CLARITY Extension Study

Study at a glance

From the registry record, last updated by the sponsor on 7 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Phase IIIb, Double-Blind, Placebo-Controlled, Multicenter, Parallel Group, Extension Trial to Evaluate the Safety and Tolerability of Oral Cladribine in Subjects With Relapsing-Remitting Multiple Sclerosis Who Have Completed Trial 25643 (CLARITY)

ClinicalTrials.gov ID

NCT00641537

Acronym / sponsor ID

27820

Conditions

Relapsing-Remitting Multiple Sclerosis

Phase

Phase 3

Study type

Interventional

Recruitment status

Completed

Enrolment

867 participants (actual)

Lead sponsor

EMD Serono Research & Development Institute, Inc.Industry (pharma, biotech, devices)

Study start

29 Feb 2008 (actual)

Primary completion

31 Dec 2011 (actual)

Study completion

31 Dec 2011 (actual)

First posted

24 Mar 2008 (estimated)

Results

Posted 2 Dec 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Parallel groups

Masking

Quadruple blind (participant, care provider, investigator, outcomes assessor)

Number of arms

8

Who may qualify

Ages

18 to 65 years

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity

   Time frame: Baseline up to Week 120

   Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events v 3.0 (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE v3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death.

2. Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120

   Time frame: Baseline, Week 120

   Mean change from baseline in absolute lymphocyte count, platelet, neutrophils and leukocytes at week 120 were reported.

3. Safety Population: Mean Change From Baseline in Hemoglobin at Week 120

   Time frame: Baseline, Week 120

   Mean change from baseline in hemoglobin at Week 120 was reported.

4. Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120

   Time frame: Baseline, Week 120

   Mean change from baseline in aspartate aminotransferase and alanine aminotransferase at week 120 were reported.

5. Safety Population: Mean Change From Baseline in Bilirubin at Week 120

   Time frame: Baseline, Week 120

   Mean Change From Baseline in Bilirubin at week 120 was reported.

6. Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

   Time frame: Baseline up to Week 120

   An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. Serious AE (SAE): Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non-serious TEAEs and serious TEAEs.

7. SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

   Time frame: Baseline up to Week 120

   An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non-serious TEAEs and serious TEAEs.

8. Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies

   Time frame: Baseline up to Week 120

   Number of participants who developed Herpes viral infection, Viral infectious disorder and Opportunistic infection are reported. Number of participants with infection related adverse events are the number of participants who had at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms under infection and infestation system organ class. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre-specified grouping Malignant and unspecified tumors.

9. SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies

   Time frame: Baseline up to Week 120

   Number of participants who developed Herpes viral infection, Viral infectious disorder and Opportunistic infection were reported. Number of participants with infection related adverse events are the number of participants who had at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms under infection and infestation system organ class. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre-specified grouping Malignant and unspecified tumors.

10. Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity

    Time frame: Baseline up to Week 120

    Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. Time to first CTCAE Grade 3 or 4 hematological or liver toxicity was analyzed by treatment group using Kaplan-Meier plots of probability of surviving toxicity-free and point estimates of percentiles. According to CTCAE version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th, 20th, 25th, 50th and 75th percentiles were estimated from Kaplan-Meier survival curve.

11. Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity

    Time frame: Baseline up to Week 120

    Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Time to recovery from grade 3 or 4 hematological or liver toxicity were reported: lymphocytes, platelets, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1.

12. Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity

    Time frame: Baseline up to Week 120

    Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE v3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Time to recovery from grade 3 or 4 hematological or liver toxicity were reported: lymphocytes, platelets, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST) and Platelets. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1.

13. Safety Population: Median Time to Nadir of Absolute Lymphocyte Count

    Time frame: Baseline up to Week 120

    Median time to nadir of absolute lymphocyte count was reported.

14. Safety Population: Mean Time to Nadir of Absolute Lymphocyte Count

    Time frame: Baseline up to Week 120

    Mean time to nadir of absolute lymphocyte count was reported.

15. Safety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value

    Time frame: Baseline up to Week 120

    Mean time to recovery from nadir of absolute lymphocyte count to normal was reported. Recovery from Nadir is defined as a return to baseline value. Normal absolute lymphocyte count is 1.02 x 10^3 cells/microliter.

16. Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline

    Time frame: Baseline, Week 5, 48, 52 and 96

    The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Mean change in corrected QT (QTc) interval from baseline was reported.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2020.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 36017797Stefano N, Sormani MP, Giovannoni G, Rammohan K, Leist TP, Coyle PK, Dangond F, Alexandri N, Galazka A. Relapses in people with multiple sclerosis treated with cladribine tablets followed for up to 5 years: a plain language summary. Neurodegener Dis Manag. 2022 Dec;12(6):303-310. doi: 10.2217/nmt-2022-0019. Epub 2022 Aug 26.
• Derived from this study: PubMed 36017780Giovannoni G, Comi G, Rammohan K, Rieckmann P, Dangond F, Jack D, Vermersch P. Disease stability over five years in people with multiple sclerosis treated with cladribine tablets: a plain language summary. Neurodegener Dis Manag. 2022 Dec;12(6):295-301. doi: 10.2217/nmt-2022-0018. Epub 2022 Aug 26.
• Derived from this study: PubMed 35003076Giovannoni G, Coyle PK, Vermersch P, Walker B, Aldridge J, Nolting A, Galazka A, Lemieux C, Leist TP. Integrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets. Front Immunol. 2021 Dec 24;12:763433. doi: 10.3389/fimmu.2021.763433. eCollection 2021.
• Derived from this study: PubMed 34370275Giovannoni G, Comi G, Rammohan K, Rieckmann P, Dangond F, Keller B, Jack D, Vermersch P. Long-Term Disease Stability Assessed by the Expanded Disability Status Scale in Patients Treated with Cladribine Tablets 3.5 mg/kg for Relapsing Multiple Sclerosis: An Exploratory Post Hoc Analysis of the CLARITY and CLARITY Extension Studies. Adv Ther. 2021 Sep;38(9):4975-4985. doi: 10.1007/s12325-021-01865-w. Epub 2021 Aug 9.
• Derived from this study: PubMed 33969750De Stefano N, Sormani MP, Giovannoni G, Rammohan K, Leist T, Coyle PK, Dangond F, Keller B, Alexandri N, Galazka A. Analysis of frequency and severity of relapses in multiple sclerosis patients treated with cladribine tablets or placebo: The CLARITY and CLARITY Extension studies. Mult Scler. 2022 Jan;28(1):111-120. doi: 10.1177/13524585211010294. Epub 2021 May 10.
• Derived from this study: PubMed 32447743Giovannoni G, Galazka A, Schick R, Leist T, Comi G, Montalban X, Damian D, Dangond F, Cook S. Pregnancy Outcomes During the Clinical Development Program of Cladribine in Multiple Sclerosis: An Integrated Analysis of Safety. Drug Saf. 2020 Jul;43(7):635-643. doi: 10.1007/s40264-020-00948-x.
• Derived from this study: PubMed 29399054Comi G, Cook S, Rammohan K, Soelberg Sorensen P, Vermersch P, Adeniji AK, Dangond F, Giovannoni G. Long-term effects of cladribine tablets on MRI activity outcomes in patients with relapsing-remitting multiple sclerosis: the CLARITY Extension study. Ther Adv Neurol Disord. 2018 Jan 23;11:1756285617753365. doi: 10.1177/1756285617753365. eCollection 2018.
• Trial Awareness and Transparency websiteLink provided by the sponsor.
• US Medical Information website, Medical ResourcesLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

116 sites in 31 countries: see every site and its status.