Study of Efficacy, Safety and Tolerability of ACZ885 (Canakinumab) in Pediatric and Young Adult Patients With Sickle Cell Anemia

This was an ambulatory-based 24-week study followed by an additional 24-week open label phase. It was a subject- and investigator-blinded, randomized, placebo-controlled, parallel group, non-confirmatory study to assess the clinical efficacy of ACZ885 administered s.c. in six injections given 28 days apart (in each phase of the study).

Pediatric and young adult subjects diagnosed with sickle cell anemia (SCA) were planned to be randomized to either ACZ885 treatment or placebo treatment in a 1:1 ratio,.

For each subject, there was a maximum 28-day screening period that included recording of daily pain frequency and intensity by e-diary for at least 1 week. Subjects who met the eligibility criteria at screening underwent evaluation of baseline clinical and biomarker assessments prior to first dose administration.

On Day 1, monthly s.c. dosing with ACZ885 started at 4 mg/kg for subjects weighing ≤40 kg and 300 mg for all other subjects. Subjects in the placebo treatment arm were injected with placebo in a like manner. All subjects returned to the study centers for safety checks on a monthly basis when they received treatment with either ACZ885 or placebo.

The final blinded dosing was given on Week 20, followed by blinded clinical assessments at Week 24. Subjects from both study arms were then offered optional, open label monthly dosing of ACZ885 for an additional 24 weeks (Weeks 24-48) with clinical outcome assessment.

Subjects returned for the end of study (EOS) visit at Week 56. For subjects who chose not to participate in the optional, open label portion of the study, or for those stopping treatment early for any other reason, an EOS visit occurred approximately 8 weeks after last dose received.

After enrollment of 49 subjects, Novartis decided to terminate the study early due to strategic reasons not related to safety and decided that no additional enrollment was needed in order to interpret the study objectives.

Inclusion criteria

• Male and female subjects ages 8-20 years of age (both inclusive) diagnosed with sickle cell anemia (HbSS) or sickle beta0 thalassemia (documented by family studies, or analysis of either hemoglobin or DNA).
• Patient's written informed consent from those ≥18 years of age must be obtained before any assessment is performed. Parent or legal guardian's written informed consent and child's assent, if appropriate, are required before any assessment is performed for patients < 18 years of age.
• Detectable baseline of background or episodic pain measured by daily e-diary over 1 to 2 weeks during screening period as defined below: Average daily pain score ≥ 1 cm without analgesic use over a period of at least 7 days and/or, At least one episode of pain requiring analgesic use during a period of up to 14 days.
• History of ≥2 vaso-occlusive pain episodes in the past year, as defined as pain with no other, non-sickle cell identifiable cause that requires analgesia and interferes with the patient's normal daily routine.

Exclusion criteria

• History of known hypersensitivity to canakinumab.
• Ongoing or treatment with the past 3 months with red blood cell transfusion therapy, or have evidence of iron overload requiring chelation therapy.
• Transcranial Doppler ultrasound in the past year or at screening in patients with an accessible transtemporal window, demonstrating velocity in middle or anterior cerebral or internal carotid artery ≥200 cm/sec.
• Administration of any other blood products within 3 weeks of screening visit.

Other protocol-defined inclusion/exclusion criteria may apply.