Trial Outcomes & Findings for Efficacy and Safety of ACZ885 in Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease (NCT NCT00685373)

Last Updated: 2016-11-04

Results Overview

The number of participants with Adverse Events and Infections \& Infestations are regardless of study drug relationship by primary system organ class preferred term equal and/or greater than 2% in any group. The number of participants with mild injection site reactions= mild reactions observed on at least one occasion but no moderate or severe reactions. The number of participants with moderate injection site reactions= moderate reactions observed on at least one occasion but no severe reactions.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

166 participants

Primary outcome timeframe

2 years depending on when the participant enters the study

Results posted on

2016-11-04

Participant Flow

This study included participants previously enrolled in CACZ885A2102 (NCT00487708), CACZ885D2304 (NCT00465985) and ACZ885 naive patients.

Participant milestones

Participant milestones
Measure	Canakinumab (ACZ885) Subcutaneous injection every 8 weeks based on participant's body weight. Body weight \>40 kilogram (kg): 150 milligrams (mg) per injection and body weight \<= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.
Overall Study STARTED	166
Overall Study COMPLETED	151
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Canakinumab (ACZ885) Subcutaneous injection every 8 weeks based on participant's body weight. Body weight \>40 kilogram (kg): 150 milligrams (mg) per injection and body weight \<= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.
Overall Study Adverse Event	3
Overall Study Withdrawal by Subject	5
Overall Study Lack of Efficacy	3
Overall Study Condition no longer requires study drug	1
Overall Study Lost to Follow-up	2
Overall Study Protocol Violation	1

Baseline Characteristics

Efficacy and Safety of ACZ885 in Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Canakinumab (ACZ885) n=166 Participants Subcutaneous injection every 8 weeks based on participant's body weight. Body weight \>40 kilogram (kg): 150 milligrams (mg) per injection and body weight \<= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.
Age, Customized >= 41 to < 75 years	52 participants n=5 Participants
Age, Customized >= 3 to < 18 years	47 participants n=5 Participants
Age, Customized >= 18 to < 41 years	65 participants n=5 Participants
Age, Customized >= 75 years	2 participants n=5 Participants
Gender Female	97 Participants n=5 Participants
Gender Male	69 Participants n=5 Participants
Disease Characteristics Muckle-Wells Syndrome	103 participants n=5 Participants
Disease Characteristics Familial Cold Autoinflammatory Syndrome	30 participants n=5 Participants
Disease Characteristics Neonatal Onset Multi-System Inflammatory Syndrome	32 participants n=5 Participants
Disease Characteristics Information Missing	1 participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years depending on when the participant enters the study

Population: Safety Population defined as all participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Canakinumab (ACZ885) n=166 Participants Subcutaneous injection every 8 weeks based on participant's body weight. Body weight \>40 kilogram (kg): 150 milligrams (mg) per injection and body weight \<= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.
The Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs), Discontinuation of Study Drug Due to an AE, Infections and Infestations and Injection Site Reactions Serious Adverse Event	18 participants
The Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs), Discontinuation of Study Drug Due to an AE, Infections and Infestations and Injection Site Reactions Adverse Event	150 participants
The Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs), Discontinuation of Study Drug Due to an AE, Infections and Infestations and Injection Site Reactions Death	0 participants
The Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs), Discontinuation of Study Drug Due to an AE, Infections and Infestations and Injection Site Reactions Discontinuation of study drug due to an AE	4 participants
The Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs), Discontinuation of Study Drug Due to an AE, Infections and Infestations and Injection Site Reactions Infections and Infestations	109 participants
The Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs), Discontinuation of Study Drug Due to an AE, Infections and Infestations and Injection Site Reactions Any Injection Site Reactions	13 participants
The Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs), Discontinuation of Study Drug Due to an AE, Infections and Infestations and Injection Site Reactions Mild Injection Site Reactions	11 participants
The Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs), Discontinuation of Study Drug Due to an AE, Infections and Infestations and Injection Site Reactions Moderate Injection Site Reactions	2 participants

SECONDARY outcome

Timeframe: Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years

Population: Safety Population defined as all participants who had at least one dose of study drug and were included in the Relapse Assessment.

Disease relapse following complete response is defined as inflammation markers: C-Reactive Protein (CRP) and/or Serum Amyloid A (SAA) result \> 30 mg/L AND Physician's Global Assessment of Autoinflammatory Disease Activity \> minimal or Physician's Global Assessment \>= minimal AND Skin Disease Assessment \> minimal. Physician's Global Assessment of Autoinflammatory Disease Activity and Skin Disease Assessment (urticarial skin rash) are completed by the investigator using a 5 point rating scale: absent, minimal, mild, moderate and severe.

