Trial Outcomes & Findings for Efficacy and Safety of MEDI7352 in Participants With Painful Diabetic Neuropathy (NCT NCT03755934)

Last Updated: 2024-09-19

Results Overview

Change from baseline to Week 12 in weekly average of average daily pain score is reported. Participants assessed their perceived daily average neuropathic pain over the previous 24 hours using an 11-point numerical rating scale (NRS), with 0 representing no pain and 10 representing the worst pain imaginable. Participants were instructed to assess their average daily pain at approximately the same time every morning, and to record the response in a subject diary (electronic patient-reported outcome \[ePRO\]).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

112 participants

Primary outcome timeframe

Baseline (Day -7 to Day -1, inclusive) through Week 12

Results posted on

2024-09-19

Participant Flow

The study was conducted at 45 sites in 4 countries (the United Kingdom, Hungary, Poland, and Romania).

A total of 112 participants were randomized, of which 107 participants received at least one dose of study drug.

Participant milestones

Participant milestones
Measure	Placebo Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.	MEDl7352 Low Dose Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose Participants received 6 doses of IV MEDl7352 during 12-week treatment period.
Overall Study STARTED	54	6	16	36
Overall Study Treated	54	4	14	35
Overall Study COMPLETED	40	4	12	30
Overall Study NOT COMPLETED	14	2	4	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.	MEDl7352 Low Dose Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose Participants received 6 doses of IV MEDl7352 during 12-week treatment period.
Overall Study Adverse Event	4	1	1	3
Overall Study Physician Decision	2	0	0	1
Overall Study Withdrawal by Subject	5	0	0	1
Overall Study Other	3	1	3	1

Baseline Characteristics

Efficacy and Safety of MEDI7352 in Participants With Painful Diabetic Neuropathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.	MEDl7352 Low Dose n=6 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=16 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=36 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Total n=112 Participants Total of all reporting groups
Age, Continuous	60.7 Years STANDARD_DEVIATION 8.02 • n=5 Participants	60.7 Years STANDARD_DEVIATION 17.14 • n=7 Participants	60.1 Years STANDARD_DEVIATION 11.49 • n=5 Participants	60.1 Years STANDARD_DEVIATION 10.21 • n=4 Participants	60.4 Years STANDARD_DEVIATION 9.73 • n=21 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	15 Participants n=4 Participants	40 Participants n=21 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants	21 Participants n=4 Participants	72 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	54 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants	36 Participants n=4 Participants	112 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) White	53 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants	36 Participants n=4 Participants	109 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Day -7 to Day -1, inclusive) through Week 12

Population: Modified intent-to-treat (mITT) population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Change From Baseline in Weekly Average of Average Daily Pain Score to Week 12	-3.387 Units on a scale Standard Deviation 1.9605	-0.615 Units on a scale Standard Deviation 1.0431	-2.699 Units on a scale Standard Deviation 2.0819	-1.244 Units on a scale Standard Deviation 1.7327

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1, inclusive), Weeks 2, 4, 6, 8, 10, and 18

Population: mITT population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment. Here, number analyzed (n) denotes those participants who were evaluable at the specified time point.

Change from baseline to Weeks 2, 4, 6, 8, 10, and 18 in weekly average of average daily pain score is reported. Participants assessed their perceived daily average neuropathic pain over the previous 24 hours using an 11-point NRS, with 0 representing no pain and 10 representing the worst pain imaginable. Participants were instructed to assess their average daily pain at approximately the same time every morning, and to record the response in a subject diary (ePRO).

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Change From Baseline in Weekly Average of Average Daily Pain Score Week 4	-2.173 Units on a scale Standard Deviation 1.4266	-0.144 Units on a scale Standard Deviation 0.9143	-1.508 Units on a scale Standard Deviation 1.5130	-0.563 Units on a scale Standard Deviation 1.0173
Change From Baseline in Weekly Average of Average Daily Pain Score Week 10	-2.595 Units on a scale Standard Deviation 2.2003	-0.712 Units on a scale Standard Deviation 1.2164	-2.629 Units on a scale Standard Deviation 1.9943	-1.418 Units on a scale Standard Deviation 1.6274
Change From Baseline in Weekly Average of Average Daily Pain Score Week 18	-2.607 Units on a scale Standard Deviation 2.2020	-0.550 Units on a scale Standard Deviation 1.2333	-2.559 Units on a scale Standard Deviation 2.1241	-1.764 Units on a scale Standard Deviation 1.8415
Change From Baseline in Weekly Average of Average Daily Pain Score Week 2	-1.089 Units on a scale Standard Deviation 1.0258	-0.311 Units on a scale Standard Deviation 0.6285	-0.540 Units on a scale Standard Deviation 1.2503	-0.385 Units on a scale Standard Deviation 0.6863
Change From Baseline in Weekly Average of Average Daily Pain Score Week 6	-2.458 Units on a scale Standard Deviation 2.2156	-0.578 Units on a scale Standard Deviation 1.0715	-2.044 Units on a scale Standard Deviation 1.7916	-0.955 Units on a scale Standard Deviation 1.3236
Change From Baseline in Weekly Average of Average Daily Pain Score Week 8	-2.393 Units on a scale Standard Deviation 2.0249	-0.690 Units on a scale Standard Deviation 1.2819	-2.372 Units on a scale Standard Deviation 2.0607	-1.236 Units on a scale Standard Deviation 1.6026

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)

Population: mITT population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment. Here, number of participants analyzed (N) denotes those participants who were evaluable for the specified outcome measure.

Percentage of participants with \>= 30% and \>= 50% decrease in weekly average of average daily pain score from baseline is reported. Participants assessed their perceived daily average neuropathic pain over the previous 24 hours using an 11-point NRS, with 0 representing no pain and 10 representing the worst pain imaginable. Participants were instructed to assess their average daily pain at approximately the same time every morning, and to record the response in a subject diary (ePRO).

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=13 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score >=30%: Week 4	75.0 Percentage of participants	7.7 Percentage of participants	34.3 Percentage of participants	3.7 Percentage of participants
Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score >=30%: Week 8	75.0 Percentage of participants	16.7 Percentage of participants	57.6 Percentage of participants	28.3 Percentage of participants
Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score >=30%: Week 12	75.0 Percentage of participants	8.3 Percentage of participants	66.7 Percentage of participants	32.6 Percentage of participants
Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score >=30%: Week 18	50.0 Percentage of participants	25.0 Percentage of participants	56.7 Percentage of participants	35.0 Percentage of participants
Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score >=50%: Week 4	0 Percentage of participants	0 Percentage of participants	14.3 Percentage of participants	1.9 Percentage of participants
Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score >=50%: Week 8	25.0 Percentage of participants	8.3 Percentage of participants	36.4 Percentage of participants	13.0 Percentage of participants
Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score >=50%: Week 12	50.0 Percentage of participants	8.3 Percentage of participants	42.4 Percentage of participants	11.6 Percentage of participants
Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score >=50%: Week 18	25.0 Percentage of participants	0 Percentage of participants	40.0 Percentage of participants	15.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)

Population: mITT population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Here, number analyzed (n) denotes those participants who were evaluable at the specified time point.

