E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cachexia, a loss of weight due to the catabolism of muscle and fat tissue. The progressive worsening of cachexia impacts a cancer patient’s quality of life and contributes to poor survival. |
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E.1.1.1 | Medical condition in easily understood language |
Cachexia is a loss of appetite with wasting of the body and weakness due to a severe chronic illness such as cancer. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064015 |
E.1.2 | Term | Cancer cachexia |
E.1.2 | System Organ Class | 100000004861 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of ponsegromab compared with placebo on body weight in participants with cancer, cachexia, and elevated concentrations of GDF-15 |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the effect of ponsegromab compared to placebo on physical activity and gait as measured by wearable digital sensors in participants with cancer, cachexia, and elevated concentrations of GDF-15. - To evaluate the effect of ponsegromab compared to placebo on the appetite-related symptoms as measured by FAACT in participants with cancer, cachexia, and elevated concentrations of GDF-15. - To evaluate the effect of ponsegromab compared to placebo on anorexia/appetite nausea, vomiting, and fatigue measured by the CRCSD, Pfizer-developed instrument, in participants with cancer, cachexia, and elevated concentrations of GDF-15. - To characterize the safety and tolerability of repeated SC administrations of ponsegromab compared to placebo in participants with cancer, cachexia, and elevated concentrations of GDF-15. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age and Sex: 1.Participants aged ≥18 years (or the minimum age of consent if >18 in accordance with local regulations) at Screening who have signed informed consent. a.A female participant is eligible to participate if she is not pregnant or breastfeeding. b.Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants. Disease Characteristics: 2.Documented histologic or cytologic active diagnosis of NSCLC, PANC, or CRC and are currently receiving, or have completed, SOC treatment for this cancer (which may include systemic therapy). 3.Cachexia defined by Fearon criteria of weight loss as (See Section 8.1.1 for details if the participant’s body weight is unavailable from medical record): •BMI <20 kg/m2 with involuntary weight loss of >2% within 6 months prior to Screening; or •involuntary weight loss of >5% within 6 months prior to screening irrespective of BMI. 4.Serum GDF-15 concentrations of ≥1.5 ng/mL (as measured using the Investigational Use Only Roche Elecsys GDF 15 assay)10 at Screening. 5.Participants who are assessed by the investigator to have: •an ECOG PS ≤3, and, •a life expectancy of at least 4 months to be able to complete Part A. Other Inclusion Criteria: 6.Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. |
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E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply: Medical Conditions: 1.Current active reversible causes of decreased food intake, as determined by the Investigator. These causes may include, but are not limited to: •NCI CTCAE Grade 3 or 4 oral mucositis; •NCI CTCAE Grade 3 or 4 GI disorders (nausea, vomiting, diarrhea, and constipation); •Mechanical obstructions interfering with the participant’s ability to eat. 2.Receiving tube feedings or parenteral nutrition (either total or partial) at the time of Screening or Randomization. 3.Cachexia caused by other reasons, as determined by the investigator, including, but not limited to: •Severe COPD requiring use of home O2; •NYHA class III-IV heart failure; •AIDS. 4.Undergoing major surgery (central venous access placement and tumor biopsies are not considered major surgery) within 4 weeks prior to randomization. Patient must have recovered from acute effects of surgery prior to Screening. Patient should not have plans to undergo major surgical procedures during the study. 5.Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study. 6.History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibody. Prior/Concurrent Therapy: 7.Current use of any prohibited concomitant medication(s) within 4 weeks prior to first dose of study intervention. Refer to Section 6.9. Prior/Concurrent Clinical Study Experience: 8.Concurrent administration of investigational products (including drug, biologic agents, or vaccines) are not permitted within 30 days (or as determined by the local requirement) or 5 half lives (whichever is longer) of the first dose of study intervention. Refer to Section 6.9 . 9.Enrollment and previously dosed in a prior study with ponsegromab. Diagnostic Assessments: 10.History of severe liver disease or cirrhosis, unrelated to metastatic cancer. Potential study participants with the following liver function test abnormalities will also be excluded; result may be confirmed by a single repeat test, if necessary: •Total bilirubin ≥1.5 × ULN (except for Gilbert’s syndrome) •AST >3 × ULN (AST > 5X ULN if there is liver involvement by the tumor) •ALT >3 × ULN (ALT >5X ULN if there is liver involvement by the tumor) •Alkaline phosphatase >3 x ULN (Alkaline phosphatase >5X ULN if there is liver involvement by the tumor and/or in case of bone metastases, or if considered related to prior surgery e.g. pancreaticoduodenectomy). 11.Renal disease requiring dialysis. Other Exclusion Criteria: 12.Current adherence to a calorie-restricted diet with the intention weight loss. 13.Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in body weight at Week 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Change from baseline in physical activity and gait endpoints measured with remote digital sensors at Week 12. •Moderate to vigorous physical activity time; •Sedentary activity time; •Non sedentary activity time; •Total vector magnitude; •Mean activity level during M6min; •Mean gait speed; •95th percentile gait speed. •Change from baseline in FAACT sub scale scores at Week 12: •FAACT-ACS; •FAACT-5IASS •Change from baseline score for the questions from the CRCSD at Week 12 related to: -Anorexia/appetite; -Nausea and vomiting; - Fatigue. •Incidence of adverse events, safety laboratory tests, vital signs and ECG abnormalities |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-week 12 - thorough the study for secondary endpoint |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Taiwan |
Australia |
Canada |
China |
Japan |
United States |
Bulgaria |
Czechia |
Hungary |
Poland |
Slovakia |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 28 |