Cachexia, Colorectal Cancer, Fatigue, Loss of Appetite, Non-small Cell Lung Cancer, Pancreatic Cancer
Conditions
Keywords
cancer, anorexia, cachexia, weight loss, loss of appetite, fatigue
Brief summary
Study to evaluate the efficacy, safety and tolerability of ponsegromab compared to placebo in patients with cancer, cachexia, and elevated GDF 15.
Detailed description
A 12 week double blind study to evaluate the efficacy, safety and tolerability of ponsegromab compared to placebo in patients with cancer, cachexia, and elevated GDF 15. During the initial 12-week treatment period (Part A), a total of 3 doses of ponsegromab or placebo will be administered 4 weeks apart subcutaneously. Each dose contains two injections. Part B is an optional open-label treatment period consisting of ponsegromab administered every 4 weeks subcutaneously for up to one year. Part B does not include placebo. Assessments include: * Body weight measurements * Measure the impact of ponsegromab compared to placebo on physical activity. * Measure the impact of ponsegromab compared to placebo on appetite, fatigue, nausea, vomiting and physical function questionnaires. * Blood samples to evaluate safety and additional endpoints including the amount of study drug in the blood and the effects of the study drug on levels of GDF15 * Up to 3 additional blood samples (two samples during Part A and one sample during Part B, if relevant) in a subset of participants as part of a substudy for more comprehensive assessment of the amount of study drug in the blood and of the effects of the study drug on levels of GDF-15.
Interventions
DRUGponsegromab
Double-Blind ponsegromab Treatment followed by Open Label ponsegromab Treatment
DRUGPlacebo for ponsegromab
Double-Blind placebo Treatment followed by Open Label ponsegromab Treatment
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind for 12-week double-blind treatment period followed by an up to 1 year optional open-label treatment period
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Documented active diagnosis of non-small cell lung, pancreatic, colorectal cancer * Cachexia defined by Fearon criteria of weight loss * Serum GDF-15 concentrations * Signed informed consent * ECOG PS ≤3 with life expectancy of at least 4 months to be able to complete Part A. Key
Exclusion criteria
* Receiving tube feedings or parenteral nutrition at the time of Screening or Randomization. * Current active reversible causes of decreased food intake. * Cachexia caused by other reasons. * History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody. * inadequate liver function * renal disease requiring dialysis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Change From Baseline in Body Weight at Week 12 | Baseline, Week 12 | Body weight was measured in kilograms using a calibrated weighing scale. Baseline was defined as the last average of the duplicate measurements prior to, or on Day 1. The average of the duplicate body weights collected at assessment time was considered. The posterior medians and 90 percent (%) credible intervals (5th and 95th percentiles of the relevant posterior distribution) were reported for each randomized dose (including placebo). 4-Parameter maximal effect (E max) model: change from baseline = E 0 + (E max \* dose\^Hill) / (ED 50\^Hill + dose\^Hill), where E0 is the placebo effect, E max is the maximum effect, ED 50 is the dose producing 50% of the maximum effect, and Hill is the slope parameter. Model utilized a Bayesian methodology with a robustified, informative meta-analytic predictive prior for the placebo change from baseline at week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Change From Baseline in Physical Activity at Week 12 | Baseline, Week 12 | Physical activity was monitored using accelerometry (wearable digital sensors). Physical activity was categorized as: sedentary activity, non-sedentary physical activity, and moderate to vigorous physical activity. In this outcome measure time for each type of physical activity per day was considered. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using mixed models repeated measures (MMRM) model. |
| Part A: Change From Baseline in Mean Activity Level During Maximum 6 Minutes at Week 12 | Baseline, Week 12 | Physical activity was monitored using accelerometry (wearable digital sensors). In this outcome measure mean activity level during maximum 6 minutes was considered. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using MMRM model. |
| Part A: Change From Baseline in Total Vector Magnitude at Week 12 | Baseline, Week 12 | Total vector magnitude is a measure of overall physical activity. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using MMRM model. |
| Part A: Change From Baseline in Gait at Week 12 | Baseline, Week 12 | Gait was monitored using accelerometry (wearable digital sensors). Analysis was performed using MMRM model. Gait included: gait speed and 95th percentile of gait speed. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using MMRM model. |
