Phase 3
Completed N=1,314
An Extension Protocol for Multiple Sclerosis Patients Who Participated in Genzyme-Sponsored Studies of Alemtuzumab
Multiple Sclerosis, Relapsing-Remitting
Source: ClinicalTrials.gov NCT00930553 ↗
Enrolled (actual)
1,314
Serious AEs
28.6%
Results posted
May 2017
Primary outcomePrimary: Annualized Relapse Rate (ARR) — 0.19; 0.22; 0.16; 0.24 relapses per participant per year
◆ Published Evidence
Established
35citations · ~9 / year
Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing-remitting MS.
Summary
This open-label, rater-blinded extension study enrolled participants who had relapsing-remitting multiple sclerosis (RRMS) and who participated in one of three prior Genzyme-sponsored studies of alemtuzumab (CAMMS223 [NCT00050778], CAMMS323 [NCT00530348] also known as CARE-MS I, or CAMMS324 [NCT00548405] also known as CARE-MS II). The purposes of this study were:
1. To examine the long term safety and efficacy of alemtuzumab treatment in participants who received alemtuzumab as their study treatment in one of the prior studies.
2. To examine the safety and efficacy of initial alemtuzumab treatment in this study for participants who received Rebif® (interferon beta-1a) as their study treatment in one of the prior studies.
3. To determine the safety and efficacy of additional "as needed" alemtuzumab treatment courses. This applied both to participants who received alemtuzumab for the first time in one of the prior studies or for the first time in this extension study.
Linked Publications (5)
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Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing-remitting MS.
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Autoimmunity and long-term safety and efficacy of alemtuzumab for multiple sclerosis: Benefit/risk following review of trial and post-marketing data.
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Safety and efficacy with alemtuzumab over 13 years in relapsing-remitting multiple sclerosis: final results from the open-label TOPAZ study.
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Endocrine and multiple sclerosis outcomes in patients with autoimmune thyroid events in the alemtuzumab CARE-MS studies.
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Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annualized Relapse Rate (ARR) |
0.19; 0.22; 0.16; 0.24; 0.15; 0.19 | — |
| PRIMARY Annualized Relapse Rate (ARR) Before and After Receiving Alemtuzumab |
0.42; 0.14; 0.60; 0.15 | — |
| PRIMARY Annualized Relapse Rate (ARR) Before and After Alemtuzumab Retreatment |
0.79; 0.18; 0.29; 0.30 | — |
| PRIMARY Number of Participants With Sustained Accumulation of Disability (SAD) |
79; 118 | — |
| PRIMARY Number of Participants With Sustained Accumulation of Disability (SAD) Before and After Alemtuzumab Treatment: 2 Year Comparison |
13; 11; 29; 17 | — |
| SECONDARY Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS at Year 6 |
74; 130 | — |
| SECONDARY Number of Participants With Sustained Reduction in Disability (SRD) Assessed by EDSS (After Alemtuzumab Treatment) at Year 2 of the Extension Study |
11; 14 | — |
| SECONDARY Change From Initial Study Baseline in EDSS Score at Year 3, 4, 5 and 6 |
-0.08; -0.02; -0.06; 0.06; 0.06; 0.13 | — |
| SECONDARY Change From Initial Study Baseline in EDSS Score Before and After Alemtuzumab Treatment: 2 Year Comparison |
-0.15; -0.07; 0.11; -0.02; -0.21; 0.08 | — |
| SECONDARY Change From Retreatment Baseline in EDSS Score After Alemtuzumab Retreatment |
2.89; -0.22; -0.13; 0.07 | — |
| SECONDARY Percentage of Participants Without New or Enlarging Magnetic Resonance Imaging (MRI)-T2-Hypertense Lesion Activity |
72.6; 68.8; 70.3; 70.2; 70.2; 67.0 | — |
| SECONDARY Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Treatment |
57; 79.3; 44.6; 63.8; 60.7; 81.8 | — |
| SECONDARY Percentage of Participants Without New or Enlarging MRI-T2-Hypertense Lesion Activity Before and After Alemtuzumab Retreatment |
49.2; 64.1; 66.0; 60.2 | — |
| SECONDARY Percentage Change From Baseline in MRI-T2-Hypertense Lesion Volumes at Year 3, 4, 5, 6 |
-6.57; 1.69; -5.04; 4.97; -4.09; 12.37 | — |
| SECONDARY Percentage of Participants Without New Gadolinium-enhancing MRI Lesion Activity |
90.6; 86.5; 87.1; 88.8; 87.5; 89.4 | — |
| SECONDARY Percent Change From Baseline in Brain Parenchymal Fractions (BPF) at Year 3, 4, 5 and 6 |
-1.068; -0.761; -1.251; -0.949; -1.437; -0.983 | — |
| SECONDARY Percentage of Relapse Free Participants |
84.14; 80.56; 86.84; 79.27; 87.35; 83.29 | — |
| SECONDARY Change From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey at Year 3, 4, 5 and 6 |
1.90; 1.72; 2.15; 1.34; 1.85; 1.34 | — |
| SECONDARY Change From Baseline in Physical Component Score (PCS) of Short Form-36 (SF-36) Health Survey Before and After Alemtuzumab Treatment: 2 Year Comparison |
1.16; 2.00; 0.79; 1.56; 1.20; 0.41 | — |
| SECONDARY Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) at Year 3, 4, 5, and 6 |
2.43; 1.96; 3.17; 1.91; 2.54; 1.75 | — |
| SECONDARY Change From Baseline in Mental Component Score (MCS) of Short Form-36 (SF-36) Before and After Alemtuzumab Treatment: 2 Year Comparison |
2.88; 1.98; 1.83; 1.21; 2.32; 2.08 | — |
| SECONDARY Change From Baseline in Self-reported Quality of Life as Assessed by Functional Assessment of Multiple Sclerosis (FAMS) Score at Year 3, 4, 5 and 6 |
5.28; 4.55; 6.81; 3.65; 4.82; 3.57 | — |
| SECONDARY Change From Baseline in Self-reported Quality of Life as Assessed by Functional Assessment of Multiple Sclerosis (FAMS) Score Before and After Alemtuzumab Treatment: 2 Year Comparison |
4.27; 4.82; 3.19; 5.83; 1.88; 3.10 | — |
| SECONDARY Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score at Year 3, 4, 5 and 6 |
3.505; 2.859; 5.144; 2.992; 4.409; 3.034 | — |
| SECONDARY Change From Baseline in European Quality of Life -5 Dimension (EQ-5D) Visual Analog Scale Score Before and After Alemtuzumab Treatment: 2 Year Comparison |
4.165; 4.576; 1.663; 4.337; 2.359; 4.515 | — |
Eligibility Criteria
Inclusion Criteria
- 1.Received alemtuzumab in CAMMS323 or CAMMS324, completed the 2-year study period, and had not subsequently received disease modifying treatments (other than glatiramer acetate or interferon beta); or
- 2.Received Rebif® in CAMMS323 or CAMMS324, completed the 2-year study period, and had not subsequently received alternative disease modifying treatments (other than glatiramer acetate or another interferon beta); or
- 3.Participated in CAMMS223.
- NOTE: Criteria 1 and 2 above meant that participants who enrolled in CAMMS323 or CAMMS324 but did not complete the 2-year study period or went on to receive non-study drug DMTs after randomization were not eligible for inclusion in the Extension Study. Participants who enrolled in CAMMS324 after participation in CAMMS223 must meet criteria 1 or 2 to be eligible for inclusion in the Extension Study.
Exclusion Criteria
- Any alemtuzumab participant from CAMMS223, CAMMS323, or CAMMS324 who had received alemtuzumab off-label (ie, outside of one of the prior Genzyme-sponsored studies), or was participating in any other investigational study, unless approved by Genzyme. In addition, these participants must be screened for disqualifying safety concerns before receiving alemtuzumab retreatment.
- Any Rebif® participants from CAMMS223, CAMMS323, or CAMMS324 who met any of the following criteria. In addition, these participants must be screened for disqualifying safety concerns before receiving alemtuzumab treatment. a) Did not wish to receive alemtuzumab; b) Ongoing participation in any other investigational study, unless approved by Genzyme; c) Had received alemtuzumab off-label (ie, outside of one of the prior Genzyme-sponsored studies); d) Known bleeding disorder or therapeutic anticoagulation; e) Diagnosis of idiopathic thrombocytopenia purpura or other autoimmune hematologic abnormality; f) History of malignancy, except basal cell skin carcinoma; g) Intolerance of pulsed corticosteroids, especially a history of steroid psychosis h) Significant Autoimmune disorder (other than MS); i) Major psychiatric disorder or epileptic seizures not adequately controlled by treatment; j) Active infection or high risk for infection k) Unwilling to use a reliable and acceptable contraceptive method during and for at least 6 months following each alemtuzumab treatment cycle (fertile participants only).
Data sourced from ClinicalTrials.gov (NCT00930553) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.