Trial Outcomes & Findings for Safety and Tolerability of AIN457 in Adults (18-65 Years) With Moderate to Severe Ankylosing Spondylitis (NCT NCT01109940)

Last Updated: 2021-06-24

Results Overview

AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

39 participants

Primary outcome timeframe

From start of the study up to 64 weeks

Results posted on

2021-06-24

Participant Flow

The study was conducted at 15 centers in four countries (Germany, Netherlands, United Kingdom, United States).

A total of 39 participants enrolled in the study of which 28 completed the study and 11 discontinued the study. Few participants were enrolled into the extension study (CAIN457A2209E1 \[NCT01109940\]) prior to completion of the core study (CAIN457A2209 \[NCT00809159\]).

Participant milestones

Participant milestones
Measure	Dose Group 1 Participants received 3 milligrams per kilogram (mg/kg) of intravenous (IV) secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x10 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group 2 Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x1.0 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group 3 Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x0.1 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Secukinumab/Placebo Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received placebo in the core study (CAIN457A2209 \[NCT00809159\]).
Overall Study STARTED	21	8	7	3
Overall Study COMPLETED	13	6	6	3
Overall Study NOT COMPLETED	8	2	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Group 1 Participants received 3 milligrams per kilogram (mg/kg) of intravenous (IV) secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x10 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group 2 Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x1.0 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group 3 Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x0.1 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).
Overall Study Administrative problems	2	0	0
Overall Study Serious Adverse Event	2	1	0
Overall Study Lost to Follow-up	1	0	0
Overall Study Patient withdrew consent	1	1	0
Overall Study Unsatisfactory therapeutic effect	2	0	1

Baseline Characteristics

Safety and Tolerability of AIN457 in Adults (18-65 Years) With Moderate to Severe Ankylosing Spondylitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Group 1 n=21 Participants Participants received 3 milligrams per kilogram (mg/kg) of intravenous (IV) secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x10 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group 2 n=8 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x1.0 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group 3 n=7 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x0.1 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Secukinumab/Placebo n=3 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received placebo in the core study (CAIN457A2209 \[NCT00809159\]).	Total n=39 Participants Total of all reporting groups
Age, Continuous	39.5 Years STANDARD_DEVIATION 7.56 • n=93 Participants	47.9 Years STANDARD_DEVIATION 11.27 • n=4 Participants	45.9 Years STANDARD_DEVIATION 8.61 • n=27 Participants	41.7 Years STANDARD_DEVIATION 11.59 • n=483 Participants	42.5 Years STANDARD_DEVIATION 9.25 • n=36 Participants
Sex: Female, Male Female	10 Participants n=93 Participants	4 Participants n=4 Participants	2 Participants n=27 Participants	0 Participants n=483 Participants	16 Participants n=36 Participants
Sex: Female, Male Male	11 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants	3 Participants n=483 Participants	23 Participants n=36 Participants
Race/Ethnicity, Customized Caucasian	18 Participants n=93 Participants	8 Participants n=4 Participants	6 Participants n=27 Participants	3 Participants n=483 Participants	35 Participants n=36 Participants
Race/Ethnicity, Customized Other	2 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	3 Participants n=36 Participants
Race/Ethnicity, Customized Black	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants

PRIMARY outcome

Timeframe: From start of the study up to 64 weeks

Population: Safety analysis set.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=21 Participants Participants received 3 milligrams per kilogram (mg/kg) of intravenous (IV) secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x10 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group 2 n=8 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x1.0 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group 3 n=7 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x0.1 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Secukinumab/Placebo n=3 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received placebo in the core study (CAIN457A2209 \[NCT00809159\]).
Number of Participants Reported Adverse Events (AE's)	21 Participants	6 Participants	6 Participants	3 Participants

SECONDARY outcome

Timeframe: Pre-dose, Week 0, 8, 24, 40 and Week 64

Population: Safety analysis set.

Immunogenicity (anti-drug antibodies) was assessed using an MSD bridging assay and a 3-tiered approach (screening, confirmation, titration).

