CLARITY Extension Study

NCT ID: NCT00641537

Last Updated: 2020-12-07

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

867 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-02-29

Study Completion Date

2011-12-31

Brief Summary

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The purpose of this extension trial was to further evaluate the safety and tolerability of oral cladribine in subjects who have previously completed treatment within Trial 25643 (CLARITY). This trial also explored clinical benefit of prolonged 192-week versus 96-week treatment.

Detailed Description

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Conditions

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Relapsing-Remitting Multiple Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Cladribine Low/Placebo (LLPP)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants who received Cladribine 3.5 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive placebo matched to cladribine tablet 0.875 mg/kg orally administered over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 during the treatment period of 96 weeks.

Cladribine High Dose/Placebo (HLPP)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants who received Cladribine 5.25 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive placebo matched to cladribine tablet 0.875 mg/kg orally administered over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 during the treatment period of 96 weeks.

Cladribine Low/Low Dose (LLLL)

Group Type EXPERIMENTAL

Cladribine

Intervention Type DRUG

Participants who received Cladribine 3.5 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.

Cladribine High/Low Dose (HLLL)

Group Type EXPERIMENTAL

Cladribine

Intervention Type DRUG

Participants who received Cladribine 5.25 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.

Placebo/Cladribine Low Dose (PPLL)

Group Type EXPERIMENTAL

Cladribine

Intervention Type DRUG

Participants who received placebo in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.

Placebo/No Treatment

Group Type NO_INTERVENTION

No interventions assigned to this group

Cladribine 3.5 mg/kg/No Treatment

Participants who received cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period).

Group Type NO_INTERVENTION

No interventions assigned to this group

Cladribine 5.25 mg/kg/No Treatment

Participants who received cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period).

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Cladribine

Participants who received Cladribine 3.5 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.

Intervention Type DRUG

Placebo

Participants who received Cladribine 3.5 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive placebo matched to cladribine tablet 0.875 mg/kg orally administered over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 during the treatment period of 96 weeks.

Intervention Type DRUG

Cladribine

Participants who received Cladribine 5.25 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.

Intervention Type DRUG

Cladribine

Participants who received placebo in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks.

Intervention Type DRUG

Placebo

Participants who received Cladribine 5.25 mg/kg in the previous study 25643 (NCT00213135) and completed will be re-randomized in this extension study and receive placebo matched to cladribine tablet 0.875 mg/kg orally administered over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 during the treatment period of 96 weeks.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Randomized in Trial 25643 and satisfied one of the following:

* Completed randomized treatment course and scheduled visits for the full 96 weeks; or
* Did not complete the randomized treatment course in Trial 25643 but elected to receive rescue treatment with Rebif®, another beta-interferon, or glatiramer acetate and completed scheduled clinic visits for the full 96 weeks; or
* Did not complete the randomized treatment course in Trial 25643, declined rescue with Rebif®, another beta-interferon, or glatiramer acetate and still completed scheduled clinic visits for the full 96 weeks; or
* Did not complete the randomized treatment course in Trial 25643, were not eligible for rescue option with Rebif®, and still completed scheduled clinic visits for the full 96 weeks
* Male or female, between 18 and 65 years of age (inclusive, at time of informed consent for Trial 25643)
* No medical history or evidence of latent tuberculosis infection (LTBI) or tuberculosis (TB), as evidenced by TB skin test or chest X-ray
* All of the following laboratory hematologic parameters evaluated as normal (as define below, inclusively) within 28 days of first dosing of blinded study medication at study Day 1:

* Hemoglobin = 11.6 to 16.2 gram per deciliter (g/dL)
* Leukocytes (total white blood cell) = 4.1 to 12.3\*10\^3 per microliter
* Absolute lymphocyte count (ALC) = 1.02 to 3.36\*10\^3 per microliter
* Absolute neutrophil count (ANC) = 2.03 to 8.36\*10\^3 per microliter
* Platelet count = 140 to 450\*10\^3 per microliter

Exclusion Criteria

* Participants who were not enrolled in Trial 25643
* Participant has moderate to severe renal impairment
* Use of mitoxantrone, total lymphoid irradiation, myelosuppressive therapy, campath-1h, cyclophosphamide, azathioprine, methotrexate or natalizumab at any time during and since Trial 25643
* Use of cytokine or anti-cytokine therapy, intravenous immunoglobulin (IVIG) or plasmapheresis at any time during and since Trial 25643
* Treatment with oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days before Study Day 1
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Locations