Participants were assessed for their neuropathic pain using the Galer NPS, which included 2 descriptors of pain, including intensity and unpleasantness, and 8 descriptors that assessed specific qualities of neuropathic pain: sharp, hot, dull, cold, sensitive, itchy, deep, and surface pain. Each of these 10 dimensions had a 0 to 10 NRS in which 0 is equal to no pain and 10 equals most intense pain. Galer NPS total score (ranges from 0 to 100; with 0 and 100 representing the no and highest degree of neuropathic-like symptoms, respectively) is sum of pain intensity, pain unpleasantness, pain sharpness, pain hotness, pain dullness, pain coldness, pain sensitivity, pain itching, deep pain intensity, and surface pain intensity (all in an 11-point NRS). Change from baseline to Weeks 4, 8, 12, and 18 (follow-up) in Galer NPS total score is reported.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=12 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=31 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=48 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Change From Baseline in Galer Neuropathic Pain Scale (NPS) Week 4	-5.750 Units on a scale Standard Deviation 10.5317	-10.727 Units on a scale Standard Deviation 21.3967	-26.387 Units on a scale Standard Deviation 26.9922	-13.333 Units on a scale Standard Deviation 29.0461
Change From Baseline in Galer Neuropathic Pain Scale (NPS) Week 8	-8.750 Units on a scale Standard Deviation 18.2094	-19.333 Units on a scale Standard Deviation 23.7538	-29.516 Units on a scale Standard Deviation 32.3140	-19.136 Units on a scale Standard Deviation 31.5577
Change From Baseline in Galer Neuropathic Pain Scale (NPS) Week 12	-28.750 Units on a scale Standard Deviation 16.6808	-22.000 Units on a scale Standard Deviation 28.9379	-34.586 Units on a scale Standard Deviation 31.2622	-24.385 Units on a scale Standard Deviation 31.1081
Change From Baseline in Galer Neuropathic Pain Scale (NPS) Week 18 (follow-up)	-23.000 Units on a scale Standard Deviation 23.3095	-27.909 Units on a scale Standard Deviation 30.3725	-25.414 Units on a scale Standard Deviation 25.8947	-25.722 Units on a scale Standard Deviation 33.6151

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)

Population: mITT population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Here, number analyzed (n) denotes those participants who were evaluable at the specified time point.

Participants were assessed for how their neuropathic pain interferes with their sleep using the DSIS. It has an 11 point Likert response scale (0-10) that asked participants to "select the number that best describes how much your pain has interfered with your sleep during the past 24 hours". Responses vary from 0 (did not interfere with sleep) to 10 (completely interfered with sleep-unable to sleep due to pain). The DSIS was completed by participants once a day (upon awakening) to accurately capture variability in sleep interference due to pain on a daily basis, thus minimizing recall bias. Change from baseline to Weeks 4, 8, 12, and 18 (follow-up) in DSIS is reported.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=13 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=52 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Change From Baseline in Daily Sleep Interference Scale (DSIS) Week 4	-2.810 Units on a scale Standard Deviation 2.6979	-0.979 Units on a scale Standard Deviation 1.7930	-1.790 Units on a scale Standard Deviation 1.5688	-0.760 Units on a scale Standard Deviation 1.1212
Change From Baseline in Daily Sleep Interference Scale (DSIS) Week 8	-3.143 Units on a scale Standard Deviation 2.7430	-1.127 Units on a scale Standard Deviation 1.4907	-2.373 Units on a scale Standard Deviation 2.1368	-1.417 Units on a scale Standard Deviation 1.7654
Change From Baseline in Daily Sleep Interference Scale (DSIS) Week 12	-3.735 Units on a scale Standard Deviation 2.7598	-1.077 Units on a scale Standard Deviation 1.4769	-2.725 Units on a scale Standard Deviation 2.2484	-1.668 Units on a scale Standard Deviation 2.1928
Change From Baseline in Daily Sleep Interference Scale (DSIS) Week 18 (follow-up)	-3.036 Units on a scale Standard Deviation 2.6557	-0.865 Units on a scale Standard Deviation 1.2795	-2.602 Units on a scale Standard Deviation 2.4427	-1.824 Units on a scale Standard Deviation 2.2582

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)

Population: mITT population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment. Number of participants analyzed (N) denotes the number of participants who were PGIC responders. Here, number analyzed (n) denotes those participants who were evaluable at the specified time point.