Outcome measures

Outcome measures
Measure	Dose Group 1 n=21 Participants Participants received 3 milligrams per kilogram (mg/kg) of intravenous (IV) secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x10 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group 2 n=8 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x1.0 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group 3 n=7 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x0.1 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Secukinumab/Placebo n=3 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received placebo in the core study (CAIN457A2209 \[NCT00809159\]).
Number of Participants Reported Positive Antibodies for Secukinumab Week 0	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reported Positive Antibodies for Secukinumab Week 24	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reported Positive Antibodies for Secukinumab Week 40	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reported Positive Antibodies for Secukinumab Week 64	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reported Positive Antibodies for Secukinumab Week 8	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre-dose and at the end of infusion (up to 64 weeks)

Population: IL-17A measurements were planned for this study but could not be measured because the assay for total IL-17A, samples was not robust.

Total serum IL17A was not measured due to assay limitations.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At end of infusion (Week 64)

Population: All completed participants with quantifiable pharmacokinetics (PK) measurements and no major protocol deviations with impact on PK data were included in the PK analysis set. Here, the number of participants analyzed refer to the participants evaluable for this outcome measure.

Concentration of Secukinumab at the end of infusion (Cmax,ss) was reported.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=7 Participants Participants received 3 milligrams per kilogram (mg/kg) of intravenous (IV) secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x10 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group 2 n=6 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x1.0 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group 3 n=5 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x0.1 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Secukinumab/Placebo n=3 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received placebo in the core study (CAIN457A2209 \[NCT00809159\]).
Maximum (Peak) Observed in Serum at Steady-State (Cmax,ss)	10.5 micrograms per milliliter (μg/mL) Standard Deviation 3.03	10.6 micrograms per milliliter (μg/mL) Standard Deviation 3.82	11.3 micrograms per milliliter (μg/mL) Standard Deviation 4.81	17.1 micrograms per milliliter (μg/mL) Standard Deviation 10.9

SECONDARY outcome

Timeframe: Pre-dose (Week 0)

The concentration of secukinumab at pre-dose (Cmin,ss) in serum was reported.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=21 Participants Participants received 3 milligrams per kilogram (mg/kg) of intravenous (IV) secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x10 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group 2 n=7 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x1.0 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group 3 n=5 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x0.1 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Secukinumab/Placebo n=3 Participants Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received placebo in the core study (CAIN457A2209 \[NCT00809159\]).
Minimum (Trough) Observed in Serum at Steady State (Cmin,ss)	4.73 micrograms per milliliter (μg/mL) Standard Deviation 10.1	15.0 micrograms per milliliter (μg/mL) Standard Deviation 38.4	0.0428 micrograms per milliliter (μg/mL) Standard Deviation 0.0586	27.1 micrograms per milliliter (μg/mL) Standard Deviation 46.9

Adverse Events

Dose Group-1

Serious events: 4 serious events

Other events: 18 other events

Deaths: 0 deaths

Dose Group-2

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Dose Group-3

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo/Secukinumab

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dose Group-1 n=21 participants at risk Participants received 3 milligrams per kilogram (mg/kg) of intravenous (IV) secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x10 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group-2 n=8 participants at risk Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x1.0 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Dose Group-3 n=7 participants at risk Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received secukinumab 2x0.1 mg/kg in the core study (CAIN457A2209 \[NCT00809159\]).	Placebo/Secukinumab n=3 participants at risk Participants received 3 mg/kg of IV secukinumab for every 4 weeks up to one year in the extension study (CAIN457A2209E1 \[NCT01109940\]) and who received placebo in the core study (CAIN457A2209 \[NCT00809159\]).
Gastrointestinal disorders Crohn's disease	4.8% 1/21 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/8 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/7 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/3 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.
Infections and infestations Folliculitis	0.00% 0/21 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	12.5% 1/8 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/7 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/3 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.
Infections and infestations Sinusitis	4.8% 1/21 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/8 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/7 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/3 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.
Infections and infestations Staphylococcal abscess	0.00% 0/21 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	12.5% 1/8 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/7 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/3 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.
Musculoskeletal and connective tissue disorders Arthritis	4.8% 1/21 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/8 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/7 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/3 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.
Psychiatric disorders Depression	4.8% 1/21 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/8 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/7 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.	0.00% 0/3 • From Start of the Study up to 64 Weeks The analysis was performed on Safety analysis population (SAP) consisted of all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place