COSMOS: Study to Evaluate Safety and Preliminary Efficacy of Tafasitamab With Idelalisib or Venetoclax in R/R CLL/SLL Patients Pretreated With BTKi

• Sponsor: MorphoSys AG (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02639910
• Collaborator: (none)
• Enrollment: 24
• Locations: 17
• Arms: 2
• Actual Duration (Months): 61
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a two-cohort, multicenter, open-label study of tafasitamab (MOR208) combined with idelalisib or venetoclax in adult patients with R/R CLL or R/R SLL pretreated with a BTK inhibitor (e.g., ibrutinib) as single agent or as part of combination therapy. Patients completing the study treatment are invited to participate in an optional biomarker sub-study.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Lymphocytic, Chronic, B-Cell; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma	Biological: Tafasitamab; Drug: Idelalisib; Drug: Venetoclax	Phase 2

Detailed Description

The purpose of this study is to evaluate the clinical safety and preliminary efficacy of tafasitamab (MOR208) combined with idelalisib or venetoclax. The study will include safety run-in phase for each cohort with an evaluation of the safety data by an Independent Data Monitoring Committee.

An optional sub-study has been introduced to collect biological samples for investigations on biomarkers (e.g., CD19 expression) after tafasitamab treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Two-Cohort, Open-Label, Multicenter Study to Evaluate the Safety and Preliminary Efficacy of MOR00208 Combined With Idelalisib or Venetoclax in Patients With Relapsed or Refractory CLL/SLL Previously Treated With Bruton's Tyrosine Kinase (BTK) Inhibitor
• Actual Study Start Date: Nov 1, 2016
• Actual Primary Completion Date: Nov 1, 2018
• Actual Study Completion Date: Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A tafasitamab (MOR208) in combination with idelalisib	Biological: Tafasitamab; tafasitamab (MOR208) dose: 12 mg/kg intravenous infusion; Other Names: MOR208 MOR00208 ; Drug: Idelalisib; idelalisib dose: 150 mg twice daily orally; Other Names: Zydelig; GS-1101 or CAL-101
Experimental: Cohort B tafasitamab (MOR208) in combination with venetoclax	Biological: Tafasitamab; tafasitamab (MOR208) dose: 12 mg/kg intravenous infusion; Other Names: MOR208 MOR00208 ; Drug: Venetoclax; venetoclax dose: 400 mg once daily orally; Other Names: Venclexta, Venclyxto; ABT-199

Outcome Measures

Primary Outcome Measures

1. Incidence and Severity of Adverse Events (AEs) [2 years]

   For details please see Section of Adverse Events Overview

Secondary Outcome Measures

1. Best Objective Response Rate (ORR) [2 years]

   ORR = complete response [CR] + partial response [PR]; Local Evaluation

2. Number of Participants With Treatment-emergent or Treatment-boosted Anti-MOR00208 Antibody Formation [2 years]

   Number of participants with treatment-emergent or treatment-boosted anti-MOR00208 (anti-tafasitamab) antibody formation

3. Maximum Plasma Concentration (Cmax) of MOR00208 [At Cycle 3 Day 15]

   Mean Cmax of tafasitamab (MOR00208) at Cycle 3 Day 15 (after the weekly dosing of tafasitamab in Cycles 1 to 3 including a loading dose at C1D4)

Other Outcome Measures

1. Proportion of Patients With MRD-negativity [2 years]

   Proportion of patients who reached MRD-negativity in peripheral blood

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Major inclusion criteria

Diagnosis/Trial Population

• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL):

• history of diagnosis of CLL or SLL that meets IWCLL diagnostic criteria

• histologically confirmed diagnosis of SLL by lymph node biopsy

• indication for treatment as defined by the IWCLL guidelines

• Patients must have both of the following:

• relapsed or refractory disease while receiving a BTKi therapy or intolerance of such therapy

• single-agent or combination therapy with a BTKi for at least one month must be the patient's most recent prior anticancer therapy

• ECOG performance status of 0 to 2

• Patients with a past medical history of autologous or allogeneic stem cell transplantation must exhibit full hematological recovery

Laboratory Values

• Patients must meet adequate bone marrow function and adequate hepatic and renal function

Other Inclusion Criteria

• Females of childbearing potential must use a highly effective method of contraception

Major exclusion criteria

Diagnosis

• Patients who have:

