A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of CC-99677 in Healthy Adult Subjects

NCT03554993 | Completed Phase 1

• 3 other identifiers: CC-99677-CP-001U1111-1213-88602017-004849-24
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, randomized, single-center, 3-part, FIH study to assess the safety, tolerability, pharmacokinetics (PK, or how the drug behaves in the body), and pharmacodynamics (PD, or what the drug does to the body) of single and multiple doses of CC-99677 and to characterize the effect of food on the single-dose PK of CC-99677 in healthy adult subjects.

Conditions

Healthy Volunteer

Keywords

Healthy Volunteer; Safety; CC-99677

Outcome Measures

Primary Outcomes (1)

• Adverse Events (AEs)

  Number of subjects with adverse events

  From enrollment until at least 28 days after completion of treatment

Secondary Outcomes (8)

• Pharmacokinetics - Cmax

  up to 28 days

• Pharmacokinetics - Tmax

  up to 28 days

• Pharmacokinetics - AUC0-∞

  up to 28 days

• Pharmacokinetics - AUC0-t

  up to 28 days

• Pharmacokinetics - t1/2,z

  up to 28 days

Study Arms (3)

CC-99677 Under Fasted Conditions

EXPERIMENTAL

CC-99677 Under Fasted Conditions

Drug: CC-99677

Placebo

EXPERIMENTAL

Placebo under fasted conditions

Other: Placebo

CC-99677 Under Fed Conditions

EXPERIMENTAL

CC-99677 Under Fed Conditions

Drug: CC-99677

Interventions

CC-99677 DRUG

CC-99677

CC-99677 Under Fasted Conditions; CC-99677 Under Fed Conditions

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Subject is ≥ 18 and ≤ 55 years of age at the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Subject is in good health, as determined by the Investigator based on a physical examination at screening.
• Female subjects of childbearing potential (FCBP) must:
• Have 2 negative pregnancy tests as verified by the Investigator prior to the first dose of IP. She must agree to ongoing pregnancy testing during the course of the study, and prior to discharge from the study site. This applies even if the FCBP subject practices true abstinence from heterosexual contact.
• Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis, as applicable, and source documented) or agree to use, and be able to comply with, one highly effective method and one effective barrier method of contraception without interruption, during the study (including any dose interruptions), and for at least 30 days after discontinuation of IP. The female subject's chosen form of highly effective contraception must be effective by the time the female subject is enrolled into the study (eg, hormonal contraception should be initiated at least 28 days prior to enrollment).
• Female subjects NOT of childbearing potential must:
• \- Have been surgically sterilized (hysterectomy or bilateral oophorectomy; proper documentation is required) at least 6 months before screening, or be postmenopausal (defined as 24 consecutive months without menses before screening, with a follicle-stimulating hormone \[FSH\] level of \> 40 IU/L at screening).
• Male subjects must:
• \- Practice true abstinence (which must be reviewed on a monthly basis, as applicable, and source documented) or agree to use a condom during sexual contact with a pregnant female or a FCBP while participating in the study, during any dose interruptions, and for at least 90 days after discontinuation of IP, even if he has undergone a successful vasectomy. In addition, any non-pregnant FCBP partner of a male subject must use an approved method of effective contraception, without interruption, during the study (including any dose interruptions) and for at least 30 days after discontinuation of IP. Examples of approved methods of effective contraception for non-pregnant FCBP partners include progestogen-only oral hormonal contraception; male or female condom with or without spermicide; or cap, diaphragm, or sponge with spermicide.
• Subject has a body mass index (BMI) ≥ 18 and ≤ 33 kg/m2 at screening.
• Subject has clinical laboratory safety test results that are within normal limits or considered not clinically significant by the Investigator. In addition, ALT, AST, and total bilirubin must be ≤ the upper limit of normal at screening and on Day -1 (of Period 1, when applicable \[ie, in Part 3\]). Platelet count, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) must be ≥ the lower limit of normal at screening and on Day -1 (of Period 1, when applicable \[ie, in Part 3\]).
• Subject is afebrile, with supine systolic blood pressure (BP) ≥ 90 and ≤ 140 mmHG, supine diastolic BP ≥ 50 and ≤ 90 mmHg, and pulse rate ≥ 40 and ≤ 110 bpm at screening.

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Subject has any significant medical condition (including but not limited to neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematological, allergic disease, drug allergies, or other major disorders), laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• Subject has any condition that confounds the ability to interpret data from the study.
• Subject is pregnant or breastfeeding.
• Subject was exposed to an investigational drug (new chemical entity) within 30 days preceding the first dose administration, or 5 half-lives of that investigational drug, if known (whichever is longer).
• Subject has used any prescribed systemic or topical medication (including but not limited to analgesics, anesthetics, etc) within 30 days prior to the first dose administration.
• Exceptions may apply on a case-by-case basis if considered not to interfere with the study objectives as agreed to by the Investigator and Sponsor's Medical Monitor.
• Subject has used any non-prescribed systemic or topical medication (including vitamin/mineral supplements, and herbal medicines) within 14 days prior to the first dose administration. Exceptions may apply on a case-by-case basis if considered not to interfere with the study objectives as agreed to by the Investigator and Sponsor's Medical Monitor.
• Subject has used CYP3A inducers and/or inhibitors (including St. John's Wort) within 30 days preceding the first dose administration. The Indiana University (2016) "Cytochrome P450 Drug Interaction Table" should be utilized to determine inducers and/or inhibitors of CYP3A (http://medicine.iupui.edu/clinpharm/ddis/table.aspx). The Sponsor's Medical Monitor or designee should be queried in case of uncertainty.
• Subject has any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism, or excretion, eg, bariatric procedure. Appendectomy and cholecystectomy are acceptable. Other previous surgeries may be acceptable with concurrence of the Sponsor's Medical Monitor.
• Subject donated blood or serum within 8 weeks before the first dose administration to a blood bank or blood donation center.
• Subject has a history of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual \[DSM; American Psychiatric Association, 2013\]) within 2 years before the first dose administration, or positive drug screening test reflecting consumption of illicit drugs.
• Subject has a history of alcohol abuse (as defined by the current version of the DSM \[American Psychiatric Association, 2013\]) within 2 years before the first dose administration, or positive alcohol screen.
• Subject is known to have a history of hepatitis B and/or hepatitis C, or have a positive result to the test for human immunodeficiency virus (HIV) antibodies at screening.

Sponsors & Collaborators

• Celgene: lead

Study Sites (1)

Quotient Clinical

Ruddington, NG11 6JS, United Kingdom

Location

Related Publications (2)

• Gaur R, Mensah KA, Stricker J, Adams M, Parton A, Cedzik D, Connarn J, Thomas M, Horan G, Schafer P, Mair S, Palmisano M, Ramirez-Valle F. CC-99677, a novel, oral, selective covalent MK2 inhibitor, sustainably reduces pro-inflammatory cytokine production. Arthritis Res Ther. 2022 Aug 18;24(1):199. doi: 10.1186/s13075-022-02850-6.

  PMID: 35982464 DERIVED

• Malona J, Chuaqui C, Seletsky BM, Beebe L, Cantin S, Kalken DV, Fahnoe K, Wang Z, Browning B, Szabo H, Koopman LA, Oravecz T, McDonald JJ, Ramirez-Valle F, Gaur R, Mensah KA, Thomas M, Connarn JN, Hu H, Alexander MD, Corin AF. Discovery of CC-99677, a selective targeted covalent MAPKAPK2 (MK2) inhibitor for autoimmune disorders. Transl Res. 2022 Nov;249:49-73. doi: 10.1016/j.trsl.2022.06.005. Epub 2022 Jun 9.

  PMID: 35691544 DERIVED

Study Officials

• Francisco Ramirez-Valle, MD, PhD

  Celgene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: June 13, 2018
• Study Start: May 23, 2018
• Primary Completion: July 3, 2019
• Study Completion: July 3, 2019
• Last Updated: February 26, 2020

Record last verified: 2020-02

Locations

GB (1)