Participants rated their overall improvement in health status using the PGIC. The PGIC consisted of a 7-point scale where 1 = very much improved and 7 = very much worse. The participants were asked the following question: How would you rate your overall improvement with treatment during the clinical study?, where the response options included the following: Very Much Improved, Much Improved, Minimally Improved, No Change, Minimally Worse, Much Worse, and Very Much Worse.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=12 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=31 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=48 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) Week 18: Very Much Improved	25.0 Percentage of participants	9.1 Percentage of participants	13.8 Percentage of participants	11.1 Percentage of participants
Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) Week 4: Improved	50.0 Percentage of participants	45.5 Percentage of participants	41.9 Percentage of participants	50.0 Percentage of participants
Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) Week 4: Much Improved	25.0 Percentage of participants	27.3 Percentage of participants	29.0 Percentage of participants	2.1 Percentage of participants
Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) Week 4: Very Much Improved	0 Percentage of participants	0 Percentage of participants	6.5 Percentage of participants	2.1 Percentage of participants
Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) Week 8: Improved	25.0 Percentage of participants	58.3 Percentage of participants	41.9 Percentage of participants	36.4 Percentage of participants
Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) Week 8: Much Improved	50.0 Percentage of participants	41.7 Percentage of participants	38.7 Percentage of participants	31.8 Percentage of participants
Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) Week 8: Very Much Improved	0 Percentage of participants	0 Percentage of participants	6.5 Percentage of participants	2.3 Percentage of participants
Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) Week 12: Improved	0 Percentage of participants	54.5 Percentage of participants	44.8 Percentage of participants	48.7 Percentage of participants
Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) Week 12: Much Improved	75.0 Percentage of participants	36.4 Percentage of participants	41.4 Percentage of participants	28.2 Percentage of participants
Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) Week 12: Very Much Improved	25.0 Percentage of participants	0 Percentage of participants	10.3 Percentage of participants	5.1 Percentage of participants
Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) Week 18: Improved	25.0 Percentage of participants	27.3 Percentage of participants	31.0 Percentage of participants	36.1 Percentage of participants
Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC) Week 18: Much Improved	50.0 Percentage of participants	54.5 Percentage of participants	41.4 Percentage of participants	25.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1, inclusive) and Week 12

Population: mITT population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure.

Change from baseline to Week 12 in SF-36 is reported. The SF-36 assesses 8 health concepts: 1) limitations in physical activities because of health problems (physical functioning); 2) limitations in social activities because of physical or emotional problems (social functioning); 3) limitations in usual role activities because of physical health problems (role physical); 4) bodily pain; 5) general mental health; 6) limitations in usual role activities because of emotional problems (role emotional); 7) vitality; and 8) general health perceptions. The items use Likert-type scales with either 5 or 6 points, or 2 or 3 points. Higher SF-36 scores indicate a better state of health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=12 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=29 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=39 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Change From Baseline in 36-item Short-Form Health Survey (SF-36) Physical Functioning	21.248 Units on a scale Standard Deviation 13.1526	0.417 Units on a scale Standard Deviation 19.7084	12.759 Units on a scale Standard Deviation 16.6141	11.282 Units on a scale Standard Deviation 17.0412
Change From Baseline in 36-item Short-Form Health Survey (SF-36) Role Physical	28.125 Units on a scale Standard Deviation 27.7169	0.000 Units on a scale Standard Deviation 37.3101	6.681 Units on a scale Standard Deviation 17.4338	7.372 Units on a scale Standard Deviation 18.0159
Change From Baseline in 36-item Short-Form Health Survey (SF-36) Bodily Pain	9.8 Units on a scale Standard Deviation 22.75	12.1 Units on a scale Standard Deviation 23.11	14.9 Units on a scale Standard Deviation 17.30	8.3 Units on a scale Standard Deviation 20.51
Change From Baseline in 36-item Short-Form Health Survey (SF-36) General Health	-2.5 Units on a scale Standard Deviation 5.00	-5.3 Units on a scale Standard Deviation 17.72	0.0 Units on a scale Standard Deviation 19.98	-2.6 Units on a scale Standard Deviation 17.70
Change From Baseline in 36-item Short-Form Health Survey (SF-36) Vitality	3.125 Units on a scale Standard Deviation 16.5359	-0.521 Units on a scale Standard Deviation 17.7695	-4.095 Units on a scale Standard Deviation 24.0486	-0.160 Units on a scale Standard Deviation 20.6039
Change From Baseline in 36-item Short-Form Health Survey (SF-36) Social Functioning	31.25 Units on a scale Standard Deviation 23.936	-1.04 Units on a scale Standard Deviation 24.108	9.05 Units on a scale Standard Deviation 23.121	1.92 Units on a scale Standard Deviation 19.772
Change From Baseline in 36-item Short-Form Health Survey (SF-36) Role Emotional	8.333 Units on a scale Standard Deviation 31.9110	-5.556 Units on a scale Standard Deviation 34.8748	-1.724 Units on a scale Standard Deviation 19.9681	-1.923 Units on a scale Standard Deviation 25.3248
Change From Baseline in 36-item Short-Form Health Survey (SF-36) Mental Health	10.0 Units on a scale Standard Deviation 20.41	-1.3 Units on a scale Standard Deviation 14.48	-0.7 Units on a scale Standard Deviation 18.41	-5.9 Units on a scale Standard Deviation 21.82

