A Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of BIIB091, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Healthy Adult Participants

• ClinicalTrials.gov Identifier: NCT03943056
• Recruitment Status: Recruiting
• First Posted: May 9, 2019
• Last Update Posted: July 31, 2019
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Study Description

Brief Summary:

This study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple oral doses of BIIB091 in healthy participants.This study will also determine the effect of food on the single oral dose pharmacokinetic (PK).

Condition or disease	Intervention/treatment	Phase
Healthy Volunteer	Drug: BIIB091; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Blinded Study
• Primary Purpose: Treatment
• Official Title: A Phase 1, Randomized, Blinded, Placebo-Controlled, Single- and Multiple-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of BIIB091, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Healthy Adult Participants
• Actual Study Start Date: May 13, 2019
• Estimated Primary Completion Date: December 24, 2019
• Estimated Study Completion Date: December 24, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Single Ascending Dose (SAD): Cohort 1A; Participants will receive dose level 1 of BIIB091 or placebo, orally, while fasting on Day 1.	Drug: BIIB091; Administered as specified in the treatment arm.; Drug: Placebo; Administered as specified in the treatment arm.
Experimental: (SAD): Cohort 2A; Participants will receive dose level 2 of BIIB091 or placebo, orally, while fasting on Day 1.	Drug: BIIB091; Administered as specified in the treatment arm.; Drug: Placebo; Administered as specified in the treatment arm.
Experimental: (SAD): Cohort 3A; Participants will receive dose level 3 of BIIB091 or placebo, orally, while fasting on Day 1, then again following a 7 day washout and high-fat meal.	Drug: BIIB091; Administered as specified in the treatment arm.; Drug: Placebo; Administered as specified in the treatment arm.
Experimental: (SAD): Cohort 4A; Participants will receive dose level 4 of BIIB091 or placebo, orally, while fasting on Day 1.	Drug: BIIB091; Administered as specified in the treatment arm.; Drug: Placebo; Administered as specified in the treatment arm.
Experimental: (SAD): Cohort 5A; Participants will receive dose level 5 of BIIB091 or placebo, orally, while fasting on Day 1.	Drug: BIIB091; Administered as specified in the treatment arm.; Drug: Placebo; Administered as specified in the treatment arm.
Experimental: Multiple Ascending Dose (MAD): Cohort 1B; Participants will receive dose level 1 of BIIB091 or placebo, orally, twice daily (BID) for 13 days, and a single dose on Day 14.	Drug: BIIB091; Administered as specified in the treatment arm.; Drug: Placebo; Administered as specified in the treatment arm.
Experimental: (MAD): Cohort 2B; Participants will receive dose level 2 of BIIB091 or placebo, orally, BID for 13 days, and a single dose on Day 14.	Drug: BIIB091; Administered as specified in the treatment arm.; Drug: Placebo; Administered as specified in the treatment arm.
Experimental: (MAD): Cohort 3B; Participants will receive dose level 3 of BIIB091 or placebo, orally, BID for 13 days, and a single dose on Day 14.	Drug: BIIB091; Administered as specified in the treatment arm.; Drug: Placebo; Administered as specified in the treatment arm.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Day 9 for SAD Cohorts; Baseline up to Day 24 for MAD Cohorts ]
   An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death, in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event), however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect or is a medically important event.

Secondary Outcome Measures :

1. Area Under the Curve from Time 0 to the Time of the Last Measurable Concentration (AUClast) [ Time Frame: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 16 for MAD Cohorts ]
2. Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) [ Time Frame: Baseline and multiple timepoints up to Day 3 ]
3. Maximum Observed Concentration (Cmax) [ Time Frame: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 14 for MAD Cohorts ]
4. Time to Reach Maximum Observed Concentration (Tmax) [ Time Frame: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 14 for MAD Cohorts ]
5. Elimination Half-Life (t½) [ Time Frame: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 16 for MAD Cohorts ]
6. Apparent Total Body Clearance (CL/F) [ Time Frame: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 16 for MAD Cohorts ]
7. Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) [ Time Frame: Baseline and multiple timepoints up to Day 3 for SAD Cohorts; Baseline and multiple timepoints up to Day 16 for MAD Cohorts ]
8. Amount of BIIB091 Excreted in Urine per Sampling Interval (Aeu) [ Time Frame: Baseline and multiple timepoints up to Day 3 ]
9. Percentage of BIIB091 Excreted in Urine per Sampling Interval (%Feu) [ Time Frame: Baseline and multiple timepoints up to Day 3 ]
10. Renal clearance (CLr) [ Time Frame: Baseline and multiple timepoints up to Day 3 ]
11. Area Under the Concentration-Time Curve Within a Dosing Interval (AUCtau) [ Time Frame: Baseline and multiple timepoints up to Day 16 ]
12. Accumulation Ratio (R) [ Time Frame: Baseline and multiple timepoints up to Day 16 ]
13. Trough concentration (Ctrough) [ Time Frame: Baseline and multiple timepoints up to Day 16 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Key Inclusion Criteria:

• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with applicable participant privacy regulations.
• Have a body mass index between 18 and 30 kg/m2, inclusive.
• All male participants must practice highly effective methods of contraception and not donate sperm during the study and for at least 1 spermatogenic cycle (90 days) after administration of last dose of study treatment.
• All female participants of childbearing potential must practice highly effective methods of contraception and not donate eggs during the study and for at least 90 days after their last dose of study treatment.
• Must be in good health as by the Investigator, based on medical history and screening evaluations.

Key Exclusion Criteria:

• History of any clinically significant cardiac, endocrine, gastrointestinal, hematologic,hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, or renal disease, or other major disease, as determined by the Investigator.
• History of severe allergic or anaphylactic reactions, or of any allergic reactions that in the opinion of the Investigator are likely to be exacerbated by any component of the study treatment.
• History of, or ongoing, malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell carcinomas and squamous cell carcinomas that have been completely excised and considered cured at least 12 months prior to Check-in).
• Current enrollment or plan to enroll in any other drug, biological, device, or clinical study, or treatment with an investigational drug or approved therapy for investigational use within 30 days prior to Check-in, or 5 half-lives of the drug or therapy, whichever is longer.
• Breastfeeding, pregnant, or planning to become pregnant during study participation.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Contacts

Contact: US Biogen Clinical Trial Center; 866-633-4636; clinicaltrials@biogen.com

Contact: Global Biogen Clinical Trial Center; clinicaltrials@biogen.com

Locations

United States, Texas

Research Site; Recruiting

Dallas, Texas, United States, 75247

Sponsors and Collaborators

Biogen

Investigators

• Study Director: Medical Director; Biogen

More Information

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT03943056 History of Changes
• Other Study ID Numbers: 257HV101
• First Posted: May 9, 2019
• Last Update Posted: July 31, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/
• URL: http://www.biogenclinicaldatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No