Sporadic Inclusion Body Myositis (sIBM) Clinical Trial
— BYM338Official title:
An Open-label, Long-term Study to Evaluate the Safety and Tolerability of BYM338 in Patients With Sporadic Inclusion Body Myositis
| Verified date | March 2019 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This study is an open-label, long-term study for those patients who participated in the prior proof-of-concept protocol, in which the preliminary efficacy for BYM338 in patients with sIBM was demonstrated after a single 30 mg/kg i.v. dose of BYM338. This study is designed to confirm the efficacy, safety and tolerability of BYM338 in sIBM with long-term dosing. However due to lack of efficacy in patients with sIBM, the study was terminated early.
| Status | Completed |
| Enrollment | 10 |
| Est. completion date | August 23, 2016 |
| Est. primary completion date | August 23, 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 40 Years to 75 Years |
| Eligibility | Inclusion Criteria: - Written informed consent must be obtained before any assessment is performed. - Patients who participated in the CBYM338X2205 study. A patient is defined as participating in the study if they were enrolled and received study medication. - Able to communicate well with the investigator, to understand and comply with the requirements of the study. Exclusion Criteria: - Patients for whom the treating physician considers it inappropriate for continuation into the study, including consideration of physical and laboratory assessment of the patient at screening. - Patients who were non-compliant or demonstrated a serious protocol deviation in the previous study. - Use of other investigational drugs at the time of enrollment, within 30 days or 5 half-lives of enrollment, or until the expected PD effect has returned to baseline, whichever is longer; or longer if required by local regulations. - History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes - Swallowing difficulty or other reason that precludes adequate intake of energy and protein, defined as at least 20 kcal/kg/day and 0.6 g protein/kg/day as determined by the investigators assessment. - On the Columbia-Suicide Severity Rating Scale, a score of 4 or 5 on the Suicidal Ideation item or any "yes" on the Suicidal Behavior item that is related to suicidal behavior occurring during the last 2 years. - Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and for 5 half-lives (14 weeks) after stopping treatment. Highly effective contraception is defined as either: 1. Total abstinence: When this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception]. 2. Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. 3. Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). [For female study subjects, the vasectomized male partner should be the sole partner for that patient]. 4. Use of a combination of any two of the following (a+b or a+c or b+c): 1. Use of oral, injected or implanted hormonal methods of contraception. 2. Placement of an intrauterine device (IUD) or intrauterine system (IUS). 3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Postmenopausal females must have had no regular menstrual bleeding for at least one (1) year prior to initial dosing. Menopause will be confirmed by a plasma FSH level of > 40 IU/L (or as determined by the cut off used by the local clinical laboratory) at screening. Female patients who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the eCRF. All female patients must have negative pregnancy test results at screening and baseline. - Use of oral beta agonists, oral corticosteroids, androgens or androgen inhibitors (including LHRH agonists), or intravenous gamma globulin (IVIG) within the previous 6 months. Short-term corticosteroids for unrelated indications, defined as < 20 mg/d for < 30 days and ending at least 60 days prior to screening, are acceptable. - Patients with known bleeding disorders, or who are under treatment with anti-coagulants. - A presence or history of clinically relevant ECG abnormalities, or including but not limited to Long QT syndrome, ischemic changes that cannot be shown to be stable for at least 6 months by previous ECG, or 2nd degree Mobitz II or 3rd degree heart block. - History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. - Significant illness which has not resolved within two (2) weeks prior to initial dosing. - A positive HIV, Hepatitis B surface antigen or Hepatitis C test result. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Novartis Investigative Site | Boston | Massachusetts |
| United States | Novartis Investigative Site | Phoenix | Arizona |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Any Adverse Event was defined as occurrence of any symptom regardless of intensity grade, Serious Adverse Event (SAEs) assessed as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in persistent or significant disability/incapacity | Up to 29 month | |
| Secondary | Changes From Baseline in Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA) | To assess the effect of multiple doses of BYM338 on lean body mass as measured by DXA in terms of change from baseline. | Baseline, Day 1, 57, 113, 169, 365, 533, and day 729 | |
| Secondary | Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing | To obtain pharmacokinetic data from multiple i.v. dosing of BYM338 in this patient population. Pre-dose, 30 mins & 4 hours post-dose on Day 1. Pre-dose only on each subsequent administration | Day 29, 85, 169, 253, 337, 421, 505, 589, 673, 757, 1177 | |
| Secondary | Changes From Baseline in Physical Function Reported by Patients | Self-reported physical function was assessed by a newly developed patient reported outcome named sporadic inclusion body myositis (sIBM) functional assessment (sIFA). The sIFA consists of 11 items scored on an 11 point numerical rating scale from 0 (no difficulty) to 10 (unable to do) across 3 domains: upper body functioning, lower body functioning and general functioning. Participants completed the assessment where the recall period was the past week prior to completing the patient reported outcome (PRO). The total score on the sIFA scale ranges from 0 (minimum) to 110 (maximum). Higher values represent a worse outcome. A positive change from baseline indicates deterioration. Due to the no-signal this analysis was cancelled. | Baseline, Week 104 | |
| Secondary | Changes From Baseline in Muscle Strength. | Quadriceps muscle strength was measured, Quadriceps Quantitative Muscle Testing (QMT) by portable fixed dynamometry (PFD). A negative change from baseline indicates deterioration | Baseline, Day 1, 113, 169, 365, 533, 729 | |
| Secondary | Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) | The effect of BYM338 on additional muscle function measures (hand-grip and pinch-grip dynamometry). | Baseline,Day 1, 113, 169, 365, 533, 729 | |
| Secondary | Changes From Baseline in Muscle Function 6 Minute Walking Distance | The effect of BYM338 on additional muscle function measures (6 minute walking distance). The 6MWD test measured the distance (in meters) that a participant walked in a 6 minute timeframe. A positive change from baseline indicates improvement. | Baseline,Day 1, 113, 169, 365, 533, 729 | |
| Secondary | Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan | Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was equal or more than 2% at Week 8 and 16 were considered responders | Baseline, Day 1, 57, 113 | |
| Secondary | Pharmacokinetics (PK) Parameter of Cmax | To obtain pharmacokinetic data from multiple i.v. dosing of BYM338 in this patient population. Pre-dose, 30 mins & 4 hours post-dose on Day 1. | Day 1 | |
| Secondary | Time to Reach the Maximum Concentration After Drug Administration (Tmax) | The time to reach the maximum concentration after drug administration | Day 1 |