| Part A: Change From Baseline in Functional Assessment of Anorexia-Cachexia Therapy- Anorexia and Cachexia Subscale (FAACT-ACS) at Week 12 | Baseline (prior to dose on Day 1), Week 12 | FAACT-ACS is a 12-item symptom-specific subscale to measure participants' concerns about their anorexia (appetite) or cachexia (weight) for past 7 days. Each item was scored from 0 to 4, where 0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, and 4= very much. The total FAACT-ACS score ranged from 0 to 48. Higher scores are associated with a higher health-related quality of life. FAACT-ACS was analyzed using an MMRM model. |
| Part A: Change From Baseline in FAACT- 5-Item Anorexia Symptom Scale (5IASS) at Week 12 | Baseline (prior to dose on Day 1), Week 12 | FAACT-5IASS is a 5-item subscale to measure participants' perceptions of anorexia (appetite) concerns for past 7 days. Each item was scored from 0 to 4, where 0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, and 4= very much. The total FAACT-5IASS score ranged from 0 to 20. Higher scores are associated with a higher health-related quality of life. FAACT-5IASS was analyzed using an MMRM model. |
| Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue | Baseline, Week 12 | The CRCSD is a daily, self-reported questionnaire that measured severity of symptoms related to cancer cachexia: appetite, nausea, vomiting, and fatigue. Participants rated appetite, nausea and physical fatigue symptom every day, and weekly averages were calculated over the 7 days prior, from 0 to 10, where 0 = no symptom and 10 = worst possible symptom. Higher scores indicated more severe disease. CRCSD was analyzed using an MMRM model. |
| Part A: Median Change From Baseline in CRCSD Scores at Week 12: Vomiting Frequency | Baseline, Week 12 | The CRCSD is a daily, self-reported questionnaire that measured severity of symptoms related to cancer cachexia: vomiting frequency. Participants rated vomiting frequency over the past 24 hours, from 0 to 30, where 0 = no symptom and 30 = worst possible symptom. Higher scores indicated more severe disease. |
| Part A: Number of Participants With Treatment Emergent Adverse Events (TEAE) | From the first dose of study drug until first dose of open-label ponsegromab 400 mg for participants entering Part B or through Week 16 follow-up for participants not entering Part B (including 8 weeks of follow-up from last dose of study drug in part A) | An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. TEAE were defined as any event that was not present before exposure to study drug, or any event already present that worsened in either intensity or frequency after exposure to study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included serious AEs and all non-SAEs. |
| Part A: Number of Participants With Incidence of Laboratory Test Abnormalities | Day 1 up to Week 12 | Laboratory test abnormality parameters included: hematology- hemoglobin (gram per deciliter \[g/dL\]), hematocrit (%), erythrocytes (10\^12/Liter \[L\]) less than (\<) 0.8\*lower limit of normal (LLN); platelets (10\^9/L) \<0.5\*LLN to more than (\>) 1.75\*upper limit of normal (ULN); leukocytes (10\^9/L) \<0.6\*LLN to \>1.5\*ULN; lymphocytes, neutrophils (10\^9/L) \<0.8\*LLN to \>1.2\*ULN. Clinical chemistry- bilirubin, glucose (mg/dL) \>1.5\*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (Units/L \[U/L\]) \>3.0\*ULN; protein, albumin (gram \[g\]/dL) \<0.8\*LLN; urea (mmol/L) \>1.3xULN; creatinine (mg/dL) \>1.3\*ULN; sodium (milliequivalents \[mEq\]/L) \<0.95\*LLN; potassium (mEq/L) \<0.9\*LLN to \>1.1\*ULN. |
| Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Day 1 up to Week 12 | Vital signs criteria included: supine systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg), increase and decrease in change of more than or equal to (\>=) 30mmHg; supine diastolic blood pressure (DBP) \<50 mmHg, increase and decrease in change of \>= 20mmHg; pulse rate \<40 beats per minute (bpm) to \>120 bpm. Only rows which included at least 1 participant in any reporting group with abnormality were reported in this outcome measure. |
| Part A: Number of Participants With Clinically Significant Echocardiogram (ECG) Abnormalities | Day 1 up to Week 12 | ECG parameters included heart rate (HR), PR interval, QT interval, QTc corrected using Fridericia's formula (QTcF) and QRS complex. HR: RR (interval between 2 successive R waves on ECG) decrease \>25% and to a VR (interval between QRS wave and T wave on ECG) \>100, RR increase \>25% and to a VR \<50; PR interval: baseline less than or equal to (\<=) 200 and % change \>= 50%; QT interval: \>450, \>480, \>500, increase from baseline \>30, increase from baseline \>60; QTcF: 470 \< value \<= 480, 480 \< value \<= 500, value \> 500, 30 \< change \<= 60 and change \>60; QRS complex: value \>= 140, % change \>=50%. Clinically significant values were determined by the investigator. |
Countries
Australia, Bulgaria, Canada, China, Hungary, Japan, Poland, Slovakia, Spain, Taiwan, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Recruitment details
A total of 187 participants were enrolled in this study. This study had 2 parts: Part A and Part B. On completion of Part A, participants had the opportunity to enter open-label extension period Part B (optional).
