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HealthyPhase 1NCT02667223

Pharmacokinetic and Pharmacodynamic Study of Bococizumab Alone and When Combined With Recombinant Human Hyaluronidase

A Phase 1 study testing Cohort 1: bococizumab 150 mg + rHuPH20, Cohort 2: bococizumab 300 mg and Cohort 3: bococizumab 300 mg + rHuPH20 in people with Healthy and Hypercholesterolemia, run by Pfizer at 1 site in Belgium.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a Phase 1, open-label, single-dose, randomized, dose escalation study in healthy and hypercholesterolemic subjects. Each subject will receive 1 of 5 treatments as a single subcutaneous injection. Subjects will remain confined at the research clinic for approximately 2 days. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Healthy, Hypercholesterolemia
What is being tested?
Cohort 1: bococizumab 150 mg + rHuPH20, Cohort 2: bococizumab 300 mg and Cohort 3: bococizumab 300 mg + rHuPH20
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteBelgium
Study dates
Feb 2016to Jul 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Healthy and hypercholesterolemic subjects between the ages of 18 and 65 years.
  • Healthy subjects must have fasting LDL-C >/= 70 to </= 190 mg/dL at two qualifying visits.
  • Hypercholesterolemic subjects must be on a stable daily dose of statin for at least 45 days before dosing and fasting LDL-C must be >/= 70 mg/dL.

Who cannot join

  • Use of prescription or non-prescription drugs within 7 days or 5 half-lives (whichever) is longer prior to the first dose of study medication. For hypercholesterolemic subjects the use of statin class medication is allowed.
  • Prior exposure to bococizumab (also known as PF-04950615 or RN316) or other investigational PCSK9 inhibitors.
  • Treatment with monoclonal antibodies within 6 months or 5 half-lives (whichever is longer) before dosing.

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • Pfizer Clinical Research Unit

    Brussels, B-1070

Other trials in Belgium

About this study

Official title: A Phase 1, Open Label, Randomized, Single Dose, Dose Escalation Study To Assess The Subcutaneous Pharmacokinetics And Pharmacodynamics Of Bococizumab (pf 04950615) Alone And In Co Mixture With Recombinant Human Hyaluronidase (rhuph20, Pf 06744547) In Healthy And Hypercholesterolemic Adult Subjects

This is a Phase 1, open-label, single-dose, randomized, dose escalation study in healthy and hypercholesterolemic subjects. Each subject will receive 1 of 5 treatments as a single subcutaneous injection. Subjects will remain confined at the research clinic for approximately 2 days. After discharge, subjects will return to the research clinic 15 times during 12 weeks.

Being tested
Cohort 1: bococizumab 150 mg + rHuPH20, Cohort 2: bococizumab 300 mg, Cohort 3: bococizumab 300 mg + rHuPH20, Cohort 5: bococizumab 450 mg + rHuPH20, Cohort 4: bococizumab 300 mg + rHuPH20
Keywords
pharmacokinetics, pharmacodynamics, RN316, recombinant human hyaluronidase
Medical subject headings
Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cohort 1: bococizumab 150 mg + rHuPH20Biological

    bococizumab 150 mg + rHuPH20 administered SC to healthy volunteers

  • Cohort 2: bococizumab 300 mgBiological

    bococizumab 300 mg administered SC to healthy volunteers

  • Cohort 3: bococizumab 300 mg + rHuPH20Biological

    bococizumab 300 mg + rHuPH20 administered SC to healthy volunteers

  • Cohort 5: bococizumab 450 mg + rHuPH20Biological

    bococizumab 450 mg + rHuPH20 administered SC to healthy volunteers

  • Cohort 4: bococizumab 300 mg + rHuPH20Biological

    bococizumab 300 mg + rHuPH20 administered SC to subjects with hypercholesterolemia receiving a statin

