i

A multicenter, double-blind, randomized withdrawal extension study of subcutaneous secukinumab to demonstrate long-term efficacy, safety and tolerability in subjects with moderate to severe hidradenitis suppurativa

PHRR201110-003133

CAIN457M2301E1

2020-CT0547

A multicenter, double-blind, randomized withdrawal extension study of subcutaneous secukinumab to demonstrate long-term efficacy, safety and tolerability in subjects with moderate to severe hidradenitis suppurativa

This is a multicenter extension study to both core Phase III studies CAIN457M2301 and CAIN457M2302 (Core studies). This study contains a randomized withdrawal design, double blinded and placebo controlled up to Week 104 or loss of response. The subjects with HiSCR response after 52 weeks of treatment in the “Core studies” will be randomized at 2:1 ratio to either continue on one of the two secukinumab dosing regimens assigned in “Core studies” for another 52 weeks or will be placed on placebo.  The primary endpoint is loss of response (LOR) assessed during the 52-week treatment duration (up to Week 104). Subjects who attained LOR will be transferred to open-label treatment to continue until the end of the study. Subjects on placebo who did not reach LOR up to Week 104 will be offered to continue in the open-label treatment or discontinue the study. Thus for subjects who were HiSCR responders at Week 52 of “Core studies”, the open label treatment duration will vary and start either from the time of LOR or from Week 104 dose and last until Week 260 followed by 8 weeks of a post treatment follow-up period to week 268.

Subjects who were HiSCR non-responders at the end of “Core studies” will be offered to continue in open-label treatment until Week 260. 

Subjects who prematurely discontinue the study, or who complete the study will enter a post-treatment follow up period (8 weeks).

Start Date Duration in Months Target Completion Date Actual Completion Date
2021-01-29 64 2026-05-29 0000-00-00

Ongoing

Institution Classification Region LTO #
Novartis Healthcare Philippines, Inc. Private Business NCR LTO-3000006283930
Institution Region
Novartis Pharma Services AG Switzerland
Name E-Mail Institution and Institution Address
Anna Liza Calingasin anna_liza.calingasin@novartis.com Novartis Healthcare Philippines, Inc. 5th Floor, Ayala North Exchange Tower 1, Ayala Avenue corner Amorsolo Street, Legazpi Village, Makati City 1229
Name E-Mail Institution and Institution Address
Ivy Emily Peneyro-Vergara, MD ivy_emily.peneyrovergara@ novartis.com Novartis Healthcare Philippines, Inc. 5th Floor, Ayala North Exchange Tower 1, Ayala Avenue corner Amorsolo Street, Legazpi Village, Makati City 1229
Name Expertise Affiliation
Jenifer R. Otadoy-Agustin, MD Allergy, Asthma and Immunology University of Perpetual Help DALTA Medical Center
Lily Lyralin Laconico Tumalad, MD Dermatology East Avenue Medical Center
Vermen Verallo-Rowell, MD Dermatology VMV Skin Research Centre + Clinics
Project Location Institutional Ethics Review Board
University of Perpetual Help DALTA Medical Center University of Perpetual Help DALTA Medical Center Ethics Review Committee
East Avenue Medical Center East Avenue Medical Center (Ethics Review Committee)
VMV Skin Research Centre + Clinics VMV Skin Research Centre + Clinics - Institutional Review Board

moderate to severe hidradenitis suppurativa

Time to loss of response up to Week 104 (Randomized Withdrawal period) in subjects who were Hidradenitis Suppurativa Clinical Response (HiSCR) responders at Week 52 in the core studies.

HiSCR response is defined as at least 50% decrease in Abscess and inflammatory Nodule (AN) number with no increase in the number of abscesses and in the number of draining fistulae.

