Trial Outcomes & Findings for Canakinumab to Treat Neonatal-Onset Multisystem Inflammatory Disease (NCT NCT00770601)

Last Updated: 2021-06-10

Results Overview

The primary endpoint of the study was the percentage of participants experiencing a relapse Central nervous system (CNS) relapse and/or inflammatory relapse) during 6-month open label administration of canakinumab in participant with NOMID/Chronic Infantile Neurological, Cutaneous, Articular Syndrome (CINCA). Complete remission consisted of inflammatory remission and CNS remission. 1 Inflammatory (systemic) remission was defined as follows (all criteria to be fulfilled): -Serum C-reactive protein (CRP) AND serum amyloid A (SAA) ≤ 10 milligrams/litre AND -daily diary score (mean score/week) ≤ 2. 2) CNS remission was defined as follows: Headache score (from the daily diary, mean score/week) \< 0.5 AND, when a lumbar puncture was performed: Normal values of white cell count (WBC) (≤15 cells/mm3) in CSF.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

7 participants

Primary outcome timeframe

6 months

Results posted on

2021-06-10

Participant Flow

The study was conducted at a single center in United States

A total of 7 participants were screened of which only 6 participants were randomized into the study, as one participant withdrew consent before dosing.

Participant milestones

Participant milestones
Measure	Canakinumab (ACZ885) Participants received body-weight stratified dosage of canakinumab treatment at 300 milligrams (mg) (for participants weighing more than 40 kilograms (kg)) and at 2 mg/kg (for participants weight less than or equal to 40 kg) subcutaneously every 4-8 weeks as per investigator discretion for a treatment period of 6 months. The first 3 Neonatal-Onset Multisystem Inflammatory Disease (NOMID) participants enrolled received a dose of 150 mg (\>40 kg) and 2 mg/kg for children \<40 kg. Since this dose was insufficient to fully control the symptoms of the disease the 300 mg / 4mg/kg dose was introduced by Protocol Amendment 2.
Overall Study STARTED	7
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Canakinumab (ACZ885) Participants received body-weight stratified dosage of canakinumab treatment at 300 milligrams (mg) (for participants weighing more than 40 kilograms (kg)) and at 2 mg/kg (for participants weight less than or equal to 40 kg) subcutaneously every 4-8 weeks as per investigator discretion for a treatment period of 6 months. The first 3 Neonatal-Onset Multisystem Inflammatory Disease (NOMID) participants enrolled received a dose of 150 mg (\>40 kg) and 2 mg/kg for children \<40 kg. Since this dose was insufficient to fully control the symptoms of the disease the 300 mg / 4mg/kg dose was introduced by Protocol Amendment 2.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Canakinumab to Treat Neonatal-Onset Multisystem Inflammatory Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Canakinumab (ACZ885) n=6 Participants Participants received body-weight stratified dosage of canakinumab treatment at 300 mg (for participants weighing more than 40 kg) and at 2 mg/kg (for participants weight less than or equal to 40 kg) subcutaneously every 4-8 weeks as per investigator discretion for a treatment period of 6 months. The first 3 NOMID participants enrolled received a dose of 150 mg (\>40 kg) and 2 mg/kg for children \<40 kg. Since this dose was insufficient to fully control the symptoms of the disease the 300 mg / 4mg/kg dose was introduced by Protocol Amendment 2.
Age, Continuous	18.7 years STANDARD_DEVIATION 8.09 • n=99 Participants
Age, Customized Children (2-11 years)	1 Participants n=99 Participants
Age, Customized Adolescents (12-17 years)	3 Participants n=99 Participants
Age, Customized Adults (18-64 years)	2 Participants n=99 Participants
Sex: Female, Male Female	2 Participants n=99 Participants
Sex: Female, Male Male	4 Participants n=99 Participants
Race/Ethnicity, Customized Caucasian	4 Participants n=99 Participants
Race/Ethnicity, Customized Black	1 Participants n=99 Participants
Race/Ethnicity, Customized Asian	1 Participants n=99 Participants
Race/Ethnicity, Customized Hispanic/Latino	1 Participants n=99 Participants
Race/Ethnicity, Customized Japanese	1 Participants n=99 Participants
Race/Ethnicity, Customized Mixed Ethinicity	2 Participants n=99 Participants
Race/Ethnicity, Customized Other	2 Participants n=99 Participants

PRIMARY outcome

Timeframe: 6 months

Population: The primary analysis was performed on all participants randomized and received at least one dose of study drug. No participant was in stable full remission state as defined by the protocol.

