HypercholesterolemiaPhase 4V-DIFFERENCENCT05192941
Study of Efficacy, Safety, Tolerability and Quality of Life of Inclisiran (KJX839) vs Placebo, on Top of Ongoing Individually Optimized Lipid-lowering Therapy, in Participants With Hypercholesterolemia
A Phase 4 study testing Inclisiran Sodium in people with Hypercholesterolemia, run by Novartis Pharmaceuticals at 136 sites in 8 countries.
Trial summary
Study of efficacy, safety, tolerability and quality of life of inclisiran (KJX839) vs placebo, on top of ongoing individually optimized lipid-lowering therapy, in participants with hypercholesterolemia Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Hypercholesterolemia
- What is being tested?
- Inclisiran Sodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,770 participants
- Where
- 136 sitesin 8 countries
- Study dates
- 8 Apr 2022to 19 Mar 2025
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants eligible for inclusion in this study must meet all of the following criteria:
- Written informed consent must be obtained before any assessment is performed.
- Male or female participants ≥18 years of age.
- Participants categorized as very high or high CV risk, as defined below:
- •Very high risk participants with at least one of the following: A. Documented Atherosclerotic Cardiovascular Disease (ASCVD) i) Acute Coronary Syndrome: Unstable angina or myocardial infarction ii) Stable angina iii) Unequivocally documented ASCVD upon prior imaging v) Stroke and Transient Ischaemic Attack (TIA) vi) Peripheral Artery Disease (PAD) B. Diabetes mellitus (DM) with target organ damage (defined as microalbuminuria, retinopathy, or neuropathy), or at least ≥ 3 major risk factors, or early onset of Type 1 DM of long duration (> 20 years) C. A calculated SCORE2 ≥ 7.5% for age < 50 years; SCORE2 ≥ 10% for age 50-69 years; SCORE2-OP ≥ 15% for age ≥ 70 years to estimate 10-year risk of fatal and non-fatal CVD D. Pre-existing diagnosis of heterozygous familial hypercholesterolemia (HeFH) with ASCVD or with another major risk factor.
- OR
Show all 51Show fewer
- •High risk participants with at least one of the following: A. Markedly elevated single risk factors, in particular total cholesterol > 310 mg/dL, LDL-C > 190 mg/dL, or blood pressure ≥ 180/110 mmHg B. Pre-existing diagnosis of HeFH without other major risk factors C. DM without target organ damage (defined as microalbuminuria, retinopathy, or neuropathy), with DM duration ≥ 10 years or other additional risk factor D. Moderate chronic kidney disease (eGFR 30-59 mL/min/1.73m2) E. A calculated SCORE2 2.5 to <7.5% for age under 50 years; SCORE2 5 to <10% for age 50-69 years; SCORE2-OP 7.5 to <15% for age ≥70 years to estimate 10-year risk of fatal and non-fatal CVD as defined by the cardiovascular risk categories in the 2019 ESC/EAS guideline (Mach et al 2020)
- LDL-C levels:
- in participants with very high cardiovascular risk: serum LDL-C ≥55 mg/dL
- in participants with high cardiovascular risk: serum LDL-C ≥70 mg/dL
- Participant on a stable dose of a statin for ≥ 30 days.
- Up to approximately 20% of total participants can be on a stable dose (for ≥ 30 days prior to screening) of another LLT on top of statin such as a cholesterol absorbing inhibitor or a bile acid sequestrant, or alternatively, an adenosine triphosphate citrate lyase (ACL) inhibitor, as indicated.
- Fasting triglyceride < 400 mg/dL.
- At Baseline:
- Fasting triglyceride < 400 mg/dL.
- Before randomization, despite being treated with the individual MTD of a statin for ≥ 30 days and, if applicable, with another LLT on top of statin (stable for ≥ 30 days),
- in participants with very high cardiovascular risk: serum LDL-C ≥ 55mg/dL.
- in participants with high cardiovascular risk: serum LDL-C ≥ 70mg/dL.
- Key Exclusion Criteria: Participants meeting any of the following criteria are not eligible for inclusion in this study.
- Severe concomitant non-CV disease that is expected to reduce life expectancy to less than 2 years at screening or baseline visit.