SECONDARY outcome

Timeframe: Baseline (Day -7 to Day -1, inclusive) through Week 12

Population: mITT population included all participants who received at least 1 dose of any double-blind study drug and have at least 1 daily NRS assessment while receiving the treatment.

Percentage of participants taking any rescue medication are reported. Participants were asked to record all rescue medications they take for neuropathic pain in a paper diary.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Percentage of Participants Taking Any Rescue Medication	0 Percentage of participants	14.3 Percentage of participants	8.6 Percentage of participants	13 Percentage of participants

SECONDARY outcome

Timeframe: Day 1 through 20.42 weeks (maximum observed duration)

Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Any TEAEs	4 Participants	10 Participants	23 Participants	30 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Any TESAEs	0 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1 through 20.42 weeks (maximum observed duration)

Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.

Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body temperature, diastolic blood pressure, systolic blood pressure, heart \[pulse\] rate, and respiratory rate).

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Number of Participants With Abnormal Vital Signs Reported as TEAEs Hypertension	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Blood pressure increased	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Hypotension	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Orthostatic hypertension	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Orthostatic hypotension	0 Participants	0 Participants	0 Participants	3 Participants

SECONDARY outcome

Timeframe: Day 1 through 20.42 weeks (maximum observed duration)

Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Number of participants analyzed (N) denotes the number of participants who were evaluable for the specified outcome measure. Here, number analyzed (n) denotes those participants who were evaluable at the specified time point.

Number of participants with clinically significant abnormal ECGs are reported.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) Day 1	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) Week 4	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) Week 8	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) Week 12	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) Week 18 (follow-up)	0 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 through 20.42 weeks (maximum observed duration)

Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.

Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of hematology, clinical chemistry, coagulation, and urinalysis.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Alanine aminotransferase increased	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Blood glucose decreased	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Aspartate aminotransferase increased	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Blood glucose increased	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs C-reactive protein increased	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Coagulation test abnormal	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Glomerular filtration rate decreased	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs White blood cells urine positive	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Bacterial test positive	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Blood bilirubin increased	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Protein urine present	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Urine analysis abnormal	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Hypoglycemia	0 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Hypercholesterolaemia	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Hyperglycaemia	0 Participants	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1 through 20.42 weeks (maximum observed duration)

Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.

Number of participants with clinically significant findings in physical examination reported as TEAE are reported. A complete physical examination (excluding the genitourinary examination, unless warranted) was performed.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs	0 Participants	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1 through 20.42 weeks (maximum observed duration)

Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.

Number of participants with clinically significant findings in neurological examination is reported.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Number of Participants With Clinically Significant Findings in Neurological Examination	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 through 20.42 weeks (maximum observed duration)

Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were assessed for strength and deep tendon reflexes assessment.

Number of participants with abnormal dorsiflexion strength is reported. Dorsiflexion strength is scored on 0-4 scale. The scale indicated 0 = normal power, 1 = mild weakness, 2 = moderate weakness, 3 = severe weakness, and 4 = paralysis.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=12 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=30 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=40 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Number of Participants With Abnormal Dorsiflexion Strength Paralysis	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Dorsiflexion Strength Mild Weakness	0 Participants	7 Participants	18 Participants	9 Participants
Number of Participants With Abnormal Dorsiflexion Strength Moderate Weakness	0 Participants	0 Participants	2 Participants	8 Participants
Number of Participants With Abnormal Dorsiflexion Strength Severe Weakness	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 through 20.42 weeks (maximum observed duration)

Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were assessed for strength and deep tendon reflexes assessment.

Number of participants with abnormal deep tendon reflex are reported. Deep tendon reflex (knee and ankle) strength is scored on 0-4 scale. The scale indicated 0 = normal, 1 = ankle reflex reduced, 2 = ankle reflex absent, 3 = ankle reflex absent and knee reflex reduced, and 4 = all reflexes (both ankle and knee) absent. Participants within a specific row are not included in any other row in the data table below.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=12 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=30 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=40 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) Ankle reflex absent	0 Participants	1 Participants	5 Participants	4 Participants
Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) Ankle reflex reduced	2 Participants	2 Participants	3 Participants	5 Participants
Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) Ankle reflex absent and knee reflex reduced	1 Participants	3 Participants	13 Participants	11 Participants
Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle) All reflexes absent	0 Participants	6 Participants	5 Participants	15 Participants

SECONDARY outcome

Timeframe: Baseline (Day -45 to -1), pre-dose on Day 1, Weeks 2, 4, 6, 8, 10, 12, and 18/early termination

Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Here, number analyzed (n) denotes those participants who were evaluable at the specified time point.

The TNSn, a semi-quantitative clinical assessment of peripheral nervous system function, was administered at baseline (Screening), Day 1, Weeks 2, 4, 6, 8, 10, 12 and Week 18/early termination. The TNSn provides for an assessment of motor symptom score, autonomic symptom score, pin sensibility score, and vibration sensibility score. Each neuropathy item is scored on a 0-4 scale. The scores are summed to obtain a total score ranging from 0 to 20. Higher total scores correlate with more severe neuropathy. Not all of the early terminated participants completed the 18 week assessment. Only 3 early terminated participants contributed data at the Week 18 assessment.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=13 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=34 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=50 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Change From Baseline in Total Neuropathy Score-Nurse (TNSn) Week 4	-2.50 Units on a scale Standard Deviation 3.786	-0.85 Units on a scale Standard Deviation 1.819	-1.19 Units on a scale Standard Deviation 1.891	-0.90 Units on a scale Standard Deviation 1.982
Change From Baseline in Total Neuropathy Score-Nurse (TNSn) Week 12	-2.25 Units on a scale Standard Deviation 2.062	-2.17 Units on a scale Standard Deviation 1.899	-2.53 Units on a scale Standard Deviation 2.515	-1.73 Units on a scale Standard Deviation 2.562
Change From Baseline in Total Neuropathy Score-Nurse (TNSn) Week 18	-2.50 Units on a scale Standard Deviation 3.512	-2.17 Units on a scale Standard Deviation 2.329	-2.30 Units on a scale Standard Deviation 3.053	-2.00 Units on a scale Standard Deviation 2.631
Change From Baseline in Total Neuropathy Score-Nurse (TNSn) Day 1	—	—	1.00 Units on a scale Standard Deviation NA Standard deviation was not reported as only one participant was evaluable for this arm	-0.25 Units on a scale Standard Deviation 0.957
Change From Baseline in Total Neuropathy Score-Nurse (TNSn) Week 2	-1.25 Units on a scale Standard Deviation 1.258	0.00 Units on a scale Standard Deviation 1.354	-0.94 Units on a scale Standard Deviation 2.117	-0.54 Units on a scale Standard Deviation 1.304
Change From Baseline in Total Neuropathy Score-Nurse (TNSn) Week 6	-0.75 Units on a scale Standard Deviation 2.872	-1.00 Units on a scale Standard Deviation 1.859	-1.85 Units on a scale Standard Deviation 2.093	-1.40 Units on a scale Standard Deviation 2.071
Change From Baseline in Total Neuropathy Score-Nurse (TNSn) Week 8	-2.50 Units on a scale Standard Deviation 3.000	-0.92 Units on a scale Standard Deviation 1.881	-1.84 Units on a scale Standard Deviation 2.665	-1.40 Units on a scale Standard Deviation 2.082
Change From Baseline in Total Neuropathy Score-Nurse (TNSn) Week 10	-2.00 Units on a scale Standard Deviation 3.916	-1.67 Units on a scale Standard Deviation 1.435	-2.45 Units on a scale Standard Deviation 3.042	-1.90 Units on a scale Standard Deviation 2.458

SECONDARY outcome

Timeframe: Day 1 through 20.42 weeks (maximum observed duration)

Population: Safety population included all participants who received at least 1 dose of any study drug and were analyzed according to the treatment they actually received.

Motor and sensory nerve conduction studies were performed in relevant lower and upper limb nerves (sural, peroneal, median/ulnar, fibular, and tibial nerves) wherein amplitude, peak latency, conduction velocity, and duration of nerve action potentials were recorded.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Number of Participants With Investigator Reported Significant Changes From Baseline in Motor and Sensory Nerve Conduction	0 Participants	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 1 through 20.42 weeks (maximum observed duration)

Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.

Number of participants with at least one concomitant medication is reported. A concomitant medication is defined as any medication continuing or starting after first dose of study medication.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Number of Participants With at Least One Concomitant Medication	4 Participants	14 Participants	35 Participants	54 Participants

SECONDARY outcome

Timeframe: Day 1 through 20.42 weeks (maximum observed duration)

Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.

Number of participants with injection site reaction is reported.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Number of Participants With Injection Site Reaction	1 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1 through 20.42 weeks (maximum observed duration)

Population: Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.

Number of participants with infusion reaction is reported.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=54 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Number of Participants With Infusion Reaction	0 Participants	0 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 (pre-dose; baseline), Weeks 2, 4, 6, 8, 10 (Day 70; pre-dose, immediately before end of infusion, 8 hours and 24 hours post Day 70 infusion [Day 71]), 11, and 12 (approximately same time of day as Week 10 infusion)

Population: Safety population: participants received at least 1 dose of any double-blind study drug and were analyzed according to treatment actually received. Number of participants analyzed: participants evaluated for this outcome measure. Number analyzed (n): participants evaluable at specified time point. MEDl7352 low and medium dose group data is not reported due to change in assay during course of study and stability data not supporting re-analysis of early study samples with new in-house assay.

Serum concentrations of total NGF in ADA positive or negative participants are reported.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=31 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=30 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Serum Total Nerve Growth Factor (NGF) Concentrations Week 11	—	—	1743.100 pg/mL Standard Deviation 2621.0687	59.441 pg/mL Standard Deviation 13.6892
Serum Total Nerve Growth Factor (NGF) Concentrations Day 1	—	—	65.687 pg/mL Standard Deviation 60.4036	52.303 pg/mL Standard Deviation 11.6178
Serum Total Nerve Growth Factor (NGF) Concentrations Week 2	—	—	2384.760 pg/mL Standard Deviation 1989.0309	62.613 pg/mL Standard Deviation 15.1088
Serum Total Nerve Growth Factor (NGF) Concentrations Week 4	—	—	2213.699 pg/mL Standard Deviation 2408.3112	78.209 pg/mL Standard Deviation 92.0122
Serum Total Nerve Growth Factor (NGF) Concentrations Week 6	—	—	2361.855 pg/mL Standard Deviation 2645.8141	64.661 pg/mL Standard Deviation 18.6478
Serum Total Nerve Growth Factor (NGF) Concentrations Week 8	—	—	1992.129 pg/mL Standard Deviation 2507.9826	63.291 pg/mL Standard Deviation 16.5332
Serum Total Nerve Growth Factor (NGF) Concentrations Week 10 (pre-dose)	—	—	1681.073 pg/mL Standard Deviation 2455.0666	173.383 pg/mL Standard Deviation 563.8921
Serum Total Nerve Growth Factor (NGF) Concentrations Week 10 (before end of infusion)	—	—	1992.756 pg/mL Standard Deviation 2968.1285	57.308 pg/mL Standard Deviation 13.3588
Serum Total Nerve Growth Factor (NGF) Concentrations Week 10 (8 hours post-dose)	—	—	2012.384 pg/mL Standard Deviation 2795.8138	177.323 pg/mL Standard Deviation 554.8131
Serum Total Nerve Growth Factor (NGF) Concentrations Week 10 (post 24 hours)	—	—	1849.835 pg/mL Standard Deviation 2671.9526	222.980 pg/mL Standard Deviation 772.9408
Serum Total Nerve Growth Factor (NGF) Concentrations Week 12	—	—	1710.966 pg/mL Standard Deviation 2838.0975	63.416 pg/mL Standard Deviation 18.4243

SECONDARY outcome

Timeframe: Pre-dose at baseline (Day -45 to -1) and Study Weeks 2, 4, 8, 10, 12, and 18 (follow-up)

Number of participants with positive ADA to MEDI7352 are reported. Treatment-induced ADA positive is defined as ADA negative at baseline and positive at least 1 post-baseline assessment. Treatment-boosted ADA positive is defined as ADA positive at baseline with pre-existing titre boosted by 4-fold or greater during the study period. Persistent positive is defined as ADA negative at baseline and positive at least 2 post-baseline assessments (with \>= 16 weeks between first and last positive) or ADA positive at last post-baseline assessment. Transiently positive is defined as ADA negative at baseline and at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.

Outcome measures

Outcome measures
Measure	MEDl7352 Low Dose n=4 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 Participants Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	Placebo n=53 Participants Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 Treatment-induced ADA	3 Participants	7 Participants	28 Participants	0 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 Treatment-boosted ADA	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 Persistently positive ADA	3 Participants	6 Participants	26 Participants	0 Participants
Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352 Transiently positive ADA	0 Participants	1 Participants	2 Participants	0 Participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 30 other events

Deaths: 0 deaths

MEDl7352 Low Dose

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

MEDl7352 Meduim Dose

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

MEDI7352 High Dose

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=54 participants at risk Participants received 6 doses of intravenous (IV) placebo infusion matched to MEDl7352 during 12-week treatment period.	MEDl7352 Low Dose n=4 participants at risk Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDl7352 Meduim Dose n=14 participants at risk Participants received 6 doses of IV MEDl7352 during 12-week treatment period.	MEDI7352 High Dose n=35 participants at risk Participants received 6 doses of IV MEDl7352 during 12-week treatment period.
Infections and infestations Lung abscess	1.9% 1/54 • Number of events 1 • Day 1 through 20.42 weeks (maximum observed duration) Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.	0.00% 0/4 • Day 1 through 20.42 weeks (maximum observed duration) Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.	0.00% 0/14 • Day 1 through 20.42 weeks (maximum observed duration) Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.	0.00% 0/35 • Day 1 through 20.42 weeks (maximum observed duration) Safety population included all participants who received at least 1 dose of any double-blind study drug and were analyzed according to the treatment they actually received.

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca Clinical Study Information Center

Phone: +1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee AstraZeneca has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
Publication restrictions are in place

Restriction type: OTHER