A Pilot Study of CC-220 to Treat Systemic Lupus Erythematosus.

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02185040
• Date of registration: 07/07/2014
• Prospective Registration: Yes
• Primary sponsor: Celgene
• Public title: A Pilot Study of CC-220 to Treat Systemic Lupus Erythematosus.
• Scientific title: A Pilot, Phase 2, Randomized, Placebo-Controlled, Double-Blind, Study To Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Pharmacogenetics of CC-220 In Subjects With Systemic Lupus Erythematosus
• Date of first enrolment: September 16, 2014
• Target sample size: 42
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02185040
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Shimon Korish, M.D.
• Affiliation: Celgene

Key inclusion & exclusion criteria

Inclusion Criteria:

Part 1

- The subject has an established diagnosis of systemic lupus erythematosus (SLE) as
defined by the 1997 Update of the 1982 ACR Revised Criteria for Classification of SLE
at screening. The diagnosis is fulfilled provided that at least 4 criteria are met.

- Disease history of SLE = 6 months at baseline

- Females of childbearing potential (FCBP) must:

- Have two negative pregnancy tests as verified by the study doctor prior to
starting study therapy. She must agree to ongoing pregnancy testing during the
course of the study, and after end of study therapy. This applies even if the
subject practices true abstinence from heterosexual contact.

- Either commit to true abstinence from heterosexual contact (which must be
reviewed on a monthly basis) or agree to use, and be able to comply with,
effective contraception without interruption, 28 days prior to starting IP,
during the study therapy (including dose interruptions), and for 28 days after
discontinuation of study therapy.

- Male subjects must:

- Must practice true abstinence or agree to use a condom during sexual contact with
a pregnant female or a female of childbearing potential while participating in
the study, during dose interruptions and for at least 28 days following IP
discontinuation, even if he has undergone a successful vasectomy.

- If the subject is using oral corticosteroids, the daily dose must be less than or
equal to 10 mg of prednisone or equivalent during the study; the dose must be
stable over the 4 weeks preceding screening and throughout the study.

- All subjects taking hydroxychloroquine, chloroquine and/or quinacrine during the
study must have documentation of a normal ophthalmologic examination performed
within 1 year of the Baseline Visit.

- For subjects not taking corticosteroids, or antimalarials, the last dose (in case
of previous use) must be at least 4 weeks prior to screening.

ATEP

- Male or female 18 years of age or older

- Understand and voluntarily sign an ICD prior to the initiation of any study related
assessments/procedures

- Able to adhere to the study visit schedule and other protocol requirements. Pregnancy

- Females of childbearing potential (FCBP) must:

- Have two negative pregnancy tests as verified by the study doctor prior to
starting study therapy. She must agree to ongoing pregnancy testing during the
course of the study, and after end of study therapy. This applies even if the
subject practices true abstinence* from heterosexual contact.

- Either commit to true abstinence* from heterosexual contact (which must be
reviewed on a monthly basis) or agree to use, and be able to comply with,
effective contraception without interruption, 28 days prior to starting IP,
during the study therapy (including dose interruptions), and for 28 days after
discontinuation of study therapy.

- Male subjects must:

- Practice true abstinence or agree to use a condom during sexual contact with a
pregnant female or a female of childbearing potential while participating in the
study, during dose interruptions and for at least 28 days following IP
discontinuation, even if he has undergone a successful vasectomy. True abstinence is
acceptable when this is in line with the preferred and usual lifestyle of the subject.
(Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods]
and withdrawal are not acceptable methods of contraception.)

- Male subjects must agree not to donate semen or sperm during therapy and for at least
90 days following the discontinuation of IP.

- All subjects must:

- Understand that the IP could have potential teratogenic risk

- Agree to abstain from donating blood while taking IP and for 28 days following
discontinuation of the IP

- Agree not to share IP with another person

- Other than the subject, FCBP and males able to father a child should not handle
the IP or touch the capsules unless gloves are worn

- Be counseled about pregnancy precautions and risks of fetal exposure as described
in the Pregnancy Prevention Plan. Concomitant Medications

- If the subject is using oral corticosteroids, the daily dose must be less than or
equal to 10 mg of prednisone or equivalent during the study; the dose must be stable
over the 4 weeks preceding randomization and throughout the study.

- All subjects taking hydroxychloroquine, chloroquine or quinacrine during the study
must have documentation of a normal ophthalmologic examination performed within 1 year
of the Baseline Visit.

- For subjects not taking corticosteroids the last dose (in case of previous use) must
be at least 4 weeks prior to screening.

Exclusion Criteria

- The subject has been treated with intra-articular, intramuscular or IV pulse
corticosteroids within 4 weeks of screening.

- The subject has received high dose oral prednisone (> 100 mg/day) within 4 weeks of
screening.

- The subject has received cyclophosphamide, azathioprine or mycophenolate mofetil
within 12 weeks of screening.

- The subject has participated in a clinical trial and has received an investigational
product within 30 days, 5 pharmacokinetic half-lives or twice the duration of the
biological effect of the investigational product (whichever is longer) prior to
screening; OR participation in two or more investigational drug trials within 12
months of screening.

- Unstable lupus nephritis defined as: proteinuria > 1.0 g/24 hour /1.73 m2 OR eGFR of
less than 60 mL/1.73 m2 CNS disease, including active severe CNS lupus (including
seizures, psychosis, organic brain syndrome, cerebrovascular accident (CVA),
cerebritis or CNS vasculitis) requiring therapeutic intervention within 6 months of
screening.

- The subject has New York Heart Association (NYHA) Class III or IV congestive heart
failure.

- Presence of hepatitis B surface antigen (HBsAG). Subjects may have a positive
anti-hepatitis B core antibody (anti-HBc) if the anti-hepatitis B surface antibody
(anti-HBs) is positive as well.

- Antibodies to hepatitis C at Screening.

- The subject has a known positive history of antibodies to human immunodeficiency virus <


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Drug: Placebo

Drug: CC-220

Primary Outcome(s)

Number of Participants With Treatment Emergent Adverse Events (TEAEs) in Part 1 Treatment Phase [Time Frame: From the start of the first dose of IP until 28 days after the last dose or study discontinuation in Part 1; median treatment duration = 12.0 weeks for the placebo, 0.3 mg QOD and 0.3 mg iberdomide QD arms, 11.9 weeks for the 0.6/0.3 ALT and 0.6 cohorts.]

Number of Participants With Treatment Emergent Adverse Events (TEAEs) in the Active Treatment Extension Phase [Time Frame: From the date of the first dose of IP in the ATEP until 28 days after the last dose in the ATEP or study discontinuation; median duration of IP was 95.86 weeks for the 0.3 mg iberdomide QD cohort and 60.64 weeks for the 0.6 mg/0.3 mg ALT QD cohorts.]

Secondary Outcome(s)

Change From Baseline in the Pericardial/Pleuritic Pain Scale During ATEP by Time Poimt [Time Frame: Baseline to Weeks 1, 4, 12, 24, 36, 48, 60, 72, 84, 96 and follow-up at Week 100 during the ATEP.]

Percentage of Participants Who Achieved =4 Points Reduction From Baseline in Hybrid Safety of Estrogens in Systemic Lupus Erythematosus National Assessment SLE Disease Activity Index Score (SELENA SLEDAI) During the ATEP by Time Point [Time Frame: Baseline to Weeks 1, 4, 12, 24, 36, 48, 60, 72, 84, 96 and follow-up at Week 100 during the ATEP.]

Terminal Phase Half-Life (T1/2) Of Iberdomide [Time Frame: Pharmacokinetic blood samples were collected on Day 1 and Day 29 at pre-dose (Time = 0 hours) and at 1, 2, 3, 4, between 6 and 8 hours and 24 hours after administration of IP.]

Change From Baseline in Swollen Joint Count During the ATEP by Time Point [Time Frame: Baseline to Weeks 1, 4, 12, 24, 36, 48, 60, 72, 84, 96 and follow-up at Week 100 during the ATEP.]

Change From Baseline in the Cutaneous Lupus Area and Severity Index (CLASI) Damage Score During the ATEP by Time Point [Time Frame: Baseline to Weeks 1, 4, 12, 24, 36, 48, 60, 72, 84, 96 and follow-up at Week 100 during the ATEP.]

Change From Baseline in the Fatigue Visual Analog Scale (VAS) During the ATEP by Time Point [Time Frame: Baseline to Weeks 1, 4, 12, 24, 36, 48, 60, 72, 84, 96 and follow-up at Week 100 during the ATEP.]

Change From Baseline in the Physician's Global Assessment (PGA) Score During the ATEP by Time Point [Time Frame: Baseline to Weeks 1, 4, 12, 24, 36, 48, 60, 72, 84, 96 and follow-up at Week 100 during the ATEP.]

Change From Baseline in the British Isles Lupus Assessment Group (BILAG) 2004 Global Score During the ATEP by Time Point [Time Frame: Baseline to Weeks 1, 4, 12, 24, 36, 48, 60, 72, 84, 96 and follow-up at Week 100 during the ATEP.]

Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUCt) of Iberdomide [Time Frame: Pharmacokinetic (PK) blood samples were collected on Day 1 and Day 29 pre-dose (Time = 0 hours) and at 1, 2, 3, 4, between 6 and 8 hours and 24 hours after administration of IP.]

Maximum Observed Concentration (Cmax) Of Iberdomide [Time Frame: Pharmacokinetic blood samples were collected on Day 1 and Day 29 at pre-dose (Time = 0 hours) and at 1, 2, 3, 4, between 6 and 8 hours and 24 hours after administration of IP.]

Percent Change From Baseline in Cutaneous Lupus Area and Severity Index (CLASI) Activity Score During the ATEP by Time Point [Time Frame: Baseline to Weeks 1, 4, 12, 24, 36, 48, 60, 72, 84, 96 and follow-up at Week 100 during the ATEP.]

Change From Baseline in the Hybrid Systemic Lupus Erythematosus Disease Activity Index (SELENA SLEDAI) During the ATEP by Time Point [Time Frame: Baseline to Weeks 1, 4, 12, 24, 36, 48, 60, 72, 84, 96 and follow-up at Week 100 during the ATEP.]

Change From Baseline in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Systemic Lupus Erythematosus (SLICC/ACR SLE) Damage Index Score During the ATEP by Time Point [Time Frame: Baseline to Weeks 1, 4, 12, 24, 36, 48, 60, 72, 84, 96 and follow-up at Week 100 during the ATEP.]

Time to Reach Maximum Concentration (Tmax) of Iberdomide [Time Frame: Pharmacokinetic blood samples were collected on Day 1 and Day 29 at pre-dose (Time = 0 hours) and at 1, 2, 3, 4, between 6 and 8 hours and 24 hours after administration of IP.]

Change From Baseline in Tender Joint Count During the ATEP by Time Point [Time Frame: Baseline to Weeks 1, 4, 12, 24, 36, 48, 60, 72, 84, 96 and follow-up at Week 100 during the ATEP.]

Secondary ID(s)

CC-220-SLE-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 19/03/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02185040