Outcome measures

Outcome measures
Measure	Canakinumab (ACZ885) n=6 Participants Participants received body-weight stratified dosage of canakinumab treatment at 300 mg (for participants weighing more than 40 kg) and at 2 mg/kg (for participants weight less than or equal to 40 kg) subcutaneously every 4-8 weeks as per investigator discretion for a treatment period of 6 months. The first 3 NOMID participants enrolled received a dose of 150 mg (\>40 kg) and 2 mg/kg for children \<40 kg. Since this dose was insufficient to fully control the symptoms of the disease the 300 mg / 4mg/kg dose was introduced by Protocol Amendment 2.
Percentage of Participants With Complete Remission and Relapse After 6 Months of Canakinumab Treatment.	0 Percentage of participants

Adverse Events

Canakinumab (ACZ885)

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Canakinumab (ACZ885) n=6 participants at risk Participants received body-weight stratified dosage of canakinumab treatment at 300 mg (for participants weighing more than 40 kg) and at 2 mg/kg (for participants weight less than or equal to 40 kg) subcutaneously every 4-8 weeks as per investigator discretion for a treatment period of 6 months. The first 3 NOMID participants enrolled received a dose of 150 mg (\>40 kg) and 2 mg/kg for children \<40 kg. Since this dose was insufficient to fully control the symptoms of the disease the 300 mg / 4mg/kg dose was introduced by Protocol Amendment 2.
Infections and infestations Staphylococcal infection	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years

Other adverse events

Other adverse events
Measure	Canakinumab (ACZ885) n=6 participants at risk Participants received body-weight stratified dosage of canakinumab treatment at 300 mg (for participants weighing more than 40 kg) and at 2 mg/kg (for participants weight less than or equal to 40 kg) subcutaneously every 4-8 weeks as per investigator discretion for a treatment period of 6 months. The first 3 NOMID participants enrolled received a dose of 150 mg (\>40 kg) and 2 mg/kg for children \<40 kg. Since this dose was insufficient to fully control the symptoms of the disease the 300 mg / 4mg/kg dose was introduced by Protocol Amendment 2.
Blood and lymphatic system disorders Neutropenia	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Blood and lymphatic system disorders Thrombocytopenia	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Ear and labyrinth disorders Ear pain	33.3% 2/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Eye disorders Conjunctivitis allergic	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Eye disorders Lacrimation increased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Eye disorders Vision blurred	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Gastrointestinal disorders Gastrooesophageal reflux disease	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Gastrointestinal disorders Nausea	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
General disorders Condition aggravated	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
General disorders Pyrexia	33.3% 2/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Infections and infestations Ear infection	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Infections and infestations Fungal infection	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Infections and infestations Influenza	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Infections and infestations Localised infection	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Infections and infestations Sinusitis	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Infections and infestations Subcutaneous abscess	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Injury, poisoning and procedural complications Joint injury	33.3% 2/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Injury, poisoning and procedural complications Procedural pain	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Basophil count increased	33.3% 2/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Blood albumin decreased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Blood albumin increased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Blood alkaline phosphatase increased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Blood chloride increased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Blood creatine phosphokinase decreased	50.0% 3/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Blood creatine phosphokinase increased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Blood creatinine decreased	83.3% 5/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Blood glucose increased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Blood triglycerides increased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Blood uric acid decreased	33.3% 2/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations C-reactive protein increased	50.0% 3/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations CSF neutrophil count increased	83.3% 5/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations CSF protein increased	66.7% 4/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations CSF white blood cell count increased	83.3% 5/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Eosinophil count increased	50.0% 3/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Haematocrit decreased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Haemoglobin decreased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Heart rate increased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations High density lipoprotein decreased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Lymphocyte count increased	33.3% 2/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Monocyte count increased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Neutrophil count increased	33.3% 2/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Platelet count decreased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Platelet count increased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Red blood cell count increased	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations Red blood cell sedimentation rate increased	33.3% 2/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Investigations White blood cell count increased	33.3% 2/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Musculoskeletal and connective tissue disorders Arthralgia	50.0% 3/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Musculoskeletal and connective tissue disorders Costochondritis	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Musculoskeletal and connective tissue disorders Joint stiffness	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Nervous system disorders Dizziness	50.0% 3/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Nervous system disorders Headache	66.7% 4/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Nervous system disorders Memory impairment	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Nervous system disorders Sinus headache	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Reproductive system and breast disorders Amenorrhoea	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Respiratory, thoracic and mediastinal disorders Cough	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Respiratory, thoracic and mediastinal disorders Nasal congestion	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Skin and subcutaneous tissue disorders Acne	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Skin and subcutaneous tissue disorders Eczema	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Skin and subcutaneous tissue disorders Pityriasis rosea	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years
Skin and subcutaneous tissue disorders Rash	16.7% 1/6 • Adverse Events were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) for approx. 2 years

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: +1 (862) 778-8300

Email: [email protected]

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 (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER