individual item of the ALS Functional Rating Scale – Revised [ALSFRS-R; described below])
2.Normal respiratory function (defined as percent-predicted forced vital capacity values of [%FVC] ≥ 80%)
3.Definite or Probable ALS based on El Escorial revised criteria
4.Disease duration of 2 years or less
The study enrolled 69 patients in the RADICAVA arm and 68 in the placebo arm. Baseline characteristics were similar between these groups, with over 90% of patients in each group being treated with riluzole.
RADICAVA was administered as an intravenous infusion of 60 mg given over a 60 minute period according to the following schedule:
•An initial treatment cycle with daily dosing for 14 days, followed by a 14-day drug-free period (Cycle 1)
•Subsequent treatment cycles with daily dosing for 10 days out of 14-day periods, followed by 14-day drug-free periods (Cycles 2-6).
The primary efficacy endpoint was a comparison of the change between treatment arms in the ALSFRS-R total scores from baseline to Week 24. The ALSFRS-R scale consists of 12 questions that eva luate the fine motor, gross motor, bulbar, and respiratory function of patients with ALS (speech, salivation, swallowing, handwriting, cutting food, dressing/hygiene, turning in bed, walking, climbing stairs, dyspnea, orthopnea, and respiratory insufficiency). Each item is scored from 0-4, with higher scores representing greater functional ability. The decline in ALSFRS-R scores from baseline was significantly less in the RADICAVA-treated patients as compared to placebo (see Table 2). The distribution of change in ALSFRS-R scores from baseline to Week 24 by percent of patients is shown in Figure 1.
Table 2: Analysis of Change from Baseline to Week 24 in ALSFRS-R Scores
Treatment
Change from Baseline
LS Mean ± SE (95% CI)
Treatment Difference (RADICAVA – placebo [95% CI])
p-value
RADICAVA 60mg
−5.01±0.64
2.49 (0.99, 3.98)
0.0013
Placebo
−7.50±0.66
Figure 1: Distribution of Change from Baseline to Week 24 in ALSFRS-R Scores
figure1
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
RADICAVA injection is supplied as a 30 mg/100 mL (0.3 mg/mL) clear, colorless, sterile solution for intravenous infusion in single-dose polypropylene bags, each overwrapped with polyvinyl alcohol (PVA) secondary packaging containing an oxygen absorber and oxygen indicator, which should be pink to reflect appropriate oxygen levels [see DOSAGE AND ADMINISTRATION (2.2) and HOW SUPPLIED/STORAGE AND HANDLING(16.2)]. These are supplied in cartons as listed below.
NDC 70510-2171-1 30 mg/100 mL (0.3 mg/mL) single-dose bag
NDC 70510-2171-2 2 bags per carton
16.2 Storage and Handling
Store at up to 25°C (77°F). Excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from light. Store in overwrapped package to protect from oxygen degradation until time of use. The oxygen indicator will turn blue or purple if the oxygen has exceeded acceptable levels. Once the overwrap package is opened, use within 24 hours.
17 PATIENT COUNSELING INFORMATION
Advise the patients to read the FDA-approved patient labeling (Patient Information).
Hypersensitivity Reactions
Advise patients to seek immediate medical care if they experience signs or symptoms of a hypersensitivity reaction [see WARNINGS AND PRECAUTIONS (5.1)]. |