Participants by arm
| Arm | Count |
|---|---|
| Part A: Placebo/ Part B: Ponsegromab 400 mg Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year. | 45 |
| Part A: Ponsegromab 100 mg/ Part B: Ponsegromab 400 mg Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year. | 46 |
| Part A: Ponsegromab 200 mg/ Part B: Ponsegromab 400 mg Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year. | 46 |
| Part A: Ponsegromab 400 mg/ Part B: Ponsegromab 400 mg Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year. | 50 |
| Total | 187 |
Baseline characteristics
| Characteristic | Part A: Placebo/ Part B: Ponsegromab 400 mg | Part A: Ponsegromab 100 mg/ Part B: Ponsegromab 400 mg | Part A: Ponsegromab 200 mg/ Part B: Ponsegromab 400 mg | Part A: Ponsegromab 400 mg/ Part B: Ponsegromab 400 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.2 Years STANDARD_DEVIATION 11.26 | 70.1 Years STANDARD_DEVIATION 9.38 | 65.9 Years STANDARD_DEVIATION 9.61 | 66.1 Years STANDARD_DEVIATION 9.93 | 66.4 Years STANDARD_DEVIATION 10.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants | 5 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 42 Participants | 44 Participants | 43 Participants | 172 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 19 Participants | 18 Participants | 15 Participants | 70 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 26 Participants | 27 Participants | 28 Participants | 35 Participants | 116 Participants |
| Sex: Female, Male Female | 17 Participants | 19 Participants | 15 Participants | 18 Participants | 69 Participants |
| Sex: Female, Male Male | 28 Participants | 27 Participants | 31 Participants | 32 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 45 | 6 / 46 | 6 / 46 | 9 / 50 | 8 / 24 | 10 / 27 | 13 / 34 | 5 / 29 |
| other Total, other adverse events | 26 / 45 | 22 / 46 | 19 / 46 | 24 / 50 | 16 / 24 | 22 / 27 | 24 / 34 | 19 / 29 |
| serious Total, serious adverse events | 11 / 45 | 15 / 46 | 10 / 46 | 20 / 50 | 9 / 24 | 14 / 27 | 16 / 34 | 11 / 29 |
Outcome results
Primary
Part A: Change From Baseline in Body Weight at Week 12
Body weight was measured in kilograms using a calibrated weighing scale. Baseline was defined as the last average of the duplicate measurements prior to, or on Day 1. The average of the duplicate body weights collected at assessment time was considered. The posterior medians and 90 percent (%) credible intervals (5th and 95th percentiles of the relevant posterior distribution) were reported for each randomized dose (including placebo). 4-Parameter maximal effect (E max) model: change from baseline = E 0 + (E max \* dose\^Hill) / (ED 50\^Hill + dose\^Hill), where E0 is the placebo effect, E max is the maximum effect, ED 50 is the dose producing 50% of the maximum effect, and Hill is the slope parameter. Model utilized a Bayesian methodology with a robustified, informative meta-analytic predictive prior for the placebo change from baseline at week 12.
Time frame: Baseline, Week 12
Population: Censored analysis set included all evaluable participants. For participants who discontinued study intervention, or received a prohibited procedure or prohibited medication, all observations post-discontinuation, or post-procedure, were censored and treated as missing data. For participants who missed a dose, or received an incomplete dose, all observations post-missed/incomplete dose were censored and treated as missing data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Body Weight at Week 12 | NA Kilogram |
| Part A: Ponsegromab 100 mg | Part A: Change From Baseline in Body Weight at Week 12 | NA Kilogram |
| Part A: Ponsegromab 200 mg | Part A: Change From Baseline in Body Weight at Week 12 | NA Kilogram |
| Part A: Ponsegromab 400 mg | Part A: Change From Baseline in Body Weight at Week 12 | NA Kilogram |
Comparison: Bayesian Emax model was used for statistical calculation. The posterior medians and 90% credible intervals (5th and 95th percentiles of the relevant posterior distribution) were reported for differences relative to placebo). No adjustments were made for multiplicity.90% CI: [0.49, 2.34]
Comparison: Bayesian Emax model was used for statistical calculation. The posterior medians and 90% credible intervals (5th and 95th percentiles of the relevant posterior distribution) were reported for differences relative to placebo). No adjustments were made for multiplicity.90% CI: [1.08, 3.15]
Comparison: Bayesian Emax model was used for statistical calculation. The posterior medians and 90% credible intervals (5th and 95th percentiles of the relevant posterior distribution) were reported for differences relative to placebo). No adjustments were made for multiplicity.90% CI: [1.68, 4.34]
Secondary
Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue
The CRCSD is a daily, self-reported questionnaire that measured severity of symptoms related to cancer cachexia: appetite, nausea, vomiting, and fatigue. Participants rated appetite, nausea and physical fatigue symptom every day, and weekly averages were calculated over the 7 days prior, from 0 to 10, where 0 = no symptom and 10 = worst possible symptom. Higher scores indicated more severe disease. CRCSD was analyzed using an MMRM model.
Time frame: Baseline, Week 12
Population: Censored analysis set:all evaluable participants.For participants who discontinued study intervention/received prohibited procedure/ prohibited medication,all observations post-discontinuation/post-procedure,were censored and treated as missing data.For participants who missed dose/received incomplete dose,all observations post-missed/incomplete dose were censored and treated as missing data.''Overall Number of Participants Analyzed'' =participants evaluable for this outcome measure at Week 12.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue | Appetite | -0.23 Units on a scale |
| Part A: Placebo | Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue | Physical Fatigue | -0.27 Units on a scale |
| Part A: Placebo | Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue | Nausea | -0.33 Units on a scale |
| Part A: Ponsegromab 100 mg | Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue | Appetite | 0.20 Units on a scale |
| Part A: Ponsegromab 100 mg | Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue | Physical Fatigue | 0.39 Units on a scale |
| Part A: Ponsegromab 100 mg | Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue | Nausea | 0.14 Units on a scale |
| Part A: Ponsegromab 200 mg | Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue | Nausea | 0.06 Units on a scale |
| Part A: Ponsegromab 200 mg | Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue | Appetite | 0.23 Units on a scale |
| Part A: Ponsegromab 200 mg | Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue | Physical Fatigue | 0.38 Units on a scale |
| Part A: Ponsegromab 400 mg | Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue | Appetite | 0.69 Units on a scale |
| Part A: Ponsegromab 400 mg | Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue | Physical Fatigue | -0.06 Units on a scale |
| Part A: Ponsegromab 400 mg | Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue | Nausea | -0.50 Units on a scale |
Comparison: Appetite: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.191290% CI: [-0.38, 1.24]MMRM analysis; 1-sided
Comparison: Appetite: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.186690% CI: [-0.39, 1.3]MMRM analysis; 1-sided
Comparison: Appetite: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.034990% CI: [0.09, 1.75]MMRM analysis; 1-sided
Comparison: Nausea: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.875490% CI: [-0.2, 1.14]MMRM analysis; 1-sided
Comparison: Nausea: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.820590% CI: [-0.31, 1.08]MMRM analysis; 1-sided
Comparison: Nausea: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.337590% CI: [-0.86, 0.51]MMRM analysis; 1-sided
Comparison: Physical Fatigue: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.913890% CI: [-0.14, 1.45]MMRM analysis; 1-sided
Comparison: Physical Fatigue: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.901190% CI: [-0.18, 1.46]MMRM analysis; 1-sided
Comparison: Physical Fatigue: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.661890% CI: [-0.61, 1.02]MMRM analysis; 1-sided
Secondary
Part A: Change From Baseline in FAACT- 5-Item Anorexia Symptom Scale (5IASS) at Week 12
FAACT-5IASS is a 5-item subscale to measure participants' perceptions of anorexia (appetite) concerns for past 7 days. Each item was scored from 0 to 4, where 0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, and 4= very much. The total FAACT-5IASS score ranged from 0 to 20. Higher scores are associated with a higher health-related quality of life. FAACT-5IASS was analyzed using an MMRM model.
Time frame: Baseline (prior to dose on Day 1), Week 12
Population: Censored analysis set:all evaluable participants.For participants who discontinued study intervention/received prohibited procedure/ prohibited medication,all observations post-discontinuation/post-procedure,were censored and treated as missing data.For participants who missed dose/received incomplete dose,all observations post-missed/incomplete dose were censored and treated as missing data.''Overall Number of Participants Analyzed'' =participants evaluable for this outcome measure at Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in FAACT- 5-Item Anorexia Symptom Scale (5IASS) at Week 12 | 0.15 Units on a scale |
| Part A: Ponsegromab 100 mg | Part A: Change From Baseline in FAACT- 5-Item Anorexia Symptom Scale (5IASS) at Week 12 | 2.50 Units on a scale |
| Part A: Ponsegromab 200 mg | Part A: Change From Baseline in FAACT- 5-Item Anorexia Symptom Scale (5IASS) at Week 12 | 0.15 Units on a scale |
| Part A: Ponsegromab 400 mg | Part A: Change From Baseline in FAACT- 5-Item Anorexia Symptom Scale (5IASS) at Week 12 | 2.45 Units on a scale |
Comparison: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.00990% CI: [0.72, 3.97]MMRM analysis; 1-sided
Comparison: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.498790% CI: [-1.55, 1.56]MMRM analysis; 1-sided
Comparison: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.0190% CI: [0.68, 3.92]MMRM analysis; 1-sided
Secondary
Part A: Change From Baseline in Functional Assessment of Anorexia-Cachexia Therapy- Anorexia and Cachexia Subscale (FAACT-ACS) at Week 12
FAACT-ACS is a 12-item symptom-specific subscale to measure participants' concerns about their anorexia (appetite) or cachexia (weight) for past 7 days. Each item was scored from 0 to 4, where 0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, and 4= very much. The total FAACT-ACS score ranged from 0 to 48. Higher scores are associated with a higher health-related quality of life. FAACT-ACS was analyzed using an MMRM model.
