Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, Cladribine, PREMIERE, Observational study
Brief summary
Prospective Observational Long-term Safety Registry of Multiple Sclerosis Participants who Have Participated in Cladribine Clinical Trials
Interventions
None listed
Sponsors
EMD Serono
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Prior enrollment into selected oral cladribine clinical trials as of randomization to either study drug or placebo, once participation in the clinical trial has ended * Written informed consent was given
Exclusion criteria
* Participants who cannot be reached by telephone * Participants unable to answer the registry questionnaires and who do not have a next of kin or caregiver able to answer the registry questionnaires * Participants who - either during the lag interval or subsequently enter an interventional study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Drug Reactions (SADRs) | up to 3251 days | SADR is an adverse drug reaction that fulfils at least one of the seriousness criterion; results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is otherwise considered as medically important. An adverse drug reaction (ADR) is a response to a medicinal product which is noxious and unintended, and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for the restoration, correction, or modification or physiological functions. Number of participants with SADRs were reported. |
| Time to Resolution of Lymphopenia, Among Registry Participants With Persistent Lymphopenia | up to 3251 days | Persistent lymphopenia was defined as Grade 3 (less than \[\<\] 500-200 per millimeter \[mm\] \^3 or \< 0.5-0.2 multiply \[\*\]10\^9 per Liter) or Grade 4 (\< 200/mm\^3 or \< 0.2\*10\^9 per Liter) lymphopenia as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The resolution is the achievement of a CTCAE Grade 1 (\< lower limit of normal \[LLN\] to 800 per mm\^3 or \< LLN to 0.8\*10\^9 per Liter) or Grade 0 (\< 910 per mm\^3 ) lymphocyte count. Persistent Lymphopenia was reported only in Cladribine group, hence results are reported only for Exposed to Cladribine arm. Time to resolution is reported. |
| Number of Participants With Adverse Events (AEs) in the Blood and Lymphatic System Disorders System Organ Class (SOC) and in the Neoplasms Benign, Malignant, and Unspecified SOC | up to 3251 days | An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Pregnancy Outcomes | up to 3251 days | Pregnancies occurred among female participants exposed to cladribine were identified by a participant-reported positive pregnancy test and at least a 2-week delay in menses, or a participant-reported pregnancy diagnosed by a physician. Pregnancy outcomes were Live birth, Induced abortion (Termination), Spontaneous loss (Miscarriage) (\< 22 weeks), Foetal death (stillbirth) (\>=22 weeks), Ectopic pregnancy, Congenital malformations and others (unknown). Number of participants as per pregnancy outcome category were reported. |
Countries
United States
Participant flow
Pre-assignment details
Study enrolled participants from previous clinical trials (NCT00213135, NCT00436826, NCT00641537, NCT00938366 and NCT00725985) and were exposed either to placebo matched to cladribine or cladribine itself. 13 enrolled participants from NCT00938366 were excluded from safety analysis as the dose was relatively lower compared with other studies.
Participants by arm
| Arm | Count |
|---|---|
| Never Exposed to Cladribine All participants who received placebo matched to cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537 and NCT00725985). | 198 |
| Exposed to Cladribine All participants who received cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537 and NCT00725985). | 950 |
| Total | 1,148 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 3 | 5 |
| Overall Study | Lost to Follow-up | 15 | 95 |
| Overall Study | Other | 1 | 25 |
| Overall Study | Participant entered interventional study | 0 | 8 |
| Overall Study | Physician Decision | 4 | 20 |
| Overall Study | Withdrawal by Subject | 15 | 38 |
Baseline characteristics
| Characteristic | Exposed to Cladribine | Total | Never Exposed to Cladribine |
|---|---|---|---|
| Age, Continuous | 40.6 years STANDARD_DEVIATION 10.8 | 40.1 years STANDARD_DEVIATION 10.8 | 37.4 years STANDARD_DEVIATION 10.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 18 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 7 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 7 Participants | 2 Participants |
| Race (NIH/OMB) White | 925 Participants | 1115 Participants | 190 Participants |
| Sex: Female, Male Female | 632 Participants | 773 Participants | 141 Participants |
| Sex: Female, Male Male | 318 Participants | 375 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 198 | 5 / 950 |
| other Total, other adverse events | 26 / 198 | 124 / 950 |
| serious Total, serious adverse events | 10 / 198 | 63 / 950 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) in the Blood and Lymphatic System Disorders System Organ Class (SOC) and in the Neoplasms Benign, Malignant, and Unspecified SOC
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug.
