Combination Study of IPH2201 (Monalizumab) With Ibrutinib in Relapsed, Refractory or Previously Untreated CLL

• ClinicalTrials.gov Identifier: NCT02557516
• Recruitment Status: Terminated
• First Posted: September 23, 2015
• Results First Posted: December 17, 2019
• Last Update Posted: December 17, 2019
• Sponsor: Innate Pharma
• Information provided by (Responsible Party): Innate Pharma

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Lymphocytic Leukemia
• Intervention: Drug: monalizumab
• Enrollment: 22

Participant Flow

Recruitment Details	It was anticipated that up to 24 patients (3 to 6 patients; 4 dose levels) would be enrolled in Phase 1 part of the study and up to 24 patients in the Phase 2 part with a total of up to 45 patients in the trial. A total of 22 patients were actually enrolled in the study: 13 patients in the Phase 1 part and 9 patients in the Phase 2 part.
Pre-assignment Details	The first part of the study had a 3+3 design. Four dose levels of monalizumab were planned: 1 mg/kg, 2 mg/kg, 4 mg/kg and 10 mg/kg. Dose-escalation decisions were made by a Safety Committee.The dose of monalizumab for all patients in phase 2 of the study (2 mg/kg) was also chosen by the Safety Committee based on phase 1 data.

Arm/Group Title	Phase 1 Level 1 - 1 mg/kg	Phase 1 Level 2 - 2 mg/kg	Phase 1 Level 3 - 4 mg/kg	Phase 2 RP2D - 2 mg/kg
Arm/Group Description	During phase 1, patients received monalizumab, IV, at the dose of 1mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks. The first 4 administrations of monalizumab occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.	During phase 1, patients received monalizumab, IV, at the dose of 2 mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks. The first 4 administrations of monalizumab occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.	During phase 1, patients received monalizumab, IV, at the dose of 4 mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks. The first 4 administrations of monalizumab occured every 2 weeks. From the 5th administration IPH2201 was administered every 4 weeks.	During phase 2, patients received monalizumab, IV, at the dose recommended upon completion of phase 1 part (2 mg/kg), combined with ibrutinib 420 mg orally, once daily, from the first administration and during 52 weeks. The first 4 administrations of monalizumab occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.
Period Title: Overall Study
Started	3	6	4	9
Completed	2	1	0	0
Not Completed	1	5	4	9
Reason Not Completed
Adverse Event	1	0	2	1
Disease progression	0	2	0	0
Physician Decision	0	2	0	0
Sponsor decision	0	1	2	8

Baseline Characteristics

Arm/Group Title		Phase 1 Level 1 - 1 mg/kg	Phase 1 Level 2 - 2 mg/kg	Phase 1 Level 3 - 4 mg/kg	Phase 2 RP2D - 2 mg/kg	Total
Arm/Group Description		During phase 1, patients received monalizumab, IV, at the dose of 1 mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.	During phase 1, patients received monalizumab, IV, at the dose of 2 mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.	During phase 1, patients received monalizumab, IV, at the dose of 4 mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.	During phase 2, patients received monalizumab, IV, at the dose recommended upon completion of phase 1 part, combined with ibrutinib 420 mg orally, once daily, from the first cycle and during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		3	6	4	9	22
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	3 participants	6 participants	4 participants	9 participants	22 participants
		59.3 (11.15)	65.8 (7.14)	69.5 (10.08)	69.4 (6.33)	67.1 (8.14)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	6 participants	4 participants	9 participants	22 participants
	Female	0 0.0%	3 50.0%	3 75.0%	2 22.2%	8 36.4%
	Male	3 100.0%	3 50.0%	1 25.0%	7 77.8%	14 63.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	6 participants	4 participants	9 participants	22 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	3 100.0%	6 100.0%	4 100.0%	9 100.0%	22 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	6 participants	4 participants	9 participants	22 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	1 11.1%	1 4.5%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	1 11.1%	1 4.5%
	White	3 100.0%	6 100.0%	4 100.0%	7 77.8%	20 90.9%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	3 participants	6 participants	4 participants	9 participants	22 participants
		3	6	4	9	22
ECOG Performance Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	6 participants	4 participants	9 participants	22 participants
	ECOG 0	3 100.0%	2 33.3%	0 0.0%	7 77.8%	12 54.5%
	ECOG 1	0 0.0%	4 66.7%	4 100.0%	2 22.2%	10 45.5%
		[1] Measure Description: Eastern Cooperative Oncology Group performance status scale 0 Fully active, able to carry out all normal activity without restriction.; Restricted in physically strenuous activity but ambulatory and able to carry out light work.; Ambulatory and capable of all self-care but unable to carry out any work. Up and about more than 50% of waking hours.; Capable of only limited self-care, confined to bed or chair more than 50 % of waking hours.; Completely disabled. Cannot carry out any self-care. Totally confined to bed or chair.; Dead.
RAI Stage [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	6 participants	4 participants	9 participants	22 participants
	Stage I	0 0.0%	0 0.0%	0 0.0%	3 33.3%	3 13.6%
	Stage II	2 66.7%	1 16.7%	0 0.0%	0 0.0%	3 13.6%
	Stage III	0 0.0%	1 16.7%	1 25.0%	0 0.0%	2 9.1%
	Stage IV	1 33.3%	4 66.7%	3 75.0%	6 66.7%	14 63.6%
		[1] Measure Description: The RAI staging divides CLL into 5 stages: stage 0, bone marrow and blood lymphocytosis only; stage I, lymphocytosis with enlarged nodes; stage II, lymphocytosis with enlarged spleen or liver or both; stage III, lymphocytosis with anemia; and stage IV:lymphocytosis with thrombocytopenia. Stage 0 is low-risk, stages I and II are intermediate-risk, stages III and IV are high-risk.
Disease Status at Screening; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	6 participants	4 participants	9 participants	22 participants
	Previously Untreated CLL	0 0.0%	1 16.7%	0 0.0%	6 66.7%	7 31.8%
	Refractory CLL	0 0.0%	1 16.7%	1 25.0%	0 0.0%	2 9.1%
	Relapse CLL	3 100.0%	4 66.7%	3 75.0%	3 33.3%	13 59.1%

Outcome Measures

1. Primary Outcome

Title	Number of Dose Limiting Toxicities
Description	Number of dose-limiting toxicities, measured during the phase 1, dose escalation, part of the study.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

During phase 1 part of the study (dose escalation) the total number of patients evaluated for safety parameters is 13; 3 patients received at least one dose of monalizumab 1 mg/kg, 6 patients received 2 mg/kg , and 4 patients received 4 mg/kg.

Arm/Group Title	Phase 1 Level 1 - 1 mg/kg	Phase 1 Level 2 - 2 mg/kg	Phase 1 Level 3 - 4 mg/kg
Arm/Group Description:	Phase 1 (dose escalation) evaluating dose level 1 (1 mg/kg) of monalizumab alone during 4 weeks then in combination with ibrutinib during 52 weeks.	Phase 1 (dose escalation) evaluating dose level 2 of monalizumab (2 mg/kg) of monalizumab alone during 4 weeks then in combination with ibrutinib during 52 weeks.	Phase 1 (dose escalation) evaluating dose level 3 (4 mg/kg) of monalizumab alone during 4 weeks then in combination with ibrutinib during 52 weeks.
Overall Number of Participants Analyzed	3	6	4
Measure Type: Number; Unit of Measure: Dose Limiting Toxicy
	0	1	2

2. Primary Outcome

Title	Rate of Complete Response (CR)
Description	The rate of complete response (CR) was evaluated using the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) grading scale and confirmed by a bone marrow biopsy. Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL), Complete Response (CR) is defined as lymphocytes <4x109/l, absence of lymphadenopathy, hepatomegaly and splenomegaly at CT scan, no constitutional symptoms, no cytopenia, normocellular bone marrow. Partial Response (PR) is a reduction > 50% in lymphocytes, lymphadenopathy, spleen or liver, no cytopenia. PD if appearance of any new lesion, or increase in lymphocytes > 50%, or occurrence of cytopenia attributable to CLL.
Time Frame	CR assessed 52 weeks after the beginning of combination treatment

Outcome Measure Data

Analysis Population Description

Efficacy population: 21 patients who received at least one dose of monalizumab. According to the protocol, patients who discontinued treatment due to disease progression before the end of 8 weeks were replaced. Of note,1 patient (grade 3 hemolytic anemia due to disease progression at W4) was replaced and was then excluded from efficacy population.

Arm/Group Title	Phase 1 Level 1 - 1 mg/kg	Phase 1 Level 2 - 2 mg/kg	Phase 1 Level 3 - 4 mg/kg	Phase 2 RP2D - 2 mg/kg
Arm/Group Description:	During phase 1b, patients received monalizumab, IV, at the dose of 1mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks. In both parts of the trial, the first 4 administrations of IPH2201 occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.	During phase 1b, patients received monalizumab, IV, at the dose of 2 mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks. In both parts of the trial, the first 4 administrations of IPH2201 occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.	During phase 1b, patients received monalizumab, IV, at the dose of 4 mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks. In both parts of the trial, the first 4 administrations of IPH2201 occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.	During phase 2a, patients received monalizumab, IV, at the dose recommended upon completion of phase 1b part, combined with ibrutinib 420 mg orally, once daily, from the first cycle and during 52 weeks. In both parts of the trial, the first 4 administrations of IPH2201 occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks
Overall Number of Participants Analyzed	3	6	3	9
Measure Type: Count of Participants; Unit of Measure: Participants
	1 33.3%	1 16.7%	0 0.0%	0 0.0%

3. Secondary Outcome

Title	Best Overall Response / Remission Rates
Description	Measure of best overall response at any time during the study. cCR: confirmed complete response/remission; uCR: unconfirmed complete response / remission; PR: partial response/remission; SD: stable disease; PD: progressive disease. Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL), Complete Response (CR) is defined as lymphocytes <4x109/l, absence of lymphadenopathy, hepatomegaly and splenomegaly at CT scan, no constitutional symptoms, no cytopenia, normocellular bone marrow. Partial Response (PR) is a reduction > 50% in lymphocytes, lymphadenopathy, spleen or liver, no cytopenia. PD if appearance of any new lesion, or increase in lymphocytes > 50%, or occurrence of cytopenia attributable to CLL. In order to have a confirmed CR (cCR), the CR must be confirmed by a scan and a bone marrow assessment assessed at least 2 months after the first occurrence of CR. Otherwise it would be an unconfirmed CR (uCR).
Time Frame	From beginning of study drug treatment to the end of study (up to 24 months)

Outcome Measure Data

Analysis Population Description

Efficacy population: 21 patients who received at least one dose of monalizumab. According to the protocol, patients who discontinued treatment due to disease progression before the end of 8 weeks were replaced. Of note,1 patient (grade 3 hemolytic anemia due to disease progression at W4) was replaced and was then excluded from efficacy population.

Arm/Group Title	Phase 1 Level 1 - 1 mg/kg	Phase 1 Level 2 - 2 mg/kg	Phase 1 Level 3 - 4 mg/kg	Phase 2 RP2D - 2 mg/kg
Arm/Group Description:	During phase 1, patients received monalizumab, IV, at the dose of 1 mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.	During phase 1, patients received monalizumab, IV, at the dose of 2 mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.	During phase 1, patients receive monalizumab, IV, at the dose of 4 mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.	During phase a, patients received monalizumab, IV, at the dose recommended upon completion of phase 1, combined with ibrutinib 420 mg orally, once daily, from the first cycle and during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.
Overall Number of Participants Analyzed	3	6	3	9
Measure Type: Count of Participants; Unit of Measure: Participants
cCR	1 33.3%	1 16.7%	0 0.0%	0 0.0%
uCR	0 0.0%	1 16.7%	0 0.0%	0 0.0%
PR	2 66.7%	3 50.0%	2 66.7%	6 66.7%
SD	0 0.0%	1 16.7%	1 33.3%	3 33.3%
PD	0 0.0%	0 0.0%	0 0.0%	0 0.0%

4. Secondary Outcome

Title	Duration of Remission
Description	The duration of remission (DOR) is defined as the time from the date of first evaluation of the remission (cCR, uCR or PR) to the first documentation of progressive disease, relapsed disease or death. In case an assessment of progressive / relapsed disease or death does not exist, the DOR was censored at the time of the last disease assessment date. The DOR was calculated only for the patients with a remission that was assessed at 52 weeks.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

21 patients evaluated for efficacy. 1 patient treated at 4 mg/kg was withdrawn due to grade 3 hemolytic anemia attribuated to disease progression at W4 and considered as not evaluable for efficacy. Due to the small size of the trial no subgroup analyses have been conducted.

Arm/Group Title	Efficacy Population
Arm/Group Description:	The efficacy population included all patients who have received at least one dose of monalizumab. According to the protocol, patients who discontinued from monalizumab treatment due to disease progression before the end of 8 weeks of treatment were replaced. As one patient was withdrawn due to grade 3 hemolytic anemia attribuated to disease progressions at W4, 21 patients were included in the efficacy population.
Overall Number of Participants Analyzed	21
Median (95% Confidence Interval); Unit of Measure: Month
	NA [1]; (NA to NA)

[1]

A median DOR could not be estimated at the time of data cut-off.

5. Secondary Outcome

Title	Progression Free Survival
Description	The Progression Free Survival (PFS) is defined as the time from first dose administration until the occurrence of progressive disease, relapsed disease or death from any cause. Patients without an event at the time of the analyse were censored at his or her last disease assessment date. Patients with no post-Baseline assessment were censored at the day of the first dose administration.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

All 22 enrolled patients were included in the ITT / Safety population

Arm/Group Title	ITT / Safety Population
Arm/Group Description:	The Intent-To-Treat / Safety population is defined by all phase 1 and phase 2a patients who received at least 1 administration of monalizumab were evaluable for progression-free survival and overall survival efficacy outcomes and for safety. 22 patients were included in the ITT / Safety population.
Overall Number of Participants Analyzed	22
Median (95% Confidence Interval); Unit of Measure: Month
	NA [1]; (NA to NA)

[1]

A PFS median could not be estimated at the time of data cut-off.

6. Secondary Outcome

Title	Overall Survival
Description	The overall survival (OS) is defined as the time from first dose administration until death from any cause. Alive patients were censored at the most recent date they were known to be alive. Subjects with no assessment post-Baseline were censored at the day of the first dose administration.
Time Frame	Up to 24 months.

Outcome Measure Data

Analysis Population Description

22 patients were included in the ITT / Safety population

Arm/Group Title	All ITT / Safety Population
Arm/Group Description:	The Intent-To-Treat / Safety population is defined by all phase 1 and phase 2a patients who received at least 1 administration of monalizumab were evaluable for progression-free survival and overall survival efficacy outcomes and for safety. 22 patients were included in the ITT / Safety population.
Overall Number of Participants Analyzed	22
Median (95% Confidence Interval); Unit of Measure: Month
	NA [1]; (NA to NA)

[1]

At the time of data cut-off, all 22 phase 1 and phase 2 patients were alive.

Adverse Events

Time Frame	The occurrences of Adverse Events were recorded from the time of signed informed consent until the end of the patient's participation to the trial (up to 24 months).
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	1 mg/kg		2 mg/kg		4 mg/kg
Arm/Group Description	During phase 1b, patients received monalizumab, IV, at the dose of 1mg/kg, in combination with ibrutinib 420 mg, orally, once daily.		During phase 1b and during phase 2a patients received monalizumab, IV, at the dose of 2 mg/kg, in combination with ibrutinib 420 mg, orally, once daily.		During phase 1b, patients receivde monalizumab, IV, at the dose of 4 mg/kg, in combination with ibrutinib 420 mg, orally, once daily.
All-Cause Mortality
	1 mg/kg		2 mg/kg		4 mg/kg
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/3 (0.00%)		0/15 (0.00%)		0/4 (0.00%)
Serious Adverse Events
	1 mg/kg		2 mg/kg		4 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.67%)		5/15 (33.33%)		3/4 (75.00%)
Cardiac disorders
Supraventricular tachycardia † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Gastrointestinal disorders
Large intestinal haemorrhage † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Lower gastrointestinal haemorrhage † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
General disorders
Pyrexia † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Infections and infestations
Sinusitis † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Urinary tract infection enterococcal † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Urosepsis † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Investigations
Amylase increased † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Platelet count decreased † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer recurrent † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Myelodysplastic syndrome † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Squamous cell carcinoma † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Hypoxia † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
1 Term from vocabulary, CTCAE (4.03); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	1 mg/kg		2 mg/kg		4 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100.00%)		15/15 (100.00%)		4/4 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Autoimmune haemolytic anaemia † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Lymph node pain † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Neutropenia † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Cardiac disorders
Atrial fibrillation † 1	0/3 (0.00%)	0	3/15 (20.00%)	3	0/4 (0.00%)	0
Palpitations † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
Sinus tachycardia † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Ear and labyrinth disorders
Ear pain † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
Middle ear effusion † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Tinnitus † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Endocrine disorders
Hypothyroidism † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	2
Eye disorders
Cataract † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Dry eye † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Eye discharge † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
Ocular discomfort † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Ocular hyperaemia † 1	1/3 (33.33%)	1	1/15 (6.67%)	1	0/4 (0.00%)	0
Vision blurred † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	1/4 (25.00%)	1
Vitreous floaters † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Gastrointestinal disorders
Abdominal distension † 1	1/3 (33.33%)	1	1/15 (6.67%)	1	2/4 (50.00%)	2
Abdominal pain † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	2/4 (50.00%)	2
Constipation † 1	1/3 (33.33%)	1	3/15 (20.00%)	5	2/4 (50.00%)	2
Dental caries † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	1/4 (25.00%)	1
Diarrhoea † 1	2/3 (66.67%)	2	9/15 (60.00%)	15	4/4 (100.00%)	4
Dry mouth † 1	0/3 (0.00%)	0	3/15 (20.00%)	3	0/4 (0.00%)	0
Dyspepsia † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
Dysphagia † 1	1/3 (33.33%)	2	0/15 (0.00%)	0	0/4 (0.00%)	0
Gastrointestinal haemorrhage † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Gastrooesophageal reflux disease † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Gingival bleeding † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	2
Gingival pain † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Haematochezia † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Nausea † 1	0/3 (0.00%)	0	5/15 (33.33%)	5	0/4 (0.00%)	0
Oesophageal obstruction † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Oesophagitis † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Oral dysaesthesia † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Oral pain † 1	1/3 (33.33%)	1	4/15 (26.67%)	5	0/4 (0.00%)	0
Stomatitis † 1	0/3 (0.00%)	0	6/15 (40.00%)	9	2/4 (50.00%)	4
Toothache † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Vomiting † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
General disorders
Chest discomfort † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Chest pain † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Chills † 1	0/3 (0.00%)	0	4/15 (26.67%)	4	0/4 (0.00%)	0
Cyst † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Cyst rupture † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Facial pain † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Fatigue † 1	1/3 (33.33%)	1	4/15 (26.67%)	4	1/4 (25.00%)	1
Feeling jittery † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Localised oedema † 1	0/3 (0.00%)	0	2/15 (13.33%)	3	0/4 (0.00%)	0
Mass † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Non-cardiac chest pain † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
Oedema † 1	1/3 (33.33%)	2	1/15 (6.67%)	1	0/4 (0.00%)	0
Oedema peripheral † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Pyrexia † 1	1/3 (33.33%)	1	2/15 (13.33%)	2	0/4 (0.00%)	0
Infections and infestations
Clostridium difficile colitis † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Conjunctivitis † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Gastroenteritis viral † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Herpes zoster † 1	0/3 (0.00%)	0	3/15 (20.00%)	3	0/4 (0.00%)	0
Laryngitis † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Lip infection † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
Nail infection † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Nasopharyngitis † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Oral infection † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Sinusitis † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
Skin infection † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	1/4 (25.00%)	1
Upper respiratory tract infection † 1	1/3 (33.33%)	1	5/15 (33.33%)	6	1/4 (25.00%)	1
Urinary tract infection † 1	1/3 (33.33%)	2	2/15 (13.33%)	5	1/4 (25.00%)	1
Urinary tract infection enterococcal † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Urosepsis † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Wound infection † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Injury, poisoning and procedural complications
Arthropod bite † 1	1/3 (33.33%)	1	2/15 (13.33%)	2	0/4 (0.00%)	0
Contusion † 1	3/3 (100.00%)	4	8/15 (53.33%)	13	0/4 (0.00%)	0
Fall † 1	0/3 (0.00%)	0	3/15 (20.00%)	3	0/4 (0.00%)	0
Head injury † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Infusion related reaction † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Injury † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Joint injury † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Limb injury † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Skin laceration † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Tooth fracture † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Amylase increased † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Blood creatinine increased † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
Blood sodium decreased † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Electrocardiogram QT prolonged † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Haemoglobin decreased † 1	1/3 (33.33%)	3	0/15 (0.00%)	0	0/4 (0.00%)	0
Lipase increased † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Lymphocyte count increased † 1	1/3 (33.33%)	1	1/15 (6.67%)	1	0/4 (0.00%)	0
Neutrophil count decreased † 1	0/3 (0.00%)	0	2/15 (13.33%)	3	0/4 (0.00%)	0
Platelet count decreased † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	1/4 (25.00%)	1
Weight decreased † 1	1/3 (33.33%)	1	2/15 (13.33%)	3	0/4 (0.00%)	0
Weight increased † 1	1/3 (33.33%)	1	3/15 (20.00%)	3	1/4 (25.00%)	1
Metabolism and nutrition disorders
Decreased appetite † 1	2/3 (66.67%)	2	5/15 (33.33%)	5	0/4 (0.00%)	0
Dehydration † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Hypercalcaemia † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Hyperglycaemia † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Hyperkalaemia † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Hyperuricaemia † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Hypokalaemia † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Hypomagnesaemia † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Hyponatraemia † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/3 (33.33%)	1	8/15 (53.33%)	12	2/4 (50.00%)	2
Arthritis † 1	0/3 (0.00%)	0	3/15 (20.00%)	4	0/4 (0.00%)	0
Back pain † 1	2/3 (66.67%)	3	1/15 (6.67%)	1	0/4 (0.00%)	0
Bone pain † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Bursitis † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Flank pain † 1	0/3 (0.00%)	0	1/15 (6.67%)	2	0/4 (0.00%)	0
Muscle spasms † 1	1/3 (33.33%)	1	1/15 (6.67%)	1	1/4 (25.00%)	1
Muscular weakness † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Myalgia † 1	2/3 (66.67%)	3	7/15 (46.67%)	8	1/4 (25.00%)	1
Neck pain † 1	1/3 (33.33%)	1	2/15 (13.33%)	2	1/4 (25.00%)	1
Pain in extremity † 1	0/3 (0.00%)	0	3/15 (20.00%)	3	0/4 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acrochordon † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Basal cell carcinoma † 1	0/3 (0.00%)	0	3/15 (20.00%)	3	0/4 (0.00%)	0
Melanocytic naevus † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Nervous system disorders
Cognitive disorder † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Dizziness † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
Dysaesthesia † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Dysgeusia † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
Headache † 1	0/3 (0.00%)	0	5/15 (33.33%)	6	0/4 (0.00%)	0
Memory impairment † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Neuralgia † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Paraesthesia † 1	0/3 (0.00%)	0	3/15 (20.00%)	3	0/4 (0.00%)	0
Peripheral motor neuropathy † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
Sciatica † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Psychiatric disorders
Anxiety † 1	0/3 (0.00%)	0	3/15 (20.00%)	3	0/4 (0.00%)	0
Confusional state † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Depression † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
Insomnia † 1	0/3 (0.00%)	0	4/15 (26.67%)	4	1/4 (25.00%)	1
Renal and urinary disorders
Acute kidney injury † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Dysuria † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Haematuria † 1	0/3 (0.00%)	0	2/15 (13.33%)	2	0/4 (0.00%)	0
Proteinuria † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Urinary retention † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough † 1	1/3 (33.33%)	1	8/15 (53.33%)	8	2/4 (50.00%)	2
Dyspnoea † 1	0/3 (0.00%)	0	3/15 (20.00%)	3	2/4 (50.00%)	2
Epistaxis † 1	2/3 (66.67%)	2	5/15 (33.33%)	5	0/4 (0.00%)	0
Nasal congestion † 1	2/3 (66.67%)	2	2/15 (13.33%)	2	2/4 (50.00%)	2
Oropharyngeal pain † 1	2/3 (66.67%)	2	4/15 (26.67%)	5	0/4 (0.00%)	0
Rhinitis allergic † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Upper-airway cough syndrome † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	2/4 (50.00%)	2
Skin and subcutaneous tissue disorders
Actinic keratosis † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Alopecia † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	1/4 (25.00%)	1
Dermatitis bullous † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Dry skin † 1	0/3 (0.00%)	0	3/15 (20.00%)	3	0/4 (0.00%)	0
Ecchymosis † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Hyperhidrosis † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Nail discolouration † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Nail ridging † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Night sweats † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	1/4 (25.00%)	1
Onychalgia † 1	1/3 (33.33%)	1	0/15 (0.00%)	0	0/4 (0.00%)	0
Onychoclasis † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Petechiae † 1	0/3 (0.00%)	0	4/15 (26.67%)	4	1/4 (25.00%)	1
Pruritus † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Rash † 1	0/3 (0.00%)	0	2/15 (13.33%)	4	1/4 (25.00%)	1
Rash maculo-papular † 1	0/3 (0.00%)	0	5/15 (33.33%)	15	1/4 (25.00%)	1
Skin disorder † 1	0/3 (0.00%)	0	0/15 (0.00%)	0	1/4 (25.00%)	1
Skin lesion † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	1/4 (25.00%)	2
Vascular disorders
Haematoma † 1	0/3 (0.00%)	0	1/15 (6.67%)	1	0/4 (0.00%)	0
Hypertension † 1	1/3 (33.33%)	4	7/15 (46.67%)	20	2/4 (50.00%)	3
1 Term from vocabulary, CTCAE (4.03); † Indicates events were collected by systematic assessment

Limitations and Caveats

Due to early termination some of the secondary endpoints could not be evaluated.

More Information

Certain Agreements

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

There is NOT 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.

Results Point of Contact

• Name/Title: Dr. Agnes BOYER-CHAMMARD, Medical Director
• Organization: Innate Pharma
• Phone: +33430303030
• EMail: Agnes.BOYER-CHAMMARD@innate-pharma.fr

• Responsible Party: Innate Pharma
• ClinicalTrials.gov Identifier: NCT02557516
• Other Study ID Numbers: IPH2201-202
• First Submitted: September 22, 2015
• First Posted: September 23, 2015
• Results First Submitted: October 31, 2019
• Results First Posted: December 17, 2019
• Last Update Posted: December 17, 2019