up to a maximum duration of 5.6 years

Title

Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60

Description

Time Frame

Baseline (Month 0 of LPS13649), Month 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60

Title

Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Gadolinium Enhancing (Gd-enhancing) Lesions Per MRI Scan

Description

Time Frame

Up to a maximum duration of 5.6 years

Title

Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan

Description

Time Frame

Up to a maximum duration of 5.6 years

Title

Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New T1 (and New Hypointense T1) Lesions Per MRI Scan

Description

Time Frame

Up to a maximum duration of 5.6 years

Title

Brain Magnetic Resonance Imaging (MRI) Assessment: Percent Change From Baseline in Volume of T1 Lesions at Months 12, 24, 36, 48, and 60

Description

The total lesion volume (T1 lesions) was measured by MRI scan.

Time Frame