Time frame: Baseline (prior to dose on Day 1), Week 12
Population: Censored analysis set:all evaluable participants.For participants who discontinued study intervention/received prohibited procedure/ prohibited medication,all observations post-discontinuation/post-procedure,were censored and treated as missing data.For participants who missed dose/received incomplete dose,all observations post-missed/incomplete dose were censored and treated as missing data.''Overall Number of Participants Analyzed'' =participants evaluable for this outcome measure at Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Functional Assessment of Anorexia-Cachexia Therapy- Anorexia and Cachexia Subscale (FAACT-ACS) at Week 12 | 0.52 Units on a scale |
| Part A: Ponsegromab 100 mg | Part A: Change From Baseline in Functional Assessment of Anorexia-Cachexia Therapy- Anorexia and Cachexia Subscale (FAACT-ACS) at Week 12 | 4.76 Units on a scale |
| Part A: Ponsegromab 200 mg | Part A: Change From Baseline in Functional Assessment of Anorexia-Cachexia Therapy- Anorexia and Cachexia Subscale (FAACT-ACS) at Week 12 | 1.15 Units on a scale |
| Part A: Ponsegromab 400 mg | Part A: Change From Baseline in Functional Assessment of Anorexia-Cachexia Therapy- Anorexia and Cachexia Subscale (FAACT-ACS) at Week 12 | 4.63 Units on a scale |
Comparison: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.011490% CI: [1.19, 7.28]MMRM analysis; 1-sided
Comparison: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.3690% CI: [-2.3, 3.57]MMRM analysis; 1-sided
Comparison: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.013890% CI: [1.06, 7.17]MMRM analysis; 1-sided
Secondary
Part A: Change From Baseline in Gait at Week 12
Gait was monitored using accelerometry (wearable digital sensors). Analysis was performed using MMRM model. Gait included: gait speed and 95th percentile of gait speed. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using MMRM model.
Time frame: Baseline, Week 12
Population: Censored analysis set:all evaluable participants.For participants who discontinued study intervention/received prohibited procedure/ prohibited medication,all observations post-discontinuation/post-procedure,were censored and treated as missing data.For participants who missed dose/received incomplete dose,all observations post-missed/incomplete dose were censored and treated as missing data.''Overall Number of Participants Analyzed'' =participants evaluable for this outcome measure at Week 12.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Gait at Week 12 | Gait Speed | -0.008 Meter per second (m/s) |
| Part A: Placebo | Part A: Change From Baseline in Gait at Week 12 | 95th percentile of gait speed | 0.011 Meter per second (m/s) |
| Part A: Ponsegromab 100 mg | Part A: Change From Baseline in Gait at Week 12 | 95th percentile of gait speed | 0.011 Meter per second (m/s) |
| Part A: Ponsegromab 100 mg | Part A: Change From Baseline in Gait at Week 12 | Gait Speed | -0.009 Meter per second (m/s) |
| Part A: Ponsegromab 200 mg | Part A: Change From Baseline in Gait at Week 12 | Gait Speed | -0.012 Meter per second (m/s) |
| Part A: Ponsegromab 200 mg | Part A: Change From Baseline in Gait at Week 12 | 95th percentile of gait speed | -0.015 Meter per second (m/s) |
| Part A: Ponsegromab 400 mg | Part A: Change From Baseline in Gait at Week 12 | Gait Speed | 0.009 Meter per second (m/s) |
| Part A: Ponsegromab 400 mg | Part A: Change From Baseline in Gait at Week 12 | 95th percentile of gait speed | 0.021 Meter per second (m/s) |
Comparison: Gait Speed: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.505290% CI: [-0.046, 0.045]MMRM analysis; 1-sided
Comparison: Gait Speed: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.559990% CI: [-0.05, 0.042]MMRM analysis; 1-sided
Comparison: Gait Speed: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.27790% CI: [-0.03, 0.064]MMRM analysis; 1-sided
Comparison: 95th Percentile of Gait Speed: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.504790% CI: [-0.071, 0.07]MMRM analysis; 1-sided
Comparison: 95th Percentile of Gait Speed: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.731690% CI: [-0.097, 0.045]MMRM analysis; 1-sided
Comparison: 95th Percentile of Gait Speed: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.414590% CI: [-0.063, 0.082]MMRM analysis; 1-sided
Secondary
Part A: Change From Baseline in Mean Activity Level During Maximum 6 Minutes at Week 12
Physical activity was monitored using accelerometry (wearable digital sensors). In this outcome measure mean activity level during maximum 6 minutes was considered. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using MMRM model.
Time frame: Baseline, Week 12
Population: Censored analysis set:all evaluable participants.For participants who discontinued study intervention/received prohibited procedure/ prohibited medication,all observations post-discontinuation/post-procedure,were censored and treated as missing data.For participants who missed dose/received incomplete dose,all observations post-missed/incomplete dose were censored and treated as missing data.''Overall Number of Participants Analyzed'' =participants evaluable for this outcome measure at Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Mean Activity Level During Maximum 6 Minutes at Week 12 | 70.81 Arbitrary units per day (au/day) |
| Part A: Ponsegromab 100 mg | Part A: Change From Baseline in Mean Activity Level During Maximum 6 Minutes at Week 12 | -59.46 Arbitrary units per day (au/day) |
| Part A: Ponsegromab 200 mg | Part A: Change From Baseline in Mean Activity Level During Maximum 6 Minutes at Week 12 | 794.96 Arbitrary units per day (au/day) |
| Part A: Ponsegromab 400 mg | Part A: Change From Baseline in Mean Activity Level During Maximum 6 Minutes at Week 12 | 256.43 Arbitrary units per day (au/day) |
Comparison: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.576290% CI: [-1257.31, 996.77]MMRM analysis; 1-sided
Comparison: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.148690% CI: [-425.81, 1874.09]MMRM analysis; 1-sided
Comparison: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.397290% CI: [-997.94, 1369.18]MMRM analysis; 1-sided
Secondary
Part A: Change From Baseline in Physical Activity at Week 12
Physical activity was monitored using accelerometry (wearable digital sensors). Physical activity was categorized as: sedentary activity, non-sedentary physical activity, and moderate to vigorous physical activity. In this outcome measure time for each type of physical activity per day was considered. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using mixed models repeated measures (MMRM) model.
Time frame: Baseline, Week 12
Population: Censored analysis set:all evaluable participants.For participants who discontinued study intervention/received prohibited procedure/ prohibited medication,all observations post-discontinuation/post-procedure,were censored and treated as missing data.For participants who missed dose/received incomplete dose,all observations post-missed/incomplete dose were censored and treated as missing data.''Overall Number of Participants Analyzed'' =participants evaluable for this outcome measure at Week 12.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Physical Activity at Week 12 | Time for Sedentary Activity | -1.42 Minutes per day |
| Part A: Placebo | Part A: Change From Baseline in Physical Activity at Week 12 | Time for Moderate to Vigorous Physical Activity | -4.45 Minutes per day |
| Part A: Placebo | Part A: Change From Baseline in Physical Activity at Week 12 | Time for Non-Sedentary Physical Activity | -37.73 Minutes per day |
| Part A: Ponsegromab 100 mg | Part A: Change From Baseline in Physical Activity at Week 12 | Time for Sedentary Activity | 51.93 Minutes per day |
| Part A: Ponsegromab 100 mg | Part A: Change From Baseline in Physical Activity at Week 12 | Time for Moderate to Vigorous Physical Activity | 4.07 Minutes per day |
| Part A: Ponsegromab 100 mg | Part A: Change From Baseline in Physical Activity at Week 12 | Time for Non-Sedentary Physical Activity | 0.03 Minutes per day |
| Part A: Ponsegromab 200 mg | Part A: Change From Baseline in Physical Activity at Week 12 | Time for Non-Sedentary Physical Activity | -42.09 Minutes per day |
| Part A: Ponsegromab 200 mg | Part A: Change From Baseline in Physical Activity at Week 12 | Time for Sedentary Activity | -39.33 Minutes per day |
| Part A: Ponsegromab 200 mg | Part A: Change From Baseline in Physical Activity at Week 12 | Time for Moderate to Vigorous Physical Activity | 0.05 Minutes per day |
| Part A: Ponsegromab 400 mg | Part A: Change From Baseline in Physical Activity at Week 12 | Time for Sedentary Activity | -3.37 Minutes per day |
| Part A: Ponsegromab 400 mg | Part A: Change From Baseline in Physical Activity at Week 12 | Time for Moderate to Vigorous Physical Activity | 3.67 Minutes per day |
| Part A: Ponsegromab 400 mg | Part A: Change From Baseline in Physical Activity at Week 12 | Time for Non-Sedentary Physical Activity | 12.11 Minutes per day |
Comparison: Sedentary Activity Time: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.82690% CI: [-40.89, 147.6]MMRM analysis; 1-sided
Comparison: Sedentary Activity Time: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.25490% CI: [-132.94, 57.14]MMRM analysis; 1-sided
Comparison: Sedentary Activity Time: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.48790% CI: [-101.63, 97.73]MMRM analysis; 1-sided
Comparison: Non-Sedentary Activity Time: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.049790% CI: [0.07, 75.46]MMRM analysis; 1-sided
Comparison: Non-Sedentary Activity Time: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.574590% CI: [-42.94, 34.22]MMRM analysis; 1-sided
Comparison: Non-Sedentary Activity Time: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.018990% CI: [10.62, 89.08]MMRM analysis; 1-sided
Comparison: Moderate to Vigorous Physical Activity Time: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.130290% CI: [-4, 21.03]MMRM analysis; 1-sided
Comparison: Moderate to Vigorous Physical Activity Time: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.27890% CI: [-8.18, 17.16]MMRM analysis; 1-sided
Comparison: Moderate to Vigorous Physical Activity Time: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.152990% CI: [-5.01, 21.23]MMRM analysis; 1-sided
Secondary
Part A: Change From Baseline in Total Vector Magnitude at Week 12
Total vector magnitude is a measure of overall physical activity. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using MMRM model.
Time frame: Baseline, Week 12
Population: Censored analysis set: all evaluable participants. For participants who discontinued study intervention/received prohibited procedure/ prohibited medication,all observations post-discontinuation/post-procedure,were censored and treated as missing data.For participants who missed dose/received incomplete dose,all observations post-missed/incomplete dose were censored and treated as missing data.''Overall Number of Participants Analyzed''=participants evaluable for this outcome measure at Week 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Total Vector Magnitude at Week 12 | -1919.02 Total activity counts/100 per day |
| Part A: Ponsegromab 100 mg | Part A: Change From Baseline in Total Vector Magnitude at Week 12 | -331.76 Total activity counts/100 per day |
| Part A: Ponsegromab 200 mg | Part A: Change From Baseline in Total Vector Magnitude at Week 12 | -2017.57 Total activity counts/100 per day |
| Part A: Ponsegromab 400 mg | Part A: Change From Baseline in Total Vector Magnitude at Week 12 | 284.15 Total activity counts/100 per day |
Comparison: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.098590% CI: [-443.79, 3618.31]MMRM analysis; 1-sided
Comparison: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.531590% CI: [-2169.67, 1972.58]MMRM analysis; 1-sided
Comparison: MMRM model included participant as a random term, and baseline, time (as a factor), baseline-by-time interaction, treatment and treatment-by-time interaction, type of therapy \[platinum or not at randomization +/- 28 days\], and type of cancer as fixed terms, with an unstructured covariance matrix and Kenwood-Roger degrees of freedom.p-value: =0.043790% CI: [84.51, 4321.85]MMRM analysis; 1-sided
Secondary
Part A: Median Change From Baseline in CRCSD Scores at Week 12: Vomiting Frequency
The CRCSD is a daily, self-reported questionnaire that measured severity of symptoms related to cancer cachexia: vomiting frequency. Participants rated vomiting frequency over the past 24 hours, from 0 to 30, where 0 = no symptom and 30 = worst possible symptom. Higher scores indicated more severe disease.
Time frame: Baseline, Week 12
Population: Censored analysis set:all evaluable participants.For participants who discontinued study intervention/received prohibited procedure/ prohibited medication,all observations post-discontinuation/post-procedure,were censored and treated as missing data.For participants who missed dose/received incomplete dose,all observations post-missed/incomplete dose were censored and treated as missing data.''Overall Number of Participants Analyzed'' =participants evaluable for this outcome measure at Week 12.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Placebo | Part A: Median Change From Baseline in CRCSD Scores at Week 12: Vomiting Frequency | 0.00 Units on a scale |
| Part A: Ponsegromab 100 mg | Part A: Median Change From Baseline in CRCSD Scores at Week 12: Vomiting Frequency | 0.00 Units on a scale |
| Part A: Ponsegromab 200 mg | Part A: Median Change From Baseline in CRCSD Scores at Week 12: Vomiting Frequency | 0.00 Units on a scale |
| Part A: Ponsegromab 400 mg | Part A: Median Change From Baseline in CRCSD Scores at Week 12: Vomiting Frequency | 0.00 Units on a scale |
Secondary
Part A: Number of Participants With Clinically Significant Echocardiogram (ECG) Abnormalities
ECG parameters included heart rate (HR), PR interval, QT interval, QTc corrected using Fridericia's formula (QTcF) and QRS complex. HR: RR (interval between 2 successive R waves on ECG) decrease \>25% and to a VR (interval between QRS wave and T wave on ECG) \>100, RR increase \>25% and to a VR \<50; PR interval: baseline less than or equal to (\<=) 200 and % change \>= 50%; QT interval: \>450, \>480, \>500, increase from baseline \>30, increase from baseline \>60; QTcF: 470 \< value \<= 480, 480 \< value \<= 500, value \> 500, 30 \< change \<= 60 and change \>60; QRS complex: value \>= 140, % change \>=50%. Clinically significant values were determined by the investigator.
Time frame: Day 1 up to Week 12
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Part A: Number of Participants With Clinically Significant Echocardiogram (ECG) Abnormalities | 0 Participants |
| Part A: Ponsegromab 100 mg | Part A: Number of Participants With Clinically Significant Echocardiogram (ECG) Abnormalities | 0 Participants |
| Part A: Ponsegromab 200 mg | Part A: Number of Participants With Clinically Significant Echocardiogram (ECG) Abnormalities | 0 Participants |
| Part A: Ponsegromab 400 mg | Part A: Number of Participants With Clinically Significant Echocardiogram (ECG) Abnormalities | 0 Participants |
Secondary
Part A: Number of Participants With Incidence of Laboratory Test Abnormalities
Laboratory test abnormality parameters included: hematology- hemoglobin (gram per deciliter \[g/dL\]), hematocrit (%), erythrocytes (10\^12/Liter \[L\]) less than (\<) 0.8\*lower limit of normal (LLN); platelets (10\^9/L) \<0.5\*LLN to more than (\>) 1.75\*upper limit of normal (ULN); leukocytes (10\^9/L) \<0.6\*LLN to \>1.5\*ULN; lymphocytes, neutrophils (10\^9/L) \<0.8\*LLN to \>1.2\*ULN. Clinical chemistry- bilirubin, glucose (mg/dL) \>1.5\*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (Units/L \[U/L\]) \>3.0\*ULN; protein, albumin (gram \[g\]/dL) \<0.8\*LLN; urea (mmol/L) \>1.3xULN; creatinine (mg/dL) \>1.3\*ULN; sodium (milliequivalents \[mEq\]/L) \<0.95\*LLN; potassium (mEq/L) \<0.9\*LLN to \>1.1\*ULN.
Time frame: Day 1 up to Week 12
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received. Here, ''Overall Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Part A: Number of Participants With Incidence of Laboratory Test Abnormalities | 26 Participants |
| Part A: Ponsegromab 100 mg | Part A: Number of Participants With Incidence of Laboratory Test Abnormalities | 24 Participants |
| Part A: Ponsegromab 200 mg | Part A: Number of Participants With Incidence of Laboratory Test Abnormalities | 29 Participants |
| Part A: Ponsegromab 400 mg | Part A: Number of Participants With Incidence of Laboratory Test Abnormalities | 28 Participants |
Secondary
Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria
Vital signs criteria included: supine systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg), increase and decrease in change of more than or equal to (\>=) 30mmHg; supine diastolic blood pressure (DBP) \<50 mmHg, increase and decrease in change of \>= 20mmHg; pulse rate \<40 beats per minute (bpm) to \>120 bpm. Only rows which included at least 1 participant in any reporting group with abnormality were reported in this outcome measure.
Time frame: Day 1 up to Week 12
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received. Here, ''Overall Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Placebo | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Value < 90mmHg | 0 Participants |
| Part A: Placebo | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine DBP Decrease Change >= 20mmHg | 3 Participants |
| Part A: Placebo | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Increase Change >= 20mmHg | 4 Participants |
| Part A: Placebo | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Increase Change >= 30mmHg | 4 Participants |
| Part A: Placebo | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine Pulse Rate Value > 120mmHg | 0 Participants |
| Part A: Placebo | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Decrease Change >= 30mmHg | 2 Participants |
| Part A: Placebo | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine DBP Value < 50mmHg | 0 Participants |
| Part A: Ponsegromab 100 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine DBP Decrease Change >= 20mmHg | 4 Participants |
| Part A: Ponsegromab 100 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine DBP Value < 50mmHg | 1 Participants |
| Part A: Ponsegromab 100 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Decrease Change >= 30mmHg | 6 Participants |
| Part A: Ponsegromab 100 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Increase Change >= 20mmHg | 4 Participants |
| Part A: Ponsegromab 100 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine Pulse Rate Value > 120mmHg | 1 Participants |
| Part A: Ponsegromab 100 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Increase Change >= 30mmHg | 5 Participants |
| Part A: Ponsegromab 100 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Value < 90mmHg | 3 Participants |
| Part A: Ponsegromab 200 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine DBP Value < 50mmHg | 0 Participants |
| Part A: Ponsegromab 200 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Value < 90mmHg | 0 Participants |
| Part A: Ponsegromab 200 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Increase Change >= 30mmHg | 8 Participants |
| Part A: Ponsegromab 200 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Decrease Change >= 30mmHg | 5 Participants |
| Part A: Ponsegromab 200 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Increase Change >= 20mmHg | 3 Participants |
| Part A: Ponsegromab 200 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine DBP Decrease Change >= 20mmHg | 4 Participants |
| Part A: Ponsegromab 200 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine Pulse Rate Value > 120mmHg | 3 Participants |
| Part A: Ponsegromab 400 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Decrease Change >= 30mmHg | 4 Participants |
| Part A: Ponsegromab 400 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine Pulse Rate Value > 120mmHg | 1 Participants |
| Part A: Ponsegromab 400 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine DBP Decrease Change >= 20mmHg | 3 Participants |
| Part A: Ponsegromab 400 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Increase Change >= 30mmHg | 2 Participants |
| Part A: Ponsegromab 400 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Value < 90mmHg | 0 Participants |
| Part A: Ponsegromab 400 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine SBP Increase Change >= 20mmHg | 4 Participants |
| Part A: Ponsegromab 400 mg | Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria | Supine DBP Value < 50mmHg | 0 Participants |
Secondary
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAE)
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. TEAE were defined as any event that was not present before exposure to study drug, or any event already present that worsened in either intensity or frequency after exposure to study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included serious AEs and all non-SAEs.
Time frame: From start of study drug on Day 1 maximum up to 4 weeks post last dose on Week 12 (maximum up to approximately Week 16)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAE) | 36 Participants |
| Part A: Ponsegromab 100 mg | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAE) | 32 Participants |
| Part A: Ponsegromab 200 mg | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAE) | 31 Participants |
| Part A: Ponsegromab 400 mg | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAE) | 37 Participants |