Study groups in NCT02667223
Study groupRoleWhat they receive
Cohort 1: bococizumab 150 mg + rHuPH20Experimentalbococizumab 150 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers
Receives: Biological: Cohort 1: bococizumab 150 mg + rHuPH20
Cohort 2: bococizumab 300 mgActive comparatorbococizumab 300 mg administered subcutaneously to healthy volunteers
Receives: Biological: Cohort 2: bococizumab 300 mg
Cohort 3: bococizumab 300 mg + rHuPH20Experimentalbococizumab 300 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers
Receives: Biological: Cohort 3: bococizumab 300 mg + rHuPH20
Cohort 5: bococizumab 450 mg + rHUPH20Experimentalbococizumab 450 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers
Receives: Biological: Cohort 5: bococizumab 450 mg + rHuPH20
Cohort 4: bococizumab 300 mg + rHuPH20Experimentalbococizumab 300 mg co-mixed with rHuPH20 and administered subcutaneously to subjects with hypercholesterolemia receiving a statin
Receives: Biological: Cohort 4: bococizumab 300 mg + rHuPH20

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. AUCinf of bococizumab

    Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞), if data permits (otherwise AUClast will be used).

    Measured: Day 1 - Day 85

  2. Cmax of bococizumab

    Maximum Observed Plasma Concentration (Cmax)

    Measured: Day 1 - Day 85

Secondary outcomes (14)

  1. Tmax

    Time to Reach Maximum Observed Plasma Concentration (Tmax)

    Measured: Day 1 - Day 85

  2. CL/F

    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance is influenced by the fraction of the dose absorbed. Clearance is estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

    Measured: Day 1 - Day 85

  3. Vz/F

    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after dose (Vz/F) is influenced by the fraction absorbed.

    Measured: Day 1 - Day 85

  4. t1/2

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

    Measured: Day 1 - Day 85

  5. LDL-C at Week 4

    Absolute value, and absolute change and % change in LDL cholesterol at Week 4 following bococizumab administration alone and when co-mixed with rHuPH20.

    Measured: Baseline to Week 4

  6. MaxELDL-C

    Maximum LDL-C lowering calculated using absolute LDL-C values

    Measured: Baseline up to Day 85

  7. Tmax, LDL-C

    Time to MaxELDL-C calculated using absolute LDL-C values

    Measured: Baseline up to Day 85

  8. AUEC85

    Area under the LDL-C concentration-time curve calculated using absolute LDL-C values

    Measured: Baseline up to Day 85

  9. AEs

    Incidence, severity, and causal relationship of treatment-emergent adverse events (TEAEs)

    Measured: Baseline up to Day 85

  10. Laboratory tests

    Incidence of abnormal and clinically relevant safety laboratory tests including clinical chemistry and hematology

    Measured: Baseline up to Day 85

  11. Vital signs

    Incidence of abnormal and clinically relevant vital signs

    Measured: Baseline up to Day 85

  12. AUClast of bococizumab

    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

    Measured: Day 1 - Day 85

  13. ADA

    Incidence and titer of Anti-Drug Antibodies (ADA) following administration of bococizumab alone and when co-mixed with rHuPH20.

    Measured: Day 1 - Day 85

  14. nAb

    Incidence and titer of neutralizing antibodies (nAb), if applicable, following administration of bococizumab alone and when co-mixed with rHuPH20.

    Measured: Day 1- Day 85

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2016 (estimated)
  2. Study startFeb 2016
  3. Primary completionJul 2016
  4. Study completionJul 2016

Why it stopped: The study was terminated early on July 8, 2016 due to business priorities regarding study execution.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02667223
Sponsor's protocol ID
B1481051
Other IDs
2015-003568-36, 2015
Status last verified
Oct 2016
First submitted
6 Jan 2016
Last updated
21 Oct 2016
Results posted
No
Data monitoring committee
No

Publications

  • Bass A, Plotka A, Mridha K, Sattler C, Kim AM, Plowchalk DR. Pharmacokinetics, pharmacodynamics, and safety of bococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, in healthy subjects when administered in co-mixture with recombinant human hyaluronidase: A phase 1 randomized trial. Health Sci Rep. 2018 Jul 18;1(9):e61. doi: 10.1002/hsr2.61. eCollection 2018 Sep.

    PubMed 30623096

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cohort 1: bococizumab 150 mg + rHuPH20, Cohort 2: bococizumab 300 mg and Cohort 3: bococizumab 300 mg + rHuPH20 in people with Healthy and Hypercholesterolemia, run by Pfizer at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study was terminated early on July 8, 2016 due to business priorities regarding study execution.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUCinf of bococizumab (time frame: Day 1 - Day 85). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02667223, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2016.

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