Loss of response is defined as:

  • at least a 50% or greater increase in AN (abscess and/or nodules) at a regular or unscheduled visit compared to the average AN count from 3 previous visits or the Week 52 whichever is lower and the increase is at least of 3 AN .
  • If at a regular or unscheduled visit, the subject experiences at least a 30% increase in AN compared to the average AN count from the 3 previous visits or the Week 52 visit whichever is lower with an increase of at least 2 AN, the subject should be reassessed within 2-4 weeks. A further increase in the AN count of at least 2 AN would be considered a LOR also.

Note: If the 3 previous visits include visits from core studies, the AN count from the core study will be included in the average.

Secondary Outcomes:

  • Adverse events, laboratory values, vital signs

Exploratory Outcomes

  • Time to regain Hidradenitis Suppurativa Clinical Response (HiSCR) response following loss of response
  • HiSCR, flare, Numerical Rating Scale (NRS30) after up-titration

All endpoints will be evaluated by visit up to the end of the study:

  • HiSCR response over time.
  • Cumulative rate of subjects who experience a flare. Flare is defined as at least a 25% increase in AN counts with a minimum increase of 2 AN relative to baseline
  • NRS30 response. NRS30 is defined as at least a 30% reduction from baseline in Subject's Global Assessment of Skin Pain - at worst
  • AN50, AN75 and AN100 defined as achievement of at least 50%, 75% and 100% reductions in the AN count relative to Baseline (AN50, AN75, AN100) as well as absolute and percent change from baseline in AN counts/draining fistulas/non-draining fistulas
  • Absolute and percent change from baseline in modified Hidradenitis Suppurativa Score (mHSS)
  • Absolute and percentage change in the iSH4 score compared to baseline.
  • Hidradenitis Suppurativa Physician's Global Assessment (HS-PGA) response, defined as the achievement of at least a 2-point reduction in HS-PGA score at each visit compared to baseline
  • Dermatology Life Quality Index (DLQI) response and absolute and relative change of DLQI total score compared to baseline. DLQI response is defined as a decrease greater than 5.0 points from baseline
  • PGA-SP response. Proportion of subjects who attained a >  30%, > 40%, or > 50% reduction and > 1 unit reduction from PGA-SP score at Week 52
  • HS Symptom Diary items score change from core Baseline
  • EQ-5D-3L Categories on category questions and summary statistics on EQ-5D-3L score questions
  • Subject Global Impression of severity (PGI-s)
  • Subject Global Impression and change (PGI-c)
  • Absolute and percent change from baseline in Work Productivity and Activity Impairment Specific Health Problem (WPAI-SHP)
  • AIN457 levels in serum collected at the LOR visit
  • Biomarkers in serum at LOR visits

Recruiting

  • Argentina
  • Australia
  • Austria
  • Belgium
  • Bulgaria
  • Canada
  • Colombia
  • Croatia
  • Czech Republic
  • Denmark
  • France
  • Germany
  • Greece
  • Guatemala
  • Hungary
  • India
  • Israel
  • Italy
  • Japan
  • Lebanon
  • Lithuania
  • Malaysia
  • Mexico
  • Netherlands
  • Philippines
  • Poland
  • Portugal
  • Russia
  • Singapore
  • South Africa
  • South Korea
  • Spain
  • Sweden
  • Switzerland
  • Taiwan
  • Turkey
  • United Kingdom
  • United States
  • Vietnam

Clinical Trial

CAIN457M2301E1

CTA-2020-14-09-38

2020-09-15

0000-00-00

12

Unspecified

Unspecified

2021-01-29

Subjects eligible for inclusion in this study must meet all of the following criteria:

  1. Written informed consent must be obtained before any assessment is performed.
  2. Subjects who complete the whole study treatment period (52 weeks) in the core studies (CAIN457M2301 or CAIN457M2302) and have received secukinumab treatment during the Treatment Period 2 of the core studies.

Subjects meeting any of the following criteria are not eligible for inclusion in this study.

  1. A protocol deviation in the core study which, according to the investigator will prevent the meaningful analysis of the extension study for the individual subject.
  2. Ongoing or planned use of prohibited HS or non-HS treatments. Time of use of prohibited treatments in the core study must continue to be adhered to (see Table 6-2).
  3. Subjects not expected to benefit from participation in the extension study, as assessed by the subject and investigator.
  4. Subjects whose participation in the extension study could expose them to an undue safety risk. 
  5. Current severe progressive or uncontrolled disease which in the judgment of the investigator renders the subject unsuitable for the study.
  6. Plans for administration of live vaccines during the study.
  7. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using methods of contraception during the entire study or longer if required by locally approved prescribing information (e.g. in European Union (EU) 20 weeks). Contraception methods include:
  • Total abstinence, when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • Female sterilization (have had surgical bilateral oophorectomy [with or without hysterectomy], total hysterectomy or tubal ligation at least six weeks before taking study treatment). In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
  • Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). For United Kingdom: with spermicidal foam/gel/film/cream/vaginal suppository.
  • Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS).

In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

In case local regulations deviate from the contraception methods listed above, local regulations apply and will be described in the informed consent form (ICF).

Note: Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks prior to enrollment. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of childbearing potential.

 

Interventional

Secukinumab

Investigational/ Control Drug

(Name and Strength)

Pharmaceutical Dosage Form

Route of Administration

Supply Type

Secukinumab 300 mg

Solution for injection

Subcutaneous use

Double blinded subject packs; 2 ml pre-filled syringe

Secukinumab 300 mg

Solution for injection

Subcutaneous use

Open label subject packs

2 ml pre-filled syringe

None

Randomized

Double Blind

This study will include a blinded and open-label part. The blinded part will include a placebo controlled period lasting up to 52 weeks (between Week 52 and Week 104) to provide data for randomized withdrawal analysis. The primary endpoint (PE) will be assessed at the Week 104 visit (End of Treatment (EOT) -1). The duration of the randomized withdrawal period for each subject will be determined by the timepoint at which a subject has a loss of clinical response (LOR). After LOR has been attained, the subject will receive open label treatment with secukinumab and continue in the study for the maximum duration of 260 weeks of treatment plus 8 weeks of the post-treatment follow-up period in total or, until secukinumab is commercially available for a given trial participant. Starting from the time of LOR or Week 104 subjects will enter the open label part for an additional three years. The total duration of the extension study is estimated to last about four years providing up to approximately five years of total treatment exposure including the core study. For this protocol, years refers to the number of extension years (not core + extension) unless otherwise specified.

Single

The purpose of this extension study is to evaluate maintenance of response in either continuous or interrupted therapy (using a randomized withdrawal period) and to assess long-term efficacy, safety and tolerability of secukinumab in subjects with moderate to severe hidradenitis suppurativa (HS) completing either of the two Phase III studies, CAIN457M2301 or CAIN457M2302; both 52 weeks in duration. Primary endpoint analysis (PEA) of the extension study will be conducted on data collected at Week 104.

The data collected beyond Week 104 will deliver important information on the effect of long-term treatment of hidradenitis suppurativa with secukinumab. Additional analyses may be conducted at various time points for publications or Health Authorities interactions. Primary endpoint analysis at the end of the double-blind randomized withdrawal period will allow assessment of whether continuation of treatment with secukinumab brings benefit to subjects who already have been treated for one year in the preceding core studies in comparison to pausing the study treatment after clinical effect was achieved. In addition, data from the randomized withdrawal period will deliver important information on the effect of stopping treatment on sustainability of clinical response. This analysis will include evaluation of time to loss of response, number of flares and the effect of restarting the therapy on regaining HiSCR.  Furthermore, this study will address the question of whether an increase in dose is effective in regaining and sustaining clinical response and a favorable risk-benefit ratio. The overall objective of the study is to determine efficacious and safe treatment strategies for long-term treatment of subjects suffering from this chronic disease.

The study will also offer subjects who completed treatment in the core studies an opportunity to have long-term access to HS therapy with secukinumab.

Phase III

Utilization Utilization Info
No records found.
©2021 HERDIN PLUS. All rights reserved. | Contact Us | Keep up to date