A Study to Evaluate the Safety of GSK2398852 When Co-administered With GSK2315698 in Patients With Systemic Amyloidosis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01777243
• Date of registration: 24/01/2013
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: A Study to Evaluate the Safety of GSK2398852 When Co-administered With GSK2315698 in Patients With Systemic Amyloidosis
• Scientific title: A Single Dose First in Human Study of GSK2398852 Co-Administered With GSK2315698 in Patients With Systemic Amyloidosis
• Date of first enrolment: May 13, 2013
• Target sample size: 25
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01777243
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United Kingdom

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- Subject has been medically diagnosed with systemic amyloidosis and falls into one of
the patient groups (small to moderate amyloid load involving the spleen for Part A;
moderate to large amyloid load involving the spleen (to a moderate/large extent) for
Part A (following agreement from external safety committee); moderate to large amyloid
load involving the spleen and liver (spleen involved to a moderate/large extent) for
Part A extension (if required); and moderate to large amyloid load involving the
spleen (and liver in subset of subjects only) for Part B).

- Alanine aminotransferase (ALT) <3x upper limit of normal (ULN) and bilirubin <1.5x ULN
(isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct
bilirubin <35%).

- Male or female between 18 and 70 years of age inclusive, at the time of signing the
informed consent.

- Subject is ambulant and capable of attending for the study visit schedule.

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

- A female subject is eligible to participate if she is of non-childbearing potential;
or females on hormone replacement therapy (HRT) and whose menopausal status is in
doubt will be required to use one of the approved contraception methods.

- Male subjects with female partners of child-bearing potential must agree to use one of
the approved contraception methods.

- Smokers (<10 /day) are permitted but must be willing to abstain for the duration of
residential study sessions

Exclusion Criteria:

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening

- The subject has participated in a clinical trial and has received an investigational
therapeutic product (unlicensed) within the following time period prior to the first
dosing day in the current study: 3 months, 5 half-lives or twice the duration of the
biological effect of the investigational product (whichever is longer). This timeframe
will not apply to short term administration of GSK2315698 in study CPH114527.

- Pregnant females as determined by positive serum or urine human chorionic gonadotropin
(hCG) test at screening or prior to dosing.

- Lactating females.

- Estimated glomerular filtration rate (GFR)<30 milliliter (mL)/minute (min) [<60 mL/min
for the first 4 subjects to be enrolled]

- Evidence of an active urinary sediment on microscopy as evidenced by the presence of
red cell casts

- Decompensated cardiac failure or a recent history of syncope associated with cardiac
disease.

- In a subject in whom there is a clinical suspicion of cardiac amyloid, an
echocardiogram is consistent with significant cardiac amyloid, whether symptomatic or
not.

- Clinically significant anaemia- hemoglobin (Hb) <9 gram (g)/deciliter (dL).

- Use of prohibited medications.

- Poor or unsuitable venous access.

- Subjects with a QT interval corrected using Fridericia's formulas (QTcF) of >480 ms or
other electrocardiogram (ECG) abnormalities which, in the opinion of the investigator
are clinically significant and may increase safety risk.

- Uncontrolled hypertension with systolic blood pressure (BP) >170 mmHg and /or
diastolic >100 mmHg

- Presence of any co-morbid condition (e.g. severe or unstable coronary artery disease;
moderate-severe chronic obstructive pulmonary disease) which in the opinion of the
investigator would increase the potential risk to the subject.

- Subjects with active vasculitis

- Exclusions from Equilibrium contrast Magnetic Resonance Imaging (EqMRI) scanning
[Contraindications to Magnetic Resonance Imaging (MRI) scanning including, but not
limited to: Intracranial aneurism clips (except Sugita); History of intra-orbital
metal fragments that have not been removed by an MD (as confirmed by orbital X-Ray);
Pacemakers and non-MR compatible heart valves; Inner ear implants; History of
claustrophobia; estimated GFR <30 mL/min (gadolinium exclusion)]

- Subjects with dementia or a diagnosis of cerebral amyloid angiopathy.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Amyloidosis

Intervention(s)

Drug: GSK2398852

Drug: GSK2315698

Primary Outcome(s)

PK profile of GSK2315698 and GSK2398852 in Part A and in Part B [Time Frame: In Part A and Part B on Day -2, Day 1 (pre-dose, 1 hour [hr], 2 hr, 3 hr, 4 hr, 8 hr, 12 hr), Day 2, Day 3, Day 4, Day 6, Day 14, Day 21, Day 42]

Safety of GSK2398852 as assessed by vital signs measurements in Part A and in Part B [Time Frame: At scheduled intervals upto Day 42 in each Part.]

Safety of GSK2398852 as assessed by ECG readings in Part A and in Part B [Time Frame: At scheduled intervals upto Day 42 in each Part.]

Safety of GSK2398852 as assessed by number of subjects with AEs in Part A and in Part B [Time Frame: Continuous throughout the study]

Dose response of single doses of GSK2398852 when co-administered with GSK2315698 in Part B [Time Frame: Baseline, Day 6, Day 14 and Day 42 in Part B.]

Safety of GSK2398852 as assessed by clinical laboratory tests in Part A and in Part B [Time Frame: At scheduled intervals upto Day 42 in each Part.]

Secondary Outcome(s)

Measurement of anti-drug antibodies before and after treatment with GSK2398852 [Time Frame: Day 1 pre-dose, Day 21, Day 42 in each Part.]

SAP concentrations measurement [Time Frame: Baseline, Day -3, Day -2, Day -1, Day 42 in each Part.]

Secondary ID(s)

115570

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Quintiles, Inc.

Royal Free Hospital NHS Foundation Trust

Heart Hospital

Imperial College London