Ponsegromab for Cachexia

(PROACC-1 Trial)

Recruiting at 126 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pfizer

Disqualifiers: Tube feedings, Parenteral nutrition, Renal disease, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

187 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests Ponsegromab, a new drug, on cancer patients who are losing weight and have high GDF 15 levels. The drug aims to lower GDF 15 to improve appetite and reduce weight loss.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What is known about the safety of Ponsegromab in humans?

Ponsegromab has been studied for safety in a 24-week trial involving adults with advanced cancer and cachexia. This study was designed to assess its safety and tolerability, indicating that it has undergone initial safety evaluations in humans. ^{1 2 3 4 5}

How is the drug Ponsegromab unique in treating cachexia?

Ponsegromab is unique because it is a monoclonal antibody (a type of protein made in the lab to bind to specific substances in the body) that targets and blocks GDF-15, a protein associated with cachexia in cancer patients, which is different from other treatments that focus on stimulating appetite or increasing weight. ^{1 2 6 7 8}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adults with non-small cell lung, pancreatic, or colorectal cancer who are experiencing cachexia (significant weight loss due to illness) as defined by Fearon criteria. They must have elevated GDF-15 protein levels and be able to consent to the study. People with tube feedings, other causes of cachexia, severe allergies to monoclonal antibodies, or poor kidney/liver function cannot join.

Inclusion Criteria

Serum GDF-15 concentrations

Signed informed consent

I have significant weight loss and muscle loss.

Exclusion Criteria

My weight loss is not due to cancer.

I am currently on tube feedings or IV nutrition.

My kidney or liver is not working properly.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ponsegromab or placebo subcutaneously every 4 weeks for 12 weeks

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of ponsegromab treatment every 4 weeks for up to one year

Up to 1 year

Treatment Details

Interventions

• Placebo for Ponsegromab
• Ponsegromab

Trial Overview The trial is testing the effectiveness and safety of a drug called Ponsegromab in comparison to a placebo in patients suffering from cancer-related cachexia. Participants will either receive Ponsegromab or a placebo without knowing which one they're getting.

Participant Groups

Group I: Double-Blind ponsegromab Treatment medium dose followed by Open Label ponsegromab Treatment Experimental Treatment 1 Intervention

ponsegromab medium dose subcutaneous injection every 4 weeks

Group II: Double-Blind ponsegromab Treatment low dose followed by Open Label ponsegromab Treatment Experimental Treatment 1 Intervention

ponsegromab low dose subcutaneous injection every 4 weeks

Group III: Double-Blind ponsegromab Treatment high dose followed by Open Label ponsegromab Treatment Experimental Treatment 1 Intervention

ponsegromab high dose subcutaneous injection every 4 weeks

Group IV: Double-Blind Placebo Treatment followed by Open-Label ponsegromab Treatment Placebo Group 1 Intervention

Match placebo subcutaneous injection every 4 weeks

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

In a study of 13 patients with advanced cancer cachexia, a combination of the anabolic β2-agonist formoterol and the appetite stimulant megestrol acetate was found to be safe and well tolerated over an 8-week period, with few adverse reactions reported.

Of the patients who completed the treatment, 86% showed significant improvements in muscle size and/or function, indicating that this combination therapy could effectively address muscle loss in cancer cachexia and should be explored further in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of formoterol fumarate combined with megestrol acetate in cachectic patients with advanced malignancy. Greig, CA., Johns, N., Gray, C., et al.[2021]

In a phase Ib study involving 10 patients with advanced cancer and cachexia, ponsegromab was well tolerated with no significant adverse effects, indicating its safety for use in this population.

Ponsegromab effectively reduced serum GDF-15 levels and led to an average weight increase of 4.63 kg (about 6.6% from baseline) over 12 weeks, along with improvements in physical activity and quality of life, suggesting its potential efficacy in treating cachexia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1b First-In-Patient Study Assessing the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Ponsegromab in Participants with Cancer and Cachexia. Crawford, J., Calle, RA., Collins, SM., et al.[2023]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Phase I/II trial of formoterol fumarate combined with megestrol acetate in cachectic patients with advanced malignancy. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

A Phase 1b First-In-Patient Study Assessing the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Ponsegromab in Participants with Cancer and Cachexia. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Pilot clinical trial of macimorelin to assess safety and efficacy in patients with cancer cachexia. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of mirtazapine for cancer-related cachexia and anorexia. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Current Therapeutic Targets in Cancer Cachexia: A Pathophysiologic Approach. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Studies of high-dose megestrol acetate: potential applications in cachexia. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Pharmacological treatment of cachexia: any progress? [2017]