• non-Hodgkin's lymphomas other than CLL/SLL

• transformed CLL/SLL or Richter's syndrome

• active and uncontrolled autoimmune cytopenia

Previous and Current Treatment

• Patients who have received treatment with a BTK inhibitor within 5 days prior to Day 1 dosing

• Patients who have, within 14 days prior to D1 dosing:

• not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy

• systemic corticosteroids in doses greater than prednisone equivalent to 20 mg/day with the exception of patients with signs of rapidly progressing disease

• received live vaccines with the exception of vaccination against influenza with inactivated virus or for pneumococcal diseases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Study Site	Jacksonville	Florida	United States	32204
2	Clinical Study Site	Rochester	Minnesota	United States	55905
3	Clinical Study Site	Columbus	Ohio	United States	43210
4	Clinical Study Site	Graz		Austria	8036
5	Clinical Study Site	Salzburg		Austria	5020
6	Clinical Study Site	Wien		Austria	1090
7	Clinical Study Site	Dresden		Germany	1307
8	Clinical Study Site	Leipzig		Germany	4103
9	Clinical Study Site	Muenchen		Germany	80804
10	Clinical Study Site	Brescia		Italy	25123
11	Clinical Study Site	Milano		Italy	20162
12	Clinical Study Site	Gdansk		Poland	80952
13	Clinical Study Site	Krakow		Poland	30510
14	Clinical Study Site	Lublin		Poland	85094
15	Clinical Study Site	Opole		Poland	45372
16	Clinical Study Site	Bournemouth		United Kingdom	BH7 7DW
17	Clinical Study Site	Leeds		United Kingdom	LS9 7TF

Sponsors and Collaborators

• MorphoSys AG

Investigators

• Study Director: Anke Muth, Clinical Development, MorphoSys AG

Study Documents (Full-Text)

• Study Protocol - Jan 10, 2019
• Statistical Analysis Plan - May 27, 2019

More Information

Publications

None provided.

• Responsible Party: MorphoSys AG
• ClinicalTrials.gov Identifier: NCT02639910
• Other Study ID Numbers: MOR208C205
• First Posted: Dec 28, 2015
• Last Update Posted: Dec 20, 2021
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by MorphoSys AG: CD19; MOR208; MOR00208; CLL; SLL; COSMOS; tafasitamab
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Venetoclax; Idelalisib

Study Results

Participant Flow

Arm/Group Title	Cohort A (Tafasitamab+Idelalisib)	Cohort B (Tafasitamab+Venetoclax)
Arm/Group Description	Tafasitamab (MOR208) in combination with idelalisib Tafasitamab dose: 12 mg/kg intravenous infusion Idelalisib dose: 150 mg twice daily orally	Tafasitamab (MOR208) in combination with venetoclax Tafasitamab dose: 12 mg/kg intravenous infusion Venetoclax dose: 400 mg once daily orally
Period Title: Overall Study
STARTED	11	13
COMPLETED	7	5
NOT COMPLETED	4	8

Baseline Characteristics

Arm/Group Title	Cohort A (Tafasitamab+Idelalisib)	Cohort B (Tafasitamab+Venetoclax)	Total
Arm/Group Description	Tafasitamab in combination with idelalisib	Tafasitamab in combination with venetoclax	Total of all reporting groups
Overall Participants	11	13	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 27.3%	8 61.5%	11 45.8%
>=65 years	8 72.7%	5 38.5%	13 54.2%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	69	64	65
Sex: Female, Male (Count of Participants)
Female	5 45.5%	3 23.1%	8 33.3%
Male	6 54.5%	10 76.9%	16 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	11 100%	13 100%	24 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Austria	2 18.2%	4 30.8%	6 25%
United States	0 0%	6 46.2%	6 25%
Poland	5 45.5%	0 0%	5 20.8%
Italy	1 9.1%	0 0%	1 4.2%
United Kingdom	0 0%	2 15.4%	2 8.3%
Germany	3 27.3%	1 7.7%	4 16.7%
Number of previous systemic treatment lines (Lines) [Median (Full Range) ]
Median (Full Range) [Lines]	5	3	4

Outcome Measures

1. Primary Outcome

Title	Incidence and Severity of Adverse Events (AEs)
Description	For details please see Section of Adverse Events Overview
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A (Tafasitamab+Idelalisib)	Cohort B (Tafasitamab+Venetoclax)
Arm/Group Description	Tafasitamab in combination with idelalisib	Tafasitamab in combination with venetoclax
Measure Participants	11	13
Count of Participants [Participants]	11 100%	13 100%

2. Secondary Outcome

Title	Best Objective Response Rate (ORR)
Description	ORR = complete response [CR] + partial response [PR]; Local Evaluation
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Intention-to-treat patient population consists of all enrolled patients. As per study protocol all patients were required to have computed tomography (CT) scans of the neck, chest, abdomen and pelvis to determine tumor response. These were performed at screening, at Day 1 of Cycles 4, 7, 13, and 19, etc. and at end-of-treatment.

Arm/Group Title	Cohort A (Tafasitamab+Idelalisib)	Cohort B (Tafasitamab+Venetoclax)
Arm/Group Description	Tafasitamab in combination with idelalisib	Tafasitamab in combination with venetoclax
Measure Participants	11	13
Intention-to-treat patient population	90.9 826.4%	76.9 591.5%
Pts with tumor response assessment by CT	90.9 826.4%	100 769.2%

3. Secondary Outcome

Title	Number of Participants With Treatment-emergent or Treatment-boosted Anti-MOR00208 Antibody Formation
Description	Number of participants with treatment-emergent or treatment-boosted anti-MOR00208 (anti-tafasitamab) antibody formation
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A (Tafasitamab+Idelalisib)	Cohort B (Tafasitamab+Venetoclax)
Arm/Group Description	Tafasitamab in combination with idelalisib	Tafasitamab in combination with venetoclax
Measure Participants	11	13
Count of Participants [Participants]	0 0%	0 0%

4. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of MOR00208
Description	Mean Cmax of tafasitamab (MOR00208) at Cycle 3 Day 15 (after the weekly dosing of tafasitamab in Cycles 1 to 3 including a loading dose at C1D4)
Time Frame	At Cycle 3 Day 15

Outcome Measure Data

Analysis Population Description

All patients with available pharmacokinetic data for Cmax at Cycle 3 Day 15.

Arm/Group Title	Cohort A (Tafasitamab+Idelalisib)	Cohort B (Tafasitamab+Venetoclax)
Arm/Group Description	Tafasitamab in combination with idelalisib	Tafasitamab in combination with venetoclax
Measure Participants	7	9
Mean (Standard Deviation) [ng/mL]	278379.9 (118746.34)	306998.9 (41254.20)

5. Other Pre-specified Outcome

Title	Proportion of Patients With MRD-negativity
Description	Proportion of patients who reached MRD-negativity in peripheral blood
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A (Tafasitamab+Idelalisib)	Cohort B (Tafasitamab+Venetoclax)
Arm/Group Description	Tafasitamab in combination with idelalisib	Tafasitamab in combination with venetoclax
Measure Participants	11	13
Count of Participants [Participants]	1 9.1%	6 46.2%

Adverse Events

Time Frame	From the first administration of any study drug to the patient until the 30-day safety follow-up visit as per protocol or until the cut-off date of 09 November 2018 whichever comes first.
Arm/Group Title	Cohort A (Tafasitamab+Idelalisib)		Cohort B (Tafasitamab+Venetoclax)
Arm/Group Description	Tafasitamab in combination with idelalisib		Tafasitamab in combination with venetoclax
All Cause Mortality
	Cohort A (Tafasitamab+Idelalisib)		Cohort B (Tafasitamab+Venetoclax)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/11 (18.2%)		0/13 (0%)
Serious Adverse Events
	Cohort A (Tafasitamab+Idelalisib)		Cohort B (Tafasitamab+Venetoclax)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/11 (72.7%)		9/13 (69.2%)
Blood and lymphatic system disorders
Anaemia	1/11 (9.1%)	1	1/13 (7.7%)	1
Pancytopenia	1/11 (9.1%)	1	0/13 (0%)	0
Thrombocytopenia	1/11 (9.1%)	1	0/13 (0%)	0
Cardiac disorders
Cardiac failure	1/11 (9.1%)	1	0/13 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/11 (0%)	0	1/13 (7.7%)	1
Pancreatitis acute	1/11 (9.1%)	1	0/13 (0%)	0
General disorders
Pyrexia	0/11 (0%)	0	3/13 (23.1%)	4
Infections and infestations
Pneumonia	2/11 (18.2%)	2	1/13 (7.7%)	1
Bronchitis	1/11 (9.1%)	1	0/13 (0%)	0
Gastroenteritis salmonella	1/11 (9.1%)	1	0/13 (0%)	0
Influenza	0/11 (0%)	0	1/13 (7.7%)	1
Pulmonary sepsis	1/11 (9.1%)	1	0/13 (0%)	0
Rhinovirus infection	0/11 (0%)	0	1/13 (7.7%)	1
Septic shock	1/11 (9.1%)	1	0/13 (0%)	0
Upper respiratory tract infection	1/11 (9.1%)	1	0/13 (0%)	0
Injury, poisoning and procedural complications
Infusion related reaction	0/11 (0%)	0	2/13 (15.4%)	2
Investigations
C-reactive protein increased	1/11 (9.1%)	1	0/13 (0%)	0
Metabolism and nutrition disorders
Tumour lysis syndrome	0/11 (0%)	0	1/13 (7.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/11 (9.1%)	1	0/13 (0%)	0
Bone pain	0/11 (0%)	0	1/13 (7.7%)	1
Groin pain	0/11 (0%)	0	1/13 (7.7%)	1
Other (Not Including Serious) Adverse Events
	Cohort A (Tafasitamab+Idelalisib)		Cohort B (Tafasitamab+Venetoclax)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/11 (100%)		12/13 (92.3%)
Blood and lymphatic system disorders
Neutropenia	5/11 (45.5%)	15	6/13 (46.2%)	21
Anaemia	5/11 (45.5%)	6	2/13 (15.4%)	4
Thrombocytopenia	3/11 (27.3%)	3	1/13 (7.7%)	1
Lymphopenia	1/11 (9.1%)	1	1/13 (7.7%)	1
Anaemia of malignant disease	1/11 (9.1%)	2	0/13 (0%)	0
Leukocytosis	1/11 (9.1%)	1	0/13 (0%)	0
Leukopenia	0/11 (0%)	0	3/13 (23.1%)	4
Lymphadenopathy	0/11 (0%)	0	1/13 (7.7%)	1
Splenic infarction	0/11 (0%)	0	1/13 (7.7%)	1
Cardiac disorders
Arrhythmia	1/11 (9.1%)	1	0/13 (0%)	0
Atrial fibrillation	1/11 (9.1%)	1	0/13 (0%)	0
Cardiovascular insufficiency	1/11 (9.1%)	1	0/13 (0%)	0
Myocardial ischaemia	1/11 (9.1%)	1	0/13 (0%)	0
Tachyarrhythmia	1/11 (9.1%)	1	0/13 (0%)	0
Tachycardia	0/11 (0%)	0	2/13 (15.4%)	2
Atrioventricular block	0/11 (0%)	0	1/13 (7.7%)	1
Atrioventricular block second degree	0/11 (0%)	0	1/13 (7.7%)	1
Palpitations	0/11 (0%)	0	1/13 (7.7%)	1
Ear and labyrinth disorders
Vertigo	1/11 (9.1%)	1	0/13 (0%)	0
Deafness unilateral	0/11 (0%)	0	1/13 (7.7%)	1
Ear discomfort	0/11 (0%)	0	1/13 (7.7%)	1
Eye disorders
Erythema of eyelid	1/11 (9.1%)	1	0/13 (0%)	0
Holmes-Adie pupil	1/11 (9.1%)	1	0/13 (0%)	0
Pupils unequal	1/11 (9.1%)	1	0/13 (0%)	0
Visual impairment	1/11 (9.1%)	1	0/13 (0%)	0
Gastrointestinal disorders
Nausea	1/11 (9.1%)	1	5/13 (38.5%)	6
Diarrhoea	3/11 (27.3%)	5	2/13 (15.4%)	2
Dysphagia	1/11 (9.1%)	1	0/13 (0%)	0
Erosive duodenitis	1/11 (9.1%)	1	0/13 (0%)	0
Flatulence	1/11 (9.1%)	1	0/13 (0%)	0
Gastritis erosive	1/11 (9.1%)	1	0/13 (0%)	0
Gastrooesophageal reflux disease	1/11 (9.1%)	1	0/13 (0%)	0
Glossitis	1/11 (9.1%)	1	0/13 (0%)	0
Noninfective sialoadenitis	1/11 (9.1%)	1	0/13 (0%)	0
Dyspepsia	0/11 (0%)	0	3/13 (23.1%)	3
Vomiting	0/11 (0%)	0	3/13 (23.1%)	3
Abdominal distension	0/11 (0%)	0	1/13 (7.7%)	1
Abdominal pain	0/11 (0%)	0	1/13 (7.7%)	1
Anal haemorrhage	0/11 (0%)	0	1/13 (7.7%)	1
Constipation	0/11 (0%)	0	1/13 (7.7%)	1
Dry mouth	0/11 (0%)	0	1/13 (7.7%)	1
Haematochezia	0/11 (0%)	0	1/13 (7.7%)	1
Inguinal hernia	0/11 (0%)	0	1/13 (7.7%)	1
Oral pain	0/11 (0%)	0	1/13 (7.7%)	1
Umbilical hernia	0/11 (0%)	0	1/13 (7.7%)	1
General disorders
Pyrexia	5/11 (45.5%)	8	2/13 (15.4%)	2
Fatigue	1/11 (9.1%)	2	3/13 (23.1%)	3
General physical health deterioration	2/11 (18.2%)	2	0/13 (0%)	0
Oedema peripheral	1/11 (9.1%)	1	1/13 (7.7%)	1
Asthenia	1/11 (9.1%)	1	0/13 (0%)	0
Catheter site haematoma	1/11 (9.1%)	1	0/13 (0%)	0
Feeling hot	1/11 (9.1%)	1	0/13 (0%)	0
Gait disturbance	1/11 (9.1%)	1	0/13 (0%)	0
Mucosal inflammation	1/11 (9.1%)	1	0/13 (0%)	0
Catheter site inflammation	0/11 (0%)	0	1/13 (7.7%)	1
Chest discomfort	0/11 (0%)	0	1/13 (7.7%)	1
Chills	0/11 (0%)	0	1/13 (7.7%)	1
Drug intolerance	0/11 (0%)	0	1/13 (7.7%)	1
Face oedema	0/11 (0%)	0	1/13 (7.7%)	1
Malaise	0/11 (0%)	0	1/13 (7.7%)	1
Hepatobiliary disorders
Cholelithiasis	2/11 (18.2%)	3	1/13 (7.7%)	1
Hydrocholecystis	2/11 (18.2%)	2	0/13 (0%)	0
Hepatotoxicity	1/11 (9.1%)	1	0/13 (0%)	0
Hepatic cyst	0/11 (0%)	0	1/13 (7.7%)	1
Hyperbilirubinaemia	0/11 (0%)	0	1/13 (7.7%)	1
Immune system disorders
Immunodeficiency	2/11 (18.2%)	2	1/13 (7.7%)	1
Contrast media allergy	0/11 (0%)	0	1/13 (7.7%)	1
Drug hypersensitivity	0/11 (0%)	0	1/13 (7.7%)	1
Graft versus host disease in liver	0/11 (0%)	0	1/13 (7.7%)	1
Hypersensitivity	0/11 (0%)	0	1/13 (7.7%)	2
Infections and infestations
Urinary tract infection	3/11 (27.3%)	4	1/13 (7.7%)	1
Pneumonia	1/11 (9.1%)	1	2/13 (15.4%)	2
Respiratory tract infection	1/11 (9.1%)	1	2/13 (15.4%)	2
Upper respiratory tract infection	1/11 (9.1%)	1	2/13 (15.4%)	2
Cytomegalovirus infection	2/11 (18.2%)	2	0/13 (0%)	0
Nasopharyngitis	1/11 (9.1%)	1	1/13 (7.7%)	1
Aspergillus infection	1/11 (9.1%)	1	0/13 (0%)	0
Bronchitis	1/11 (9.1%)	1	0/13 (0%)	0
Fungal oesophagitis	1/11 (9.1%)	1	0/13 (0%)	0
Gastrointestinal candidiasis	1/11 (9.1%)	1	0/13 (0%)	0
Gastrointestinal infection	1/11 (9.1%)	1	0/13 (0%)	0
Helicobacter infection	1/11 (9.1%)	1	0/13 (0%)	0
Infection	1/11 (9.1%)	2	0/13 (0%)	0
Pharyngitis	1/11 (9.1%)	1	0/13 (0%)	0
Erysipelas	0/11 (0%)	0	1/13 (7.7%)	1
Helicobacter gastritis	0/11 (0%)	0	1/13 (7.7%)	1
Infectious pleural effusion	0/11 (0%)	0	1/13 (7.7%)	2
Lung infection	0/11 (0%)	0	1/13 (7.7%)	1
Paronychia	0/11 (0%)	0	1/13 (7.7%)	1
Pneumococcal sepsis	0/11 (0%)	0	1/13 (7.7%)	1
Rhinitis	0/11 (0%)	0	1/13 (7.7%)	1
Sinusitis	0/11 (0%)	0	1/13 (7.7%)	1
Staphylococcal infection	0/11 (0%)	0	1/13 (7.7%)	1
Injury, poisoning and procedural complications
Infusion related reaction	5/11 (45.5%)	5	5/13 (38.5%)	7
Fall	1/11 (9.1%)	1	0/13 (0%)	0
Medication error	1/11 (9.1%)	1	0/13 (0%)	0
Overdose	1/11 (9.1%)	1	0/13 (0%)	0
Arthropod bite	0/11 (0%)	0	1/13 (7.7%)	1
Tendon rupture	0/11 (0%)	0	1/13 (7.7%)	1
Investigations
Alanine aminotransferase increased	3/11 (27.3%)	3	1/13 (7.7%)	1
Weight decreased	1/11 (9.1%)	1	2/13 (15.4%)	3
Amylase increased	2/11 (18.2%)	3	0/13 (0%)	0
Aspartate aminotransferase increased	1/11 (9.1%)	1	1/13 (7.7%)	1
C-reactive protein increased	1/11 (9.1%)	2	1/13 (7.7%)	1
Body temperature increased	1/11 (9.1%)	1	0/13 (0%)	0
Coagulation time prolonged	1/11 (9.1%)	1	0/13 (0%)	0
Lipase increased	1/11 (9.1%)	1	0/13 (0%)	0
Transaminases increased	1/11 (9.1%)	1	0/13 (0%)	0
Blood lactate dehydrogenase increased	0/11 (0%)	0	4/13 (30.8%)	4
Troponin T increased	0/11 (0%)	0	3/13 (23.1%)	3
Brain natriuretic peptide increased	0/11 (0%)	0	2/13 (15.4%)	2
Coombs test positive	0/11 (0%)	0	2/13 (15.4%)	2
Blood alkaline phosphatase increased	0/11 (0%)	0	1/13 (7.7%)	1
Electrocardiogram T wave abnormal	0/11 (0%)	0	1/13 (7.7%)	1
Gamma-glutamyltransferase increased	0/11 (0%)	0	1/13 (7.7%)	1
Hepatic enzyme increased	0/11 (0%)	0	1/13 (7.7%)	1
Weight increased	0/11 (0%)	0	1/13 (7.7%)	2
Metabolism and nutrition disorders
Hypocalcaemia	2/11 (18.2%)	2	3/13 (23.1%)	3
Hypokalaemia	1/11 (9.1%)	1	3/13 (23.1%)	4
Hyperkalaemia	2/11 (18.2%)	2	1/13 (7.7%)	1
Hypoalbuminaemia	2/11 (18.2%)	2	1/13 (7.7%)	1
Hypomagnesaemia	1/11 (9.1%)	1	1/13 (7.7%)	1
Dehydration	1/11 (9.1%)	1	0/13 (0%)	0
Hypercholesterolaemia	1/11 (9.1%)	1	0/13 (0%)	0
Hypoproteinaemia	1/11 (9.1%)	1	0/13 (0%)	0
Type 2 diabetes mellitus	1/11 (9.1%)	1	0/13 (0%)	0
Hyperuricaemia	0/11 (0%)	0	5/13 (38.5%)	6
Hypophosphataemia	0/11 (0%)	0	4/13 (30.8%)	4
Iron deficiency	0/11 (0%)	0	3/13 (23.1%)	3
Hyperglycaemia	0/11 (0%)	0	2/13 (15.4%)	2
Decreased appetite	0/11 (0%)	0	1/13 (7.7%)	1
Hypercalcaemia	0/11 (0%)	0	1/13 (7.7%)	1
Hypermagnesaemia	0/11 (0%)	0	1/13 (7.7%)	1
Musculoskeletal and connective tissue disorders
Pain in extremity	1/11 (9.1%)	1	1/13 (7.7%)	1
Bone pain	1/11 (9.1%)	1	0/13 (0%)	0
Arthralgia	0/11 (0%)	0	2/13 (15.4%)	3
Muscle spasms	0/11 (0%)	0	2/13 (15.4%)	2
Myalgia	0/11 (0%)	0	2/13 (15.4%)	2
Exostosis	0/11 (0%)	0	1/13 (7.7%)	1
Joint swelling	0/11 (0%)	0	1/13 (7.7%)	1
Musculoskeletal pain	0/11 (0%)	0	1/13 (7.7%)	1
Osteosclerosis	0/11 (0%)	0	1/13 (7.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm	1/11 (9.1%)	1	0/13 (0%)	0
Nervous system disorders
Dizziness	1/11 (9.1%)	3	2/13 (15.4%)	4
Headache	2/11 (18.2%)	2	1/13 (7.7%)	1
Burning sensation	0/11 (0%)	0	1/13 (7.7%)	1
Hypoaesthesia	0/11 (0%)	0	1/13 (7.7%)	1
Lethargy	0/11 (0%)	0	1/13 (7.7%)	1
Neuropathy peripheral	0/11 (0%)	0	1/13 (7.7%)	1
Psychiatric disorders
Insomnia	1/11 (9.1%)	1	2/13 (15.4%)	2
Sleep disorder	1/11 (9.1%)	1	0/13 (0%)	0
Agitation	0/11 (0%)	0	1/13 (7.7%)	1
Depressed mood	0/11 (0%)	0	1/13 (7.7%)	1
Depression	0/11 (0%)	0	1/13 (7.7%)	1
Renal and urinary disorders
Acute kidney injury	1/11 (9.1%)	1	0/13 (0%)	0
Renal failure	1/11 (9.1%)	1	0/13 (0%)	0
Renal impairment	1/11 (9.1%)	1	0/13 (0%)	0
Haematuria	0/11 (0%)	0	1/13 (7.7%)	1
Respiratory, thoracic and mediastinal disorders
Cough	3/11 (27.3%)	4	5/13 (38.5%)	5
Dyspnoea	5/11 (45.5%)	5	3/13 (23.1%)	3
Pleural effusion	2/11 (18.2%)	2	1/13 (7.7%)	1
Dyspnoea exertional	1/11 (9.1%)	1	0/13 (0%)	0
Pulmonary oedema	1/11 (9.1%)	1	0/13 (0%)	0
Rales	1/11 (9.1%)	1	0/13 (0%)	0
Tachypnoea	1/11 (9.1%)	1	0/13 (0%)	0
Upper respiratory tract inflammation	1/11 (9.1%)	1	0/13 (0%)	0
Atelectasis	0/11 (0%)	0	1/13 (7.7%)	1
Haemothorax	0/11 (0%)	0	1/13 (7.7%)	1
Increased bronchial secretion	0/11 (0%)	0	1/13 (7.7%)	1
Pneumothorax	0/11 (0%)	0	1/13 (7.7%)	1
Pulmonary embolism	0/11 (0%)	0	1/13 (7.7%)	1
Rhinitis allergic	0/11 (0%)	0	1/13 (7.7%)	1
Sinus disorder	0/11 (0%)	0	1/13 (7.7%)	1
Small airways disease	0/11 (0%)	0	1/13 (7.7%)	1
Skin and subcutaneous tissue disorders
Rash	2/11 (18.2%)	2	1/13 (7.7%)	1
Dry skin	1/11 (9.1%)	1	1/13 (7.7%)	1
Hyperhidrosis	1/11 (9.1%)	1	1/13 (7.7%)	2
Skin lesion	1/11 (9.1%)	1	1/13 (7.7%)	1
Eczema	1/11 (9.1%)	1	0/13 (0%)	0
Alopecia	0/11 (0%)	0	1/13 (7.7%)	1
Onychoclasis	0/11 (0%)	0	1/13 (7.7%)	1
Pruritus	0/11 (0%)	0	1/13 (7.7%)	1
Skin haemorrhage	0/11 (0%)	0	1/13 (7.7%)	1
Vascular disorders
Hypertension	2/11 (18.2%)	2	1/13 (7.7%)	1
Aortic dilatation	1/11 (9.1%)	1	0/13 (0%)	0
Circulatory collapse	1/11 (9.1%)	1	0/13 (0%)	0
Deep vein thrombosis	0/11 (0%)	0	1/13 (7.7%)	1
Flushing	0/11 (0%)	0	1/13 (7.7%)	1
Hypotension	0/11 (0%)	0	1/13 (7.7%)	1
Orthostatic hypotension	0/11 (0%)	0	1/13 (7.7%)	1
Peripheral venous disease	0/11 (0%)	0	1/13 (7.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.