Clinical trial NCT03221179: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7049665 in Healthy Volunteers
Official title: A Randomized, Adaptive, Investigator/ Subject Blind, Single Ascending Dose, Placebo-Controlled Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered RO7049665 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-07-18
Enrollment: 49
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety and tolerability of single ascending doses of subcutaneous (SC) injections of RO7049665 in healthy volunteers. In addition, pharmacokinetics (PK) of RO7049665, the effects of single doses of RO7049665 on regulatory T-cells as well as the single dose immunogenicity of RO7049665 will be evaluated. This trial plans to evaluate approximately seven single dose-levels of RO7049665 or matching-placebo during dose-escalation in approximately 40 participants.


Eligibility criteria: Inclusion Criteria:

* Male healthy volunteers, 18 to 45 years of age, inclusive;
* Absence of evidence of any active or chronic disease;
* Body mass index (BMI) of 18-30 kilograms per square meter (kg/m\^2), inclusive;
* Contraception requirements: refrain from heterosexual intercourse or use contraceptive measures, and agreement to refrain from donating sperm.

Exclusion Criteria:

* History of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardio-vascular, endocrinological, hematological or allergic disease, metabolic disorder, cancer or cirrhosis;
* Clinically significant abnormalities (as judged by the Investigator) in laboratory test results;
* Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study;
* History of hypersensitivity to biologic agents or any of the excipients in the formulation;
* Any abnormal skin conditions or potentially obscuring tattoos, pigmentation or lesions in the area intended for subcutaneous injection;
* Prior administration of aldesleukin, or interleukin-2 (IL-2) derivatives.

Primary outcomes:
measure: Percentage of Participants with Adverse Events
timeFrame: From baseline up to approximately 8 weeks
Secondary outcomes:
measure: PK: Time to Maximum Concentration (Tmax) of RO7049665
timeFrame: Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43
measure: PK: Maximum Serum Concentration Observed (Cmax) of RO7049665
timeFrame: Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43
measure: PK: Area Under the Concentration-Time Curve (AUC) from Time 0 to Time of Last Sampling of RO7049665
timeFrame: Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43
measure: PK: AUC from Time 0 to infinity (AUCinf) of RO7049665
timeFrame: Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43
measure: PK: AUC from Time 0 to Time tau (AUC0-t) of RO7049665
timeFrame: Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43
measure: PK: Apparent Clearance (CL/F) of RO7049665
timeFrame: Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43
measure: PK: Apparent Volume of Distribution (Vz/F) of RO7049665
timeFrame: Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43
measure: PK: Half-life (t1/2) of RO7049665
timeFrame: Pre-dose on Day 1, post-dose on Day 1 at 2 hours (h), 6 h and 12 h, once daily on Days 2-8, Day 12, Day 15, Day 21, Day 29 and Day 43
measure: Change from Baseline in Regulatory T Lymphocyte (Tregs) Count
timeFrame: Day -1, Pre-dose Day 1; post-dose Day 2, 3, 4, 6, 8, 12, 15, 29, up to follow-up visit (Day 57)
measure: Percentage of Participants with Anti-Drug Antibodies
timeFrame: Pre-dose Day 1, post-dose Day 8, 15, 29, up to follow-up visit (Day 57)
Other outcomes:
Locations:
city: Zuidlaren
country: Netherlands
facility: PRA Health Sciences Early Development Services
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: