Study of Efficacy, Safety and Tolerability of AIN457 in Patients With Active Overuse Tendinopathy

• ClinicalTrials.gov Identifier: NCT03344640
• Recruitment Status: Completed
• First Posted: November 17, 2017
• Results First Posted: December 9, 2020
• Last Update Posted: October 8, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

This was a randomized, double-blind, placebo-controlled, multi-center, Phase II study of s.c. secukinumab 300 mg in 98 randomized patients with overuse rotator-cuff tendinopathy without systemic inflammatory disease.

Condition or disease	Intervention/treatment	Phase
Tendinopathy	Drug: secukinumab; Other: Placebo	Phase 2

Detailed Description:

This was a randomized, double-blind, placebo-controlled, multi-center, Phase II study of s.c. secukinumab 300 mg in 98 randomized patients with overuse rotator-cuff tendinopathy without systemic inflammatory disease and refractory to NSAIDs/acetaminophen, physiotherapy or corticosteroids.

The study consisted of a 4-week screening period, a 2-week run-in period, a 12-week treatment period and a 12-week follow-up period after last treatment. The population consisted of patients with unilateral overuse (non-systemic inflammatory) shoulder tendinopathy, 18 - 65 years of age.

Safety assessments included physical examinations, ECGs, vital signs, standard clinical laboratory evaluations (hematology, blood chemistry, and urinalysis), adverse event and serious adverse event monitoring.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Patients and investigators were blinded until EOS. Sponsor was blinded until after the analysis of the primary endpoint at week 14.
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase II, 24-week Study Investigating the Efficacy, Safety and Tolerability of AIN457 in Patients With Active Overuse Tendinopathy Refractory to Oral NSAIDs/Acetaminophen, Physiotherapy or Corticosteroid Injections
• Actual Study Start Date: December 15, 2017
• Actual Primary Completion Date: August 2, 2019
• Actual Study Completion Date: October 17, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: secukinumab; AIN457 300 mg subcutaneously (s.c.) for 12 weeks	Drug: secukinumab; AIN457 300 mg subcutaneously for 12 weeks; Other Name: AIN457
Placebo Comparator: Placebo; Placebo subcutaneously for 12 weeks	Other: Placebo; Placebo to match AIN457 subcutaneously for 12 weeks

Outcome Measures

Primary Outcome Measures :

1. The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Score at Week 14 in All Patients - Statistical Analysis Results of Total WORC Scores at Week 14 [ Time Frame: Week 14 (Day 99) ]

   WORC PRO score at week 14. The WORC Index consists of 21 items divided into 5 Domains: Physical Symptoms (6 items), Sport/Recreation (4 items), Work Function (4 items), Lifestyle Function (4 items) and Emotional Function (3 items). The total scores and sub scores used were the percentages of the normal scores with 0 being worst and 100 being best.

   All Patients - Statistical analysis results of WORC scores at Week 14

Secondary Outcome Measures :

1. The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Scores Over Time in All Patients [ Time Frame: Days 15, 29, 57, 85, 127, and End of Study ]
   WORC score at Days 15, 29, 57, 85, 127, and End of Study (day 169). The scale range for WORC total score is 0-100, 0 being the worst possible outcome (highly symptomatic patient) and 100 being the best possible outcome (asymptomatic patient)
2. Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time [ Time Frame: Days 15, 29, 57, 85, 99, 127, and End of Study ]

   Patient Reported Outcome: Disability of Arm, Shoulder and Hand (QuickDASH) This questionnaire asks about symptoms as well participant's ability to do certain activities - ranging from 1 (No difficulty) to 5 (Unable).

   The scale range for QuickDASH total score is 0-100, 0 being the best possible outcome and 100 being the worst possible outcome

3. American Shoulder and Elbow Surgeons (ASES) Score Over Time [ Time Frame: Days 15, 29, 57, 85, 99, 127, and End of Study ]
   Patient Reported Outcome: American Shoulder and Elbow Surgeons Shoulder Evaluation Form (ASES) score is self-administered and has 17 questions in the areas of shoulder symptoms and functions. The ASES total score ranges from 0 to 100 (best).
4. Your Health Today Score Over Time [ Time Frame: Days 15, 29, 57, 85, 99, 127, and End of Study ]
   Patient Reported Outcome: Statistical analysis results of EQ-5D-5L for Your health Today questionnaire, which reflects how good or bad the subjets Health is on a scale from 0 (worst health) to 100 (best health).
5. EQ-5D-5L Index Score Over Time [ Time Frame: Days 15, 29, 57, 85, 99, 127 and End of Study ]
   Patient Reported Outcome: Statistical analysis results of EQ-5D-5L Index score, which contains 5 items to assess Health Status (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression). Overall scores range from 0 to 1 with lower scores representing a higher level of dysfunction.
6. Pain Score Over Time Using a VAS Scale [ Time Frame: Days 15, 29, 57, 85, 99, 127 and End of Study ]

   Pain intensity is assessed by a Visual Analog Scale (VAS) which is measured on a 100mm line that represents a continuum between "no pain" and "worst pain".

   The scale range for pain score is 0-100, 0 being the best possible outcome (no pain) and 100 being the worst possible outcome (worst pain).

7. Patient Global Assessment (PGA) Score Over Time Using a VAS Scale [ Time Frame: Days 15, 29, 57, 85, 99, 127 and End of Study ]

   The patient's global assessment of disease activity is performed using a 100 mm Visual Analog Scale (VAS) ranging from "no activity" to "most active" in the last 24 hours.

   The scale range for PGA score is 0-100, 0 being the best possible outcome (no disease activity) and 100 being the worst possible outcome (maximal disease activity).

8. Physician Global Assessment (PhGA) Score Using a VAS Scale Over Time [ Time Frame: Days 15, 29, 57, 85, 99, 127 and End of Study ]

   Physician global assessment (PhGA) score using a VAS scale (considering the last 24 hours).

   The scale range for PhGA score is 0-100, 0 being the best possible outcome (no disease activity) and 100 being the worst possible outcome (maximal disease activity).

9. Pharmacokinetics - Cmin [ Time Frame: Days 1, 29, 85 and EoS (End of Study) ]

   Mean trough concentrations

   Cmin is a pharmacokinetics term for the minimum blood plasma concentration reached by a drug prior to administration of a second dose (mass/volume)

   Serum trough concentrations of secukinumab 300 mg group was measured at Days 1, 29, 85 and EoS

10. Immunogenicity Assessment - Treatment Emergent ADAs [ Time Frame: Day 1 and EoS ]
    Number of Participants with Treatment emergent Anti-secukinumab antibodies
11. Number of Participants With Tendinosis Grade Score 1, 2 or 3 Measured by Magnetic Resonance Imaging (MRI) Sein Scores [ Time Frame: Baseline and Day 99 ]

    Assessment of structural changes in the rotator cuff tendinopathy over time

    The MRI Sein score was used to grade supraspinatus tendinosis using a modified 4-point scale from 0 to 3 and changes in grading over time were captured in the shift table. Grade 0 is normal, grade 1 is mild, Grade 2 is moderate and grade 3 is marked tendinosis.

