Clinical trial NCT02675023: Assessment of Pharmacokinetics and Safety of M923 Administered Via Auto-injector or Prefilled Syringe, in Healthy Subjects
Official title: A Randomized, Open-label, Two-arm, Parallel Group, Single Dose Study to Assess the Pharmacokinetics and Safety of M923 Administered Via Auto-injector or Prefilled Syringe, in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Momenta Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2016-02-05
Enrollment: 603
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This study will assess the pharmacokinetic (PK) and safety of a single 0.8 mL (40 mg) subcutaneous (SC) dose of M923 administered via an auto-injector (AI) or a prefilled syringe (PFS) in healthy subjects.


Eligibility criteria: Inclusion Criteria:

1. Healthy male and female participants aged 18 to 55 years, inclusive
2. Healthy participants as determined by pre-study medical history, physical examination, vital signs and 12-lead electrocardiogram (ECG)
3. Participants with clinical laboratory test results that are not clinically significant and are acceptable to the investigator at screening and admission to the study site (Day -1)
4. Participants with a body weight between 60.0 kg and 100.0 kg and a body mass index between 18.5 kg/m2 and 34.9 kg/m2, inclusive
5. Healthy male participants must be willing to comply with the contraception restrictions for this study.

   -Male participants with non-pregnant female partners of childbearing potential should avoid conception of a child during the study (up to Day 71 post-dose) and for 90 days thereafter.
6. Healthy female participants must have a negative pregnancy test at screening and on admission to the study site (Day -1), must not be lactating and must be using an acceptable method of contraception throughout the study and for 30 days after study completion, or be of non-childbearing potential.

   -Non-pregnant female partners of male participants who are of childbearing potential should use an effective form of contraception.
7. Participants who have smoked ≤10 cigarettes or 3 cigars or 3 pipes/day for at least 3 months prior to screening and are willing to comply with smoking restrictions during residency at the study site
8. Participants who are able to understand and provide written informed consent including signature on an informed consent form (ICF) approved by an Ethics Committee (EC)/ Institutional Review Board (IRB)
9. Participants who have provided written authorization for use and disclosure of protected health information
10. Participants who agree to abide by the study schedule and dietary restrictions and to return for the required assessments

Exclusion Criteria:

1. History and/or current presence of clinically significant angioedema, or eczematous dermatitis that requires prescription medication, clinically significant hypersensitivity, or severe allergic reactions (either spontaneous or following IP administration), also including known or suspected clinically relevant drug hypersensitivity to any components of the IP or comparable drugs, including latex
2. Active or latent tuberculosis or who have a history of TB.
3. History of invasive and/or active systemic fungal infections or other severe opportunistic infections, including recurrent or clinically significant chronic local fungal infections
4. A serious infection within 6 months prior to investigational product (IP) administration and/or an infection within 2 weeks of screening or during the screening period unless resolved completely within 2 weeks of admission to the study site on Day -1
5. Herpes zoster infection in the last year or more than 2 herpes zoster infections in his/her lifetime
6. Frequent chronic or recurrent infections (defined as \>3 a year requiring prescribed treatment)
7. Previous use of adalimumab, HUMIRA®, or another recombinant human monoclonal antibody
8. Intake of any investigational drug in another study within 30 days (or 5 half-lives, whichever is greater) prior to intake of IP in this study or have received the last dose of a study drug more than 30 days ago (or 5 half-lives, whichever is greater) but who are on extended follow-up, or planned intake of an investigational drug (other than for this study) during the course of this study
9. History of alcohol abuse in the year preceding the screening visit, or history of excess alcohol consumption.
10. Known history of opioid or cocaine drug abuse or any other drug abuse in the past year or positive tests for drugs of abuse or alcohol at screening or admission to the study site (Day -1)
11. Donation of blood or blood products (eg, plasma, platelets) within 30 days prior to IP administration
12. Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), dietary supplements or herbal medication during the 2 weeks prior to IP administration or longer if the medication has a long half-life. Use of any medication deemed necessary by the participant's physician to treat or prevent any medical condition, paracetamol/acetaminophen ≤3 g/day and use of vitamins at daily recommended doses is allowed; for female volunteers, oral birth control and hormone replacement therapy is allowed
13. History of or existing congestive heart failure
14. History of or existing signs or symptoms of demyelinating disease such as optic neuritis and/or multiple sclerosis
15. History of any cancer including lymphoma, leukemia, skin cancer or cervical carcinoma in situ
16. Impaired liver function
17. History of immunodeficiency (including those participants with a positive test for human immunodeficiency virus \[HIV\] I and II at screening) or other clinically significant immunological disorders, or auto-immune disorders, (eg, rheumatoid arthritis, lupus erythematosus, scleroderma, psoriasis)
18. Positive test for anti-citrullinated protein antibodies at screening
19. Clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological (including pancytopenia, aplastic anemia, or blood dyscrasia), metabolic (including known diabetes mellitus), lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders as judged by the investigator
20. Received a live vaccine within 12 weeks prior to admission to the study site (Day -1) or plan to receive a live vaccine during the study (up to and including Day 71)
21. Volunteers who are vegans or have medical dietary restrictions
22. Volunteers who cannot communicate reliably with the investigator
23. Volunteer is a family member or employee of the investigator or study site staff or study team

Primary outcomes:
measure: Pharmacokinetics: Area under the concentration-time curve from 0 to infinity
timeFrame: Within 90 minutes pre-dose; and post-dose at 8 hours, and Day 2, 3, 4, 5, 6, 7, 9, 11, 15, 22, 29, 40, 50, and 71
measure: Pharmacokinetics: Area under the concentration-time curve from 0 to 336 hours
timeFrame: Within 90 minutes pre-dose; and post-dose at 8 hours, and Day 2, 3, 4, 5, 6, 7, 9, 11, and 15
measure: Pharmacokinetics: Maximum concentration in serum (Cmax)
timeFrame: Within 90 minutes pre-dose; and post-dose at 8 hours, and Day 2, 3, 4, 5, 6, 7, 9, 11, 15, 22, 29, 40, 50, and 71
Secondary outcomes:
measure: Pharmacokinetics: Serum M923 concentration up to Day 71
timeFrame: Within 90 minutes pre-dose; and post-dose at 8 hours, and Day 2, 3, 4, 5, 6, 7, 9, 11, 15, 22, 29, 40, 50, and 71
measure: Pharmacokinetics: Area under the concentration-time curve in serum from time zero (predose) to 1200 hours postdose [AUC(0-1200)]
timeFrame: Within 90 minutes pre-dose; and post-dose at 8 hours, and Day 2, 3, 4, 5, 6, 7, 9, 11, 15, 22, 29, 40, and 50
measure: Pharmacokinetics: Area under the concentration-time curve in serum from time zero (predose) to time of the last quantifiable concentration [AUC(0-last)]
timeFrame: Within 90 minutes pre-dose; and post-dose at 8 hours, and Day 2, 3, 4, 5, 6, 7, 9, 11, 15, 22, 29, 40, 50, and 71
measure: Pharmacokinetics: Time of maximum concentration in serum [tmax]
timeFrame: Within 90 minutes pre-dose; and post-dose at 8 hours, and Day 2, 3, 4, 5, 6, 7, 9, 11, 15, 22, 29, 40, 50, and 71
measure: Pharmacokinetics: Terminal rate constant (λ z)
timeFrame: Within 90 minutes pre-dose; and post-dose at 8 hours, and Day 2, 3, 4, 5, 6, 7, 9, 11, 15, 22, 29, 40, 50, and 71
measure: Pharmacokinetics: Terminal half-life (t½)
timeFrame: Within 90 minutes pre-dose; and post-dose at 8 hours, and Day 2, 3, 4, 5, 6, 7, 9, 11, 15, 22, 29, 40, 50, and 71
measure: Pharmacokinetics: Apparent volume of distribution (Vz/F)
timeFrame: Within 90 minutes pre-dose; and post-dose at 8 hours, and Day 2, 3, 4, 5, 6, 7, 9, 11, 15, 22, 29, 40, 50, and 71
measure: Pharmacokinetics: Apparent systemic clearance after extravascular dosing (CL/F)
timeFrame: Within 90 minutes pre-dose; and post-dose at 8 hours, and Day 2, 3, 4, 5, 6, 7, 9, 11, 15, 22, 29, 40, 50, and 71
measure: Pharmacokinetics: Area under the concentration-time curve extrapolated from time "t" to infinity [% AUCex]
timeFrame: Within 90 minutes pre-dose; and post-dose at 8 hours, and Day 2, 3, 4, 5, 6, 7, 9, 11, 15, 22, 29, 40, 50, and 71
measure: Pharmacokinetics: Area under the serum concentration-time curves from time zero (predose) to time "t" [AUC(0-t)] by which >20.0% of participants have developed neutralizing antidrug antibody [nADA]
timeFrame: Within 90 minutes pre-dose; and post-dose at 8 hours, and Day 2, 3, 4, 5, 6, 7, 9, 11, 15, 22, 29, 40, 50, and 71
measure: Non-serious and serious adverse events (SAEs)
timeFrame: Throughout the study period of approximately 8 months
measure: Incidence of injection site reactions
timeFrame: Throughout the study period of approximately 8 months
measure: Clinically significant changes in Vital signs
timeFrame: Throughout the study period of approximately 8 months
measure: Number of participants with new clinically significant findings from the physical examination
timeFrame: Throughout the study period of approximately 8 months
measure: Clinically significant changes in Twelve-lead electrocardiogram (ECG)
timeFrame: Throughout the study period of approximately 8 months
measure: Clinically significant changes in laboratory results
timeFrame: Throughout the study period of approximately 8 months
measure: Clinically significant changes in clinical chemistry
timeFrame: Throughout the study period of approximately 8 months
measure: Clinically significant changes in urinalysis
timeFrame: Throughout the study period of approximately 8 months
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: QOPK Phase 1 Clinic
state: Kansas
city: London
country: United Kingdom
facility: QLON Phase 1 Clinic
Study officials:
affiliation: Shire
name: John Caminis, MD
role: STUDY_DIRECTOR
References: