Treatment Period. Subjects will enter into Study BA058-05-005 on Day 1, and Day 1 will also serve as Visit 10 (the Follow-up Visit) for Study BA058-05-003. The Informed Consent must be signed prior to undergoing any BA058-05-005 study related procedures, and may be signed at either Visit 9 or Visit 10 of Study BA058-05-003. Subjects who received Abaloparatide-SC/Placebo in Study BA058-05-003 will receive six months of open-label oral alendronate treatment as part of this study (BA058-05-005). Following the initial six months of treatment in this study, subjects will then enter the long-term observational phase of this study during which the subjects will continue to receive alendronate care for an additional 18 months. If determined by the Investigator to be appropriate, treatment will be by oral administration of alendronate at a total dose of 70 mg once per week. Subjects will be given a weekly diary card to record missed doses of medication including calcium and vitamin D. A total of six clinic visits are scheduled during the study (Day 1, Month 3, Month 6, Month 12, Month 18 and Month 24). Subjects will be instructed to take their first dose of study drug for Study BA058-05-005 in the morning, within a week of their Day 1 visit (Day 2 of this study). Study subjects will continue calcium and vitamin D supplementation during this study as was administered during BA058-05-003 (Section 6.1). At Month 3, subjects will return to the clinic for medication resupply, subject diary review and questioning as to their use of concomitant medications and the occurrence of adverse events. At the Month 6 visit ECG, and safety labs will be performed. Vertebral fractures will be determined clinically and via protocol directed x-ray evaluation; non-vertebral fractures will be determined clinically. In addition, subjects will undergo a DXA of the hip and spine (and wrist, if the subject was enrolled in the wrist DXA sub-study in Study BA058-05-003), and have samples drawn for bone markers and anti-abaloparatide antibodies. Procedures are to be performed as described in Section 7.0, Appendix 14.1 and Appendix 14.2. At Months 12 and 18, subjects will return to the clinic for safety labs, DXA of the hip and spine (and wrist, if the subject was enrolled in the wrist DXA sub-study in Study BA058-05-003), medication resupply, subject diary review and questioning as to their use of concomitant medications and occurrence of adverse events. Serum samples for bone markers will also be drawn. At Mont...
Treatment Period. The Treatment Period starts on Day 1 and continues for 18 months (78 weeks). Patients are randomized to treatment on Day 1 and begin treatment the same day. A subset of 300 patients per group will have a wrist DXA scan, which will occur after randomization to study drug and can occur anytime up to 24 hours after the first injection. Those patients who are randomized to treatment with teriparatide will be trained with the teriparatide pen prior to the first injection on Day 1. A total of 7 clinic visits are scheduled during the Treatment Period (Visits 3-9); the final Treatment Period visit will be scheduled to occur one day after the last dose of study medication. Treatment will be daily, by self-injection. During the first 30 days of treatment patients will record drug dose, site of injection and any local reactions in a patient diary card. Local tolerance will again be assessed during a second 30-day period. This second diary will be provided to the patient either at the Month [9] (Visit 7) or will be forwarded later by mail, as appropriate, for completion by the patient during the 30 days of treatment in Month [11] of treatment. The diary will be collected and reviewed with the patient for treatment compliance and adverse events at the Month [1] (Visit 4) and Month [12] (Visit 8) visits. The patient will also maintain a diary throughout the study to summarize all study drug administration on a weekly basis. Study patients will continue Calcium and Vitamin D supplementation during the Treatment Period. Safety will be assessed at each study visit during the Treatment Period. Efficacy assessments will include one evaluation by x-ray after 18 months of treatment (End-of-Treatment, Visit 9) and evaluations of BMD by DXA after [6], [12] and [18] months of treatment (Visits 6, 8 and 9). Serum markers of bone metabolism, BA058 antibody and BA058 serum levels will also be measured during the Treatment Period. Additionally, a subset of patients treated with BA058 80 µg or Placebo (up to [100] per group to obtain [75] evaluable biopsies per treatment group) will consent and have a bone biopsy performed between Visit 8 and the End-of-Treatment visit (Visit 9). A further subset of 100 patients per treatment group (BA058 80 µg, Placebo and teriparatide) will undergo a renal CT scan at End-of-Treatment (Visit 9). Procedures are to be performed according to the Schedule of Visits and Procedures (Appendix 14.1). Patients who discontinue from the study prior to completin...
Treatment Period. 6.3.1 Status of Subjects Inpatient o Outpatient ý Either o
6.3.2 Administration of the investigational drug
(a) Administration of study drug should be performed by qualified study personnel at the study site.
(b) The solution of omega interferon for injection will be prepared by [*] the [*] by the [*] of [*] of [*]. [*]
(c) For a dose of [*], withdraw [*] of the final solution into a sterile syringe.
(d) For a dose of [*], withdraw [*] of the final solution into a sterile syringe.
(e) For a dose of [*], withdraw [*] of the final solution into a sterile syringe.
(f) Inject the dose subcutaneously into an upper extremity. The site for each injections should be recorded.
(g) Extremities should be alternated, if possible, and different injection sites on the upper extremity should be selected for each subsequent administration.
6.3.3 [*] in [*] at the Same [*]. Principal Investigators are [*], to [*] the [*]. Principal Investigators may [*] the [*] and only once if it is medically prudent to do so as follows:
(a) If the patient is initially in [*], adopt the [*] regimen.
(b) If the patient is initially in [*], adopt the [*] regimen.
(c) If the patient is initially in [*], adopt the [*] regimen.
(d) If the patient is initially in [*].
(e) Once the [*], a subject should continue to receive the [*] until that subject has completed the study. The [*] should not be [*] once it has been [*] to achieve tolerability or to mitigate adverse events.
(f) If there is a need to [*] a [*], the subject should be discontinued from the study.
6.3.4 No [*]. No [*] in individual patients is permitted.
Treatment Period. The treatment period is split into two phases: initial treatment and subsequent treatment. Initial treatment consists of six 21-day cycles where subjects receive the following per cycle: • A single dose of cisplatin or carboplatin (Day 1) • A continuous infusion of 5-FU (Days 1–4) • Three doses of cetuximab (Days 1, 8 and 15) • Two doses of IP (Days 8 and 15) Cycles 7+ consist of 28-day cycles where subjects receive the following per cycle: • Four weekly doses of cetuximab (Days 1, 8, 15, and 22) • Two doses of IP (Days 8 and 22) Treatment continues until the subject has PD. Upon independent confirmation of radiographic disease progression and completion of treatment, subjects will complete the End of Treatment visit (§6.3) and begin long-term follow-up.
Treatment Period. Subjects will receive treatment with CRV431 or matching placebo from Day 1 to Day 28. Study visit days that include treatment administration occur on Days 1, 2, 7, 14, and 28. Visit windows will be allowed and are as follows: Day 7 and Day 14, the visit window is ± 1 day and Day 28 the visit window is + 2 days. If the study visit for Day 28 is extended, the subject must continue taking study drug until the visit is completed. Whole blood samples will be collected pre-dose and through Day 42 or early termination for safety and PK assessments as shown in Table 3 and Table 6, respectively. AEs will be collected as described in Section 11.4.
Treatment Period. The treatment period will last 8 weeks. Eligibility must be confirmed prior to dosing on Day 1. Subjects will have the following procedures performed prior to dosing on Day 1: • Review of medical and surgical history • Review of prior and concomitant medications • Review of adverse events • Review of compliance with recording of daily WI-NRS • Review of clinical laboratory results from the Screening Visit • Full physical examination • Xxxxx xxxxx and weight • ECG (if more than 30 days since screening ECG) • Subjects will record their Pruritus VAS, Sleep Loss VAS and complete the 5-D Pruritus, DLQI and ItchyQoL questionnaires. • Collection of laboratory blood tests • Collection of urine for urinalysis • Pregnancy test (if applicable) • Collection of PK blood samples
Treatment Period. The treatment period will last 8 weeks.
4.1.2.1 Pre-dose
Treatment Period. NI-0501 will be administered for 8 weeks as induction treatment of HLH. The treatment period will be divided in 2 separate periods: Treatment Period 1 and 2 (please refer to Figure 1). NI-0501 treatment can be shortened, although not less than 4 weeks, if patient’s condition and donor availability allow an earlier HSCT. Based on the current knowledge, no wash-out period is required between the last administration of NI- 0501 and the start of conditioning. In the event that an appropriate donor has not been identified by Week 8 or in case of the need to delay the schedule of HSCT for reasons unrelated to the administration of NI-0501, NI-0501 treatment can be continued beyond this time upon the request of the Investigator, provided a favourable benefit/risk has been established for that patient.
Treatment Period. 2 (Weeks 3 to 8)
8.7.1 Assessments to be performed on all Infusion Days
Treatment Period. 6.2.1 Randomization (Visit 2) *** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.