    In this Sein score assessment, only data from Day 99 and baseline could be compared, as only those two time points were double read and adjudicated in case the 2 readers had different results. At any other time-points (Day 57 and EOS), images were assessed only by one reader and thus could not be compared to baseline.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or non-pregnant, non-lactating female patients 18 to 65 years of age at randomization

2. Presence of unilateral rotator cuff tendinopathy with:

   1. Symptoms present ≥6 weeks, but <12 months prior to randomization
   2. Tendinopathy with no more than a 50% tear as established by ultrasound at screening (historic data acceptable if not older than 3 months) and MRI at baseline: Sein MRI tendinopathy scoring system grade I-III; with no tear or partial tear [maximum 50% tendon thickness (Bauer tendon thickness score maximum 2); AP length maximum 10 mm (Bauer tendon length score max 2)]. Maximum 50% of patients with partial tear
   3. Pain in the affected shoulder (at rest or on movement) on at least 3 days out of 7 days in the past week prior to baseline and a score of ≥4 out of 10 on a VAS pain scale
   4. Positive "Painful Arc Test" on examination and/or nightly pain in the affected shoulder on at least 4 out of 7 days in the past week prior to baseline
3. The rotator-cuff tendinopathy must have been refractory to standard treatment, including NSAIDs and physiotherapy

Exclusion Criteria:

1. Rheumatologic, inflammatory diseases, including but not limited to: PsA, AS and RA 2. Previous shoulder surgery in affected shoulder 3. History of adhesive capsulitis/frozen shoulder or calcification in the tendon (in affected or contralateral shoulder) confirmed by X-Ray, historic X-Rays can be used if performed within 3 months of baseline 4. Symptomatic osteoarthritis of the shoulder (gleno-humeral, acromioclavicular) (in affected or contralateral shoulder confirmed by X-Ray, historic X-Rays can be used if performed within 3 months of baseline 5. Neck conditions, including but not limited to cervical spine syndrome, which in the opinion of the investigator, may explain the patient's symptoms 6. Previous platelet rich plasma injections within the last 12 months prior to randomization 7. Previous treatment with any cell-depleting therapies including but not limited to anti- CD20, investigational agents (e.g. Campath, anti-CD4, anti-CD5, anti-CD3, anti-CD19) 8. Previous exposure to any biologic immunomodulating agents, including but not limited to TNFalpha inhibitors (including, but not limited to adalimumab, infliximab), or biologics targeting IL-17 (including, but not limited to secukinumab, ixekizumab or brodalumab) or the IL-17 receptor within the last 12 months prior to baseline 9. Any intraarticular/subacromial corticosteroid treatment within 8 weeks prior to randomization and more than 3 injections for the current tendinopathy. Oral, intramuscular or i.v. corticosteroid treatment within the last 12 months prior to randomization

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Contacts and Locations

Locations

United States, Arizona

Novartis Investigative Site

Phoenix, Arizona, United States, 85053

United States, California

Novartis Investigative Site

La Mesa, California, United States, 91942

United States, Florida

Novartis Investigative Site

Clearwater, Florida, United States, 33765

Novartis Investigative Site

Miami Lakes, Florida, United States, 33014

Novartis Investigative Site

Tampa, Florida, United States, 33603

Czechia

Novartis Investigative Site

Brno, Czech Republic, Czechia, 66250

Novartis Investigative Site

Kolin, Czech Republic, Czechia, 280 02

Novartis Investigative Site

Praha, Czechia

Germany

Novartis Investigative Site

Berlin, Germany, 10117

Novartis Investigative Site

Hamburg, Germany, 22415

Netherlands

Novartis Investigative Site

Leiden, Netherlands, 2333 CL

United Kingdom

Novartis Investigative Site

Glasgow, United Kingdom, G51 4TF

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Study Protocol  [PDF] March 13, 2018

Statistical Analysis Plan  [PDF] April 14, 2020

More Information

Additional Information:

A Plain Language Trial Summary is available on novartisclinicaltrials.com 

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03344640
• Other Study ID Numbers: CAIN457X2201; 2017-003099-30 ( EudraCT Number )
• First Posted: November 17, 2017
• Results First Posted: December 9, 2020
• Last Update Posted: October 8, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Overuse tendinopathy; shoulder; rotator cuff; IL-17A-Ab; AIN457X

Additional relevant MeSH terms:

Tendinopathy; Muscular Diseases; Musculoskeletal Diseases; Tendon Injuries; Wounds and Injuries