Clazakizumab for Frailty

(RIGHT Trial)

Overseen By Michelle E. Danielson, PhD

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Anne B. Newman

Must not be taking: Immune modulators, Warfarin

Disqualifiers: Advanced neurologic disorder, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 24 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn about the effects of inflammation-lowering therapy on mobility and disability in older adults. The main questions it aims to answer are: * Will therapy improve walking speed/pace? * Will therapy improve levels of blood inflammation markers and other indicators of physical, cognitive and immune function? Participants will be asked to receive injections of drug or placebo every 4 weeks for 24 weeks. They will also be asked to undergo testing that assesses physical function, thinking ability and brain health, breathing capacity, and blood vessel stiffness, and will have blood samples collected to measure immune function and to create a bank of samples for future testing. Comparisons will be made between those who receive drug and those who receive placebo.

Will I have to stop taking my current medications?

The trial requires that participants do not use chronic immune modulating medications, such as corticosteroids or biologics, and they cannot be on Warfarin. If you are taking these medications, you may need to stop them to participate.

How is the drug Clazakizumab unique in treating frailty?

Clazakizumab is unique in treating frailty because it targets interleukin-6 (IL-6), a protein associated with inflammation and frailty, potentially addressing the underlying biological processes rather than just symptoms. ^{1 2 3 4 5}

Research Team

Anne B. Newman, MD, MPH

Principal Investigator

University of Pittsburgh

Eligibility Criteria

The RIGHT Study is for people aged 70 or older with certain levels of inflammation in their blood, up-to-date vaccinations, and difficulty walking but able to walk unassisted. Excluded are those living in nursing homes, with severe sensory loss, chronic infections like TB or hepatitis, recent hospitalizations, serious heart/lung disease requiring oxygen, uncontrolled diabetes/cancer history, abnormal lab results (blood counts/cholesterol), allergies to monoclonal antibodies, on blood thinners or immune modulators.

Inclusion Criteria

My walking speed is between slow and moderate.

IL-6 level between 2.5 pg/ml and less than 30.0 pg/ml

I am 70 years old or older.

Exclusion Criteria

I have had cancer before.

I am currently taking Warfarin.

I have not had any serious infections in the last 2 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-8 weeks

2 visits (in-person)

Treatment

Participants receive Clazakizumab or placebo injections every 4 weeks for 24 weeks, with assessments of physical and cognitive function, blood samples, and safety monitoring.

24 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and serious adverse events.

20 weeks

5 visits (in-person)

Treatment Details

Interventions

• Clazakizumab

Trial Overview This trial tests Clazakizumab against a placebo to see if it can improve walking speed and reduce inflammation markers in the elderly. Participants will receive injections every four weeks for six months and undergo various physical function tests along with cognitive assessments and blood sample collections for immune function analysis.

Participant Groups

Group I: Clazakizumab Experimental Treatment 1 Intervention

Participants received Clazakizumab 5 mg as a subcutaneous injection every 4 weeks for 24 weeks

Group II: Placebo Placebo Group 1 Intervention

Participants received Clazakizumab placebo as a 5 mg subcutaneous injection every 4 weeks for 24 weeks

Clazakizumab is already approved in United States for the following indications:

Approved in United States as Clazakizumab for:

• Organ rejection in kidney transplant patients

Who Is Running the Clinical Trial?

Anne B. Newman

Lead Sponsor

Trials

1

Recruited

60+

CSL Behring

Industry Sponsor

Trials

204

Recruited

1,207,000+

Dr. Paul McKenzie

CSL Behring

Chief Executive Officer since 2023

PhD in Chemical Engineering from Carnegie Mellon University, B.S. in Chemical Engineering from the University of Pennsylvania

Dr. Bill Mezzanotte

CSL Behring

Chief Medical Officer since 2021

MD from Duke University

Findings from Research

In a pilot study involving 78 frail patients over a year, those who discontinued antihypertensive medications showed higher skeletal muscle index (SMI) scores at the start, suggesting better muscle health compared to those who continued their medication.

After one year, the discontinuation group experienced significant improvements in physical strength and performance, indicating that stopping antihypertensive drugs may enhance physical capabilities in frail patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of discontinuation of antihypertensive drugs on frailty syndrome in outpatients: a 1-year prospectively designed retrospective chart-review pilot study. Hasegawa, S., Mizokami, F., Mase, H., et al.[2022]

In a case-control study of 59 elderly patients (average age 72), metformin was found to significantly reduce the risk of frailty syndrome, with an adjusted odds ratio of 0.043, indicating a strong protective effect.

The study suggests that metformin may be beneficial for elderly diabetics by helping to prevent frailty, a condition that can lead to increased health complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between metformin and frailty syndrome in elderly people with type 2 diabetes. Sumantri, S., Setiati, S., Purnamasari, D., et al.[2019]

In a study of 345 rheumatoid arthritis patients, those who maintained a stable disease activity score (DAS28-ESR < 3.2) were four times more likely to improve their frailty status over two years compared to those with unstable disease activity.

The results indicate that simply controlling disease activity with medication is not enough to enhance frailty status, highlighting the need for additional strategies beyond drug treatment to support patient improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Well-controlled disease activity with drug treatment will not improve the frailty status of RA patients to robust state: A multicenter observational study (T-FLAG). Ohashi, Y., Takahashi, N., Sobue, Y., et al.[2023]

In a study of 581 men aged 60-90, higher levels of serum interleukin-6 (IL-6) were found to be positively associated with frailty, indicating that IL-6 may play a role in the aging process and physical decline.

The association between IL-6 and frailty was partially influenced by age and certain medications that affect inflammation, suggesting that managing inflammation could be important in addressing frailty in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between serum interleukin-6 and frailty in older men: cross-sectional data. Tembo, MC., Holloway-Kew, KL., Bortolasci, CC., et al.[2022]

In a study of 1,280 participants aged 65 and older, frailty was found to significantly increase the likelihood of healthcare utilization due to medication-related harm, with an odds ratio of 10.06, indicating a strong association independent of age, gender, and number of medications.

The research suggests that addressing frailty and reducing inappropriate polypharmacy could help lower the incidence of medication-related harm, potentially leading to decreased healthcare utilization among older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multi-centre cohort study on healthcare use due to medication-related harm: the role of frailty and polypharmacy. Stevenson, JM., Parekh, N., Chua, KC., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Effects of discontinuation of antihypertensive drugs on frailty syndrome in outpatients: a 1-year prospectively designed retrospective chart-review pilot study. [2022]

2. Indonesia pubmed.ncbi.nlm.nih.gov

Relationship between metformin and frailty syndrome in elderly people with type 2 diabetes. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Well-controlled disease activity with drug treatment will not improve the frailty status of RA patients to robust state: A multicenter observational study (T-FLAG). [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Association between serum interleukin-6 and frailty in older men: cross-sectional data. [2022]

5. England pubmed.ncbi.nlm.nih.gov

A multi-centre cohort study on healthcare use due to medication-related harm: the role of frailty and polypharmacy. [2022]