- Participants on more than one other lipid-lowering drug on top of statin at screening visit.
- Pre-existing diagnosis of homozygous familial hypercholesterolemia at screening or baseline visit.
- Secondary hypercholesterolemia, e.g. hypothyroidism or nephrotic syndrome at screening or baseline visit.
- Previous (within 90 days of screening), current or planned treatment with a monoclonal antibody (mAb) directed towards PCSK9 (e.g. evolocumab, alirocumab) at screening or baseline visit.
- Previous exposure to inclisiran or any other non-mAb PCSK9 targeted therapy, either as an investigational or marketed drug within 2 years prior to screening or baseline visit.
- Previous, current or planned treatment with LDL-apheresis at screening or baseline visit.
- Participants with known intolerance to rosuvastatin at screening or baseline visit.
- History of hypersensitivity to any of the study treatments, inclisiran or rosuvastatin, or its excipients or to drugs of similar chemical classes at screening or baseline visit.
- Participants taking gemfibrozil at screening or baseline visit.
- Liver and CK: (a) Active liver disease defined as any current infectious, neoplastic, or metabolic pathology of the liver or (b) unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST) elevation >3x ULN, or total bilirubin elevation > 2x ULN (except for participants with Gilbert's syndrome), or (c) creatine kinase (CK) >5x ULN at screening or baseline visit.
- Participant with severe renal impairment defined by eGFR <30 mL/min/1.73m2 as calculated by the Modification in Diet in Renal Disease (MDRD) formula at screening or baseline visit.
- Acute coronary syndrome, ischemic stroke or TIA, coronary revascularization or peripheral arterial revascularization procedure or amputation due to atherosclerotic disease < 3 months prior to the screening or baseline visit.
- Planned or expected cardiac, cerebrovascular or peripheral artery surgery or coronary revascularization within the study duration.
- Heart failure New York Heart Association (NYHA) class IV at screening or baseline visit.
- History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy (excluding systemic adjuvant therapies given to prevent cancer recurrence eg: hormonotherapy for prostate or breast cancer) during the 3 years prior to screening or baseline visit.
- Participant with myopathy at screening or baseline visit.
- Participant receiving concomitant ciclosporin at screening or baseline visit.
- Participants that are predisposed to the development of renal failure secondary to rhabdomyolysis (e.g. sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders; or uncontrolled seizures).
- Participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose-malabsorption.
- Unwillingness or inability (e.g. physical or cognitive) to comply with study procedures (including study visits, fasting blood draws and compliance with study treatment regimens), and medication administration (injections) and schedule. Participant should be able and willing to read, understand and answer questionnaires.
- Any surgical or medical condition, which in the opinion of the investigator, may place the participant at higher risk from his/her participation in the study, or is likely to prevent the participant from complying with the requirements of the study or completing the study at screening or baseline visit.
- Use of other investigational drugs within 5 half-lives, 30 days or until the expected pharmacodynamic effect has returned to baseline (e.g. biologics), whichever is longer or longer if required by local regulation, prior to screening visit.
- Pregnant or nursing (lactating) women at screening or baseline visit.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment, which includes rosuvastatin, and for 5 days (= 5 times the terminal half-life of rosuvastatin) after stopping medication. Highly effective contraception methods include:
- Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. 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 bilateral 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.
- Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant.
- Use of oral, (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.
- 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.
- Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms). Women are considered not of child bearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessments and she is considered not of child bearing potential.
- If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the local ICF.
Who cannot join
None listed.
Trial locations and contacts
136 sites in 8 countries.
136 sites in 8 countries
Germany75 sites
Novartis Investigative Site
Bad Gottleuba, Saxony, 01816
Novartis Investigative Site
Bad Homburg, 61348
Novartis Investigative Site
Bad Krozingen, 79189
Novartis Investigative Site
Bad Oeynhausen, 32545
Novartis Investigative Site
Bamberg, 96049
Novartis Investigative Site
Berlin, 10367
Novartis Investigative Site
Berlin, 10559
Novartis Investigative Site
Berlin, 10787
Novartis Investigative Site
Berlin, 10789
Novartis Investigative Site
Berlin, 13347
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Bochum, 44789
Novartis Investigative Site
Bremen, 28277
Novartis Investigative Site
Coburg, 96450
Novartis Investigative Site
Cologne, North Rhine-Westphalia, 51065
Novartis Investigative Site
Cologne, 51069
Novartis Investigative Site
Dessau, 06846
Novartis Investigative Site
Dresden, Saxony, 01099
Novartis Investigative Site
Dresden, Saxony, 01307
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Duisburg, 47051
Novartis Investigative Site
Erfurt, 99089
Novartis Investigative Site
Erfurt, 99097
Novartis Investigative Site
Essen, North Rhine-Westphalia, 45355
Novartis Investigative Site
Essen, 45277
Novartis Investigative Site
Essen, 45355
Novartis Investigative Site
Essen, 45359
Novartis Investigative Site
Frankfurt am Main, Hesse, 60590
Novartis Investigative Site
Frankfurt am Main, Hesse, 60594
Novartis Investigative Site
Frankfurt am Main, Hesse, 65929
Novartis Investigative Site
Fulda, 36037
Novartis Investigative Site
Gelnhausen, 63571
Novartis Investigative Site
Gladbeck, 45968
Novartis Investigative Site
Göttingen, Lower Saxony, 37075
Novartis Investigative Site
Hamburg, 22041
Novartis Investigative Site
Hamburg, 22607
Novartis Investigative Site
Hanover, Lower Saxony, 30159
Novartis Investigative Site
Hanover, Lower Saxony, 30449
Novartis Investigative Site
Haßloch, 67454
Novartis Investigative Site
Hennigsdorf, 16761
Novartis Investigative Site
Hoyerswerda, 02977
Novartis Investigative Site
Kaiserslautern, Rhineland-Palatinate, 67655
Novartis Investigative Site
Kassel, 34121
Novartis Investigative Site
Kiel, 24105
Novartis Investigative Site
Langen, Hesse, 63225
Novartis Investigative Site
Leipzig, Saxony, 04103
Novartis Investigative Site
Lichtenfels, Bavaria, 96215
Novartis Investigative Site
Löhne, North Rhine-Westphalia, 32584
Novartis Investigative Site
Lüneburg, 21339
Novartis Investigative Site
Magdeburg, 39110
Novartis Investigative Site
Magdeburg, 39120
Novartis Investigative Site
Mainz, 55131
Novartis Investigative Site
Mannheim, Baden-Wurttemberg, 68305
Novartis Investigative Site
Mannheim, 68165
Novartis Investigative Site
Markkleeberg, 04416
Novartis Investigative Site
Muehldorf Am Inn, Bavaria, 84453
Novartis Investigative Site
Munich, Bavaria, 81377
Novartis Investigative Site
Münster, 48149
Novartis Investigative Site
Nuremberg, Bavaria, 90402
Novartis Investigative Site
Papenburg, 26871
Novartis Investigative Site
Pirna, 01796
Novartis Investigative Site
Potsdam, 14471
Novartis Investigative Site
Regensburg, Bavaria, 93053
Novartis Investigative Site
Reinfeld, 23858
Novartis Investigative Site
Rostock, 18057
Novartis Investigative Site
Rüdersdorf, 15562
Novartis Investigative Site
Saint Ingbert, Saarland, 66386
Novartis Investigative Site
Schleswig, Schleswig-Holstein, 24837
Novartis Investigative Site
Singen, 78224
Novartis Investigative Site
Stuttgart, Baden-Wurttemberg, 70376
Novartis Investigative Site
Stuttgart, 70378
Novartis Investigative Site
Wallerfing, 94574
Novartis Investigative Site
Warendorf, 48231
Novartis Investigative Site
Winsen, Lower Saxony, 21423
Novartis Investigative Site
Wuppertal, 42117
Bulgaria13 sites
Novartis Investigative Site
Burgas, Burgas, 8000
Novartis Investigative Site
Burgas, 8001
Novartis Investigative Site
Gabrovo, 5300
Novartis Investigative Site
Pleven, 5800
Novartis Investigative Site
Plovdiv, 4002
Novartis Investigative Site
Rousse, 7000
Novartis Investigative Site
Sofia, Bulgaria, 1202
Novartis Investigative Site
Sofia, 1233
Novartis Investigative Site
Sofia, 1606
Novartis Investigative Site
Sofia, 1618
Novartis Investigative Site
Stara Zagora, 6000
Novartis Investigative Site
Varna, 9010
Novartis Investigative Site
Veliko Tarnovo, 5000
Czechia10 sites
Novartis Investigative Site
Chlumec nad Cidlinou, Chlumec Nad Cidlinou, 503 51
Novartis Investigative Site
Hlučín, 748 01
Novartis Investigative Site
Hodonín, 695 01
Novartis Investigative Site
Mělník, 276 01
Novartis Investigative Site
Olomouc, 772 00
Novartis Investigative Site
Olomouc, 779 00
Novartis Investigative Site
Pardubice, 532 03
Novartis Investigative Site
Přerov, Olomouc Region, 750 02
Novartis Investigative Site
Slaný, 274 01
Novartis Investigative Site
Trutnov, 460 63
Spain10 sites
Novartis Investigative Site
Barcelona, Catalonia, 08003
Novartis Investigative Site
Barcelona, 08035
Novartis Investigative Site
Córdoba, 14004
Novartis Investigative Site
Majadahonda, Madrid, 28222
Novartis Investigative Site
Málaga, Andalusia, 29009
Novartis Investigative Site
Oviedo, Principality of Asturias, 33011
Novartis Investigative Site
San Sebastian Reyes, Madrid, 28702
Novartis Investigative Site
Sanlucar Barrameda, Cadiz, 11540
Novartis Investigative Site
Seville, Andalusia, 41014
Novartis Investigative Site
Seville, 41013
France9 sites
Novartis Investigative Site
Amiens, 80054
Novartis Investigative Site
Chambéry, 73000
Novartis Investigative Site
Le Chesnay, 78150
Novartis Investigative Site
Le Kremlin-Bicêtre, 94275
Novartis Investigative Site
Lille, 59000
Novartis Investigative Site
Marseille, 13005
Novartis Investigative Site
Nantes, 44093
Novartis Investigative Site
Paris, 75013
Novartis Investigative Site
Valenciennes, 59300
Poland9 sites
Novartis Investigative Site
Gdynia, 81-157
Novartis Investigative Site
Katowice, 40-648
Novartis Investigative Site
Krakow, Maloposkie, 31-271
Novartis Investigative Site
Krakow, 31-216
Novartis Investigative Site
Krosno, Krosno, 38-400
Novartis Investigative Site
Rzeszów, 35-055
Novartis Investigative Site
Skierniewice, 96-100
Novartis Investigative Site
Szczecin, West Pomeranian Voivodeship, 71-528
Novartis Investigative Site
Tarnów, 33-100
Latvia6 sites
Novartis Investigative Site
Daugavpils, LV-5417
Novartis Investigative Site
Ogre, 5001
Novartis Investigative Site
Riga, 1012
Novartis Investigative Site
Riga, LV 1002
Novartis Investigative Site
Riga, LV-1001
Novartis Investigative Site
Riga, LV-1012
Estonia4 sites
Novartis Investigative Site
Pärnu, 80018
Novartis Investigative Site
Tallinn, 10138
Novartis Investigative Site
Tallinn, 13419
Novartis Investigative Site
Tartu, 50406
About this study
Official title: Efficacy, Safety, Tolerability and Quality of Life of Ongoing Individually Optimized Lipid-lowering Therapy With or Without Inclisiran (KJX839) - a Randomized, Placebo-controlled, Double-blind Multicenter Phase IV Study in Participants With Hypercholesterolemia
Study of efficacy, safety, tolerability and quality of life of inclisiran (KJX839) vs placebo, on top of ongoing individually optimized lipid-lowering therapy, in participants with hypercholesterolemia
Read the detailed description
This was a double-blind, placebo-controlled multicenter study in adult participants with very high or high cardiovascular risk who did not meet their individual LDL-C target despite being treated with their individual maximum tolerated dose (MTD) of a statin, and if applicable, further Lipid-Lowering Therapy (LLT).
The purpose of this study was to demonstrate the superiority of inclisiran compared to placebo, both on top of ongoing individually optimized LLT, on reaching a participant's LDL-C target (< 55 mg/dL or < 70 mg/dL, depending on the cardiovascular risk category), according to the 2019 ESC/EAS guidelines for the management of dyslipidemias as well as on patient-relevant safety, tolerability outcomes and quality of life.
- Conditions
- Hypercholesterolemia
- Being tested
- Inclisiran Sodium, Placebo
- Keywords
- Inclisiran, rosuvastatin, PCSK9, dyslipidemia, angina pectoris, peripheral artery disease, cardiovascular disease, LDL-C
- Medical subject headings
- Hypercholesterolemia, Dyslipidemias, Angina Pectoris, Peripheral Arterial Disease, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inclisiran SodiumDrug
Also called KJX839
Subcutaneously injected on Day 1, Day 90, and Day 270
PlaceboDrug
Placebo to inclisiran 300 mg subcutaneously
| Study group | Role | What they receive |
|---|---|---|
| Inclisiran | Experimental | Inclisiran sodium 300 mg s.c. + open label rosuvastatin Open label study treatment rosuvastatin: participants receive an individually optimized rosuvastatin therapy for reaching the individual LDL-C target and tolerability Receives: Drug: Inclisiran Sodium |
| Placebo | Placebo comparator | Corresponding placebo + open label rosuvastatin Open label study treatment rosuvastatin: participants receive an individually optimized rosuvastatin therapy for reaching the individual LDL-C target and tolerability Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Achieving Individual LDL-C Target (<55 mg/dL or <70 mg/dL)
Number of participants achieving individual Low-density Lipoprotein Cholesterol (LDL-C) target (< 55 mg/dL or < 70 mg/dL) at Day 90. The individual LDL-C target of the participants was determined according to their most recent individual cardiovascular risk category. A larger proportion of participants indicates a superior outcome.
Measured: Day 90
Secondary outcomes (8)
Relative Change From Baseline to Mean LDL-C Level Over the Double-blind Treatment Period
Relative (percentage) change from baseline in Low-density Lipoprotein Cholesterol (LDL-C) level averaged over the double-blind treatment period
Measured: Baseline to Day 360
Number of Participants Experiencing at Least One Muscle-related Adverse Event From Day 1 to Day 360
The number of participants who experienced at least one muscle-related adverse event, defined as Standardized MedDRA Queries (SMQ) rhabdomyolysis / myopathy from Day 1 to Day 360. All muscle-related adverse events occurring between first dose of double-blind treatment and earliest date out of visit Day 360, death date and last contact date are considered.
Measured: Day 1 to Day 360
Number of Participants Experiencing Self-reported Pain
Self-reported pain is reported at its worst in the last 24 h on a numeric rating scale from 0 (no pain) to 10 (pain as bad as you can imagine). Days with a score of 0 are considered as days without pain.
The percentage of days with pain for each participant is calculated as number of days with pain divided by the total number of days where diary was completed, multiplied by 100.
Diary data between the first dose of double-blind treatment up to the minimum of last contact date and Day 360 visit are considered.
Measured: Day 1 to Day 360
Annualized Number of Days With Pain
Annualized rate refers to the estimated number of days with pain per year.
Self-reported pain is reported at its worst in the last 24 h on a numeric rating scale from 0 (no pain) to 10 (pain as bad as you can imagine). Days with a score of 0 are considered as days without pain.
Measured: Day 1 to Day 360
Average Absolute Change From Baseline in Short-Form Brief Pain Inventory (SF-BPI) Pain Severity Score Over the Double-blind Treatment Period
The Short-Form Brief Pain Inventory (SF-BPI) is a self-administered standardized fifteen items questionnaire that assesses how pain interferes with or influences a participant's life. The query period covers the past 24 hours and takes 5 minutes for the participant to complete.
The pain severity score was derived for each visit between screening and EOT/EOS (Day 360) as the average over the 4 items in the pain severity domain (questionnaire items number 3, 4, 5, 6). The derived pain severity score ranged between 0 (no pain) and 10 (pain as bad as you can imagine), with larger values indicating a higher level of pain severity (worse outcome).
If there was missing data for a participant and the available data was more than 50% for the corresponding domain (3 of 4 [pain severity] ), the missing items were imputed using the mean score of the non-missing item scores.
Measured: Baseline to Day 360
Average Absolute Change From Baseline in Short-Form Brief Pain Inventory (SF-BPI) Pain Interference Score Over the Double-blind Treatment Period
The Short-Form Brief Pain Inventory (SF-BPI) is a self-administered standardized fifteen items questionnaire that assesses how pain interferes with or influences a participant's life. The query period covers the past 24 hours and takes 5 minutes for the participant to complete.
The pain interference score was derived for each visit between screening and EOT/EOS (Day 360) as the average over the 7 items in the pain interference domain (questionnaire items number 9A through 9G). The derived pain interference score ranged between 0 (does not interfere) and 10 (completely interferes), with larger values indicating a higher level of pain interference (worse outcome).
If there was missing data for a participant and the available data was more than 50% for the corresponding domain (4 of 7 [pain interference] ), the missing items were imputed using the mean score of the non-missing item scores.
Measured: Baseline to Day 360
Number of Participants With Clinically Relevant Change in Short-Form Brief Pain Inventory (SF-BPI) Pain Severity Score From Baseline to Day 360.
The Short-Form Brief Pain Inventory (SF-BPI) is a self-administered standardized fifteen items questionnaire that assesses how pain interferes with or influences a participant's life. The query period covers the past 24 hours and takes 5 minutes for the participant to complete.
The pain severity score was derived for each visit between screening and EOT/EOS (Day 360) as the average over the 4 items in the pain severity domain (questionnaire items number 3, 4, 5, 6). The derived pain severity score ranged between 0 (no pain) and 10 (pain as bad as you can imagine), with larger values indicating a higher level of pain severity (worse outcome). A clinically relevant change is defined by a reduction from baseline in SF-BPI pain severity score by at least 2 points.
If there was missing data for a participant and the available data was more than 50% for the corresponding domain (3 of 4 [pain severity] ), the missing items were imputed using the mean score of the non-missing item scores.
Measured: Baseline to Day 360
Number of Participants With Clinically Relevant Change in Short-Form Brief Pain Inventory (SF-BPI) Pain Interference Score From Baseline to Day 360
The SF-BPI is a self-administered standardized fifteen items questionnaire that assesses how pain interferes with or influences a participant's life. The query period covers the past 24 hours and takes 5 minutes for the participant to complete.
The pain interference score was derived for each visit between screening and EOT/EOS (Day 360) as the average over the 7 items in the pain interference domain (questionnaire items number 9A through 9G). The derived pain interference score ranged between 0 (does not interfere) and 10 (completely interferes), with larger values indicating a higher level of pain interference (worse outcome). A clinically relevant change is defined by a reduction from baseline in SF-BPI pain interference score by at least 2 points.
If there was missing data for a participant and the available data was more than 50% for the corresponding domain (4 of 7 [pain interference] ), the missing items were imputed using the mean score of the non-missing item scores.
Measured: Baseline to Day 360
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2022
- Study start8 Apr 2022
- Primary completion11 Jun 2024
- Study completion19 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind investigational treatment inclisiran/placebo: subcutaneous injections of inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) or placebo, in 1.5 mL solution. Open label study treatment rosuvastatin: all participants received rosuvastatin, starting at the lowest indicated dose and titrating up until they reach their individual LDL-C target or MTD (Maximum tolerated dose) of statin, whichever occurs first.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,770 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05192941
- Sponsor's protocol ID
- CKJX839A12402
- Other IDs
- 2024-511263-28
- Acronym
- V-DIFFERENCE
- Status last verified
- Mar 2026
- First submitted
- 13 Dec 2021
- Last updated
- 14 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Landmesser U, Laufs U, Schatz U, Winzer EB, Nowak B, Kassner U, Gouni-Berthold I, Esteban A, Lubyayi L, Krueger A, Streich JH, Hentschke C, Achouba A, Banach M. Design and rationale of the VICTORION-Difference study: A phase 4 randomized, double-blind, placebo-controlled clinical trial to assess inclisiran's early efficacy, safety, tolerability, as well as its impact on quality of life in individuals with hypercholesterolemia. Am Heart J. 2025 Nov;289:117-126. doi: 10.1016/j.ahj.2025.05.014. Epub 2025 May 26.
PubMed 40436308