CLARITY Extension Study

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 3

Conditions: Relapsing-Remitting Multiple Sclerosis

Treatments: Drug: Placebo; Drug: Cladribine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00641537

27820

2007-000381-20 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 867 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

• Other protocol-defined inclusion/exclusion criteria may apply

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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867 participants in 8 patient groups, including a placebo group

Cladribine Low/Placebo (LLPP)

Placebo Comparator group

Treatment:

Drug: Placebo

Drug: Placebo

Cladribine High Dose/Placebo (HLPP)

Placebo Comparator group

Treatment:

Drug: Placebo

Drug: Placebo

Cladribine Low/Low Dose (LLLL)

Experimental group

Treatment:

Drug: Cladribine

Drug: Cladribine

Drug: Cladribine

Cladribine High/Low Dose (HLLL)

Experimental group

Treatment:

Drug: Cladribine

Drug: Cladribine

Drug: Cladribine

Placebo/Cladribine Low Dose (PPLL)

Experimental group

Treatment:

Drug: Cladribine

Drug: Cladribine

Drug: Cladribine

Placebo/No Treatment

No Intervention group

Cladribine 3.5 mg/kg/No Treatment

No Intervention group

Description:

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).

Cladribine 5.25 mg/kg/No Treatment

No Intervention group

Description:

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).