Psoriasis
Conditions
Keywords
CBP-0276, Randomized trial phase 2, Psoriasis
Brief summary
Randomized, controlled trial, Proof of Concept, Phase 2 aimed to evaluate the effect of CBP-0276 in dose of 200mg twice dose a day, or placebo administrated for 36 weeks to improve Psoriasis Area and Severity Index (PASI)75 or static Physician's Global Assessment (sPGA) score of 0 or 1; PASI50, PASI90, PASI100, Scalp-specific Physician's Global Assessment (Ss-PGA) 0/1 with at least a 2-point improvement among patients with a baseline ss-PGA ≥3, sPGA 0, PSSD symptom score of 0 among patients with baseline score ≥1, Dermatology Life Quality Index (DLQI) 0/1 at Week 6,12,18,24, 30 and 36 among patients with baseline DLQI ≥2, adjusted by transcriptomics profile (post-hoc analysis), Percentage of subjects which achieve The Minimum Clinically Important Difference (MCID) on DLQI (a ≥4-point reduction from baseline) at Week 4 and 8, Frequency of solicited and unsolicited adverse events (SAEs and USAEs) (Medra), and Changes on inflammatory and anti-inflammatory cytokine levels during treatment (IL-17, IL-23, IL-6, TNF-alpha, IL1-b, IL-10).
Detailed description
Safety and Efficacy of CBP-0276 in dose of 200mg/ twice dose a day, or placebo administrated for 36 weeks, to improve severity and quality of life on moderate to severe psoriasis in subjects 18y to 70y: Randomized, double blind, phase 2, Proof of Concept, placebo controlled clinical trial. Primary Aim: To assess the effect over 18 weeks of oral CBP-0276(Dose 200mg/day twice dose a day), or placebo on Psoriasis Area and Severity Index (PASI)75; Secondary Aims: To assess the effect over 6,12,18,24, 30 and 36 weeks of oral CBP-0276 (Dose 200mg/day twice dose a day), or placebo on static Physician's Global Assessment (sPGA) score of 0 or 1, PASI50, PASI90, PASI100, Scalp-specific Physician's Global Assessment (Ss-PGA) 0/1 with at least a 2-point improvement among patients with a baseline ss-PGA ≥3, sPGA 0, PSSD symptom score of 0 among patients with baseline score ≥1, Dermatology Life Quality Index (DLQI) 0/1 among patients with baseline DLQI ≥2, Percentage of subjects which achieve The Minimum Clinically Important Difference (MCID) on DLQI (a ≥4-point reduction from baseline), Frequency of solicited and unsolicited adverse events (SAEs and USAEs) (Medra), and Changes on inflammatory and anti-inflammatory cytokine levels during treatment (IL-17, IL-23, IL-6, TNF-alpha, IL1-b, IL-10). Adults 18 years to 70y of age with moderate to severe plaque psoriasis who fulfill the inclusion criteria will be included in the study. Patients with a history of prior therapy, including biologic therapy, could be included after specified washout periods before randomization. Subjects will be included in 2 different groups: Group 1 to receive 200mg oral twice dose a day of CBP-0276 for 36weeks and Group 2 to receive Placebo for CBP-0276 for 36weeks. Throughout the trial, patients, investigators, and sponsors providing oversight remained blinded to treatment assignments. The collection of nonserious AEs will start at initiation of study treatment until the final study visit. All SAEs will be collected from the date of the patient's written consent until 30 days after the final dose of the study drug or patient's participation in the study if the last scheduled visit occurred at a later time. The AEs of interest will include malignancies, infections (serious, opportunistic, fungal, tuberculosis, and herpes zoster), thromboembolic (arterial and venous) events, major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, and stroke), and skin events (acne and folliculitis). Solicited AEs will include select infection AEs, certain cardiovascular events, and suicidal ideation and behavior. All AEs will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA, version 28.0).
Interventions
DRUGCBP-0276 200mg BID
CBP-0276 200mg twice a day, orally for 30 weeks
Placebo for CBP-0276 twice a day, orally for 30 weeks
Sponsors
Clarent Biopharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The participant, study operating staff, members of the Safety Monitoring Committee, and Sponsor will remain blind to the assigned treatment. To ensure such masking, a non-blind pharmacist delegated by the Principal Investigator will be responsible for dispensing the investigational product. The Sponsor and the research center will have two blind/non-blind teams. Investigational products will have the same pharmaceutical form and will be dispensed in containers/dosers previously identified with the ID number that corresponds to each subject prior to administration. The containers will be made of plastic and identical for both products under investigation and labeled with the following information: protocol number, ID number, date and time of administration. The analysts' blindness will remain with respect to the randomization scheme.
Intervention model description
Subjects will be included in 2 different parallel groups: * Group 1 to receive 200mg twice dose a day of CBP-0276 for 36weeks * Group 2 to receive Placebo for CBP-0276 for 36weeks
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Signed written informed consent a. Patients must be willing to participate in the study and sign the informed consent form 2. Type of patient and target disease characteristics 1. Men and women, diagnosed with stable plaque psoriasis for 6 months or more. Stable psoriasis is defined as no morphology changes or significant flares of disease activity, in the opinion of the investigator 2. Deemed by the investigator to be a candidate for systemic therapy 3. ≥10% of body surface area (BSA) involvement at screening visit and Day 1 4. Psoriasis Area and Severity Index (PASI) score ≥12, and static Physician's Global Assessment (sPGA) ≥3 at screening visit and Day 1 3. Age and reproductive status 1. Men and women aged 18 years to 70 years at the time of screening visit 2. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening visit, and a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin within 24 hours prior to the start of study drug 3. Women must not be pregnant, lactating, breastfeeding, or planning pregnancy during the study period 4. Women of childbearing potential must agree to correctly use a highly effective method(s) of contraception for the duration of treatment plus 30 days (duration of ovulatory cycle) for a total of 33 days post-treatment completion (total of 33 days after last dose of study drug). WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements, but must still undergo pregnancy testing as described in this protocol 5. Male patients who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) plus 5 half-lives of the study treatment (3 days) for a total of 3 days post-treatment completion. Additionally, male patients must be willing to refrain from sperm donation during this time 6. Investigators shall counsel WOCBP, and male patients who are sexually active with WOCBP, on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly effective methods of contraception, which have a failure rate of \<1% when used consistently and correctly.
Exclusion criteria
1. Use of phototherapy 4 weeks or less prior randomization 2. Infectious/immune-related exclusions 1. History or evidence of outpatient active infection and/or febrile illness within 7 days prior to Day 1 2. History of serious bacterial, fungal, or viral infection requiring hospitalization and intravenous antimicrobial treatment within 60 days prior to Day 1 3. Any untreated bacterial infection within 60 days prior to Day 1 4. Any ongoing evidence of chronic bacterial infection (eg, chronic pyelonephritis, chronic osteomyelitis, chronic bronchiectasis) 5. Any history of proven infection of a joint prosthesis in which the prosthesis was not removed or replaced, or received antibiotics for suspected infection of a joint prosthesis in which the prosthesis was not removed or replaced 6. Received live vaccines within 60 days prior to Day 1, or plans to receive a live vaccine during the study, or within 60 days after completing study treatment 7. Presence of herpes zoster lesions at screening or Day 1 8. History of serious herpes zoster or serious herpes simplex infection, which includes, but is not limited to, any episode of disseminated herpes simplex, multidermatomal herpes zoster, herpes encephalitis, ophthalmic herpes, or recurrent herpes zoster (recurrent is defined as 2 episodes within 2 years) 9. Evidence of, or positive test for, hepatitis B virus at screening. Positive hepatitis B lab testing is defined as 1) positive hepatitis B surface antigen (HBsAg+) OR 2) presence of hepatitis B virus DNA OR 3) positive anti-hepatitis B core antibody without concurrent positive hepatitis B surface antibody (HBcAb+ and HBsAb-) 10. Evidence of, or positive test for, hepatitis C virus (HCV) at screening. A positive test for HCV is defined as: positive for hepatitis C antibody (anti-HCV Ab) AND 2) positive via a confirmatory test for HCV (for example, HCV polymerase chain reaction) 11. Positive for human immunodeficiency virus by antibody testing (HIV-1 and -2 Ab) at screening 12. Any history of known or suspected congenital or acquired immunodeficiency state or condition that would compromise the patient's immune status (eg, history of opportunistic infections \[eg, Pneumocystis jirovecii pneumonia, histoplasmosis, or coccidioidomycosis\], history of splenectomy, primary immunodeficiency) 3. Any of the following tuberculosis (TB) criteria: 1. History of active TB prior to screening visit, regardless of completion of adequate treatment 2. Signs or symptoms of active TB (eg, fever, cough, night sweats, and weight loss) during screening, as judged by the investigator 3. Any imaging of the chest (eg, chest x-ray, chest computed tomography scan) obtained during the screening period, or any time within 6 months prior to screening with documentation, showing evidence of current active or history of active pulmonary TB 4. Latent TB infection (LTBI) defined as positive interferon gamma release assay (IGRA), by QuantiFERON-TB Gold testing at screening, in the absence of clinical manifestations Note: Patient is eligible if (i) there are no current signs or symptoms of active TB AND (ii) patient has received adequate documented treatment for LTBI within 5 years of screening OR has initiated prophylactic treatment for LTBI per local guidelines and is rescreened after 1 month of treatment. To continue in the study, patient must agree to complete a locally recommended course of treatment for LTBI. Use of rifampin, however, is not recommended as it can reduce efficacy of apremilast used as a comparator in this trial Note: An IGRA test that is indeterminate must be retested for confirmation. If the second test is again indeterminate, the patient will be excluded from the study. If the retest is positive, the patient should be treated as having LTBI. If the retest is negative, the patient may be eligible provided no other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Psoriasis Area and Severity Index-75 | Week 18 | Change on 75% at least for Psoriasis Area and Severity Index (PASI)75 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Psoriasis Area and Severity Index-90 (PASI-90) | Week 6,12,18,24, 30 and 36 | Change on PASI90 after treatment |
| Scalp-specific Physician's Global Assessment | Week 6,12,18,24, 30 and 36 | Change on Scalp-specific Physician's Global Assessment (Ss-PGA) 0/1 with at least a 2-point improvement among patients with a baseline ss-PGA ≥3 |
| Psoriasis Symptoms and Signs Diary | Week 6,12,18,24, 30 and 36 | Changes on PSSD symptom score of 0 among patients with baseline score ≥1 |
| Dermatology Life Quality Index | Week 6,12,18,24, 30 and 36 | Dermatology Life Quality Index (DLQI) 0/1 at Week 4 and 8 among patients with baseline DLQI ≥2 |
| Frequency of adverse events | Week 6,12,18,24, 30 and 36 | Frequency of solicited and unsolicited adverse events (SAEs and USAEs) |
| Changes on inflammatory cytokines | Week 6,12,18,24, 30 and 36 | Changes on inflammatory and anti-inflammatory cytokine levels during treatment (IL-17, IL-23, IL-6, TNF-alpha, IL1-b, IL-10) |
Countries
Mexico
Contacts
CONTACTDiana M Andrade Plata, MD
CONTACTAraceli G Medina Nolasco, MD
PRINCIPAL_INVESTIGATORVeronica Narvaez Rosales, MD
Innovacion y Desarrollo de Estrategias en Salud
Outcome results
None listed