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Boulder, Colorado, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Northbrook, Illinois, United States

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Baltimore, Maryland, United States

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Ann Arbor, Michigan, United States

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Henderson, Nevada, United States

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Newark, New Jersey, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Columbus, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Medford, Oregon, United States

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Seattle, Washington, United States

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Tacoma, Washington, United States

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Charleston, West Virginia, United States

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Camperdown, , Australia

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Melbourne, , Australia

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Victoria, , Australia

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Linz, , Austria

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Diepenbeek, , Belgium

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Esneux, , Belgium

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Recife, , Brazil

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Pleven, , Bulgaria

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Plovdiv, , Bulgaria

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Rousse, , Bulgaria

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Shuman, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Zagora, , Bulgaria

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Burnaby, , Canada

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Greenfield Park, , Canada

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Ottawa, , Canada

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Québec, , Canada

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Karlovac, , Croatia

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Sisak, , Croatia

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Split, , Croatia

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Hradec Králové, , Czechia

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Olomouc, , Czechia

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Prague, , Czechia

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Copenhagen, , Denmark

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Tallinn, , Estonia

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Tartu, , Estonia

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Oulu, , Finland

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Turku, , Finland

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Clermont-Ferrand, , France

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Lille, , France

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Nancy, , France

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Nîmes, , France

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Paris, , France

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Rennes, , France

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Saint-Herblain, , France

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Bochum, , Germany

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Frankfurt, , Germany

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Giessen, , Germany

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Hanover, , Germany

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Regensburg, , Germany

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Rostock, , Germany

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Athens, , Greece

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Bari, , Italy

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Cagliari, , Italy

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Catania, , Italy

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Florence, , Italy

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Genova, , Italy

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Milan, , Italy

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Napoli, , Italy

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Padua, , Italy

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Roma, , Italy

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Riga, , Latvia

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Beirut, , Lebanon

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Kaunas, , Lithuania

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Casablanca, , Morocco

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Fes, , Morocco

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Rabat, , Morocco

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Sittard- Geleen, , Netherlands

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Gdansk, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Poznan, , Poland

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Warszawy, , Poland

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Lisbon, , Portugal

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Kaluga, , Russia

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Kazan', , Russia

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Kemerovo, , Russia

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Kursk, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Novosibirsk, , Russia

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Rostov-on-Don, , Russia

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Saint Petersburg, , Russia

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Samara, , Russia

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Saratov, , Russia

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Tomsk, , Russia

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Vladimir, , Russia

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Yaroslavl, , Russia

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Yekaterinburg, , Russia

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Riyadh, , Saudi Arabia

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Belgrade, , Serbia

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Lausanne, , Switzerland

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Sankt Gallen, , Switzerland

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Monastir, , Tunisia

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Sfax, , Tunisia

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Tunis, , Tunisia

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Bursa, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Kharkiv, , Ukraine

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Kiev, , Ukraine

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Lviv, , Ukraine

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Vinnitsa, , Ukraine

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Hull, , United Kingdom

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London, , United Kingdom

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Nottingham, , United Kingdom

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Oxford, , United Kingdom

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Sheffield, , United Kingdom

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Stoke-on-Trent, , United Kingdom

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Countries

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Serbia and Montenegro United States Australia Austria Belgium Brazil Bulgaria Canada Croatia Czechia Denmark Estonia Finland France Germany Greece Italy Latvia Lebanon Lithuania Morocco Netherlands Poland Portugal Russia Saudi Arabia Serbia Switzerland Tunisia Turkey (Türkiye) Ukraine United Kingdom

References

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Stefano 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.

Reference Type DERIVED
PMID: 36017797 (View on PubMed)

Giovannoni 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.

Reference Type DERIVED
PMID: 36017780 (View on PubMed)

Giovannoni 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.

Reference Type DERIVED
PMID: 35003076 (View on PubMed)

Giovannoni 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.

Reference Type DERIVED
PMID: 34370275 (View on PubMed)

De 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.

Reference Type DERIVED
PMID: 33969750 (View on PubMed)

Giovannoni 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.

Reference Type DERIVED
PMID: 32447743 (View on PubMed)

Comi 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.

Reference Type DERIVED
PMID: 29399054 (View on PubMed)

Related Links

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https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

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2007-000381-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

27820

Identifier Type: -

Identifier Source: org_study_id