Outcome measures

Outcome measures
Measure	Canakinumab (ACZ885) n=141 Participants Subcutaneous injection every 8 weeks based on participant's body weight. Body weight \>40 kilogram (kg): 150 milligrams (mg) per injection and body weight \<= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.
The Percentage of Participants Without Disease Relapse as Determined by the Physician's Global Assessment of Autoinflammatory Disease Activity, Assessment of Skin Disease and Inflammation Markers.	90.1 Percentage of participants

SECONDARY outcome

Timeframe: Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years

Population: Safety Population defined as all participants who received at least one dose of study drug and were tested for anti-ACZ885 antibodies at the end of the study.

The number of participants who tested positive for anti-ACZ885 antibodies using the Biacore Assay at the end of the study.

Outcome measures

Outcome measures
Measure	Canakinumab (ACZ885) n=156 Participants Subcutaneous injection every 8 weeks based on participant's body weight. Body weight \>40 kilogram (kg): 150 milligrams (mg) per injection and body weight \<= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.
Immunogenicity of Canakinumab (ACZ885)	0 participants

SECONDARY outcome

Timeframe: Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years

Population: Safety population defined as all participants who received at least 1 dose of study drug. 3 participants were excluded because dosing information was not available at the time of analysis.

Mean Clearance from serum in Liter per Day (CLD) in adult participants \>=18, pediatric participants \<18 with body weight \>40 kg and pediatric participants \<18 with body weight \<=40 kg.

Outcome measures

Outcome measures
Measure	Canakinumab (ACZ885) n=163 Participants Subcutaneous injection every 8 weeks based on participant's body weight. Body weight \>40 kilogram (kg): 150 milligrams (mg) per injection and body weight \<= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.
Pharmacokinetics Adult Participants >= 18 years	0.179 L/day Standard Deviation 0.084
Pharmacokinetics Pediatric Participants <18 years and >40 kg	0.180 L/day Standard Deviation 0.145
Pharmacokinetics Pediatric Participants <18 years and <= 40 kg	0.083 L/day Standard Deviation 0.033

Adverse Events

Canakinumab (ACZ885)

Serious events: 18 serious events

Other events: 124 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Canakinumab (ACZ885) n=166 participants at risk Subcutaneous injection every 8 weeks based on participant's body weight. Body weight \>40 kilogram (kg): 150 milligrams (mg) per injection and body weight \<= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.
Congenital, familial and genetic disorders Muckle-Wells syndrome	0.60% 1/166
Gastrointestinal disorders Radicular cyst	0.60% 1/166
Infections and infestations Abdominal abscess	0.60% 1/166
Infections and infestations Appendicitis	0.60% 1/166
Infections and infestations Bronchitis	0.60% 1/166
Infections and infestations Cellulitis	0.60% 1/166
Infections and infestations Chronic tonsillitis	0.60% 1/166
Infections and infestations H1N1 influenza	0.60% 1/166
Infections and infestations Pneumonia	1.2% 2/166
Infections and infestations Tonsillitis	1.2% 2/166
Injury, poisoning and procedural complications Drug exposure during pregnancy	0.60% 1/166
Injury, poisoning and procedural complications Forearm fracture	0.60% 1/166
Investigations Hepatitis C antibody positive	0.60% 1/166
Investigations Transaminases increased	0.60% 1/166
Nervous system disorders Carpal tunnel syndrome	0.60% 1/166
Nervous system disorders Headache	0.60% 1/166
Nervous system disorders Nerve root compression	0.60% 1/166
Pregnancy, puerperium and perinatal conditions Pregnancy	1.2% 2/166
Psychiatric disorders Depression	0.60% 1/166
Renal and urinary disorders Nephrotic syndrome	0.60% 1/166
Social circumstances Miscarriage of partner	0.60% 1/166
Surgical and medical procedures Abortion induced	1.2% 2/166

Other adverse events

Other adverse events
Measure	Canakinumab (ACZ885) n=166 participants at risk Subcutaneous injection every 8 weeks based on participant's body weight. Body weight \>40 kilogram (kg): 150 milligrams (mg) per injection and body weight \<= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.
Gastrointestinal disorders Abdominal pain	7.8% 13/166
Gastrointestinal disorders Diarrhoea	10.8% 18/166
Gastrointestinal disorders Nausea	6.6% 11/166
Gastrointestinal disorders Vomiting	9.6% 16/166
General disorders Pyrexia	10.8% 18/166
Infections and infestations Bronchitis	10.8% 18/166
Infections and infestations Gastroenteritis	7.2% 12/166
Infections and infestations Nasopharyngitis	28.9% 48/166
Infections and infestations Rhinitis	16.3% 27/166
Infections and infestations Upper respiratory tract infection	10.2% 17/166
Injury, poisoning and procedural complications Fall	6.6% 11/166
Musculoskeletal and connective tissue disorders Arthralgia	14.5% 24/166
Musculoskeletal and connective tissue disorders Back pain	7.2% 12/166
Musculoskeletal and connective tissue disorders Pain in extremity	5.4% 9/166
Nervous system disorders Headache	19.9% 33/166
Respiratory, thoracic and mediastinal disorders Cough	9.6% 16/166
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.4% 14/166

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER