Clinical trial NCT03168256: CF101 Therapy in Patients With Moderate-to-severe Plaque Psoriasis
Official title: A Phase 3 Randomized, Double-Blind, Placebo- and Active-Controlled Study of the Efficacy and Safety of Daily CF101 Administered Orally in Patients With Moderate-to-Severe Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Plaque Psoriasis
Lead sponsor: Can-Fite BioPharma
Sponsor class: INDUSTRY
First posted: 2017-05-30
Enrollment: 528
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial will test the hypothesis that the administration of CF101, a novel anti-inflammatory agent, to patients with moderate to severe plaque psoriasis will relieve signs and symptoms of the disease. CF101 effect will be in comparison to apremilast in this study population

Detailed description: This is a multicenter, randomized, double-blind, placebo- and active-controlled, study in adult males and females, aged 18 to 80 years, inclusive, with a diagnosis of moderate-to-severe chronic plaque psoriasis.

Eligible subjects will be randomly assigned to CF101 2 mg, 3 mg, matching apremilast 30 mg BID, or matching placebo, in a 3:3:3:2 ratio. Blinding will be maintained using a double-dummy technique.

Medication will be taken orally BID for 32 weeks in a double-blinded fashion, with the option to continue treatment through an Extension Period to 48 weeks. Subjects initially assigned to the placebo group will be re-randomized at Week 16 to either CF101 2 mg, CF101 3 mg, or apremilast (with appropriate dose titration) in a 1:1:1 ratio and treated through Week 32, while subjects originally assigned to 1 of the active treatment groups will remain on that treatment through Week 32. The primary efficacy endpoint will be assessed at Weeks 16 and 32; at Week 32, all subjects will be offered the opportunity to remain on their assigned blinded drug through Week 48 (ie, the Extension Period of Weeks 33-48).

Disease will be assessed using PASI , static PGA , the percentage of BSA involved, and PDI. Subjects will return for assessments and a new supply of study medication at Weeks 4, 8, 12, 16, 20, 24, and 28, and for final study assessments at Week 32. For those subjects continuing into the Extension Period, efficacy and safety assessments will also occur at Weeks 36, 40, 44, and 48. PK will be assessed in a subgroup of approximately 120 subjects at Weeks 0, 8, 16, 24 and 32. PK will be assessed through sparse sampling. Assessment of whole blood A3AR expression levels will occur at Screening, Week 16, and Week 32.

Eligibility criteria: Inclusion Criteria:

1. Male or female, 18 to 80 years of age, inclusive;
2. Diagnosis of moderate-to-severe chronic plaque-type psoriasis with BSA involvement ≥10%, as judged by the Investigator;
3. PASI score ≥12 (Appendix 3)
4. Static PGA ≥3 (Appendix 2)
5. Candidate for systemic treatment or phototherapy for psoriasis;
6. Duration of psoriasis of at least 6 months;
7. Elevated whole blood A3AR expression level, defined as ≥ 1.5-fold over a predetermined normal population standard at Screening;
8. Females of child-bearing potential must have a negative serum pregnancy test at screening;
9. Females of child-bearing potential must be willing to use 2 methods of contraception deemed adequate by the Investigator (for example, oral contraceptive pills plus a barrier method) to be eligible for, and continue participation in, the study;
10. Ability to complete the study in compliance with the protocol; and
11. Ability to understand and provide written informed consent.

Exclusion Criteria:

1. Psoriasis limited to erythrodermic, guttate, palmar, plantar, or generalized pustular psoriasis in the absence of plaque psoriasis;
2. Prior treatment with apremilast within 4 weeks prior to the Baseline visit, or contraindication to apremilast;
3. Treatment with systemic retinoids, corticosteroids, tofacitinib, or immunosuppressive agents (e.g., methotrexate, cyclosporine) within 4 weeks of the Baseline visit;
4. Treatment with a biological agent (etanercept, adalimumab, efalizumab, infliximab, ustekinumab, alefacept, secukinumab, or others, including investigational agents) within a period of time equal to 5 times its circulating half-life, or 30 days, whichever is longer, prior to the Baseline visit;
5. Treatment with high potency topical dermatological corticosteroids (Class I-III in US, Class III-IV in Europe), Vitamin D analogs, keratolytics, or coal tar (other than on the scalp, palms, groin, and/or soles) within 2 weeks of the Baseline visit;
6. Ultraviolet or Dead Sea therapy within 4 weeks of the Baseline visit, or anticipated need for either of these therapies during the study period;
7. Treatment with lithium, hydroxychloroquine or chloroquine within 2 weeks of the Baseline visit, or anticipated need for such drugs during the study period, unless dose has been stable for 3 months prior to the Screening visit and will remain stable throughout the trial;
8. Serum creatinine level greater than 1.5 times the laboratory's upper limit of normal at Screening;
9. Liver aminotransferase levels greater than 1.5 times the laboratory's upper limit of normal at Screening;
10. Electrocardiogram (ECG) at Screening shows abnormalities which, in the judgment of the Investigator, are clinically significant and could, in the judgment of the Principal Investigator, compromise subject safety;
11. Active gastrointestinal disease which could interfere with the absorption of oral medication;
12. Pregnancy, planned pregnancy, lactation, or inadequate contraception as judged by the Investigator;
13. Active drug or alcohol dependence;
14. History of depression or suicidal ideation within the past year;
15. Concomitant use of strong cytochrome P450 inducers, eg, rifampin, phenobarbital, phenytoin, carbamazepine;
16. Previous participation in a CF101 clinical trial;
17. Significant acute or chronic medical or psychiatric illness that, in the judgment of the Investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study;
18. Participation in another investigational drug or vaccine trial concurrently or within 30 days prior to the Screening visit.

Primary outcomes:
measure: Psoriasis Area and Severity Index (PASI) score response of ≥75% (PASI 75) at Week 16
timeFrame: 16 weeks
measure: Adverse event profile in this patient popluation
timeFrame: 16 weeks
Secondary outcomes:
measure: Psoriasis Area and Severity Index (PASI) score response of ≥50% (PASI 50) at Week 16
timeFrame: 16 weeks
measure: Physician Global Assessment (PGA)
timeFrame: 16 weeks
measure: Psoriasis Disability Index (PDI)
timeFrame: 16 weeks
measure: CF101 PASI 75 compare to apremilast
timeFrame: weeks 16-32
measure: CF101 PGA score compare to apremilast
timeFrame: weeks 16-32
measure: CF101 PASI 50 compare to apremilast
timeFrame: weeks 16-32
measure: CF101 PDI improvement compare to apremilast
timeFrame: weeks 16-32
measure: Apremilast PASI 75 compare to placebo
timeFrame: weeks 16-32
measure: Apremilast PGA compare to placebo
timeFrame: weeks 16-32
measure: Apremilast PASI 50 compare to placebo
timeFrame: weeks 16-32
measure: Apremilast PDI compare to placebo
timeFrame: 16 weeks
measure: Adverse event profile of piclidenoson through the Extension Period of up to 48 weeks of treatment
timeFrame: 48 weeks
measure: Efficacy of piclidenoson, as determined by changes in PASI score, through the Extension Period of up to 48 weeks of treatment
timeFrame: 48 weeks
measure: Determine pharmacokinetics (PK) of piclidenoson under the circumstances of this trial using sparse sampling
timeFrame: 48 weeks
measure: Evaluate the relationship between pre-treatment whole blood A3 adenosine receptor (A3AR) expression levels and response to piclidenoson treatment.
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Banja Luka
country: Bosnia and Herzegovina
facility: Clinical Centre of Republika Srpska
city: Mostar
country: Bosnia and Herzegovina
facility: University Clinical Centre Mostar
city: Sarajevo
country: Bosnia and Herzegovina
facility: Clinical Centre of Sarajevo University
city: Pazardzhik
country: Bulgaria
facility: "Multiprofile Hospital for Active Treatment - Pazardzhik"
city: Pernik
country: Bulgaria
facility: "MHAT"Rahila Angelova"AD, Department of Skin and Venereal Diseases
city: Pleven
country: Bulgaria
facility: "University Multiprofile Hospital for Active Treatment - D-r Georgi Stranski" - EAD, Pleven, Clinic of Skin and Venereal Diseases
city: Sofia
country: Bulgaria
facility: "Diagnostic-Consultative Aleksandrovska" EOOD
city: Sofia
country: Bulgaria
facility: "Diagnostic-Consultative Centre XX - Sofia" EOOD
city: Sofia
country: Bulgaria
facility: Ambulatory for Specialized Medical Help - Group Practice Dermatology - Clinic EuroDerma" OOD
city: Waterloo
country: Canada
facility: K. Papp Clinical Research
city: Rijeka
country: Croatia
facility: Clinical Hospital Center Rijeka
city: Zagreb
country: Croatia
facility: Sestre milosrdnice University Hospital Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Chisinau
country: Moldova, Republic of
facility: Institutul de Cardiologie
city: Chisinau
country: Moldova, Republic of
facility: Spitalul Clinic Municipal Nr. 3 "Sfanta Treime"
city: Chisinau
country: Moldova, Republic of
facility: Spitalul Clinic Republican
city: Bochnia
country: Poland
facility: Centrum Usług Medycznych MaxMed
city: Gdańsk
country: Poland
facility: Gdańskim Centrum Zdrowia
city: Olsztyn
country: Poland
facility: Miejski Szpital Zespolony Klinika Dermatologii Chorób Przenoszonych Drogą Płciową i Immunologii klinicznej
city: Zamość
country: Poland
facility: ETG Zamość, ul. Szczebrzeska 11i
city: Łódź
country: Poland
facility: All-MED Centrum Medyczne
city: Świdnik
country: Poland
facility: Lubelskie Centrum Diagnostyczne
city: Braşov
country: Romania
facility: Centrul Medical de Diagnostic si Tratament Ambulator Neomed SRL
city: Oradea
country: Romania
facility: SC PELICAN Impex SRL
city: Sibiu
country: Romania
facility: Spitalul Clinic Județean de Urgență Sibiu
city: Belgrade
country: Serbia
facility: Clinical Centre of Serbia
city: Niš
country: Serbia
facility: Clinical Centre Nis
city: Niš
country: Serbia
facility: Military Hospital Nis
city: Sremska Mitrovica
country: Serbia
facility: General Hospital Sremska Mitrovica
city: Zaječar
country: Serbia
facility: General Hospital Zajecar
Study officials:
affiliation: Rabin Medical Center
name: Michael David, MD
role: PRINCIPAL_INVESTIGATOR
References: