A phase II study to determine the safety, efficacy, and pharmacokinetics of multiple intravenous doses of ald518 80 mg, 160 mg, and 320 mg versus placebo administered to patients with non-small cell lung cancer-related fatigue and cachexia.
(1) ICD-10 Condition: J988||Other specified respiratory disorders, Patients with Non-Small Cell Lung Cancer-related Fatigue and Cachexia,
Intervention / Comparator Agent
Type
Name
Details
Intervention
ALD518
Group A: ALD518 80 mg every 8 weeks (3 doses)
Group B: ALD518 160 mg every 8 weeks (3 doses)
Group C: ALD518 320 mg every 8 weeks (3 doses)
Comparator Agent
Placebo
Group D: Placebo every 8 weeks (3 doses)
Inclusion Criteria
Age From
Age To
Gender
Details
1. Confirmed diagnosis of NSCLC incurable by other treatments including surgery
2. Eastern Cooperative Oncology Group2 (ECOG) performance status: 0-3
3. Able to fulfill International Classification of Diseases-10 (ICD-10) criteria for cancer?related fatigue.
4. Have experienced ≥ 5% loss of body weight in the preceding 3 months
5. Have a plasma C-reactive protein (CRP) concentration ≥ 10mg/L
6. Have a life expectancy of at least 12 weeks
7. Able to comply with the protocol
8. Able to understand the information provided to them and to give written informed consent
9. Aged ≥ 18 years of age
10. Are not pregnant and do not plan to become pregnant during the study.
Females with childbearing potential must provide a negative pregnancy test within the Screening period (Day -35 to -7) and must be using adequate contraception (oral or injectable [depot] oestrogen, and/or progestogen, or selective estrogen receptor modulator contraceptive therapeutic, intrauterine contraceptive device, or double barrier method
[e.g., condom and diaphragm or spermicidal gel]). Non-childbearing
potential is defined as post-menopausal for at least 1 year or surgical sterilization or hysterectomy at least 3 months before study start.
ExclusionCriteria
Details
Exclusion Criteria:
1. Have any past or current, acute or chronic concurrent medical condition/illness that the investigator or designated physician feels will compromise patient safety or any other aspects of the study.
2. Have serum transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) of ≥ 3 x the upper limit of normal (ULN) at Screening.
3. Have hemoglobin < 8 g/dL at Screening
4. Have neutrophil count < 1.5 x 109/L at Screening
5. Have platelet count < 75 x 109/L at Screening
6. Have had chemotherapy, large field radiotherapy, or surgery for the treatment of their cancer within 30 days before dosing in the study
7. Have planned chemotherapy, large field radiotherapy, or surgery for the treatment of their cancer during the study
8. Diagnosed with any unstable, uncontrolled brain metastases
9. Have a previous history of tuberculosis
10. Have active tuberculosis infection
11. Have a current serious infection (requiring treatment with parenteral antibiotics)
12. Have a history of hypersensitivity to monoclonal antibodies
13. Have current habitual drug abuse including alcohol
14. Have received any experimental, unregistered therapy (within or outside a clinical study) within 30 days or five plasma half-lives (which ever is shorter) before dosing
15. Have received monoclonal antibody treatment within 6 months of Screening (within or outside a clinical study)
16. Regularly take high dose corticosteroids or progestogens for purposes other than hormone replacement therapy) (>7.5 mg prednisolone or equivalent) per day
17. Are likely to require treatment during the study with drugs not permitted by the study protocol
18. Are participating in (or planning to participate in) any other clinical study during the study (Patient may be followed for survival if they have completed or withdrawn from a previous study)
19. Have any physical disability (e.g., amputation of a limb) which would interfere with completion of the hand grip strength measurement or any other protocol-related procedure.
20. Are pregnant or a nursing mother.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
Primary endpoint is change in safety as follows:
1. Incidence and severity of AEs and SAEs during the study
2. Changes in vital signs and 12-lead ECG during the study
3. Changes in physical examination during the study
4. Changes in laboratory assessments (serum chemistry, hematology, and urinalysis)
during the study.
1. Time to symptomatic progression (Functional Assessment of Chronic Illness
Therapy-Fatigue; FACIT-F), at Weeks 12 and 24
Secondary efficacy endpoints are:
2. Changes from baseline in FACIT-F, at each visit
3. Changes from baseline in Functional Assessment of Anorexia/Cachexia Therapy
(FAACT), at each visit
4. Changes from baseline in Functional Assessment of Cancer Therapy-Lung
(FACT-L), at each visit
5. Changes from baseline in Short Form-36 (SF-36), at each visit
6. Changes from baseline in hand grip strength, at each visit
7. Changes from baseline in weight and lean body mass, at each visit.
8. Time to death (survival) will be evaluated during the study.
9. The evaluation of PK over time: peak plasma concentration (Cmax), time to peak
concentration (Tmax), area under the concentration-time curve extrapolated to infinity
(AUC∞), and elimination half life (t½)
10. The evaluation of pharmacodynamic parameters over time: concentrations of CRP
and D-dimer.
11. Evaluation of immunogenicity anti-ALD518.
Total Sample Size="0" Sample Size from India="" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 2
Date of First Enrollment (India)
Date Missing
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
22/01/2009
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="" Months="0" Days="0"
Recruitment Status of Trial (Global)
Completed
Recruitment Status of Trial (India)
Publication Details
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is a phase II study to determine the safety, efficacy, and pharmacokinetics of multiple intravenous doses of ald518 80 mg, 160 mg, and 320 mg versus placebo administered to patients with non-small cell lung cancer-related fatigue and cachexia. This will be carried out in countries like Russia, Georgia, Australia, New Zealand, Romania, Poland, Serbia, Canada and India, In India it will be done in total 13 centres. A total of 120 patients are to be enrolled in the trial. We are expecting about 50 patients to be enrolled from India. The Primary safety parameters are Vital signs, physical examination, 12-lead electrocardiogram (ECG), adverse
events (AEs), serum chemistry, hematology, and urinalysis.
The efficacy parameter are Symptomatic progression, Functional Assessment of Cancer Therapy-Lung
(FACT-L), Functional Assessment of Chronic Illness Therapy-Fatigue
(FACIT-F), Functional Assessment of Anorexia/Cachexia Therapy
(FAACT), Short Form-36 (SF-36), hand grip strength, lean body mass, and time to death (survival).