Safety, Tolerability, and Bioavailability of Subcutaneously Administered XmAb®7195

NCT02881853 | Completed Phase 1

• 1 other identifier: XmAb7195-02
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1b, combined multiple dose subcutaneous (SC) bioavailability (BA) and multiple ascending dose (MAD) study evaluating safety, tolerability and BA of SC XmAb7195 in healthy subjects and in subjects with atopic disease.

Conditions

Healthy Volunteers; Atopic Disease

Keywords

healthy; atopic

Outcome Measures

Primary Outcomes (1)

• Bioavailability of SC XmAb7195 after 4 once-weekly doses as measured by the ratio of dose-normalized SC XmAb7195 area under the concentration-time curve (AUC) to dose-normalized IV XmAb7195 AUC.

  Date of randomization up to Day 50

Secondary Outcomes (7)

• Cmax, Maximum observed serum concentration

  Date of randomization up to Day 50

• Time at which Cmax was observed [Tmax]

  Date of randomization up to Day 50

• Area Under the Curve (AUC)

  Date of randomization up to Day 50

• Terminal elimination half-life [t1/2]

  Date of randomization up to Day 50

• Total body or systemic clearance [CL]

  Date of randomization up to Day 50

Study Arms (9)

Part A1

EXPERIMENTAL

XmAb7195 for IV infusion; dose level 1; 4 once-weekly doses

Drug: XmAb7195

Part A2

EXPERIMENTAL

XmAb7195 for SC injection; dose level 1; 4 once weekly doses

Drug: XmAb7195

Part A3

EXPERIMENTAL

XmAb7195 for SC injection; dose level 2; 4 once weekly doses

Drug: XmAb7195

Part A4

EXPERIMENTAL

XmAb7195 for SC injection; dose level 3; 4 once weekly doses

Drug: XmAb7195

Part A5

EXPERIMENTAL

XmAb7195 for SC injection; dose level 4; 4 once weekly doses

Drug: XmAb7195

Part B6

EXPERIMENTAL

XmAb7195 or placebo for SC injection; dose level 5; 4 once-weekly doses

Drug: XmAb7195; Drug: Placebo

Part B7

EXPERIMENTAL

XmAb7195 or placebo for SC injection; dose level 6; 4 once-weekly doses

Drug: XmAb7195; Drug: Placebo

Part B8

EXPERIMENTAL

XmAb7195 or placebo for SC injection; dose level 7; 4 once-weekly doses

Drug: XmAb7195; Drug: Placebo

Part B9

EXPERIMENTAL

XmAb7195 or placebo for SC injection dose level 8; 4 once-weekly doses

Drug: XmAb7195; Drug: Placebo

Interventions

XmAb7195 DRUG

Part A1; Part A2; Part A3; Part A4; Part A5; Part B6; Part B7; Part B8; Part B9

Placebo DRUG

Part B6; Part B7; Part B8; Part B9

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All Subjects:
• Male or female between 18 to 60 years of age (inclusive at the time of screening).
• Total body weight 50.0 to 100.0 kg, and body mass index (BMI) 19.0 to 35.0 kg/m2 (inclusive, at screening).
• Women can be of either childbearing or non-childbearing potential.
• Must be healthy with no clinically significant abnormality identified on medical or laboratory evaluation and no history of any clinically significant disorder, condition, or disease that would pose a risk to subject or interfere with the study evaluation, procedures, or completion as assessed by the Investigator.
• Subjects with Atopic Disease Only (Part B):
• Allergen skin test reactivity of ≥ 5 mm wheal greater than saline control to any 2 of the following 5 allergens: D. pteronyssinus, D. farina, ragweed, Virginia live oak, and mountain cedar within 21 days prior to dosing.

You may not qualify if:

• Subjects who have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases, or disorders that would pose a significant risk to subject's safety or significantly interfere with the study evaluation, procedures, or completion as assessed by the Investigator.
• Subjects with platelet count \< 150 k/uL at screening or at the time of initial admission.
• Subjects with peak expiratory flow rate \< 400 L/min for males and \< 350 L/min for females.
• Subjects with conditions associated with high risk of bleeding such as: past history of intracranial or gastrointestinal bleeding, hemorrhagic condition including hereditary or acquired bleeding, or coagulation disorder.
• Subjects with history of any clinically significant cardiovascular event such as: myocardial infarction, acute coronary syndrome, stroke, pulmonary embolism, and/or deep venous thrombosis.
• Subjects who do not agree to use medically acceptable methods of contraception (as defined in the protocol).
• Subjects who are pregnant or breast feeding, or planning to become pregnant within 30 days of last dose of XmAb7195.
• Subjects who have used prescription drugs within 28 days prior to randomization with the following exceptions for Part B subjects with atopic disease:
• Intranasal corticosteroids for allergic symptoms if the dose has been stable for 14 days prior to randomization.
• Inhaled short acting beta agonist (SABA) therapy for bronchospasm if dosing has been stable for 14 days prior to randomization.
• No other prescription drugs are allowed unless agreed as not clinically relevant by the Investigator and Sponsor.
• Subjects who have had an asthma exacerbation requiring hospitalization within the 1 year prior to randomization or having required oral corticosteroids within the 6 months prior to randomization.
• Subjects with poorly controlled asthma defined as SABA \> 6 times/day on any day within the 4 weeks prior to randomization.
• Subjects who have used any of the following medications within the 3 months prior to randomization: oral or inhaled corticosteroids, long acting beta agonists (LABAs), leukotriene receptor antagonists (LTRAs), or any other asthma controller medication (occasional SABA use is allowed).

Sponsors & Collaborators

• Xencor, Inc.: lead
• ICON Early Phase Services, LLC: collaborator

Study Sites (1)

ICON Early Phase Services, LLC

San Antonio, Texas, 78209, United States

Location

Study Officials

• Emanuel P DeNoia, MD

  ICON Early Phase Services, LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2016
• First Posted: August 29, 2016
• Study Start: August 17, 2016
• Primary Completion: February 24, 2017
• Study Completion: February 24, 2017
• Last Updated: July 11, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)