Trial Outcomes & Findings for Prospective Observational Long-term Safety Registry of Multiple Sclerosis Participants Who Have Participated in Cladribine Clinical Trials (NCT NCT01013350)

Last Updated: 2019-11-15

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

1161 participants

Primary outcome timeframe

up to 3251 days

Results posted on

2019-11-15

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Never Exposed to Cladribine All participants who received placebo matched to cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826 , NCT00641537, NCT00938366 and NCT00725985).	Exposed to Cladribine All participants who received cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537, NCT00938366 and NCT00725985).
Overall Study STARTED	198	963
Overall Study Safety Analysis Set	198	950
Overall Study COMPLETED	160	771
Overall Study NOT COMPLETED	38	192

Reasons for withdrawal

Reasons for withdrawal
Measure	Never Exposed to Cladribine All participants who received placebo matched to cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826 , NCT00641537, NCT00938366 and NCT00725985).	Exposed to Cladribine All participants who received cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537, NCT00938366 and NCT00725985).
Overall Study Lost to Follow-up	15	95
Overall Study Adverse Event	0	1
Overall Study Physician Decision	4	20
Overall Study Withdrawal by Subject	15	38
Overall Study Death	3	5
Overall Study Participant entered interventional study	0	8
Overall Study Other	1	25

Baseline Characteristics

Prospective Observational Long-term Safety Registry of Multiple Sclerosis Participants Who Have Participated in Cladribine Clinical Trials

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Never Exposed to Cladribine n=198 Participants All participants who received placebo matched to cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537 and NCT00725985).	Exposed to Cladribine n=950 Participants All participants who received cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537 and NCT00725985).	Total n=1148 Participants Total of all reporting groups
Age, Continuous	37.4 years STANDARD_DEVIATION 10.2 • n=5 Participants	40.6 years STANDARD_DEVIATION 10.8 • n=7 Participants	40.1 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	141 Participants n=5 Participants	632 Participants n=7 Participants	773 Participants n=5 Participants
Sex: Female, Male Male	57 Participants n=5 Participants	318 Participants n=7 Participants	375 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	13 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	190 Participants n=5 Participants	925 Participants n=7 Participants	1115 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Never Exposed to Cladribine n=198 Participants All participants who received placebo matched to cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537 and NCT00725985).	Exposed to Cladribine n=950 Participants All participants who received cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537 and NCT00725985).
Number of Participants With Serious Adverse Drug Reactions (SADRs)	1 Participants	14 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Never Exposed to Cladribine n=41 Participants All participants who received placebo matched to cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537 and NCT00725985).	Exposed to Cladribine All participants who received cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537 and NCT00725985).
Time to Resolution of Lymphopenia, Among Registry Participants With Persistent Lymphopenia	30.22 months Standard Deviation 17.78	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Never Exposed to Cladribine n=198 Participants All participants who received placebo matched to cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537 and NCT00725985).	Exposed to Cladribine n=950 Participants All participants who received cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537 and NCT00725985).
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	92 Participants
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	25 Participants

SECONDARY outcome

Timeframe: up to 3251 days

Population: Safety analysis set. Here, "Overall Number of Participants Analyzed" signifies number of participants with pregnancies.

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.

Outcome measures

Outcome measures
Measure	Never Exposed to Cladribine n=34 Participants All participants who received placebo matched to cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537 and NCT00725985).	Exposed to Cladribine n=57 Participants All participants who received cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537 and NCT00725985).
Number of Participants With Pregnancy Outcomes Live Birth	23 Participants	39 Participants
Number of Participants With Pregnancy Outcomes Induced Abortion (Termination)	3 Participants	3 Participants
Number of Participants With Pregnancy Outcomes Spontaneous Loss (Miscarriage)	2 Participants	3 Participants
Number of Participants With Pregnancy Outcomes Foetal Death (Still birth)	0 Participants	1 Participants
Number of Participants With Pregnancy Outcomes Ectopic Pregnancy	0 Participants	1 Participants
Number of Participants With Pregnancy Outcomes Congenital Malformations	0 Participants	0 Participants
Number of Participants With Pregnancy Outcomes Unknown	6 Participants	10 Participants

Adverse Events

Never Exposed to Cladribine

Serious events: 10 serious events

Other events: 26 other events

Deaths: 3 deaths

Exposed to Cladribine

Serious events: 63 serious events

Other events: 124 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Never Exposed to Cladribine n=198 participants at risk All participants who received placebo matched to cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537 and NCT00725985).	Exposed to Cladribine n=950 participants at risk All participants who received cladribine in previously conducted clinical trials (NCT Number: NCT00213135, NCT00436826, NCT00641537 and NCT00725985).
Blood and lymphatic system disorders Lymphopenia	7.6% 15/198 • up to 3251 days 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).	8.0% 76/950 • up to 3251 days 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).
Nervous system disorders Multiple sclerosis relapse	5.6% 11/198 • up to 3251 days 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).	5.1% 48/950 • up to 3251 days 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).

Additional Information

Communication Center

Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place