Time frame: up to 3251 days
Population: Safety analysis set included all participants in the current study who either received placebo matched to cladribine or cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826 , NCT00641537, NCT00725985).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Never Exposed to Cladribine | Number of Participants With Adverse Events (AEs) in the Blood and Lymphatic System Disorders System Organ Class (SOC) and in the Neoplasms Benign, Malignant, and Unspecified SOC | Blood and Lymphatic System Disorders SOC | 18 Participants |
| Never Exposed to Cladribine | Number of Participants With Adverse Events (AEs) in the Blood and Lymphatic System Disorders System Organ Class (SOC) and in the Neoplasms Benign, Malignant, and Unspecified SOC | Neoplasms Benign, Malignant, and Unspecified SOC | 4 Participants |
| Exposed to Cladribine | Number of Participants With Adverse Events (AEs) in the Blood and Lymphatic System Disorders System Organ Class (SOC) and in the Neoplasms Benign, Malignant, and Unspecified SOC | Blood and Lymphatic System Disorders SOC | 92 Participants |
| Exposed to Cladribine | Number of Participants With Adverse Events (AEs) in the Blood and Lymphatic System Disorders System Organ Class (SOC) and in the Neoplasms Benign, Malignant, and Unspecified SOC | Neoplasms Benign, Malignant, and Unspecified SOC | 25 Participants |
Primary
Number of Participants With Serious Adverse Drug Reactions (SADRs)
SADR is an adverse drug reaction that fulfils at least one of the seriousness criterion; results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is otherwise considered as medically important. An adverse drug reaction (ADR) is a response to a medicinal product which is noxious and unintended, and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for the restoration, correction, or modification or physiological functions. Number of participants with SADRs were reported.
Time frame: up to 3251 days
Population: Safety analysis set included all participants in the current study who either received placebo matched to cladribine or cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826 , NCT00641537 and NCT00725985).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Never Exposed to Cladribine | Number of Participants With Serious Adverse Drug Reactions (SADRs) | 1 Participants |
| Exposed to Cladribine | Number of Participants With Serious Adverse Drug Reactions (SADRs) | 14 Participants |
Primary
Time to Resolution of Lymphopenia, Among Registry Participants With Persistent Lymphopenia
Persistent lymphopenia was defined as Grade 3 (less than \[\<\] 500-200 per millimeter \[mm\] \^3 or \< 0.5-0.2 multiply \[\*\]10\^9 per Liter) or Grade 4 (\< 200/mm\^3 or \< 0.2\*10\^9 per Liter) lymphopenia as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The resolution is the achievement of a CTCAE Grade 1 (\< lower limit of normal \[LLN\] to 800 per mm\^3 or \< LLN to 0.8\*10\^9 per Liter) or Grade 0 (\< 910 per mm\^3 ) lymphocyte count. Persistent Lymphopenia was reported only in Cladribine group, hence results are reported only for Exposed to Cladribine arm. Time to resolution is reported.
Time frame: up to 3251 days
Population: Lymphocyte Population included participants from safety analysis set who had persistent lymphopenia. Here, overall number of participants analyzed signified participants with resolved lymphopenia.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Never Exposed to Cladribine | Time to Resolution of Lymphopenia, Among Registry Participants With Persistent Lymphopenia | 30.22 months | Standard Deviation 17.78 |
Secondary
Number of Participants With Pregnancy Outcomes
Pregnancies occurred among female participants exposed to cladribine were identified by a participant-reported positive pregnancy test and at least a 2-week delay in menses, or a participant-reported pregnancy diagnosed by a physician. Pregnancy outcomes were Live birth, Induced abortion (Termination), Spontaneous loss (Miscarriage) (\< 22 weeks), Foetal death (stillbirth) (\>=22 weeks), Ectopic pregnancy, Congenital malformations and others (unknown). Number of participants as per pregnancy outcome category were reported.
Time frame: up to 3251 days
Population: Safety analysis set. Here, Overall Number of Participants Analyzed signifies number of participants with pregnancies.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Never Exposed to Cladribine | Number of Participants With Pregnancy Outcomes | Spontaneous Loss (Miscarriage) | 2 Participants |
| Never Exposed to Cladribine | Number of Participants With Pregnancy Outcomes | Ectopic Pregnancy | 0 Participants |
| Never Exposed to Cladribine | Number of Participants With Pregnancy Outcomes | Induced Abortion (Termination) | 3 Participants |
| Never Exposed to Cladribine | Number of Participants With Pregnancy Outcomes | Congenital Malformations | 0 Participants |
| Never Exposed to Cladribine | Number of Participants With Pregnancy Outcomes | Foetal Death (Still birth) | 0 Participants |
| Never Exposed to Cladribine | Number of Participants With Pregnancy Outcomes | Unknown | 6 Participants |
| Never Exposed to Cladribine | Number of Participants With Pregnancy Outcomes | Live Birth | 23 Participants |
| Exposed to Cladribine | Number of Participants With Pregnancy Outcomes | Unknown | 10 Participants |
| Exposed to Cladribine | Number of Participants With Pregnancy Outcomes | Live Birth | 39 Participants |
| Exposed to Cladribine | Number of Participants With Pregnancy Outcomes | Induced Abortion (Termination) | 3 Participants |
| Exposed to Cladribine | Number of Participants With Pregnancy Outcomes | Spontaneous Loss (Miscarriage) | 3 Participants |
| Exposed to Cladribine | Number of Participants With Pregnancy Outcomes | Foetal Death (Still birth) | 1 Participants |
| Exposed to Cladribine | Number of Participants With Pregnancy Outcomes | Ectopic Pregnancy | 1 Participants |
| Exposed to Cladribine | Number of Participants With Pregnancy Outcomes | Congenital Malformations | 0 Participants |