A Study To Assess Distribution Of RO7248824 In The Central Nervous System Following Single Intrathecal Doses Of [89zr] Labeled RO7248824 In Healthy Male Participants

Brief Title

A Study To Assess Distribution Of RO7248824 In The Central Nervous System Following Single Intrathecal Doses Of [89zr] Labeled RO7248824 In Healthy Male Participants

Official Title

A Non-Randomized, Open-Label, Adaptive, Single Center, Positron Emission Tomography (Pet) Study To Assess Distribution Of RO7248824 In The Central Nervous System Following Single Intrathecal Doses Of [89zr] Labeled RO7248824 In Healthy Male Participants

Brief Summary

      The aim of Study BP41660 is to quantify the amount and concentration of [89Zr]DFO-RO7248824
      in the brain with positron emission tomography (PET) following a single sub-pharmacological
      dose of RO7248824 and [89Zr]DFO-RO7248824 administered via IT injection to healthy
      participants.
    


Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Quantification of [89Zr]DFO-RO7248824 distribution within the central nervous system (CNS)

Secondary Outcome

 Percentage of participants with adverse events (AEs)

Condition

Angelman Syndrome

Intervention

RO7248824

Study Arms / Comparison Groups

 RO7248824
Description:  In Part 1 of the study RO7248824 and [89Zr]-labeled RO7248824 will be administered as a single bolus IT injection following a standard IT Administration procedure. In Part 2 of the study, it is planned to test up to 3 additional IT procedures. This part is tentative with regard to its conduct and the number of procedures that may be tested.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

26

Start Date

April 29, 2021

Completion Date

January 5, 2022

Primary Completion Date

November 18, 2021

Eligibility Criteria

        Inclusion Criteria:

        Informed Consent

          1. Able and willing to provide written informed consent and to comply with the study
             protocol according to ICH and local regulations

             Age

          2. Aged from 25 to to 55 years at the time of dosing

             Type of Participants and Disease Characteristics

          3. Overtly healthy (defined by absence of evidence of any active or chronic disease) as
             determined by medical evaluation including:

               -  A detailed medical and surgical history

               -  A complete physical and neurological examination

               -  Vital signs

               -  12-lead ECG

               -  Hematology

               -  Coagulation

               -  Blood chemistry

               -  Serology and urinalysis

          4. Fluent in the language of the Investigator and study staff, and able to communicate
             with the study staff

             Weight

          5. Body mass index (BMI) of ≥ 18 to ≤ 30 kg/m2 at screening

             Sex

          6. Male participants only who, for 3 months after the dosing of RO7248824, agree to:

               -  Remain abstinent (refrain from heterosexual intercourse) or use contraceptive
                  barrier measures such as a condom, with a female partner of childbearing
                  potential, or pregnant female partner, to avoid exposing the embryo

               -  Refrain from donating sperm

        Exclusion Criteria:

        Medical Conditions

          1. Any condition or disease detected during the medical interview/physical examination
             that would render the participant unsuitable for the study, place the participant at
             undue risk or interfere with the ability of the participant to complete the study, as
             determined by the Investigator

          2. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,
             endocrine, hematological, or neurological disorders capable of significantly altering
             the absorption, metabolism, or elimination of drugs; constituting a risk when taking
             the study treatment; or interfering with the interpretation of data

          3. History or presence of clinically significant cardiovascular disease in the opinion of
             the Investigator

          4. History or presence of an abnormal ECG that is clinically significant in the
             Investigator's opinion

          5. Uncontrolled arrhythmias or history of clinically significant arrhythmias

          6. Confirmed abnormal blood pressure

          7. Abnormal pulse rate

          8. Abnormalities in brain and

          9. Evidence or history of clinically significant back pain, back pathology and/or back
             injury

         10. Evidence or history of significant active bleeding or coagulation disorder

         11. Allergy to lidocaine (Xylocaine) or its derivatives

         12. Medical or surgical conditions for which LP or associated procedures is
             contraindicated

         13. Alanine transaminase (ALT) and bilirubin > 1.5 x upper limit of normal (ULN)

         14. Current or chronic history of liver disease, or known hepatic or biliary abnormalities

         15. History of convulsions or history of loss of consciousness

         16. Sensitivity to any of the study treatments, or components thereof, or drug or other
             allergy that, in the opinion of the Investigator, contraindicates the participation in
             the study

         17. Any major illness within one month before the screening examination or any febrile
             illness within one week prior to screening and up to first study drug administration

         18. Clinically significant abnormalities in laboratory test results

             Prior/Concomitant Therapy

         19. Used or intends to use any prohibited medications

         20. Likely to need concomitant medication during the study period

             Prior/Concurrent Clinical Study Experience

         21. Participating in an investigational drug or device study within 60 days prior to
             screening, as calculated from the day of follow-up from the previous study, or more
             than 4 participations in an investigational drug or device study within a year prior
             to dosing

         22. Previously (within the past 12 months from dosing) included in medical research and/or
             a medical protocol involving PET or radiological investigations, or other exposure to
             ionizing radiation, which combined with this study would result in an effective dose
             of 10 mSv or more

             Diagnostic Assessments

         23. Positive test for drugs of abuse or alcohol

         24. Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test
             result at screening or within 3 months prior to first dose of study treatment)

         25. Evidence of HIV infection and/or positive human HIV antibodies

             Other Exclusions

         26. Any suspicion or history of alcohol abuse and/or suspicion of regular consumption of
             drug of abuse or previous history of or treatment for a dependence disorder

         27. Regularly smoking more than 5 cigarettes daily or equivalent and unable or unwilling
             not to smoke or not to use other nicotine containing products during the in-house
             period

         28. Donated over 500 mL of blood or blood products or had significant blood loss within 3
             months prior to screening

         29. Under judicial supervision, guardianship or curatorship

         30. Not able to undergo PET, CT, or MRI scans

         31. Previous lumbar surgery that is likely, in the opinion of the Investigator or surgical
             team, to make IT injection unduly difficult or hazardous

         32. Scoliosis or spinal deformity preventing IT injection
      

Gender

Male

Ages

25 Years - 55 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Clinical Trials, 888-662-6728, [email protected]

Location Countries

Netherlands

Location Countries

Netherlands

Administrative Informations


NCT ID

NCT04863794

Organization ID

BP41660


Responsible Party

Sponsor

Study Sponsor

Hoffmann-La Roche


Study Sponsor

Clinical Trials, Study Director, Hoffmann-La Roche


Verification Date

November 2021