CLARITY
Cladribine
CLARITY showed that two short annual courses of oral cladribine produced sustained reductions in relapses, disability progression, and MRI activity.
- Phase
- Phase III
- Population
- Relapsing-remitting multiple sclerosis (RRMS)
- Controlled period
- Apr 2005 — Nov 2008
What was compared
Cladribine 3.5 mg/kg
Cumulative oral dose delivered in short treatment courses
Placebo
Matching short oral courses
Additional randomized arm
Cladribine 5.25 mg/kg
Higher cumulative oral dose in short treatment coursesPrimary endpoint
Annualized relapse rate
96 weeks
Primary endpoint results
Annualized relapse rate
Relapses per participant-year
Both cumulative doses reduced relapse rate versus placebo (P<0.001).
Selected secondary outcomes
HR 0.67 for 3.5 mg/kg and 0.69 for 5.25 mg/kg versus placebo.
79.7% and 78.9% versus 60.9% with placebo.
Study population
- Randomized
- 1,326 randomized
- Age
- Mean 38.6 years; eligible 18–65
- Sex
- 898 women (68%)
- Disability
- EDSS 0–5.5
- Disease definition
- Relapsing-remitting MS with a relapse in the prior year
Who entered the trial
Key inclusion criteria
- Defined based on McDonald criteria 2001
- At least one relapse in the preceding 12 months
- Baseline EDSS 0–5.5 and body weight 40–120 kg
Key exclusion criteria
- Clinically important infection or immunodeficiency
- Prior treatment that produced substantial immunosuppression
- Pregnancy, breastfeeding, or inability to use required contraception
Safety signal
- Lymphocytopenia occurred in 21.6% and 31.5% of the cladribine groups versus 1.8% with placebo.
- Herpes zoster occurred in 8 and 12 cladribine-treated participants and none receiving placebo.
Why it mattered
CLARITY established an immune-reconstitution approach in which brief oral courses could produce efficacy extending beyond the dosing days.
Important limitation
The 96-week trial could not settle long-latency safety questions; benefit–risk interpretation depends on careful attention to lymphocyte suppression and longer follow-up.