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A Single Ascending Dose Study to Investigate the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Intravenously Administered RO7126209 in Healthy Participants

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ClinicalTrials.gov Identifier: NCT04023994
Recruitment Status : Recruiting
First Posted : July 18, 2019
Last Update Posted : July 18, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
Study BP41192 is a randomized, adaptive, placebo-controlled parallel group study to investigate the safety, tolerability, immunogenicity and pharmacokinetics of single-ascending intravenous doses of RO7126209 in healthy participants. RO7126209 is being developed for the treatment of Alzheimer's Disease.

Condition or disease Intervention/treatment Phase
Alzheimers Disease Drug: RO7126209 Drug: Placebo Phase 1

Detailed Description:
This study uses a parallel group design, with participants recruited in 5 planned sequential cohorts. Participants will receive a single IV dose of either RO7126209 or placebo. RO7126209 doses will be administered in ascending order. After the starting dose, subsequent doses will be selected in an adaptive manner during study conduct based on emerging safety, tolerability and PK data.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Single-Center, Randomized, Adaptive, Investigator/Subject Blind, Single Ascending Dose, Placebo-Controlled Phase I Study to Investigate the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Intravenously Administered RO7126209 in Healthy Participants
Estimated Study Start Date : August 3, 2019
Estimated Primary Completion Date : April 24, 2020
Estimated Study Completion Date : April 24, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1: Dose level 1 of RO7126209 and placebo
Healthy volunteers will be administered a single intravenous dose level 1 of RO7126209 or matching placebo as per schedule specified in the respective arm.
Drug: RO7126209
Participants will be administered a single-ascending intravenous doses of RO7126209 with at least 2 weeks between each dose level. After the starting dose, the subsequent doses will be selected in an adaptive design. Sentinel dosing will be employed.

Drug: Placebo
Participants will be administered a single intravenous dose of matching placebo.

Experimental: Cohort 2: Dose level 2 of RO7126209 and placebo
Healthy volunteers will be administered a single intravenous dose level 2 of RO7126209 or matching placebo as per schedule specified in the respective arm.
Drug: RO7126209
Participants will be administered a single-ascending intravenous doses of RO7126209 with at least 2 weeks between each dose level. After the starting dose, the subsequent doses will be selected in an adaptive design. Sentinel dosing will be employed.

Drug: Placebo
Participants will be administered a single intravenous dose of matching placebo.

Experimental: Cohort 3: Dose level 3 of RO7126209 and placebo
Healthy volunteers will be administered a single intravenous dose level 3 of RO7126209 or matching placebo as per schedule specified in the respective arm.
Drug: RO7126209
Participants will be administered a single-ascending intravenous doses of RO7126209 with at least 2 weeks between each dose level. After the starting dose, the subsequent doses will be selected in an adaptive design. Sentinel dosing will be employed.

Drug: Placebo
Participants will be administered a single intravenous dose of matching placebo.

Experimental: Cohort 4: Dose level 4 of RO7126209 and placebo
Healthy volunteers will be administered a single intravenous dose level 4 of RO7126209 or matching placebo as per schedule specified in the respective arm.
Drug: RO7126209
Participants will be administered a single-ascending intravenous doses of RO7126209 with at least 2 weeks between each dose level. After the starting dose, the subsequent doses will be selected in an adaptive design. Sentinel dosing will be employed.

Drug: Placebo
Participants will be administered a single intravenous dose of matching placebo.

Experimental: Cohort 5: Dose level 5 of RO7126209 and placebo
Healthy volunteers will be administered a single intravenous dose level 5 of RO7126209 or matching placebo as per schedule specified in the respective arm.
Drug: RO7126209
Participants will be administered a single-ascending intravenous doses of RO7126209 with at least 2 weeks between each dose level. After the starting dose, the subsequent doses will be selected in an adaptive design. Sentinel dosing will be employed.

Drug: Placebo
Participants will be administered a single intravenous dose of matching placebo.




Primary Outcome Measures :
  1. Incidence of Adverse Events [ Time Frame: Up to approximately 57 days ]
  2. Incidence of Abnormal Laboratory Findings [ Time Frame: Up to approximately 57 days ]
  3. Incidence of Abnormal Vital Signs and Electrocardiogram (ECG) Parameters [ Time Frame: Up to approximately 57 days ]

Secondary Outcome Measures :
  1. Concentration at the End of Infusion (Cend) of RO7126209 [ Time Frame: Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43, and 57 ]
  2. Area Under the Plasma Concentration Versus Time Curve From Zero to 24 h Postdose (AUC0-24h) of RO7126209 [ Time Frame: Days 1 and 2 ]
  3. Area Under the Plasma Concentration Versus Time Curve From Zero to 168h (AUC0-168h) of RO7126209 [ Time Frame: Days 1, 2, 3, 4, 5, and 8 ]
  4. Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Measurable Concentration (AUC0-last) of RO7126209 [ Time Frame: Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43, and 57 ]
  5. Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) [ Time Frame: Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43, and 57 ]
  6. Terminal Rate Constant of RO7126209 [ Time Frame: Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43, and 57 ]
  7. Apparent Terminal Half-Life (T1/2) of RO7126209 [ Time Frame: Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43, and 57 ]
  8. Total Body Clearance Calculated as Dose/AUC (CL) of RO7126209 [ Time Frame: Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43, and 57 ]
  9. Volume of Distribution at Steady-State (V) of RO7126209 [ Time Frame: Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43, and 57 ]
  10. CSF Concentration of RO7126209 [ Time Frame: Baseline, Day 3 or Day 5 ]
  11. Incidence of Anti-RO7126209 Antibodies (ADAs) [ Time Frame: Days 1, 8, 29, and 57 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy status is defined by the absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, ophthalmologic examination, hematology, blood chemistry, coagulation, serology, and urinalysis.
  • Body mass index (BMI) of 18-30 kg/m2 inclusive
  • During the treatment period and until the final follow up visit, agreement to: (1) Remain abstinent or use contraceptive measures such as a condom plus an additional contraceptive method that together result in a failure rate of <1% per year, with a partner who is a woman of childbearing potential. (2) With pregnant female partner, remain abstinent or use contraceptive measures such as a condom to avoid exposing the embryo. (3) Refrain from donating sperm from Day 1 of the study until 90 days after last dose.

Exclusion Criteria:

  • 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 any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardio-vascular, endocrinological, ophthalmologic, hematological or allergic disease, metabolic disorder, cancer or cirrhosis.
  • Any suspicion or history of alcohol abuse and/or suspicion of regular consumption of drug of abuse within the last 5 years.
  • Positive result on hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) 1 and 2.
  • History or presence of clinically significant ECG abnormalities or cardiovascular disease.
  • Clinically-significant abnormalities in laboratory test results.
  • Any major illness within one month before the screening examination or any febrile illness within one week prior to screening and up to first dose administration.
  • Impaired hepatic function as indicated by screening aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >=1.5 x the upper limit of normal (ULN) or abnormal total bilirubin unless due to Gilbert's disease.
  • Any clinically relevant history of hypersensitivity or allergic reactions, either spontaneous or following drug administration, or exposure to foods or environmental agents.
  • History of hypersensitivity to biologic agents or any of the excipients in the formulation.
  • History of raised intra-cerebral pressure or vertebral joint pathology
  • Use of prohibited medication or herbal remedies as described in the section of concomitant medications
  • Prior administration of gantenerumab (RO4909832)
  • Any vaccination within two months prior to Day 1
  • Participation in an investigational drug medicinal product or medical device study within 30 days before screening or within seven times the elimination half-life if known, whichever is longer.
  • Participants who regularly smoke more than 5 cigarettes daily or equivalent and are unable or unwilling not to smoke during the in-house period.
  • Donation or loss of blood over 500 mL within three months prior to Day 1 and donation of blood for the duration of the study until follow-up.
  • Evidence of clinically significant brain magnetic resonance imaging (MRI) findings, including lacunar infarct, territorial infarct or macroscopic hemorrhage, microbleed or area of leptomeningeal hemosiderosis, or deep white matter lesions corresponding to an overall Fazekas score of ≥ 2.
  • Claustrophobia, presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin, or body that would contraindicate an MRI scan.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04023994


Contacts
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Contact: Reference Study ID Number: BP41192 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
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United States, North Carolina
PRA Health Sciences Recruiting
Raleigh, North Carolina, United States, 27612
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04023994     History of Changes
Other Study ID Numbers: BP41192
First Posted: July 18, 2019    Key Record Dates
Last Update Posted: July 18, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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

Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders